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    Journal of Shanghai Jiao Tong University (Medical Science) 2022 Vol.42
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    Progress and controversy in comprehensive treatment of hilar cholangiocarcinoma
    Wei CHEN, Yingbin LIU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 1-8.   DOI: 10.3969/j.issn.1674-8115.2022.01.001
    Abstract643)   HTML100)    PDF(pc) (1076KB)(703)       Save

    Hilar cholangiocarcinoma is a tumor with a poor prognosis, which is difficult to diagnosis in the early stage and has caused lots of controversies in clinical treatment. At present, surgical resection provides the main possibility for cure. Precise evaluation and adequate preparation before surgery and safe, effective, standardized resection are the key methods to successful treatment. Comprehensive treatment based on chemotherapy improves the survival of patients. In the future, guided by concepts of oncology, comprehensive treatment of multiple modes, containing surgery, chemotherapy, targeted therapy, immune therapy and biological therapy, is the development trend of hilar cholangiocarcinoma treatment.

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    Influences of oral administration of probiotics on postoperative infection and liver function recovery in patients with partial hepatectomy
    Yi WU, Fang FANG, Hao HUANG, Ying CHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 9-15.   DOI: 10.3969/j.issn.1674-8115.2022.01.002
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    Objective

    ·To investigate the influences of oral administration of probiotics on postoperative infection and liver function recovery in patients with partial hepatectomy.

    Methods

    ·A total of 165 patients undergoing partial hepatectomy in Shanghai General Hospital, Shanghai Jiao Tong University, were involved in this prospective randomized control study. In accordance with the random number table, patients were divided into mechanical bowel preparation group (MBP group, n=55), non-bowel preparation group (NBP group, n=55) and probiotics bowel preparation group (PBP group, n=55). Patients' general information, postoperative fever, the first time of flatus and defecation, and infectious indexes and liver function indexes on the 1st,3rd and 5th day after operation were collected and compared among the groups.

    Results

    ·There was no significant difference in the basic data among the 3 groups (all P>0.05). On the 5th day after operation, the white blood count of the PBP group was significantly lower than that of the MBP group (P=0.012) and NBP group (P=0.029). The level of glutamic-pyruvic transaminase of the PBP group was significantly lower than that of the MBP group and NBP group on the 3rd day (P=0.040, P=0.036) and the 5th day (P=0.002, P=0.019) after operation.

    Conclusion

    ·Oral probiotics intestinal preparation is helpful to reduce infection after partial hepatectomy and accelerate the recovery of liver function.

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    Application of modified Nutrition Risk in the Critically Ill score to critically ill elderly patients
    Xuemei LU, Lan CHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 16-20.   DOI: 10.3969/j.issn.1674-8115.2022.01.003
    Abstract624)   HTML22)    PDF(pc) (859KB)(501)       Save
    Objective

    ·To validate the role of the modified Nutrition Risk in the Critically Ill (mNUTRIC) score in the assessment of nutritional risk and clinical prognosis in critically ill elderly patients.

    Methods

    ·A prospective observational study was carried out. The mNUTRIC score was employed to assess the nutritional risk of elderly patients who were admitted into the intensive care unit (ICU) of Shanghai General Hospital, Shanghai Jiao Tong University between October 2020 and February 2021. Patients were divided into high nutritional risk group and low nutritional risk group based on the mNUTRIC score results. The observational end-points were transferred, discharged or death. Different nutrition risk patients' nutritional support were analyzed, including nutritional support methods, the time period before nutritional support, and energy supply conditions. The length of ICU stay, days with mechanical ventilation, and 28-day mortality of different nutrition risk patients were compared.

    Results

    ·Among critically ill elderly patients, 51.8% were at high nutritional risk. The energy compliance rate of the low nutritional risk group was 73.3%, and that of the high nutritional risk group was 58.8%. It took 5.00 (1.00, 8.00) d for the low nutritional risk group and 9.00 (3.00, 12.50) d for the high nutritional risk group to reach the energy standard. There was no statistical difference in the nutritional support methods, the time period before nutritional support, and energy supply conditions between the two groups. The mechanical ventilation time of the high nutritional risk group was 5.00 (1.50, 12.50) d, longer than that of the low nutritional risk group (P=0.018). The 28-day mortality rate of the high nutritional risk group was 47.7%, higher than that of the low nutritional risk group (P=0.001). There was no statistical difference in ICU stay between the two groups.

    Conclusion

    ·mNUTRIC score can be used to evaluate nutritional risk and predict the clinical prognosis of critically ill elderly patients. It is suggested that stratified clinical nutrition management should be carried out for the critically ill elderly patients with different nutritional risks. Critically ill elderly patients can benefit from personalized nutritional support programs, and the clinical prognosis of patients may be improved.

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    Relationship between preoperative glycosylated hemoglobin and postoperative delirium in patients following off-pump coronary artery bypass grafting
    Ye HE, Fang FANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 21-27.   DOI: 10.3969/j.issn.1674-8115.2022.01.004
    Abstract495)   HTML24)    PDF(pc) (1071KB)(430)       Save
    Objective

    ·To investigate the relationship between postoperative delirium and preoperative HbA1c in patients with off-pump coronary artery bypass grafting (OPCAB), so as to provide reference for further intervention.

    Methods

    ·A prospective study was used to collect 364 surgical patients admitted to the Department of Cardiac Surgery in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. The data were collected through the general information questionnaire and the simple mental status assessment scale, and the Confusion Assessment Method of Intensive Care Unit, and Chinese Version of 3-minute Diagnostic Confusion Assessment Method were used to assess postoperative delirium. Univariate analysis was used to screen out the risk factors for delirium with P<0.05, and then a multi-factor Logistic regression analysis was used. The generalized additive model was used to observe the dynamic changes of HbA1c and the incidence of postoperative delirium, and the receiver operating characteristic (ROC) curve was drawn to clarify the boundary value.

    Results

    ·The influencing factors of postoperative delirium in OPCAB patients were age, alcohol use, peripheral vascular disease, NYHA function classification, LVEF, albumin, HbA1c, intraoperative blood transfusion, acid-base imbalance, and electrolyte imbalance. The generalized additive model and multivariate Logistic regression analysis showed that the higher the preoperative HbA1c, the higher the incidence of postoperative delirium in OPCAB patients.Through ROC curve analysis, it was determined that when the HbA1c>6.45%, the risk of delirium after OPCAB increased accordingly.

    Conclusion

    ·For patients undergoing OPCAB surgery, HbA1c is an independent risk factor for postoperative delirium. With the increase of HbA1c, the incidence of delirium gradually increases, suggesting that the preoperative HbA1c of OPCAB patients should be maintained at a normal level.

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    Development of knowledge-attitude-practice questionnaire for mechanical prophylaxis of deep venous thrombosis and its reliability and validity testing
    Chunhong HAN, Jie WANG, Yang HONG, Yahui TONG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 28-35.   DOI: 10.3969/j.issn.1674-8115.2022.01.005
    Abstract488)   HTML24)    PDF(pc) (950KB)(436)       Save
    Objective

    ·To develop a knowledge-attitude-practice questionnaire for mechanical prophylaxis of deep venous thrombosis for orthopedic nurses in China, and analyze its reliability and validity.

    Methods

    ·On the basis of literature review, combined with the characteristics of orthopedic diseases and orthopedic nurses, a preliminary questionnaire for mechanical prophylaxis of deep venous thrombosis was prepared. In January 2020, two rounds of expert letter consultation were conducted to demonstrate and modify the items in the first draft and form the test version of the questionnaire for mechanical prophylaxis of deep vein thrombosis.In March 2020, tests were conducted among 620 orthopedic nurses from 36 medical units in 13 cities in Jiangsu Province. Item analysis was carried out with critical ratio method and homogeneity test. Reliability analysis was carried out from internal consistency reliability, split-half reliability and retest reliability. Validity was analyzed from content validity and structure validity.

    Results

    ·The first draft of the questionnaire contained 37 items; after the first round of expert consultation, 4 items were revised and 7 items were added; after the second round of expert consultation, a test version of the questionnaire containing 44 items was formed. A total of 620 questionnaires were distributed. The effective recovery rate of the questionnaire was 96.77%. The critical ratio method showed that the item decision values t, which reflected the t-test results of independent samples of high and low groups, ranged from 5.89 to 20.31, and the difference was statistically significant (all P<0.05). The homogeneity test showed that Pearson correlation coefficient r, which reflected the correlation between the score of each item and the total score of the scale, ranged from 0.49 to 0.79, and the difference was statistically significant (all P<0.05). Therefore, 44 items were retained after item analysis. The Cronbach's α coefficient reflecting the internal consistency of the total questionnaire was 0.893, the Spearman-Brown coefficient reflecting the half-fold reliability was 0.794, and the intraclass correlation coefficient reflecting the retest reliability was 0.909. The scale-level content validity index reflecting content validity was 0.926 and the item-level content validity index was 0.833?1. Kaiser-Meyer-Olkin measure of sampling adequacy and Bartlett's sphericity test chi-square value which reflected the structure validity were 0.883 and 12 560.176 (df=666, P<0.05) respectively. These values indicated that the questionnaire was suitable for exploratory factor analysis. In addition, 7 items were deleted according to the absolute value of factor load. Finally, 37 items remained. Seven common factors with eigenvalue greater than 1 were extracted. The 7 common factors were named the act of mechanical prophylaxis, risk perception of mechanical prophylaxis, indications of mechanical prophylaxis, contraindications of mechanical prophylaxis, conceptual cognition of mechanical prophylaxis, mechanical preventive response and health education cognition of mechanical prophylaxis, respectively. The cumulative variance contribution rate was 61.992%.

