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    Research progress and development trend of lower extremity exoskeleton rehabilitation robot
    Jiyu HAN, Yanhong WANG, Daqian WAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 241-246.   DOI: 10.3969/j.issn.1674-8115.2022.02.017
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    Lower limb motor dysfunction caused by various causes is an important public health problem in the world today. Lower extremity exoskeleton rehabilitation robot is a new type of wearable bionic device, which is mainly used to realize the standing and walking of patients with lower extremity motor dysfunction. It is a hot research topic in rehabilitation medicine at present. By reviewing the history of lower extremity exoskeleton rehabilitation robot, some breakthroughs and developments are found to have been made in this field in recent years. In the future, if we can overcome the technical problems such as portability, intelligence and modularization, it will be possible to maximize the recovery of patients with lower limb dysfunction. In this paper, the key technologies and clinical applications of wearable lower extremity exoskeleton rehabilitation robot are reviewed comprehensively, and new prospects for the research and development in this field are proposed.

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    Establishment of a novel mice model of heart failure with preserved ejection fraction
    Xiao-nan CHEN, Jun-feng ZHANG, Chang-qian WANG, Hui-li ZHANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (5): 565-570.   DOI: 10.3969/j.issn.1674-8115.2021.05.002
    Abstract1594)   HTML46)    PDF(pc) (2075KB)(1008)       Save
    Objective

    ·To establish a novel mice model of heart failure with preserved ejection fraction (HFpEF).

    Methods

    ·Sixteen 8-week-old SPF grade male and female C57BL/6J mice each were randomly divided into control group or model group (n=8 per group). The model group was given high-fat diet containing 60% fat and drinking water containing 0.5 g/L Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). The control group was given routine feed and drinking water. The ratio of peak early mitral velocity to peak late mitral velocity (E/A ratio) and the ratio of peak early mitral velocity to peak early diastolic mitral annular velocity (E/E' ratio) were detected by echocardiography every two weeks to evaluate left ventricular diastolic function. At the 16th week after modeling, the myocardial hypertrophy and fibrosis were examined by Masson staining and hematoxylin-eosin staining. The levels of serum triacylglycerol (TAG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-Ch) and low-density lipoprotein cholesterol (LDL-Ch) were detected by automatic biochemical analyzer.

    Results

    ·HFpEF appeared in the male mice at 8 weeks after high-fat diet and L-NAME administration, with a significant increase in E/A ratio and E/E′ ratio in comparison to the male control group (both P=0.000). There was no significant difference in the left ventricular ejection fraction (LVEF) between male model group and male control group. On the other hand, the female mice fed with high-fat diet and drinking water containing L-NAME also displayed obvious HFpEF after 8 weeks. E/A ratio and E/E' ratio in female model group were significantly higher than those in the female control group (P=0.000, P=0.001). There was no significant difference in LVEF between female model group and female control group. At the 16th week after modeling, both male and female mice still displayed the characteristics of HFpEF. Systolic blood pressure and diastolic blood pressure of male and female model group were significantly higher than those of respective control groups. Male or female mice with HFpEF showed obvious myocardial hypertrophy and fibrosis along with left ventricular remodeling. The serum levels of TAG, TC, HDL-Ch and LDL-Ch in the model groups were significantly higher than those in the respective control groups.

    Conclusion

    ·High-fat feeding combined with L-NAME administration can induce HFpEF in both male and female mice.

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    Classification and treatment progress of MMRd-related endometrial cancer
    Qian YIN, Yin-cheng TENG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (11): 1509-1513.   DOI: 10.3969/j.issn.1674-8115.2021.11.016
    Abstract1468)   HTML43)    PDF(pc) (891KB)(420)       Save

    Endometrial carcinoma is a very heterogeneous gynecological cancer. According to the latest molecular classification, endometrial carcinoma is divided into mismatch repair deficiency (MMRd)-related EC and non-MMRd-related EC. And MMRd-related EC is divided into three subtypes according to the characteristics of mutation: MLH1-hypermethylationged endometrial carcinoma (EC-met); Lynch syndrome-related endometrial carcinoma (EC-ls) and mismatch repair gene double somatic variants (EC-dspv). The three subtypes of EC have different pathogenesis and clinical characteristics. Therefore, they must be distinguished according to clinical and immunological characteristics in order to adopt precise treatments. This article mainly introduces the classification of MMRd-related endometrial carcinoma, and compares the three subtypes with the mismatch repair proficiency (MMRp) of EC in terms of clinical and immune features. Finally, this review introduces recent researches and clinical trials related to the treatment and prognosis of MMR.