    Conclusion

    ·The questionnaire in this study shows good reliability and validity. It can be used as an investigation tool to study the current attitude, knowledge and behavior of mechanical prophylaxis of orthopedic nurses.

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    Enhancement of BMP4 inhibitor DMH1 on the efficiency of BiSF in human iPSC-induced differentiation into neurons
    Yanna LIU, Zhaorui REN, Jingbin YAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 36-43.   DOI: 10.3969/j.issn.1674-8115.2022.01.006
    Abstract605)   HTML39)    PDF(pc) (4932KB)(313)       Save
    Objective

    ·To obtain an efficient way of promoting induced human pluripotent stem cells (hiPSCs) to differentiate into neurons by improving existing methods BiSF.

    Methods

    ·Induction was initiated when hiPSCs reached 75% fusion, and BMP4 inhibitor (4-[6-[4-(1-methylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline,DMH1) was added based on this induction method. The growth state was observed under microscope, and the expression of neural stem cell (NSC)-specific genes was quantitatively detected by quantitative real-time PCR (qRT-PCR) and immunofluorescence analysis. The proliferation level of the induced cells was determined by cell counting kit-8 (CCK-8). Then the NSC-like cells were further induced into neurons, and the ability of differentiation was detected by qRT-PCR and immunofluorescence.

    Results

    ·Microscopically, it was found that more spindle cells appeared around the cell mass of BiSF+DMH1 group on day 9, and a small amount of spindle cells appeared in the BiSF group with irregular gray cell clusters. CCK-8 growth curve showed that the cells derived from method BiSF+DMH1 were with a significantly higher proliferation on the next day (P=0.000). The cells derived from method BiSF+DMH1 achieved higher expression of nestin and PAX6 (P=0.019, P=0.011). The number of neurons with positive neuron-specific marker βⅢ-tubulin in the BiSF+ DMH1 group was significantly higher than that in BiSF group (P=0.003). The results of qRT-PCR showed that the relative expression of MAP2 in the BiSF+DMH1 group was significantly higher than that in the BiSF group (P=0.006).

    Conclusion

    ·The synergistic effect of DMH1 can significantly improve the efficiency of hiPSCs to differentiate into neurons.

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    Role of autosis of fibroblasts in hypertrophic scar regression
    Jian ZHANG, Fei SONG, Xiqiao WANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 44-50.   DOI: 10.3969/j.issn.1674-8115.2022.01.007
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    Objective

    ·To investigate whether autosis occurred in fibroblasts during hypertrophic scar regression.

    Methods

    ·The scar tissues of 16 burn patients were collected from June 2018 to June 2019 in the Burn Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. They were divided into two groups: hyperplasia group (control group, 8 cases) and regression group (experimental group, 8 cases). Autophagy was observed by transmission electron microscopy. Fibroblasts of the two groups were cultured in vitro to establish a hypoxia model. The fibroblasts were collected at 12, 24 and 48 h respectively, and autophagy was observed by transmission electron microscopy. Live/dead cells were detected by using Calcein /PI fluorescent dye kit. The autophagy and apoptosis were observed by immunofluorescence. The numbers of apoptosis and autophagic death were detected by flow cytometry. Then the expression of hypoxia inducible factor1 (HIF-1), beclin-1, microtuble-associated protein light chain 3 (LC3), caspase-3 and caspase-9 were assayed at the protein level. Student's t test was used for quantitative data between the two groups, and One-way ANOVA test was used for quantitative data among multiple groups.

    Results

    ·The electron microscopy showed that autophagosome existed in hyperplasia scar, and autosis occured in the regressive scar. In vitro study by electron microscopy was consistent with in vivo tissue observation. The dead cells had a marked increase at 24 hours, and further increased at 48 hours. Among them, the cell death type was mainly autosis, and a small amount of apoptosis. High expression of LC3 was responsible for this.

    Conclusion

    ·In addition to apoptosis, autosis may be the major cell death during hypertrophic scar regression, and LC3 plays an important role.

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    Screening potential hub genes associated with myocardial ischemia-reperfusion injury in mice based on GEO database and bioinformatics analysis
    Jianru WANG, Guangcao PENG, Mingjun ZHU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 51-62.   DOI: 10.3969/j.issn.1674-8115.2022.01.008
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    Objective

    ·To screen the potential hub genes associated with myocardial ischemia-reperfusion injury (MIRI) in mice by bioinformatics analysis based on gene expression omnibus (GEO) database.

    Methods

    ·The mouse MIRI data sets GSE61592, GSE83472 and GSE160516 were obtained from GEO database. The differentially expressed genes (DEGs) in each data set were screened by limma package, and then robust DEGs were screened by robust sorting integration (RRA) method. The protein-protein interaction (PPI) network of robust DEGs was constructed, and the submodules and hub genes in the PPI network were screened. The clusterProfiler package was used to analyze the robust DEGs, the most important submodule genes and hub genes by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Eighteen male C57BL/6 J mice aged 6?8 weeks were randomly divided into sham group and MIRI group, 9 mice each group. The MIRI model was constructed by left anterior descending coronary artery ligation for 30 min ischemia and 24 h reperfusion, and the mRNA expression of hub genes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

    Results

    ·RRA method identified 294 robust DEGs in three data sets. In PPI network, a total of 14 sub-modules were screened, of which module 1 was the most important and 17 hub genes were found. GO and KEGG analysis showed that the robust DEGs, module 1 genes, and the hub genes were mainly involved in regulating the migration of inflammatory cells, the activity of chemokines and cytokines and their receptors, Toll-like receptors and other biological function and signaling pathways. RT-qPCR results showed that compared with the sham group, the expressions of chemokine (C-C motif) ligand 4 (Ccl4), Ccl6, Ccl7, chemokine (C-X-C motif) receptor 4 (Cxcr4), chemokine (C-C motif) receptor 2 (Ccr2), signal-regulatory protein β1 (Sirpb1), low affinity immunoglobulin gamma Fc region receptor Ⅱb (Fcgr2b), leukocyte surface antigen CD53 (Cd53), arachidonate 5-lipoxygenase activating protein (Alox5ap), myeloid differentiation primary response gene 88 (Myd88), macrophage scavenger receptor 1 (Msr1), matrix metallopeptidase 14 (Mmp14), triggering receptor expressed on myeloid cells 2 (Trem2) and leupaxin (Lpxn) were up-regulated in the myocardium of the MIRI group, but there was no difference in low affinity immunoglobulin gamma Fc region receptor Ⅲ (Fcgr3), complement C1q subcomponent subunit B (C1qb) and a disintegrin and metalloproteinase domain-containing protein 8 (Adam8). By reviewing the literatures, Trem2, Lpxn, Cd53, Alox5ap, Sirpb1 and Fcgr2b were not reported to participate in MIRI.

    Conclusion

    ·This study has unearthed 6 potential hub genes for MIRI in mice, and the results can provide new ideas and entry points for further exploring the molecular mechanism and therapeutic targets of MIRI.

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    Molecular genetic diagnosis of 9 cases with 46,XY complete gonadal dysgenesis
    Haicheng WANG, Yu LIU, Hui YE, Lin NI, Ying CAO, Yunlong SUN, Bing XIAO, Caixia MA, Lifang TANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 63-69.   DOI: 10.3969/j.issn.1674-8115.2022.01.009
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    Objective

    ·To identify the genetic causes of 9 patients with 46,XY complete gonadal dysgenesis (CGD) .

    Methods

    ·The genetic variations of 9 patients with 46,XY CGD were analyzed by combining SRY mutation screening, next generation sequencing (NGS) and chromosome microarray (CMA).

    Results

    ·SRY mutations were identified in 4 of nine 46,XY CGD probands, including 2 patients with novel SRY gene pathogenic/likely pathogenic mutations, namely SRY deletion and c.208T>C (p.Trp70Arg) missense variation, and 2 patients with reported SRY pathogenic mutation, namely c.169C>T(p.Gln57X) and c.264dup(p.Glu89fs*15). One patient was identified with a heterozygous mutation in MAP3K1 gene c.1016G>A (p.Arg339Gln) by NGS, which was likely pathogenic mutation. In addition, CMA analysis and NGS found no pathogenic copy number variations (CNVs) in other 2 sporadic patients. Whole exome sequencing (WES) was performed on the younger of two sisters, whose parents were consanguineous marriage, filtered homozygous variants in the homozygous regions, no specific deleterious variants or likely variants associated with sexual development were found. CNVs analysis found an approximate 14 kb homozygous deletion in intron 2 of DMRT1 gene in both sister cases (Chr9: 866, 388-880, 086, hg19), and PCR sequencing with amplified spanned the junction revealed that healthy parents were heterozygous deletion carriers. Then PhastCons software was used to analyze the conserved fragments of the deletion intron sequences and two conserved non-coding elements (CNEs) were found.

    Conclusion

    ·SRY mutation was the frequent cause accounted for 46,XY CGD, and 2 novel pathogenic mutations in SRY gene were found. The 14 kb homozygous deletion in intron 2 of DMRT1 might be candidate pathogenic mutation for the sister patients. Stepwise analysis of genetic causes of 46,XY CGD patients might help to fully learn about the molecular changes in these patients.

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    Comparative analysis of 30 cases of metaplastic carcinoma of the breast
    Cui CHEN, Ye JIN, Lin WANG, Hongli LI, Caifeng WAN, Lixin JIANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 70-76.   DOI: 10.3969/j.issn.1674-8115.2022.01.010
    Abstract587)   HTML21)    PDF(pc) (2397KB)(185)       Save
    Objective

    ·To comparatively analyze features of metaplastic carcinoma of the breast (MBC) images and immunological characteristics.

    Methods

    ·The data of 30 patients with MBC treated in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2008 to January 2021 were analyzed retrospectively, and the imaging findings and immunohistochemical results of tumors were analyzed and compared.

    Results

    ·A total of 31 lesions were found in 30 cases of MBC, including 18 squamous cell carcinomas, 3 mixed metaplastic carcinomas, 7 mesenchymal differentiated carcinomas, 1 myoepithelial carcinoma, and 2 spindle cell carcinomas. All patients were female, aged from 33 to 89 years old, with an average age of (61.8±14.2) years. The maximum size of the tumors was 101.0 mm while the minimal was 6.6 mm, with the medium size 25.5 mm and the average size (33.1±18.5) mm. A total of 29 patients underwent ultrasound examination before operation, with a total of 30 lesions. Among them, 23 lesions were irregular-shaped (76.7%), 19 lesions were hypoechoic (63.3%), 11 lesions were mixed echogenicity (36.7%), 14 lesions were found with unclear boundary (46.7%), and 7 lesions were accompanied by small internal calcifications (23.3%). Five cases of axillary lymph nodes were found, in which 3 cases were confirmed by pathology as lymph node metastasis (10.3%). Eight patients were examined by computed radiography (CR), showing lobulated, lumpy or asymmetrical shape, with unclear boundary, and some of them were found with coarse, heterogeneous or fine sand-like calcification. Magnetic resonance imaging (MRI) showed low signal intensity on T1 weighted imaging (T1WI) and T2WI in 6 patients. After enhancement, uneven signal, obscure border, and lobulated shape were shown. The MRI images of 3 patients showed that there was the possibility of surrounding tissue invasion and axillary lymph node metastasis respectively, but ultrasound examination did not show that. Except the invasion of pectoralis major, which was confirmed by pathology, the other 2 cases were all false positive. Four cases accepted CR, MRI and ultrasound, 2 cases of small calcification were missed by MRI and 1 case of axillary lymph node was missed by ultrasound. Sixteen lesions were triple-negative (51.6%), estrogen receptor (ER)/progesterone receptor (PR) expression rate was 32.2% and the over-expression rate of human epidermal growth factor receptor 2 (HER2) was 25.8%.

    Conclusion

    ·Ultrasound, MRI and CR can complement each other and improve the accuracy of diagnosing the malignant degree of MBC.

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    Effect of psychomotor therapy on negative symptoms and cognitive function of patients with stable schizophrenia
    Ruping LU, Hui GAO, Linna JIANG, Xiaoya CHEN, Hong PENG, Hui SHEN, Qing FAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 77-81.   DOI: 10.3969/j.issn.1674-8115.2022.01.011
    Abstract483)   HTML27)    PDF(pc) (832KB)(330)       Save
    Objective

    ·To explore the effect of psychomotor therapy on negative symptoms and cognitive function of patients with stable schizophrenia.

    Methods

    ·A random number table was used to divide 64 stable schizophrenia patients from Shanghai No.1 Civil Mental Health Center into a study group and a control group. The control group was given routine treatment, nursing and daily rehabilitation, and the study group increased psychomotor therapy on this basis. Both groups were intervened for 10 weeks, and the patients in the two groups were evaluated by the Positive and Negative Symptom Scale (PANSS), Mini Mental State Examination (MMSE), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after the intervention.

    Results

    ·Thirty patients in the study group and the control group completed the observation. The repeated-measures analysis of variance (ANOVA) showed that after 10 weeks of intervention, the score of PANSS negative symptom subscale and PANSS total score were lower than those of the control group (all P=0.000), while the scores of MMSE and RBANS were higher than those of the control group (P=0.008, P=0.000). After 10 weeks, the negative symptom subscale score and PANSS total score of the study group were lower than those before the study (all P=0.000), while the MMSE and RBANS scores were higher than those before the study (all P=0.000).

    Conclusion

    ·Psychomotor therapy can improve the negative symptoms and cognitive function of patients with stable schizophrenia.

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    Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion
    Yu ZHANG, Xiaoyuan WU, Lihua GUAN, Yiyuan LIU, Xingyue PENG, Haiyan XIE, Wei HU, Keke HAO, Ning XIA, Guojun LU, Zhibo HOU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 82-89.   DOI: 10.3969/j.issn.1674-8115.2022.01.012
    Abstract521)   HTML72)    PDF(pc) (2900KB)(231)       Save
    Objective

    ·To explore the feasibility of individualized treatment of malignant pleural effusion (MPE) patients with non-small cell lung cancer (NSCLC) guided by in vitro high-throughput drug sensitivity screening system.

    Methods

    ·Thirty NSCLC patients with MPE treated in Nanjing Chest Hospital from January 2019 to May 2020 were included. The tumor cells in MPE were collected and isolated, and primary cells were cultured. The ex vivo drug sensitivity of primary cells was assessed for 30 chemotherapeutical and molecular targeted drugs by using the high-throughput drug sensitivity screening system of automated digital fluorescence imager. The consistency between the drug sensitivity assay results and the clinical efficacy of patients was evaluated.

    Results

    ·The ex vivo drug sensitivity results of primary tumor cells cultured from MPE revealed considerable heterogeneity in drug response. Most of the primary cells were sensitive to Epirubicin, Lobaplatin, Gemcitabine and Irinotecan. Clinical efficacy of 23 patients can be evaluated. For patients with previously untreated, epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC, the consistency between the efficacy of targeted therapy and the high-throughput drug sensitivity assay results was 44.4% (4/9). For the EGFR negative untreated patients and EGFR mutation-positive advanced NSCLC patients with acquired resistance to targeted treatment, the consistency between the therapeutic effect of chemotherapy and the high-throughput drug sensitivity assay results was 85.7% (12/14).

    Conclusion

    ·The high-throughput drug sensitivity assay based on MPE primary cell culture in NSCLC patients has a high consistency with the clinical efficacy of chemotherapy, which is helpful for decision-making of personalized chemotherapy.

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    Clinical comparison on patients undergoing general anesthesia and tracheal intubation between Jinhoujian and lidocaine aerosol
    Lei WU, Chonglin DU, Yimeng XIA
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 90-94.   DOI: 10.3969/j.issn.1674-8115.2022.01.013
    Abstract592)   HTML22)    PDF(pc) (893KB)(327)       Save
    Objective

    ·To compare the clinical application of Jinhoujian spray and Lishuka aerosol (lidocaine) in tracheal intubation under general anesthesia.

    Methods

    ·A total of 100 patients undergoing elective laparoscopic cholecystectomy with tracheal intubation under general anesthesia were enrolled in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. They were randomly divided into Jinhoujian spray group (research group) and lidocaine aerosol group (control group), with 50 patients each. 1 min after anesthesia induction, the glottis was exposed by UE visual laryngoscope and Jinhoujian spray or lidocaine aerosol was applied to the throat by 2 press respectively. Mean arterial pressure (MAP) and heart rate (HR) were recorded at different time points, including before anesthesia induction (T0) , the time (T1),3 min (T2), 5 min (T3) and 10 min (T4) after intubation of endotracheal tube, the time (T5), 3 min (T6) and 5 min (T7) after extubation of endotracheal tube. MAP and HR were observed at different time points, including before (T0) and immediately after intubation (T1), 3 min (T2), 5 min (T3) and 10 min after intubation (T4), immediately (T5), 3 min (T6) and 5 min after extubation (T7). The emergence agitation and acceptance of tracheal tube were also recorded before and after extubation. The patients were followed up 24 h after the operation to observe pharyngalgia, hoarseness and extubation responses.

    Results

    ·There was no significant difference in general features between the two groups. After drug treatment, both groups could prevent the cardiovascular stress response caused by endotracheal intubation and extubation. And there was no statistical significance in MAP, HR and emergence agitation scores. Compared with the control group, the tolerance satisfaction of tracheal catheter (P=0.021) and acceptability (P=0.021) were significantly improved in the research group, and the incidence of pharyngeal pain within 24 h after surgery was significantly reduced (P=0.020).

    Conclusion

    ·The application of Jinhoujian spray can effectively reduce the cardiovascular stress response caused by tracheal intubation under general anesthesia, improve the tolerance of patients undergoing laparoscopic cholecystectomy to tracheal catheter, and reduce the incidence of postoperative pharyngeal pain.

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    Meta-analysis of impacts of inhaled nitric oxide on postoperative renal injury and hemorrhage
    Dewei QIAN, Ren ZHOU, Lichun GUAN, Hang ZHANG, Min YU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 95-100.   DOI: 10.3969/j.issn.1674-8115.2022.01.014
    Abstract492)   HTML17)    PDF(pc) (1964KB)(272)       Save
    Objective

    ·To evaluate the effects of inhaled nitric oxide on renal injury and hemorrhage after surgery.

    Methods

    ·China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), WanFang Data, PubMed, Embase, Web of Science and The Cochrane Library were searched systematically from the establishment of each database to March 26, 2021. “外科手术” and “一氧化氮” were used as Chinese keywords for retrieval. Correspondingly, the “nitric oxide”“surgical procedures, operative”“cardiac surgical procedures”“cardiac surgery” and “transplantation” were used as subject words and free words for searching. The literatures were screened according to the pre-established inclusion and exclusion criteria. Meta-analysis was performed by using RevMan 5.3. The study end points were the incidences of renal injury and hemorrhage.

    Results

    ·Seven literatures were included for analysis, with a total of 689 surgical patients. Of them, 337 received nitric oxide treatment and 352 received placebo treatment. Compared with the control group, patients treated with nitric oxide demonstrated a statistically difference in reducing the incidence of postoperative renal injury (RR= 0.75, 95%CI 0.61?0.92, P=0.005). There was no significant difference in the incidence of hemorrhage (RR=0.79, 95%CI 0.22?2.83, P=0.710) between the two groups.