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    Spatio-temporal analysis of incidence rate of syphilis in China
    Ting-ting TIAN, Ya-xuan HOU, Yu-qing LI, Hong-jiao QI, Mo CHEN, Mei-xia LÜ
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (5): 648-652.   DOI: 10.3969/j.issn.1674-8115.2021.05.015
    Abstract1466)   HTML41)    PDF(pc) (1308KB)(1349)       Save
    Objective

    ·To get the spatio-temporal distribution of the syphilis epidemic in 31 provinces, municipalities directly under the Central Government and autonomous regions of the mainland of China in 2017.

    Methods

    ·The data of syphilis incidence in 31 provinces, municipalities and autonomous regions of the mainland of China in 2017 were obtained from the China Public Health Science Data Center, and the time distrbution characteristics of the incidence rates were described. The global Moran′s I index and Anselin local Moran′s I index were used to analyze the spatial cluster characteristics of the syphilis cases, and then space-time scan analysis based on Poisson distribution was used to explore the spatio-temporal distribution characteristics.

    Results

    ·In 2017, the number of syphilis cases in the 31 provinces, municipalities, and autonomous regions of the mainland of China was 475 860, and the incidence rate was 34.49/100 000. Latent syphilis accounted for most of the cases, reaching 76.78% (365 353/475 860). August had the highest incidence rate. For the spatial distribution, Xinjiang Uygur Autonomous Region was the provincial-level unit with the highest incidence rate of syphilis, reaching 91.80/100 000. The incidence rates of latent, secondary, tertiary, and congenital syphilis appeared with positive spatial autocorrelation (all P<0.05). The high-high clusters of secondary and tertiary syphilis appeared in Shanghai, Jiangsu, and Zhejiang (all P<0.05), respectively, while the high-high clusters of congenital syphilis appeared in Xinjiang and Tibet (P=0.000). The results of space-time scan analysis showed that the main cluster appeared from April to September in Fujian, Jiangxi, Zhejiang, Shanghai, Jiangsu, Hunan, Anhui, and Guangdong (P=0.000). Compared with the outside area, the relative risk of syphilis in this cluster was 1.59 times.

    Conclusion

    ·The incidence rate of syphilis in China is relatively high. There are differences in the types and periods of syphilis prevention and control among provinces, municipalities and autonomous regions. From April to September, Fujian, Jiangxi, Zhejiang, Shanghai, Jiangsu, Hunan, Anhui and Guangdong are the key areas for syphilis prevention and control in the mainland of China.

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    Review of immunosuppressive tumor microenvironment of pancreatic cancer
    Jing-wei LI, Li-wen WANG, Ling-xi JIANG, Qian ZHAN, Hao CHEN, Bai-yong SHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (8): 1103-1108.   DOI: 10.3969/j.issn.1674-8115.2021.08.018
    Abstract1437)   HTML111)    PDF(pc) (908KB)(761)       Save

    Pancreatic cancer is a highly malignant tumor. The difficulty of early diagnosis and scarcity of effective clinical treatment strategies lead to poor prognosis. Tumor microenvironment (TME) of pancreatic cancer is composed of tumor cells, immune cells, stromal cells, extracellular matrix and soluble factors. TME plays an important role in the development, progression, invasion and metastasis of tumors. The pancreatic cancer microenvironment has significant immune cell infiltration, which is highly immunosuppressive. On the one hand, tumor cells edit the immune system so that cancer cells cannot be recognized by the immune system; on the other hand, they can recruit and activate various immunosuppressive cells such as pancreatic stellate cells, myeloid-derived inhibitory cells, tumor-associated macrophages, regulatory T cells and so on. These immunosuppressive cells can secrete immunosuppressive molecules, affect the function of anti-tumor immune cells, inhibit the host′s anti-tumor immune response, lead to tumor immune escape, and promote tumor development and metastasis. In this review, the mechanisms and effects of these immunosuppressive components are discussed and the updated results of immunotherapy on pancreatic cancer are studied, which may provide novel insights on TME and immunotherapy of pancreatic cancer.