    Conclusion

    ·Application of nitric oxide after surgery does not increase the risks of renal injury and hemorrhage. In contrast, the use of nitric oxide in cardiopulmonary bypass might protect renal function.

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    Research progress of interleukin-1 receptor accessory protein in the pathogenesis of neuropsychiatric diseases
    Peipei CHENG, Yasong DU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 101-106.   DOI: 10.3969/j.issn.1674-8115.2022.01.015
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    Interleukin-1 receptor accessory protein (IL1RAP) is one of the important components of interleukin-1 (IL-1) signaling pathway, which can participant in the formation of IL-1/ IL-1RⅠ (interleukin-1 receptor Ⅰ)/IL1RAP complex and recruit adaptor proteins and downstream signal intermediates, further activate protein kinases, and ultimately induce the synthesis of proinflammatory mediators and the occurrence of acute inflammation response. In addition, IL1RAP is also involved in regulating the formation of neural synapses, which is an important molecular link between immune system and nervous system, and may be involved in the pathological process of neuropsychiatric diseases. This paper reviews the latest research results of IL1RAP in neuropsychiatric diseases (such as glioma, Alzheimer's disease, schizophrenia, etc.) in recent years, in order to explore the role and mechanism of IL1RAP in the pathogenesis of these diseases and provide theoretical support for its diagnosis and treatment.

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    Research progress on the role of PD-1/PD-L1 pathway in autoimmune eye diseases
    Chenling YANG, Huifang ZHOU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 107-112.   DOI: 10.3969/j.issn.1674-8115.2022.01.016
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    Autoimmune eye diseases are a kind of inflammatory eye disease caused by autoimmune reaction, mainly including autoimmune uveitis, thyroid-associated ophthalmopathy, Sj?gren's syndrome-related ophthalmoxerosis, neuromyelitis optica spectrum disorder and so on. The pathogenesis of these diseases is complex, involving the ocular surface, intraocular and orbital lesions. Traditional treatment methods mainly include corticosteroids and immune inhibitors, which have low efficiency and many side effects. Therefore, more in-depth research on the pathogenesis of autoimmune eye diseases is needed in order to find therapeutic targets for the etiological treatment. Programmed death 1 (PD-1) has been confirmed to be associated with many autoimmune diseases, and PD-1/programmed death ligand 1 (PD-L1) pathway plays a key role in the regulation of immune responses. Inactivation of the PD-1/PD-L1 pathway may lead to abnormal activation of autoimmune T cells, leading to the occurrence and development of autoimmune diseases. In this review, the immune regulation mechanism of PD-1/PD-L1 pathway that has been discovered at the present stage, as well as its role in autoimmune ophthalmopathy, is systematically summarized, and the potential of targeted treatment of autoimmune eye diseases in the future is prospected.

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    Research progress of botulinum toxin A in treatment of neurogenic bladder
    Lin ZHANG, Zhong CHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 113-118.   DOI: 10.3969/j.issn.1674-8115.2022.01.017
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    In recent years, intradetrusor injection of botulinum toxin A (BTX-A) has achieved satisfactory therapeutic effects on the treatment of neurogenic bladder, improving the bladder function and reducing the lower urinary tract symptoms while improving patients' quality of life. In addition, this therapy has advantages including minimal invasiveness, mild side effects, and allowing repeated injections. At present, there is no international consensus on the injection plan for BTX-A. Therefore, based on the recent clinical research results, this paper reviews the mechanism of action, types, usage, therapeutic effects, influencing factors, as well as adverse reactions and contraindications of BTX-A, in an attempt to provide evidence for its clinical application.

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    Research progress in influencing factors of early rehabilitation among patients in ICU environment
    Fu YANG, Fang FANG, Lan CHEN, Qiuli WANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 119-123.   DOI: 10.3969/j.issn.1674-8115.2022.01.018
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    Bed rest and long-term immobilization are common phenomena among patients in intensive care unit (ICU), which can increase the risk of ICU-acquired weakness and other complications. Early rehabilitation is helpful to improve the physical function of ICU patients, reduce the occurrence of delirium and other psychological problems, and improve their quality of life, which is of great significance to promote their early return to family or society. This paper reviews the current situation and influencing factors of early rehabilitation in ICU environment.

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    Application progress of machine learning in the study of facial features of patients with depression
    Xin LI, Qing FAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 124-129.   DOI: 10.3969/j.issn.1674-8115.2022.01.019
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    Major depressive disorder (MDD) is a mental illness that severely affects the quality of life, accompanied by changes in facial expressions and other behaviors. The current diagnosis for MDD mainly relies on self-reports and observations from doctors, which has subjective errors. There is a lack of objective and effective automated MDD detection methods. Facial expressions are important nonverbal behaviors, and the researchers have begun to use facial features to assist in identifying and diagnosing depression. As the core of artificial intelligence, machine learning has outstanding advantages in image feature extraction and classification. Taking IEEE Xplore database as the data source, this article sorts out the researches on the facial features of MDD patients based on machine learning from 2016 to 2021, and prospects the future research directions, to provide reference for clinical intelligent diagnosis and tracking of MDD in the future.

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    Research progress of Gd-EOB-DTPA-enhanced magnetic resonance imaging in the evaluation of biological behavior of hepatocellular carcinoma
    Yihuan WANG, Ruokun LI, Huanhuan CHONG, Fuhua YAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 130-134.   DOI: 10.3969/j.issn.1674-8115.2022.01.020
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    Hepatocellular carcinoma is the most common primary malignant tumor of liver tumors and ranked as the third leading cause of cancer death. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is a new hepatocyte-specific contrast agent commonly used at present. Its sensitivity and specificity for the diagnosis of small hepatocellular carcinoma can both be over 90%. Early diagnosis of hepatocellular carcinoma can benefit patients clinically, but as hepatocellular carcinoma is a highly heterogeneous tumor, the tumor biological behavior is also a key factor affecting the prognosis. Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) can provide relevant information about identification of molecular typing, evaluation of immune microenvironment, and prediction of microvascular invasion and postoperative recurrence in hepatocellular carcinoma. This article reviews the research progress of EOB-MRI in the evaluation of biological behavior of hepatocellular carcinoma to provide reference for the diagnosis and treatment of hepatocellular carcinoma.

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    Study on the expression of B-cell leukemia/lymphoma 11B in the organ of Corti during mice cochlea development
    JIANG Zhenglin, GAO Yunge, WU Hao
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1361-1374.   DOI: 10.3969/j.issn.1674-8115.2022.10.001
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    Objective ·To explore the expression of B-cell leukemia/lymphoma 11B (BCL11B) in the organ of Corti during mice cochlea development. Methods ·A total of 24 wild-type C57BL/6J mice of random sex at different ages before and after birth [embryonic 14.5 days (E14.5), E15.5, E16.5 and E18.5, and postnatal 0 day (P0), P2, P4 and P7] were selected, with 3 at each age point. After the mice were killed, the bilateral cochleae of the mice were sampled and fixed. The left cochleae were dissected to obtain complete basement membranes, and right cochleae were dehydrated by sucrose solution following cross section. BCL11B antibody was combined with MYOSIN 6 antibody were used for immunohistochemical analysis of whole mount samples of mouse cochlea basement membrane and cross section samples. Confocal fluorescence microscope was used for observing the tissue samples at different age points after staining, and counting the numbers to calculate the percentage of BCL11B-expressing hair cells. Results ·Whole mount samples of mouse cochlear basement membrane and cross section samples at eight age points were successfully prepared. Confocal fluorescence microscope showed that BCL11B expression was first detected specifically in outer three rolls of MYOSIN6 positive hair cells in E15.5 middle-basal turn of mouse cochlea; with the development of mouse cochlea, BCL11B expression gradually strengthened until P2, at which time point BCL11B reached top expression level and started to weaken in P4, with almost no BCL11B expression detected in P7. During the whole period of BCL11B expression in outer hair cells, no BCL11B expression was detected in other cell types in the organ of Corti. The results of the number and percentage of BCL11B-expressing hair cells showed that there was no significant difference among the three age points of E16.5, P0, and P4 (both P>0.05). Conclusion ·It is confirmed that BCL11B is a specifically expressed protein in the early development of outer hair cells in the organ of Corti by co-immunostaining of BCL11B and MYOSIN6.

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    Effect of intragastric treatment of sodium cromoglycate on dextran sulfate sodium-induced ulcerative colitis in BALB/c mice
    GE Yiqin, HUANG Yuji, LI Weize, LI Yanning, LI Li
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1375-1382.   DOI: 10.3969/j.issn.1674-8115.2022.10.002
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    Objective ·To explore the role of mast cell membrane stabilizer sodium cromoglycate (Crom) in the modeling of ulcerative colitis (UC) in mice. Methods ·Mice were divided into 3 groups, i.e.control group (n=5), dextran sulfate sodium (DSS) group (n=5) and DSS+Crom group (n=5). Mice in the control group drank water for 7 d, and mice in the DSS group drank 3% DSS for 7 d to establish UC model. Meanwhile, mice in the DSS+Crom group were treated with Crom since the 3rd day during the establishment of UC. The changes of body mass and disease activity index (DAI) scores among the three groups were compared. Hematoxylin-eosin staining (H-E staining) and toluidine blue staining were used to observe the histopathology injury and the number of mast cells in colon tissues. Flow cytometry was used to detect the immune cell infiltration of spleen. Differences among the three groups were compared by using one-way ANOVA. Least significant difference (LSD) was used to further compare the differences between each two groups. Results ·Compared with the control group, the mice in the DSS group had severe hematochezia and intestinal barrier injury, the body weight of the mice in the DSS group decreased significantly (P=0.005), the DAI score increased significantly (P=0.001), the colon length shortened significantly (P=0.003), and toluidine blue staining showed that the number of mast cells in the intestine increased (P=0.000). Moreover, compared with the DSS group, the blood in the stool of the mice in the DSS+Crom group decreased, and the colon length increased (P=0.013); the intestinal pathology showed that the inflammation was improved, and the number of mast cells was reduced (P=0.000). Conclusion ·Stabilizing mast cells with sodium cromoglycate could effectively reduce colon inflammation of mice in UC, which indirectly indicates that mast cells participate in the pathogenesis of UC.

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    Function of UCHL3 in maintaining the survival of FLT3-ITD positive acute myeloid leukemia cells
    HU Jiacheng, ZHU Qian, WANG Jiaqi, WU Yingli, LEI Hu
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1383-1393.   DOI: 10.3969/j.issn.1674-8115.2022.10.003
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    Objective ·To explore differently expressed deubiquitinases in acute myeloid leukemia (AML) cells with internal tandem duplications of the FLT3 (FLT3-ITD) gene mutation. Methods ·The expressions of some deubiquitinases were detected by Western blotting after transforming exogenous FLT3-ITD or the use of FLT3-ITD inhibitor. The Cancer Genome Atlas (TCGA) public database was used to analyze the expression of UCHL3 in FLT3-ITD-positive patients and its correlation with the prognosis of AML patients. Certain deubiquitinase was knocked down by short hairpin RNA (shRNA) in AML cell lines. Cell counting, CCK-8 assay, flow cytometry and wright stain were used to detect the effect of certain deubiquitinase on the function of AML cells and the combined effect of knockdown of corresponding deubiquitinase or using its inhibitor with all-trans-retinoic acid (ATRA). Results ·Expression of FLT3-ITD in Ba/F3 cells significantly induced the protein expression of UCHL3, while inhibition of FLT3-ITD activity in MOLM-13 and MV4-11 cell lines significantly inhibited the expression of UCHL3 in a time- and concentration-dependent manner. TCGA database analysis showed that there was a significant positive correlation between the expression of FLT3 and the expression of UCHL3 in AML (P=0.000), and a significant negative correlation between the expression of UCHL3 and the survival rate of AML patients (P=0.016). UCHL3 knockdown inhibited proliferation and promoted apoptosis of MOLM-13 and MV4-11 cells, and the expression of differentiation-related transcription factors PU.1 and C/EBPβ were significantly increased. Knockdown of UCHL3 significantly enhanced the apoptosis of MOLM-13 and MV4-11 cells induced by 100 nmol/L ATRA, and the apoptosis-related caspase proteins PARP1, caspase 9 and caspase 3 were significantly cleaved. Meanwhile, UCHL3 knockdown cells showed more features of small nuclear volume, nuclear depression, and rod-shaped or irregular cells after ATRA treatment. The dose-response curves of ATRA and TCID detected by CCK-8 assay showed that UCHL3 inhibitor TCID and ATRA synergistic inhibited FLT3-ITD-positive AML cells survival. Conclusion ·FLT3-ITD up-regulates UCHL3 expression and promotes the survival of AML cells. UCHL3 is negatively correlated with the prognosis of AML patients. Knockdown or inhibition of UCHL3 combines with ATRA to inhibit the survival of FLT3-ITD-positive AML cells.

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    Construction of a prediction model of immune-related long non-coding RNA in gastric cancer
    CHEN Bin, CUI Hongquan, YANG Yijin, XU Haiyan, ZHANG Ling
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1394-1403.   DOI: 10.3969/j.issn.1674-8115.2022.10.004
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    Objective ·To construct a prediction model of immune-related long non-coding RNA (lncRNA) in gastric cancer patients by bioinformatics method, and explore its application value. Methods ·Transcriptome sequencing (RNA sequencing, RNA-seq) data of 413 gastric cancer samples were downloaded from the cancer genome atlas (TCGA) database, including 32 normal samples and 381 tumor samples. Immune-related genes were obtained from ImmPort website. The immune-related lncRNAs (irlncRNAs) were obtained by correlation analysis. The differentially expressed irlncRNAs (DEirlncRNAs) were obtained by the limma R package, and heat maps and volcano maps were drawn. Batch effects of sample were corrected by constructing DEirlncRNA pairs. The clinicopathological characteristic data of TCGA gastric cancer patients were downloaded, and the DEirlncRNA pairs related to prognosis were obtained by univariate analysis, and screened by LASSO regression analysis. Finally, a risk prediction model was constructed by COX proportional hazards regression analysis. The predictive performance of the model and traditional clinicopathological features were analyzed and compared by calculating the area under the curve (AUC). The patient risk value was calculated according to the formula, and the patients were divided into high and low risk groups according to the optimal cutoff value. Survival maps were drawn by using Kaplan-Meier curves, and differences in survival rates between the two groups were compared by Log-rank test. The relationship between risk scores and clinicopathological characteristics was analyzed according to the Wilcoxon signed-rank test. The independent prognostic factors of gastric cancer patients were verified by univariate analysis and multivariate analysis. The relationship between risk scores and immune infiltrating cells and immune-related genes was validated according to Spearman correlation analysis. The half-maximal inhibitory concentration (IC50) values of drugs in high and low risk groups were compared by using the pRRophetic R package. Results ·Compared with normal tissues, 106 irlncRNAs were differentially expressed in gastric cancer tissues, of which 11 were low-expressed and 95 were high-expressed. A total of 32 DEirlncRNAs pairs were included in the COX proportional hazards model, 20 of which were independent prognostic factors for gastric cancer. The 1-, 2- and 3-year AUC values of the risk prediction model were 0.889, 0.966 and 0.935, respectively, which were significantly higher than those of traditional clinicopathological features. The survival rate of patients in the high risk group was significantly lower than that in the low risk group (P=0.000). High risk scores were more closely related to high tumor stage, distant metastasis and patient death. Univariate analysis showed that age, TNM stage, T stage, N stage, M stage and risk score were closely related to the prognosis of gastric cancer patients (all P<0.05). Multivariate analysis showed that age, TNM stage and risk score were independent prognostic factors for gastric cancer patients (all P<0.05). Risk scores were negatively correlated with various T cells and mast cells, and positively correlated with tumor-associated fibroblasts, macrophages and endothelial cells. In the high risk group, the expression levels of immune-related genes IFNG and MSH2 were lower than those in the low risk group. In the high risk group, the sensitivity of the drugs doxorubicin, cisplatin, tipifarnib and mitomycin were lower than those in the low risk group (all P<0.05). Conclusion ·The COX proportional hazards model constructed with irlncRNAs pairs can accurately predict the survival status and survival rate of gastric cancer patients and its sensitivity to chemotherapy drugs.

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    Effect of chloroquine phosphate on vascular endothelial cell injury induced by double-stranded RNA
    ZHANG Jiaojiao, SUN Junnan, WANG Hairong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1404-1412.   DOI: 10.3969/j.issn.1674-8115.2022.10.005
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    Objective ·To investigate the inhibitory effect of chloroquine phosphate (CQ) on vascular endothelial cell injury induced by double-stranded RNA (dsRNA) and its mechanism. Methods ·An in vitro model of vascular endothelial cell injury induced by dsRNA in viral sepsis was established via stimulating human umbilical vein endothelial cells (HUVECs) with polyinosinic-polycytidylic acid (poly I:C). HUVECs were randomly divided into normal control group (NC group), poly I:C group with different concentrations and CQ+poly I:C group. The cell viability of HUVECs before and after poly I:C treatment was detected by using Cell Counting Kit-8 (CCK-8). The morphological changes of HUVECs were observed by using optical microscope. The integrity of cell membrane was assessed by calculating the rate of propidium iodide (PI) positive cells by using flow cytometry. The expression level of mature proinflammatory cytokine interleukin 1β (IL-1β), and key proteins of pyroptosis were detected by Western blotting. Results ·Compared with the NC group, HUVECs treated with poly I:C showed a decreased cell viability, more expanded "Vesicles" and more ruptured cells. An increased level of IL-1β expression and positive rate of PI+ cells were also observed. The expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and cleaved caspase-1 and gasdermin D N-terminal (GSDMD-N) were increased significantly (all P<0.05) under the treatment of poly I:C and the changes were concentration-dependent. Interestingly, compared with poly I:C group, the cell viability of HUVEC pretreated by CQ was significantly increased, and a decreased IL-1β level were observed. The phenomena of cell swelling and rupture was improved, and a lower positive rate of PI+ cells was detected. The expression levels of cleaved caspase-1 and GSDMD-N of cell pyrosis were also decreased (all P<0.05). CQ pretreatment did not reduce NLRP3 expression induced by dsRNA, but it did inhibit the expression of Toll-like receptor 3 (TLR3). Conclusion ·Pyroptosis is involved in vascular endothelial cells injury induced by dsRNA, and CQ inhibits dsRNA-induced pyroptosis, which could be related to TLR3 regulation.