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    Research progress in health risk assessment of perfluorinated compounds among Chinese population
    Qian YAO, Ying TIAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (6): 803-808.   DOI: 10.3969/j.issn.1674-8115.2021.06.017
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    Perfluorinated compounds (PFAS) are a new class of persistent organic pollutants that have attracted wide attention in recent years. With the increasing restrictions on PFAS in Europe and the United States, the production of PFAS is gradually transferring to China. The amount of PFAS used in China is increasing year by year, but there are no strict restrictions on the use of them. Furthermore, the safety limits are heading down in Europe and the United States. Based on the updated safety limits, studies in Chinese population have gradually indicated the potential risk of PFAS. This review summarizes the updated international safety limits, and introduces the research progress in health risk assessment of PFAS exposure in Chinese population according to different sources of exposure (diet, milk, drinking water, dust, atmosphere, placental transfer and comprehensive sources). The existing studies mainly focus on the health risk of PFAS exposure in high PFAS-polluted areas and in sensitive infant population in China, while the health risk of PFAS exposure in general population still needs to be further evaluated. It is necessary to carry out relevant work, which can provide reference for relevant government departments to formulate PFAS control standards and safety limits in line with China's national conditions as soon as possible. In addition, the future assessment research should pay more attention to complex evaluation of various sources of PFAS and the health hazards of PFAS alternatives.

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    Identification of core genes in pancreatic cancer progression by bioinformatics analysis
    Lu-di YANG, Gao-ming WANG, Ren-hao HU, Xiao-hua JIANG, Ran CUI
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (5): 571-578.   DOI: 10.3969/j.issn.1674-8115.2021.05.003
    Abstract1285)   HTML44)    PDF(pc) (5114KB)(503)       Save
    Objective

    ·To select pancreatic cancer progression-related core genes and key pathways.

    Methods

    ·The dataset GSE28735 for pancreatic cancer was obtained by searching and screening in the Gene Expression Omnibus (GEO) database. Genes in 45 cases of cancer tissues and 45 cases of normal tissues adjacent to cancer were extracted by GEO2R and combined with RStudio to screen and visualize differentially expressed genes (DEGs). Genes with significant differential expression were analyzed by gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis through the gene utilization function annotation online tool DAVID. The protein-protein interaction (PPI) network was constructed by using the interactive gene retrieval tool, STRING and Cytoscape, to further screen core genes based on the node degree value. The relationship between the expression levels of core genes and overall survival (OS), disease-free survival (DFS) and tumor stage of 179 cases of patients was analyzed through the gene expression profile analysis database GEPIA.

    Results

    ·A total of 131 DEGs were screened from the dataset GSE28735, including 115 up-regulated genes and 16 down-regulated genes. GO function enrichment analysis showed that DEGs were mainly enriched in cell adhesion, plasma membrane, and protein binding. KEGG pathway enrichment suggested that phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) was the main signaling pathway for DEG enrichment. Five core genes, fibronectin1 (FN1), mesenchymal to epithelial transition factor (MET), polyclonal antibody to laminin β3 (LAMB3), laminin subunit α3 (LAMA3), and integrin subunit α3 (ITGA3), were obtained through PPI network screening. The expression levels of MET, LAMA3, LAMB3 and ITGA3 were associated with OS of patients, and the expression levels of MET, LAMB3 and ITGA3 were associated with DFS. The prognosis of low gene expression group was significantly better than that of high gene expression group. There were significant differences in the expression levels of FN1, MET, LAMA3 and LAMB3 in the different stages of pancreatic cancer.

    Conclusion

    ·The abnormal expression of FN1, MET, LAMB3, LAMA3 and ITGA3 is related to the changes of cell adhesion, plasma membrane component, protein binding function and PI3K/Akt pathway. The increased expression of MET and LAMB3 may predict poor prognosis of patients with pancreatic cancer.

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    Association of triglyceride-glucose index with cardiovascular disease in people without traditional risk factors
    ZHANG Tong, TIAN Xue, ZUO Yingting, ZHENG Manqi, ZHANG Yijun, WU Shouling, CHEN Shuohua, MA Gaoting, TONG Xu, WANG Anxin, MO Dapeng
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (3): 267-274.   DOI: 10.3969/j.issn.1674-8115.2022.03.002
    Abstract1196)   HTML8)    PDF(pc) (1658KB)(275)       Save
    Objective

    ·To examine the association of triglyceride-glucose index with cardiovascular disease (CVD) in participants without atherosclerotic CVD (ASCVD) risk factors.