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    Treatment-free remission after imatinib discontinuation in patients with chronic myeloid leukemia
    XU Tianxue, QIAN Ying, LIU Zhanyun, CAI Gang, WU Yingli, LI Junmin, SHEN Zhixiang, ZHOU Li
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1413-1419.   DOI: 10.3969/j.issn.1674-8115.2022.10.006
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    Objective ·To analyze the outcomes of treatment-free remission (TFR) after imatinib discontinuation in patients with chronic myeloid leukemia in chronic phase (CML-CP) who meet the criteria for TFR and are willing to monitor the disease regularly, the prognostic factors and the application of droplet digital polymerase chain reaction (ddPCR) technique in monitoring TFR. Methods ·The patients with CML-CP enrolled in this study were monitored regularly after imatinib discontinuation. Molecular response and relapse were analyzed by quantitative polymerase chain reaction (QPCR) for detection of BCR-ABL transcripts. The lymphocytes subsets pre- and post-imatinib discontinuation were evaluated by flow cytometry. ddPCR was used to detect BCR-ABL and the predictive role in TFR was analyzed. Results ·① Forty-two CML-CP patients who met the criteria for TFR were assessed. With median follow-up time 41(5?93) months, 32 (76.2%) patients maintained TFR.The estimated TFR rate by 12, 24 and 48 months were 85.1%, 75.1% and 70.1%, respectively. Median TFR duration was 41 (2?93) months. The most common adverse event post-discontinuation was musculoskeletal pain of grade Ⅰ?Ⅱ (31.0%). Eight patients achieved deep molecular response (DMR) after restart of imatinib. ②58.3% of patients with continuous positive ddPCR developed molecular relapse after imatinib discontinuation, while none relapsed in those with negative detection (P<0.01). ③ The percentage of CD8+CD28- cells pre-discontinuation was lower, while the percentage of CD4+CD25+ cells post-discontinuation was higher in relapsed patients than that in TFR patients (6.2% vs 12.6%, P=0.026; 3.2% vs 2.1%, P=0.021). Conclusion ·CML-CP patients who meet the criteria of TFR may successfully maintain TFR after TKI discontinuation. ddPCR may help to predict the outcome of TFR and detect the molecular relapse earlier. Immune regulation by different T cell subsets may play a role in TFR duration to prevent relapse of disease.

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    Weekly paclitaxel in combination with cisplatin in the first-line treatment of metastatic breast cancer: a retrospective study
    WANG Yuzheng, SU Juncheng, TANG Lei, XU Yingchun, ZHANG Fengchun
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1420-1427.   DOI: 10.3969/j.issn.1674-8115.2022.10.007
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    Objective ·To investigate the efficacy and safety of weekly paclitaxel in combination with cisplatin (DP) as first-line regimen compared with other treatment of physician's choices (TPC) for metastatic breast cancer (MBC). Methods ·The clinical data of 117 MBC patients who were hospitalized in the Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from July 2008 to June 2021 were retrospectively analyzed. Fifty-five patients were divided into DP group and 62 patients were divided into TPC group, according to whether the DP regimen was used as first-line chemotherapy. The DP group received paclitaxel 80 mg/m2 combined with cisplatin 25 mg/m2, administered on the 1st, 8th and 15th day, respectively, every 28 d as a cycle, a total of 6 cycles of treatment. TPC group received other first-linechemotherapy regimens, including single or combined regimens of capecitabine, gemcitabine, docetaxel and other regimens.Clinicopathologic characteristics including age, menopausal status, pathological results and molecular subtypes were collected and analyzed. Objective response rate (ORR) and clinical benefit rate (CBR) were used to evaluate the efficacy of different regimens based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The adverse effects (AEs) were assessed in accordance with National Cancer Institute's criteria for common adverse effect 5.0 (NCI CTC 5.0), and NCI Ⅲ/Ⅳ AEs were analyzed as severe AEs. The numbers and sites of MBC relapses were analyzed as progression pattern. The differences of clinicopathologic characteristics, efficacy and severe AEs between the two groups were compared by χ2 test. Kaplan-Meier survival analysis was used to compare the difference of first-line progression free survival (PFS1) between the two groups, and the factors with probable influence on PFS1, including clinicopathologic characteristics, treatments and other factors were analyzed. The univariate Cox regression analysis was further applied to analysis of the possible influencing factors screened above. Results ·Except the progesterone receptor (PR) expression (P=0.048), there was no significant difference in clinicopathologic characteristics between the two groups (P>0.05). The ORR (47.3% vs 22.6%, P=0.009) and CBR (78.2% vs 41.9%, P=0.002) in the DP group were significantly higher than those in the TPC group. The median PFS1 was 12.0 months (95%CI 10.0?15.0 months) in the DP group, while the median PFS1 was 6.0 months (95%CI 5.0?9.0 month) in the TPC group, demonstrating significant difference (Log-rank P=0.000). Only the factor "receiving DP regimen as first-line chemotherapy" was recognized as a protective factor for MBC progression by univariate Cox analysis (P=0.000, HR=0.419, 95%CI 0.271?0.649). There was no significant difference (P>0.05) in the progression pattern between the two groups except for fewer bone metastasis (P=0.006). The AEs of the two groups were tolerable, and there was no significant difference in the proportion of severe AEs between the two groups (P>0.05). Conclusion ·The first-line DP regimen demonstrates better efficacy and prolonged PFS1 than TPC regimens. It could be an effective selection and should be considered for MBC according to the clinical situations.

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    Optimum spinal anesthesia dose of ropivacaine combined with a single low-dose S-ketamine during elective cesarean delivery: a double-blind sequential study
    SUN Yuanqing, XU Tao, ZHANG Xiaoyu, XU Zifeng, CHAI Jing
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1428-1434.   DOI: 10.3969/j.issn.1674-8115.2022.10.008
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    Objective ·To explore the optimal dose of ropivacaine for elective cesarean section under spinal anesthesia combined with a single low-dose of intravenous S-ketamine, and observe the rates of hypotension associated with this method. Methods ·Forty eligible women were included in the study for spinal anesthesia block combined with intravenous low-dose S-ketamine (0.15 mg/kg). The first patient received a 12 mg spinal anesthesia dose of ropivacaine. If the upper sensory block level of the patient was not lower than the sixth thoracic vertebra (T6) and visual analog scale (VAS) score was ≤2 before delivery, the next patient had 1/9 chance of receiving a lower dose or 8/9 chance of receiving the same dose of ropivacaine as the previous patient. If the patient had VAS score>2 or needed an extra epidural analgesics before delivery, a higher dose of ropivacaine was used for the next patient. The primary outcome was whether the effect of spina anesthesia was accurate, that is, the amount of ropivacaine to maintain patients' VAS score ≤2 before delivery, and the incidence of post-spinal anesthesia hypotension. Secondary outcomes mainly included the rate of hypotension-related symptoms and drug interventions, upper sensory block level of anesthesia, level of sedation (Ramsay sedation scale was used as the evaluation standard) and neonatal outcomes. 90% effective dose (ED90) and 95% confidence interval (95% CI) of ropivacaine were estimated by Isotonic regression. Results ·In combination with low-dose S-ketamine, the ED90 of ropivacaine for cesarean section spinal anesthesia was 11.8 mg (95%CI 11.7-12.7). The incidence of hypotension and hypoxemia of forty parturients was 5.0% (2 cases) and 2.5% (1 case), respectively, and there was no bradycardia occurring. All parturients did not use phenylephrine injection as a remedy, and there was no adverse reactions related to hypotension occurring (dyspnea, nausea, vomiting, shiver and blurred vision). There was no reflux and aspiration occurring. Only one parturient before delivery had a Ramsay sedation score of 2 (awake, quiet and cooperative), and the rest scored 3 (sleepy but respond quickly to instruction). At 5 min after delivery, according to the Ramsay sedation scale, 32 parturients were 2 scores, and 8 parturients were 3 scores. At the end of the operation, the Ramsay sedation scale of all parturients was 2 scores. During the cesarean section, the incidence of visceral traction pain, nightmare and dizziness of patients was 7.5%, 62.5% and 52.5%, respectively. In addition, the Apgar scores of 40 newborns at 1 min and 5 min after birth were all 10, and the umbilical vein blood gas analysis showed that the pH was (7.37±0.03). Conclusion ·Combined with a intravenous single low-dose of S-ketamine during spinal anesthesia for elective cesarean section, the ED90 of ropivacaine is 11.8 mg, and this method can effectively reduce the incidence of hypotension.

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    Risk factors of recurrent wheezing in preschool children
    LI Aiqiu, ZHANG Xiaoxiao, JIANG Yunli, XIAO Yanshang, DING Guodong, WU Beirong, DONG Xiaoyan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1435-1440.   DOI: 10.3969/j.issn.1674-8115.2022.10.009
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    Objective ·To investigate the potential risk factors of recurrent wheezing in preschool children. Methods ·A case-control study was conducted in 370 children with wheezing admitted to the Department of Respiratory Medicine in a specialized hospital for children in Shanghai from December 2019 to December 2020. The children were preschool children aged 3?6 years. According to the frequency of wheezing, pediatric patients were divided into occasional wheezing group (1?2 attacks per year) and recurrent wheezing group (≥3 attacks per year). The face-to-face questionnaire was performed to the parents responding for basic information and recurrent wheezing risk factors including the children age, gender, gestational age, birth weight, history of eczema, history of allergic rhinitis, history of food allergy, history of inhalational pollen allergy, history of bronchiolitis, maternal age, production mode, feeding pattern, history of parental asthma, resident area (city/village), passive smoking, history of pet contact, seasonal factors, etc. Univariate analysis was used to compare risk factors of recurrent wheezing between the two groups. Logistic regression analysis was used to analyze the independent risk factors associated with recurrent wheezing. Results ·Three hundred and seventy cases were enrolled, including 204 cases (55.14%) in the occasional wheezing group and 166 cases (44.86%) in the recurrent wheezing group. A total of 10 risk factors were determined for recurrent wheezing, which included children's age (χ2=36.608, P=0.000), gender (χ2=4.290, P=0.038), eczema (χ2=6.250, P=0.012), allergic rhinitis (χ2=10.787, P=0.001), inhaling pollen (χ2=8.868, P=0.003), history of bronchiolitis (χ2=27.898, P=0.000), gestational age (χ2=5.141, P=0.023), feeding pattern (χ2=4.316, P=0.038), parental asthma history (χ2=5.050, P=0.025) and resident area (χ2=31.013, P=0.000). The Logistic regression showed that allergic rhinitis (OR=4.759, 95%CI 1.665?13.603), bronchiolitis (OR=12.113, 95%CI 5.686?25.802), premature birth (OR=3.092, 95%CI 1.120?8.539) and living in city (OR=2.395, 95%CI 1.326?4.324) were the independent risk factors of recurrent wheezing. Conclusion ·The independent risk factors for recurrent wheezing in preschoolers include allergic rhinitis, bronchiolitis, premature birth and living in city.

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    Chinese version of Fear of Self Questionnaire and its reliability and validity test
    LIU Jinjun, WANG Yuan, WU Yanru, XIAO Zeping
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1441-1447.   DOI: 10.3969/j.issn.1674-8115.2022.10.010
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    Objective ·To examine the reliability and validity of the Chinese version of Fear of Self Questionnaire (FSQ) among Chinese university students. Methods ·Based on the standard questionnaire translation model, the English version of FSQ was translated into Chinese and the cultural debugging was conducted. A total of 396 students from three science and engineering majors of a comprehensive university in Shanghai from December 2021 to January 2022 were tested with the general information questionnaire, the Chinese version of FSQ, the Chinese version of Ego Identity Scale (EIS), the Chinese version of Self Acceptance Questionnaire (SAQ) and the Chinese version of Obsessive Belief Questionnaire-44 (OBQ-44). The Chinese version of FSQ was tested by item analysis, and the reliability and validity of the Chinese version of FSQ were tested by item analysis, internal consistency reliability, split half reliability, retest reliability, criterion validity, exploratory factor analysis and confirmatory factor analysis. Results ·A total of 386 valid questionnaires were recovered in the initial test, and 163 valid questionnaires were recovered in the retest. A total of 20 items in the Chinese version of FSQ passed the item analysis test, and all items were retained. The internal consistency reliability, split half reliability and retest reliability of the Chinese version of FSQ were 0.931, 0.869 and 0.736, respectively, which met the requirements of metrology. The criterion validity of the Chinese version of FSQ was good, and the total score of the Chinese version of FSQ was significantly correlated with the total score of the three criterion validity questionnaires [Chinese version of EIS (r=-0.279, P=0.000), Chinese version of SAQ (r=-0.568, P=0.000) and Chinese version of OBQ-44 (r=0.418, P=0.000)]. The exploratory factor analysis of the Chinese version of FSQ showed that the questionnaire contained three factors: self fear, self assurance and self questioning. The confirmatory factor analysis of the Chinese version of FSQ showed that the indicators of the three-factor structural equation model fitted well, including χ2/df = 2.790, CFI=0.862, GFI=0.834, AGFI=0.791, RMSEA=0.090, TLI=0.843, NFI=0.802. Conclusion ·The Chinese version of FSQ in this study has good reliability and validity among Chinese university students, and can be used to measure the level of feared self of this group.

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    Investigation and related factor analysis of barriers to outpatient cardiac rehabilitation in patients with coronary heart disease
    LIU Xia, WEN Fule, ZHANG Yaqing
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1448-1457.   DOI: 10.3969/j.issn.1674-8115.2022.10.011
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    Objective ·To evaluate the current status of barriers to outpatient cardiac rehabilitation (CR) in patients with coronary heart disease (CHD) and analyze related factors. Methods ·From October to December 2017, the inpatients or outpatients with CHD from seven tertiary general hospitals in Yangpu District, Hongkou District, Baoshan District and Songjiang District of Shanghai were selected as the research objects by convenient sampling method. The general information questionnaire, the Cardiac Rehabilitation Information Awareness Questionnaire (CRIAQ) and the Chinese/Mandarin Cardiac Rehabilitation Barriers Scale (CRBS-C/M) were used to investigate the awareness of CR information, the barriers to CR and related factors in the patients with CHD. Results ·A total of 390 questionnaires were distributed, and 342 valid questionnaires were recovered, with an effective recovery rate of 87.7%. The average age of the CHD patients was (67.03±10.83) years old. Among them, 42 patients (12.3%) had heard of CR. The overall median score of CRBS-C/M was 3.10 (2.71, 3.43) points, and the median scores of five dimensions ranged from 3.00 to 3.50 points. The median score of external logistical factors was the highest, which was 3.50 (3.00, 4.00) points. The top three barriers were "distance" "severe weather" and "I did not know about cardiac rehabilitation", with 75.4% (258/342), 69.3% (237/342) and 67.8% (232/342) of the patients agreeing or strongly agreeing, respectively. The average score of CRIAQ was (46.48±12.54) points. Multiple linear regression analysis showed that CRIAQ score (β=-0.242, P=0.000), whether diagnosed as unstable angina or not (β=0.194, P=0.000), gender (β=0.154, P=0.002) and whether participating in outpatient CR programs or not (β=-0.128, P=0.016) were the related factors of CR barriers in the patients with CHD (F=8.909, P=0.000), which explained 25.9% of the total variation. Conclusion ·The CR barrier of the patients with CHD is in the upper middle level, and the biggest barrier factor is the external logistical factor. The top three reasons that patients think hindering their participation in CR are long distance, severe weather and not knowing about CR. The patients with high awareness of CR information, or participating in outpatient CR programs have a low level of CR barriers, while the patients with unstable angina pectoris or the female patients have a high level.

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    Advances in single-cell RNA sequencing in glomerular diseases
    XING Haifan, FAN Ying
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1458-1465.   DOI: 10.3969/j.issn.1674-8115.2022.10.012
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    Glomerular diseases are a leading cause of chronic kidney disease and end-stage renal failure. Understanding the molecular mechanism underlying the initiation and progression of glomerular diseases is important to early identify risk factors for disease development and rescue renal function. The kidney is composed of complex and highly differentiated cells, which is a major challenge in the study of glomerular diseases. Bulk RNA sequencing cannot assess differential transcription or the interactions between cell types. Single-cell RNA sequencing (scRNA-seq) technology has developed rapidly in recent years, making it possible to study a wide range of cell types in kidney, urine and blood. The application of scRNA-seq to glomerular diseases helps to construct a comprehensive cell atlas, elucidate complex cellular and molecular mechanisms, develop efficient and accurate prognostic biomarkers and cell-specific therapies. This review focuses on the latest research advances in scRNA-seq in primary and secondary glomerular diseases.

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    Potential role of SIRT1 in unexplained recurrent spontaneous abortion
    LIU Ziwei, CAO Wenwen, WANG Yunrui, FENG Xiaoling
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1466-1473.   DOI: 10.3969/j.issn.1674-8115.2022.10.013
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    Unexplained recurrent spontaneous abortion (URSA) is also known as alloimmune recurrent abortion. It is suggested that the main pathogenesis of URSA is immune imbalance at the maternal-fetal interface, abnormal trophoblast invasion and abnormal placental angiogenesis. Existing studies have revealed the important role of SIRT1 gene in the field of reproduction and the regulation of immune diseases. However, there is still a lack of systematic and comprehensive research overview on the mechanism of SIRT1 in improving URSA. SIRT1 may affect oxidative stress and autophagy by regulating the acetylation process of histones and key transcription factors, thus participating in numerous feedback loops and networks of URSA occurrence and development. Finally, SIRT1 can play a role in regulating trophoblast cell invasion and maternal-fetal interface angiogenesis. At the same time, the production of proinflammatory cytokines is suppressed to improve the excessive maternal immune inflammatory response during pregnancy. The activity of SIRT1 determines its deacetylation ability, which is crucial for downstream pathways and protein stability. Therefore, improving its activity is of great significance for improving URSA. Studies have shown that metformin and resveratrol can activate SIRT1 and protect SIRT1 and its downstream target proteins, which may be potential therapeutic agents for URSA. Based on the function of SIRT1, this article reviews the potential role of SIRT1 in the pathogenesis of URSA and the exogenous drugs targeting SIRT1 activation, in order to provide reference for the prevention and treatment of URSA in clinical research.

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    Advances in the role of muscle blind-like protein 1 in malignant tumors
    ZHU Nan, LIU Bingya, YU Beiqin
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1474-1481.   DOI: 10.3969/j.issn.1674-8115.2022.10.014
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    Muscle blind-like protein 1 (MBNL1) is a class of RNA binding protein. As an alternative splicing factor of precursor mRNA (pre-mRNA), it plays a fundamental role in the regulation of the development process and the post transcriptional regulation of specific transcripts, which affects multiple steps in the process of RNA maturation and expression, including pre-mRNA splicing, degradation, RNA output, stability maintenance, modification and translation. MBNL1 was first considered as a contributing factor in the pathogenesis of myotonic dystrophy. With going deep into the research, its role in a variety of non-tumor and tumor diseases has become increasingly prominent. Studies have shown that MBNL1 is abnormally expressed in many types of tumors and is closely related to the occurrence, development and metastasis of various malignant tumors, such as gastric cancer, colorectal cancer, breast cancer, prostate cancer, glioblastoma, lung cancer, hematological system tumors, etc. According to different cell types and development environments, the changes of MBNL1 protein levels in normal and tumor cells are diverse. MBNL1 can not only act as a transcriptional activator to promote the occurrence and development of tumors, but also play as a transcriptional repressor to inhibit the growth and metastasis of tumors. The present review summarizes the molecular mechanism, biological characteristics, expression and function of MBNL1 in the occurrence and development of various malignancies to provide several new insights into tumor-targeted therapy and prognosis evaluation.