    Methods

    ·This study included 32 532 participants [64.01% male, mean age (48.26±12.89) years] who had no history of CVD and no ASCVD risk factors (including dyslipidemia, hypertension, smoking and diabetes) at baseline from Kailuan Study during 2006?2007. Participants were divided into 4 groups according to the quintiles of TyG index at baseline (Q1, Q2, Q3 and Q4). TyG index was calculated as ln[triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]. The outcome was the first occurrence of CVD from baseline to the end of follow-up (December 31, 2019). Baseline characteristics were compared with one-way ANOVA or Kruskal-Wallis test for continuous variables, and chi-square for categorized variables. Multivariable-adjusted Cox proportional hazards models were performed to evaluate the associations. Restricted cubic spline with 5 knots at the 5th, 25th, 50th, 75th and 95th percentile was used to explore the dose-response association between TyG index and incident CVD. A two-sided P<0.05 was considered statistically significant.

    Results

    ·During a median follow-up of 12.97 (12.67, 13.17) years, we observed 1 324 incident CVD events (including 1 084 cases of stroke and 255 cases of myocardial infarction). Compared with participants in the Q1 group, the multivariable adjusted hazard ratios in the Q2, Q3 and Q4 group were 1.16 (95%CI 0.97?1.38), 1.29 (95%CI 1.08?1.53) and 1.60 (95%CI 1.35?1.90) for CVD, 1.12 (95%CI 0.93?1.36), 1.21 (95%CI 1.00?1.46) and 1.44 (95%CI 1.20?1.73) for stroke, and 1.32 (95%CI 0.84?2.06), 1.64 (95%CI 1.07?2.51) and 2.41 (95%CI 1.60?3.65) for myocardial infarction, respectively. Sensitivity analyses yielded similar results. Subgroup analysis showed that the association between TyG index and CVD was consistent across different gender populations, and there was no significant interaction between gender and TyG index in relation to the risk of CVD. Multivariable-adjusted spline regression model showed a J-shaped association between TyG index and the risk of CVD, stroke and myocardial infarction. Similar results were observed when stroke and myocardial infarction were the interest of outcomes.

    Conclusion

    ·Among the individuals without traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing TyG index level.

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    Application of a tent-pole screw technology in reconstruction of severe alveolar bone defect: a retrospective study of 30 patients
    WU Jing, ZHAO Zhengyi, ZOU Duohong, YANG Chi, ZHANG Zhiyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (6): 768-777.   DOI: 10.3969/j.issn.1674-8115.2022.06.011
    Abstract1185)   HTML45)    PDF(pc) (6442KB)(545)       Save
    Objective

    ·To explore the effect of a tent-pole screw technology on reconstruction of severe alveolar bone defect.

    Methods

    ·Thirty patients underwent tent-pole screw technology to reconstruct severe alveolar bone defects in the Department of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to January 2021 were enrolled. By analyzing and reconstructing the image data of cone-beam computed tomography (CBCT) before and 8 months after operation, the effects of repairing and reconstructing the horizontal, vertical and mixed alveolar bone defects were counted. The alveolar bone volumetric parameters were evaluated by micro-computed tomography (Micro-CT), and trabecular bone number (Tb. N), trabecular bone thickness (Tb. Th), bone volume/total volume (BV/TV) and bone mineral density (BMD) were calculated to assess the maturity of regenerated bone. The regeneration of alveolar bone and remanent scaffold were calculated by analyzing histological sections.

    Results

    ·Eight months after using the tent-pole screw, the vertical bone gain value was 4.81 (1.58, 7.66) mm, and the horizontal post-operative width was 3.96 (2.38, 5.67) mm. Additionally, the bone volume gain was 2 157.22 (776.59, 2 831.63) mm3. Micro-CT analysis of bone core, which was collected 8 months after the surgery, and Tb. N was (3.09±0.68)/mm, Tb. Th was (0.08±0.01) μm, BV/TV was (25.24±5.60)% and BMD was (0.24±0.05) g/cm3. Histological sections showed that the percentages of regenerated bone and remanent scaffold were (16.30±3.57)% and 34% (31.75%, 38.25%), respectively. These data suggested good new bone formation in targeted area. There were no complications or adverse events during surgery or post-operative healing.

    Conclusions

    ·Based on “stability-oriented” alveolar ridge augmentation, using tent-pole screw, membrane pins and packaging structure in a standard operation procedure can achieve beneficial results for bone augmentation, while complications seldom occurre. The tent-pole screw may offer predictable and exceptional outcomes for implantation site preparation, especially for large alveolar defects, which will provide advantages to subsequent implantation and restoration.

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    Establishment and optimization of co-culture technology for breast cancer organoids
    Tian-hao ZHOU, Zhao-chen XIN, Shao-qian DU, Yuan CAO, Jing-xuan XU, Zeng-hong LAO, Hong-xia WANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (8): 1017-1024.   DOI: 10.3969/j.issn.1674-8115.2021.08.004
    Abstract1184)   HTML227)    PDF(pc) (4693KB)(813)       Save
    Objective

    ·To improve the cultivating and passaging method of breast cancer organoids, and establish a co-culture system enriching cancer associated fibroblasts (CAFs).