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    Initiation and regulatory mechanism of C9ORF72 (G 4C 2) n RAN translation
    FENG Yiyuan, XU Zhongyun, DING Lin, YIN Yafu, WANG Hui, CHENG Weiwei
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1482-1489.   DOI: 10.3969/j.issn.1674-8115.2022.10.015
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    As one of the main pathogenic mechanisms of the microsatellite repeat expansion diseases, the repeats from the abnormal DNA expansion produce toxic proteins through repeat-associated non-AUG (RAN) translation, which can causes neuronal death. Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons, while frontotemporal dementia (FTD) is a less common early-onset dementia compared to Alzheimer′s disease. C9ORF72 (G4C2)n abnormal expansion is the most common cause of ALS/FTD. Three mechanisms have been proposed for abnormal expansion of (G4C2)n in C9ORF72: ① The C9ORF72 loss-of-function results from the transcription suppression of C9ORF72 caused by the abnormal expansion of (G4C2)n in C9ORF72. ② The RNA foci from the abnormal expansion of (G4C2)n in C9ORF72, which bind to multiple RNA binding protein (RBP), lead to the dysfunction of these RBP. ③ The repeats from the abnormal expansion of (G4C2)n in C9ORF72 undergoing RAN translation produce the dipeptide repeat proteins (DPRs), which results in their toxic gain-of-function. Many studies have evidenced that RAN translation plays a pivotal role in disease progression. While a lot of studies focus on the pathologic mechanism of DPRs, the initiation and regulation mechanism of C9ORF72 (G4C2)n RAN translation is unknown and severely hinders the application of RAN translation as the therapeutic target in ALS/FTD. This review summarizes the most updated literatures on initiation and regulation mechanism of C9ORF72 (G4C2)n RAN translation and discusses the feasibility of reducing cellular toxicity and increasing neuron survival by targeting C9ORF72 (G4C2)n RAN translation.

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    Research progress in the role of Akkermansia muciniphila in gut-related diseases
    JIANG Yi, JIANG Ping, ZHANG Mingming, FANG Jingyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1490-1497.   DOI: 10.3969/j.issn.1674-8115.2022.10.016
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    Akkermansia muciniphila (A. muciniphila) is one of the normal gut symbionts using mucin as the sole source of carbon and nitrogen elements to maintain colonization and growth. Intestinal homeostasis is crucial for maintaining physiological functions. Intestinal dysfunction is closely related to the occurrence and development of metabolic diseases, immune diseases, infectious diseases and tumors. Gut microbiota is a key factor that influences the intestinal health. As a member of the gut microbes, A. muciniphila plays a convincing role in intestinal inflammation, intestinal tumor and other intestinal disorders involving diseases such as liver diseases and metabolic diseases. The mechanism is under exploration and revealed gradually. Hence, A. muciniphila is considered to be a promising candidate of probiotics. The characteristics of A. muciniphila, its distribution in the gut, its relationship with gut-related diseases and the mechanism are reviewed.

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    Status and prospect of prenatal genetic diagnosis of fetal congenital heart disease
    LI Min, WU Yi, CHENG Weiwei
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1498-1503.   DOI: 10.3969/j.issn.1674-8115.2022.10.017
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    Congenital heart disease (CHD) is diagnosed as the birth defect that causes heart or blood vessel structure abnormality due to genetic or environmental factors, leading to cardiac dysfunction. It is the most common disease among birth defects in China recently, and its incidence is increasing year by year, seriously affecting the health of newborns, especially for some complicated CHD fetuses. The birth survival rate is very low, and surgical interventions are necessary, which bring heavy psychological and economic burden to the families of fetuses, and seriously affect the aristogenesis and aristogenesis in China. The etiology of CHD is complex. Nowadays, it is believed that the occurrence of CHD is closely related to genetic and environmental factors. Some studies showed that genetic factors were the main causes of CHD, and approximately one of ten fetuses with CHD were related to genetic inheritance. Therefore, prenatal diagnosis to investigate the genetic causes of fetal CHD is crucial for evaluating fetal prognosis. In recent years, more and more studies at home and abroad have focused on the genetic etiology of congenital heart disease. Relevant review articles published in China only focused on the progress of certain genetic testing techniques for the detection of chromosomal abnormalities of CHD, and there is still a lack of comprehensive summary of various prenatal genetic testing techniques on the detection of genetic causes of CHD. This article reviews and prospects various genetic testing techniques for CHD.

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    Acute suppurative thyroiditis: a case report and literature review
    WANG Juan, CHEN Qimou, LIU Qicong, CHEN Guangmin, JIANG Peng, ZHANG Rui, ZHOU Houdi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1504-1510.   DOI: 10.3969/j.issn.1674-8115.2022.10.018
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    Acute suppurative thyroiditis (AST) is a rare and possibly fatal thyroid disease. A case with "sore throat one month accompanied by left neck mass for two weeks" as the main presentation was reported. The clinical presentation was atypical, and was mistaken for subacute thyroiditis. She was treated with glucocorticoid. The diagnosis of AST was confirmed after ultrasound-guided fine needle aspiration, due to poor efficacy. The features of AST patients over the age of fifty years were also analyzed.

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    A case of protein S deficiency complicated with cerebral embolism and peripheral arterial embolism
    LÜ Mingshun, ZHANG Zihong, WANG Mei
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1511-1516.   DOI: 10.3969/j.issn.1674-8115.2022.10.019
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    The patient, a 49-year-old male, was admitted to Zhoushan Hospital Affiliated to Wenzhou Medical University in January 2022. He complained of walking instability without obvious inducement for more than 1 month. He had a history of thrombophlebitis and no family history of arterial or venous thrombosis. He had two episodes of acute cerebral infarction, and the tests for thrombophilia in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine showed that the total amount of protein S was 26.7%, and he had a heterozygous mutation C.1955A>T, p.Asp652Val in the exon 15 of PROS1 gene. Then he was diagnosed as having hereditary protein S deficiency (PSD), and thereafter he was given long-term oral rivaroxaban tablets for anticoagulation. This time the physical examinations showed no abnormalities except slightly unsteady walking. The patient scored 6 points in the Venous Thromboembolism (VTE) Risk Assessment Scale (Padua model) with high risk of VTE. Holter testing showed sinus rhythms with occasional premature atrial beats and premature ventricular beats. B-ultrasound for the vessels in the extremities showed multiple thrombus formation with local stenosis in the bilateral popliteal arteries and the posterior tibial arteries, and occlusion in the right radial artery. Echocardiography and carotid ultrasound showed no obvious abnormalities. Cranial MRI showed an old cerebral infarction lesion in the left basal ganglia region. CT angiography combined with three-dimensional reconstruction showed severe stenosis and possible occlusion in the M1 segment of the left middle cerebral artery, and stenosis and sclerosis of the siphon segment of the bilateral internal carotid arteries. Finally, the patient was diagnosed as having PSD with cerebral infarction and peripheral arterials obstruction. He was treated with rosuvastatin calcium for stabilizing plaques, rivaroxaban for anticoagulation, metoprolol succinate for controlling ventricular rhythms, and folic acid for improving metabolism. After 10 d of treatment, the patient 's symptoms were improved.

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    Effect of Leptospira interrogans 56606v on apoptosis of murine neutrophil
    DU Lin, HE Ping
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1517-1523.   DOI: 10.3969/j.issn.1674-8115.2022.11.001
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    Objective ·To investigate the effect of Leptospira interrogans 56606v on apoptosis of murine neutrophils and related mechanisms. Methods ·Murine neutrophils were infected with Leptospira interrogans 56606v at indicated multiplicity of infection (MOI was 100, 300 and 500 respectively) and time points (0.5,6,12 and 24 h), with uninfected neutrophils as control. Cells treated with an equal amount of cell culture medium containing 4 μmol/L astrosporine (STS) were used as positive control for apoptosis. The apoptosis was analyzed by using flow cytometry. The cleavage of caspase-3 and activation of nuclear factor-κB (NF-κB) pathway were detected in murine neutrophils infected with Leptospira interrogans 56606v by Western blotting, and the inhibitory effect of NF-κB inhibitor BAY 11-7082 on NF-κB pathway was also verified by Western blotting. The role of NF-κB pathway in the inhibition of neutrophil apoptosis induced by Leptospira interrogans 56606v was further explored by adding NF-κB inhibitor BAY 11-7082. Macrophages were co-incubated with Leptospira-infected or-uninfected carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled neutrophils, and flow cytometry was used to detect the phagocytosis of neutrophils by macrophages to reflect the effect of the neutrophil apoptosis inhibition induced by Leptospirainterrogans 56606v infection on efferocytosis. Results ·The results of flow cytometry showed that the apoptosis rate of neutrophils in Leptospira infection group was decreased compared with the uninfected control group. The inhibition of Leptospirainterrogans 56606v on neutrophil apoptosis was enhanced with the increase of MOI. Compared with the uninfected control group, the difference was statistically significant under different MOIS (P=0.000). The apoptosis rate was lower than that of the corresponding uninfected control group when Leptospirainterrogans 56606v with MOI=100 infected neutrophils for 0.5, 6 and 12 h (P<0.05), and the apoptosis of neutrophils was enhanced after treatment with STS. The cleavage of caspase-3 was significantly reduced after infection with Leptospira interrogans 56606v and the phosphorylation of NF-κB was significantly increased after infection demonstrated by Western blotting. The activation of NF-κB pathway in both post-infection and non-infection conditions was significantly inhibited by BAY 11-7082. The apoptosis rate of murine neutrophils infected with or without Leptospira interrogans 56606v was significantly increased by BAY 11-7082 (P=0.000). The neutrophils infected with Leptospira interrogans 56606v were significantly less phagocytosed by macrophages than those uninfected (P=0.027). Conclusion ·Leptospira interrogans 56606v inhibits the apoptosis of murine neutrophils by activating the NF-κB pathway, which further reduces efferocytosis of macrophages on neutrophils.

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