    Methods

    ·Different types of collagenases (type Ⅰ, type Ⅲ and type Ⅳ) were used to digest fresh tissues from 5 breast cancer patients. The number of cells after tissue digestion was counted by cell counting method, and cell viability was analyzed by cell flow cytometry. Three-dimensional culture of primary breast cancer single cells was carried out by using culture system containing different contents of fibroblast growth factor 7 (FGF7), FGF10 and epidermal growth factor (EGF). The success rate of cell culture and the growing status of organoids were observed and compared. Different centrifugation speeds were used to compare the advantages and disadvantages of passaging methods and simplify the passaging steps. CCK8 assay was used to study the effect of CAFs on the growth of organoids in the co-culture system of primary CAFs and organoids, and the morphological changes of organoids were observed under optical microscope.

    Results

    ·Compared with type Ⅰ and type Ⅲ collagenase, type Ⅳ collagenase got the highest cell yields (P=0.045, P=0.017), and maintained the highest cell viability (P=0.005, P=0.048). By optimizing the composition of organoid medium (omitting FGF7 and FGF10, reducing EGF concentration) and passaging process (improving centrifugal velocity to 900×g), a more economical, effective and rapid method of organoid culture was obtained. Compared with organoids cultured alone, the growth rate (P<0.05) and heterogeneity of organoids increased when organoids were co-cultured with CAFs.

    Conclusion

    ·The optimized culture system can significantly increase the success rate of organoids, simplify the culture steps and reduce the culture cost. The establishment of primary CAFs and organoids co-culture system provides a good in vitro model for the study of breast cancer heterogeneity and tumor microenvironment.

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    Research progress in animal model of acute lung injury
    Jing-yi FU, Lei WANG, Yi YANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (5): 690-694.   DOI: 10.3969/j.issn.1674-8115.2021.05.022
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    Acute lung injury (ALI) refers to the occurrence of hypoxic respiratory failure and even acute respiratory distress syndrome caused by various factors. The morbidity and fatality rate of ALI are very high, but the research on its pathogenesis and treatment methods has not made much progress. Therefore, it is very necessary to establish animal models to simulate acute lung injury. In this paper, the literature on animal models of ALI in recent years is collected and summarized, and the selection of animal models of acute lung injury and the evaluation methods of lung injury are reviewed, so as to provide reference for the establishment of animal models of ALI.

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    Clinical characteristics and prognosis of pediatric acute leukemia patients with MLL gene rearrangements
    Qing LIU, Na ZHANG, Jing-bo SHAO, Hong LI, Kai CHEN, Cheng-kan DU, Zhen WANG, Hui JIANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (7): 903-909.   DOI: 10.3969/j.issn.1674-8115.2021.07.009
    Abstract991)   HTML21)    PDF(pc) (1094KB)(488)       Save
    Objective

    ·To analyze the clinical characteristics and prognosis of pediatric acute leukemia (AL) patients with positive mixed linage leukemia (MLL) gene rearrangement (MLL-r).

    Methods

    ·Forty-five children with MLL-r AL admitted to Shanghai Children′s Hospital, Shanghai Jiao Tong University from January 1, 2009 to December 31, 2019 were retrospectively analyzed. Fluorescence in situ hybridization and/or fluorescent real-time PCR were used to detect the MLL-r. Kaplan-Meier method was used to evaluate the survival of children. Log-rank test was used to compare the difference of survival rate. Univariate analysis and multivariate analysis were performed on the factors influencing survival, such as gender, age and the number of white blood cells.

    Results

    ·The incidence rate of MLL-r in children with AL in our center was 7.1%, and the incidence rate of MLL-r in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were 5.4% and 13.3%, respectively. The difference between the two groups was statistically significant (P=0.002). The age of the two groups of children (>1 year and ≤1 year) and the number of white blood cells at the time of onset (≥50×109/L and <50×109/L) were compared. The differences were statistically significant (P=0.032 and 0.021). The main immunophenotype of children with MLL-r ALL was early precursor B-ALL, accounting for 79.2%. The main immunophenotype of children with MLL-r AML was M5, accounting for 77.8%. MLL partner gene analysis showed that MLL/AF4 accounted for 59.2% (16/27) of MLL-r ALL children, of which 68.7% (11/16) were children younger than 1 year old. Compared with the children younger than 1 year old in the non-MLL/AF4 group, the difference was statistically significant (P=0.034). The majority of children with MLL-r AML were MLL/AF9, accounting for 33.3%. Of the 45 patients, 42 cases were included for the prognosis analysis. The complete remission rate was 97.6% (41/42), and the median follow-up time was 26 (2?138) months. The median event-free survival (EFS) and overall survival (OS) time were 21 months and 24.5 months, respectively. The 3-year EFS and OS rates were (41.8±9.4) % and (60.9±9.3) %, respectively. The median duration of EFS and OS in children with MLL-r ALL were 21.5 months and 28 months, respectively, and the 3-year EFS and OS rates were (44.3±11.7) % and (58.2±12.1) %, respectively. The median EFS and OS time in children with MLL-r AML were 16 months and 23 months, respectively. The 2-year EFS and OS rates were (36.5±15.8) % and (64.7±14.5) %, respectively. Eight cases of ALL children relapsed, with a median recurrence time of 20 (2?36) months; 7 cases of AML children relapsed, with a median recurrence time of 16 (5?38) months, and the cumulative recurrence rates were 48.4% and 63.9%, respectively. There was no statistically significant difference between them (P=0.398). Univariate analysis showed that between the groups of MLL-r ALL children >1 year and ≤1 year, white blood cell count ≥50×109/L and <50×109/L, platelet count ≥30×109/L and <30×109/L, there were statistically significant differences in the EFS rate. The P values were 0.028, 0.024 and 0.027 respectively. Multivariate analysis showed that the number of white blood cells at onset was an independent prognostic factor affecting EFS in children with MLL-r ALL (RR=6.113, 95% CI 0.017?1.050, P=0.013).

    Conclusion

    ·The incidence of MLL-r in children with AML is higher than that in children with ALL. The main immunophenotype of MLL-r ALL is early precursor B-ALL. The main immunophenotype of MLL-r AML is M5. Conventional chemotherapy produces a high response rate, which is likely to relapse. The number of white blood cells at the onset ≥50×109/L is a poor prognostic factor for children with MLL-r ALL.

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    Protocols for diagnosis and treatment of temporomandibular joint osteoarthritis: experience from the TMJ Center of Shanghai Ninth People 's Hospital, Shanghai Jiao Tong University School of Medicine
    ZHANG Shanyong, YANG Chi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (6): 709-716.   DOI: 10.3969/j.issn.1674-8115.2022.06.003
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    Temporomandibular joint osteoarthritis (TMJOA) is the most common degenerative disease in the temporomandibular joint, mainly manifesting with pain in the joints and the muscles, joint locking, popping, crepitus, and limited mouth opening, which may undermine the quality of patients' life. The main pathological features of TMJOA include chronic synovitis, progressive articular cartilage degeneration, and abnormal subchondral bone remodeling. At present, its pathogenesis is still unclear, and abnormal mechanical load, trauma, heredity, metabolism, gender and age can all be regarded as pathogenic factors. Commonly used diagnostic methods for TMJOA include magnetic resonance imaging (MRI) and computed tomography [(CT/cone beam CT (CBCT)]. The staging standards of TMJOA mainly include Wilkes staging system and Yang's staging system. The clinical treatment of TMJOA mainly includes two categories: non-surgical treatment and surgical treatment. Non-surgical treatment includes health education, psychological consultation, medication, occlusion treatment, etc. Surgical treatment includes arthrocentesis, arthroscopic surgery, disc anchoring, autogenous tissue graft, and total joint replacement. This paper summarizes the diagnosis, staging, surgical treatment and postoperative evaluation of TMJOA on the basis of literature review, and proposes diagnosis and treatment protocols based on the experience of the TMJ Center of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, so as to provide reference for clinicians.

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    Advances in resilience research
    Shuang-yi CHEN, Jian-yin QIU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (10): 1397-1400.   DOI: 10.3969/j.issn.1674-8115.2021.10.021
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    Resilience refers to the dynamic process of individual's positive adaptation to adversity, which is closely related to the symptoms of mental disorders and can be improved through intervention. This paper reviews the definition, evaluation method and intervention of resilience, and proposes that resilience can be used as an indicator of mental disorders related to stressor exposure, which has certain reference significance for improving individual resilience and promoting individual mental health development.

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    Exploratory study on downregulation of PD-L1 in KRAS G12V-mutant non-small cell lung cancer cells by selumetinib
    Yun-fang MA, Li-na PAN, Zhen LI, Bei-li GAO, Jia-an HU, Zhi-hong XU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (6): 741-748.   DOI: 10.3969/j.issn.1674-8115.2021.06.006
    Abstract919)   HTML7)    PDF(pc) (3442KB)(317)       Save
    Objective

    ·To investigate the correlation between Kirsten rat sarcoma viral oncogene (KRAS)-mutant subtypes and programmed cell death ligand 1 (PD-L1) expression in the non-small cell lung cancer (NSCLC) tissues and cell lines, and the possible underlying mechanism.

    Methods

    ·Real-time quantitative PCR and fluorescence-activated cell sorting were used to verify the correlation between PD-L1 mRNA or protein and KRAS mutation status in the NSCLC cell lines. Immunohistochemistry was used to detect the expression of PD-L1 in the tumor tissues of 77 NSCLC patients with early stages (Ⅰa?Ⅱb). The effect of KRAS mutation on the cytokines in the RAS downstream signaling pathway, i.e., protein kinase B (PKB or AKT), mammalian target of rapamycin (mTOR), ribosomal S6 protein kinase (p70S6K), and extracellular regulated protein kinase (ERK), was studied by Western blotting. Dabrafenib (RAF inhibitor), selumetinib [mitogen activated-protein kinase (MEK) inhibitor], GDC0941 (phosphoinositide 3-kinase inhibitor), MK2206 (AKT inhibitor), and rapamycin (mTOR inhibitor) were used to treat 6 KRAS-mutant cell lines, respectively, to detect the regulation of these five tyrosine kinase inhibitors on PD-L1 expression.

    Results

    ·In the NSCLC cell lines, the expressions of PD-L1 mRNA and protein in the KRAS mutant cell lines were significantly higher than those in the KARS wild-type cell lines (P<0.05). KRAS G12V- and G12C-mutant cell lines showed the highest expression of PD-L1 mRNA and protein, respectively. For the NSCLC patients with early stages, the proportions of PD-L1 overexpression in the tumor tissues of the patients with KRAS G12V and G12D mutants were significantly higher than those of the patients with KRAS wild-type. Western blotting showed that in the KRAS-mutated NSCLC cell lines, p70S6K was activated, while ERK, AKT and mTOR were not activated. Moreover, 1 μmol/L GDC0941, 0.5 μmol/L MK2206, and 10 nmol/L rapamycin could not affect the expression of PD-L1 in the 6 KRAS-mutant cell lines. Darafenib (5 nmol/L) up-regulated PD-L1 in only one KRAS G12V-mutant cell line and one L19F-mutant cell line (P<0.05), while selumetinib (0.1 μmol/L ) inhibited the expressions of PD-L1 in three KRAS G12V-mutant cell lines and one L19F-mutant cell line (P<0.05) in a dose-dependent manner.

    Conclusion

    ·The expressions of PD-L1 in the tumor tissues and cell lines of NSCLC with KRAS mutation, especially G12V mutation subtype, were higher than those in the NSCLC tissues and cell lines with KRAS wild-type. Selumetinib can downregulate the expression of PD-L1 in KRAS G12V-mutant NSCLC cells, which suggests that KRAS G12V-mutant NSCLC cells may up-regulate the expression of PD-L1 by upregulating MEK.

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    Report of 3 cases of 47,XXX syndrome with growth retardation
    YANG-Li, Ya-qin FENG, Yu YANG, Li-ling XIE, Di-lan WANG, Hui HUANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (11): 1425-1428.   DOI: 10.3969/j.issn.1674-8115.2021.11.004
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    To analyze the clinical data of 3 children with growth retardation, including height, chromosome karyotype, and the levels of growth hormone, insulin-like growth factor-1 and gonadal development. All the 3 cases of children were found to be slow in growth rate, no special face, and normal level of insulin-like growth factor-1; the 3 cases all underwent growth hormone provocation test, of which 1 case was partial growth hormone deficiency and 2 cases were idiopathic short; 3 cases of chromosomal karyotypes were 47, XXX, in line with the diagnosis of super-female syndrome.

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    Research progress of osteosarcopenia
    Miao-miao CAI, Yan-hong GAO
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (5): 678-683.   DOI: 10.3969/j.issn.1674-8115.2021.05.020
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    Osreosarcopenia is a geriatric syndrome that describes the co-existence of osteoporosis and sarcopenia, which is widespread in the elderly. Osteoporosis is a condition of low bone mass and micro-architectural of bone, and sarcopenia, the loss of muscle mass, strength and muscle physiological functions. Sarcopenia and osteoporosis are age-related degenerative diseases with similar pathophysiology, including mechanical factors, genetics, fatty infiltration and endocrine factors. Studying the pathogenesis of sarcopenia-osteoporosis is of great significance in preventing and treating the disease, improving the quality of life and physical and mental health of the elderly. This review introduces the diagnosis, pathogenesis, intervention and treatment of osteosarcopenia.

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    Review of clinical application of peripheral neuropathy scales
    Qun-feng WANG, Li CAO, Xing-hua LUAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (11): 1518-1523.   DOI: 10.3969/j.issn.1674-8115.2021.11.018
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    Peripheral neuropathy (PN) refers to a group of diseases caused by the dysfunction and structural changes of peripheral motor, sensory and autonomic nerves. Scales for screening and assessing PN are continuously being used in clinical practice. This article summarizes PN score scales for four kinds of PN, including chronic inflammatory demyelinating polyradiculoneuropathy, Charcot-Marie-Tooth disease, diabetic PN and neuropathic pain, aiming to improve medical staff's understanding and application ability of the PN assessment scale.

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    Practice for multidisciplinary diagnosis and treatment of dermatofibrosarcoma protuberans: expert consensus of Shanghai Ninth People 's Hospital, Shanghai Jiao Tong University School of Medicine (2020 edition)
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (12): 1669-1675.   DOI: 10.3969/j.issn.1674-8115.2021.12.018
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    Dermatofibrosarcoma protuberans (DFSP) is a low- to intermediate-grade malignant soft tissue sarcoma occurring in the skin and subcutaneous tissues. The high misdiagnosis rate often delays the best treatment opportunity, and the wrong treatment method leads to the high recurrence rate of surgery. Traditional extended resection requires 3?5 cm expansion around the tumor, and the huge tissue defect increases the difficulty of surgery, which is also hard to be accepted. In Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, under the support of the multi-disciplinary treatment group, cutaneous spindle cell neoplasms multi-disciplinary team of accurate diagnosis and treatment normatively conducted treatment of DFSP comprehensive diagnosis and treatment. Modified Mohs micrographic surgery was used to remove the tumor while preserving as much normal tissue as possible. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine expert consensus of diagnosis and treatment of specification of DFSP multidisciplinary specification was formed.

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    Clinical features of 23 patients with 45,X/46,XY mosaicism
    Xiu-li CHEN, Hai-ying WU, Ming-cui FU, Hong-ying WANG, Ou XU, Lin-qi CHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (11): 1417-1424.   DOI: 10.3969/j.issn.1674-8115.2021.11.003
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    Objective

    ·To analyze the clinical features of the patients with 45,X/46,XY mosaicism, and improve the understanding, diagnosis and treatment of the disease.

    Methods

    ·The clinical manifestations, the level of sex hormones, and the gonads pathology of the patients with 45,X/46,XY mosaicism diagnosed by G-banding karyotype analysis and fluorescence in situ hybridization (FISH) were retrospectively analyzed, who were admitted in Children's Hospital of Soochow University from January 2014 to December 2020.

    Results

    ·Twenty-three patients with 45,X/46,XY mosaicism were included, among whom 11 cases were the female phenotype, and 12 cases were the male phenotype. In these patients, 12 patients were diagnosed by G-banding karyotype analysis, 10 patients were diagnosed by FISH, and only 1 patient was diagnosed by array-based comparative genomic hybridization. The age of the first diagnosis was 0.3?14.9 years. The mean age of the patients with the female phenotype was (9.3±3.9) years, which was bigger than that of the male phenotype [(4.4±3.7) years, P<0.05]. All the patients above 1 year old had different degrees of short stature, especially in the female phenotype patients. In the female phenotype patients, three patients had clitoromegaly, while the other patients had no masculine appearance of external genitalia. The external masculinisation scores (EMS) of the patients with the female phenotype were 0?2.5. Twelve patients with the male phenotype were in pre-adolescent state, among whom 4 patients had hypospadias combined with cryptorchidism, 3 patients had hypospadias, 3 patients had small testicles, and 2 patients had normal external genitalia. The EMS of them ranged from 4 to 12, with a mean score of 10.5. All the patients with the female phenotype had hypergonadotropic hypogonadism, while most of the patients with the male phenotype had gonadotropin levels matched with their age. There were 3 patients with the female phenotype having gonadoblastomas.

    Conclusion

    ·The 45,X/46,XY mosaicism patients present a wide spectrum of manifestations. The risk of gonadal malignancy onset should be emphasized. EMS has guiding significance for clinical evaluation of these patients.

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