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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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    Progress in research on the mechanism of drug resistance to conventional chemotherapeutic drugs in children with acute lymphoblastic leukemia
    Yanyan LIN, Yan XU, Hui LI
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 211-217.   DOI: 10.3969/j.issn.1674-8115.2022.02.012
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    Acute lymphoblastic leukemia (ALL) has the highest incidence of hematological tumors in children, accounting for about one-third of all childhood cancer cases. With the continuous optimization of the treatment plan and the expansion of health care coverage in China, remarkable improvements have been achieved in the treatment of childhood ALL, and the overall survival rate of more than 5 years has reached 90%. Lack of effective treatment and unacceptably high recurrence rate are the leading causes of severe decrease in the survival and quality of life of children with drug resistance. In recent years, pathogenesis and regulation mechanism of ALL drug resistance has become a hot topic and a difficulty of research at home and abroad. Studies have shown that children with ALL may not only antagonize a certain chemotherapy (chemotherapeutic) drug, but also have a thorny situation of multi-drug resistance. Therefore, it is of great significance to improve the research on the mechanism of drug resistance of ALL to improve the prognosis of children with ALL. This review summarizes recent research progress in drug resistance mechanisms of conventional chemotherapy drugs for childhood ALL, including hormones, antimetabolite drugs (folate antagonists, thiopurines, and amino acid metabolizing drugs), alkaloids and anthracyclines, in order to provide theoretical basis for coping with clinical drug resistance.

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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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    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 in roles of follicular helper T cells in autoimmune diseases
    Xindi WEI, Xiaoyin NIU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 218-224.   DOI: 10.3969/j.issn.1674-8115.2022.02.013
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    Follicular helper T cells (Tfh cells) have been defined as a new subset of CD4+ T cells in recent years, mainly expressing surface molecules such as C-X-C motif chemokine receptor type 5, inducible co-stimulator, and secreting cytokine interleukin-21, a key transcription factor of which is B cell lymphoma 6. They exist in the germinal center (GC) of lymphoid tissue and in the peripheral blood as well. With the ability to promote B cell maturation and differentiation, GC formation and antibody production, Tfh cells play important roles in the pathogenesis of many autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and primary Sj?gren's syndrome. The abnormal quantity and/or quality of Tfh cells will cause pathological processes like tissue injury and promote disease progression. This article reviews the biological characteristics of Tfh cells and their roles in different autoimmune diseases, which may help to further reveal the pathogenesis of certain autoimmune diseases and provide a new way to treat these diseases by targeting these cells.

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    Interventional effects of nicotinamide mononucleotide on metabolism in aging mice
    Guodong DANG, Xinyu HONG, Meiqin CAI
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 158-165.   DOI: 10.3969/j.issn.1674-8115.2022.02.004
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    Objective

    ·To investigate the effects of nicotinamide mononucleotide (NMN) on metabolism in aging mice.

    Methods

    ·Seventy C57BL/6N male mice were randomly divided into 5 groups by using a table of random numbers. They were the control group, the premature aging model group, the aging model group, the intervention group Ⅰand the intervention group Ⅱ. Each group contained 14 mice. Except the control group, D-galactose (D-gal) (150 mg/kg) was subcutaneously injected into the napes of mice in the other 4 groups to establish the aging model of mice. NMN (300 mg/kg) was given to the intervention group Ⅰ and the intervention group Ⅱ by intragastric administration at the same time, and the other groups were given the same amount of distilled water, once a day, for 6 weeks in the premature aging model group and the intervention group Ⅰ, and for 12 weeks in the aging model group and the intervention group Ⅱ. The control group was given the same amount of normal saline and distilled water, once a day, for 6 weeks. Six weeks after modeling, the energy metabolism levels of the mice in the control group, the premature aging model group and the intervention group Ⅰ were detected, including respiratory metabolism, activity level and energy consumption. The organ indexes of thymus, spleen, liver and kidney were calculated. The glucose tolerance and insulin sensitivity were measured. In addition, the content of superoxide dismutase (SOD) and the activities of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the serum and liver tissue were detected. Twelve weeks after modeling, the above indexes were detected in the aging model group and the intervention group Ⅱ.

    Results

    ·Compared with the control group, the thymus index (P=0.035, P=0.000) and renal index (P=0.009, P=0.002) of the model groups were significantly decreased. The O2 consumption (P=0.018, P=0.000), CO2 exhalation (P=0.044, P=0.003), energy consumption (P=0.010, P=0.001) and activity ability (both P=0.000) of the premature aging model group and the aging model group were significantly decreased at night. The insulin sensitivity was significantly reduced (P=0.012, P=0.011). The activities of SOD (P=0.002, P=0.001) and GSH-Px (P=0.001, P=0.011) in serum were significantly decreased and the content of MDA in serum was significantly increased (both P=0.000). The decline of energy metabolism levels, thymus and kidney indexes and antioxidant index verified the success of D-gal aging model. Compared with the premature aging model group, the intervention group Ⅰ had no significant difference in respiratory metabolism, energy consumption, glucose tolerance, insulin sensitivity and other indicators (all P>0.05). But in the intervention group Ⅰ, the activity ability was significantly improved (P=0.022), the activities of SOD (P=0.026) and GSH-Px (P=0.006) in serum were significantly increased, and the MDA content in serum was significantly decreased (P=0.011). Compared with the aging model group, the O2 consumption (P=0.045), CO2 exhalation (P=0.030), activity ability (P=0.049) and energy consumption (P=0.043) in the intervention group Ⅱ were significantly increased at night. Compared with the aging model group, the impaired glucose tolerance was improved (P=0.030), the insulin sensitivity was increased (P=0.010)in the intervention group Ⅱ, the activity of SOD in serum was significantly increased (P=0.046), and the MDA content in serum and liver tissue was significantly decreased (P=0.000). There was no significant difference in the activity of GSH-Px in serum and liver tissue between the two groups (P>0.05).

    Conclusion

    ·NMN can improve the metabolic level of aging mice to a certain extent, and its mechanism may be related to improving the antioxidant capacity of the body.

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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
    Abstract251)   HTML31)    PDF(pc) (8936KB)(177)       Save
    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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    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
    Abstract249)   HTML5)    PDF(pc) (1658KB)(78)       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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    Ameliorative effect of atorvastatin on hepatic fibrosis and its mechanism
    Nan WANG, Ye LU, Feng-jie HAO, Jun-qing WANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (12): 1619-1626.   DOI: 10.3969/j.issn.1674-8115.2021.12.011
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    Objective

    ·To investigate the role of atorvastatin and its mechanisms in patients and animal models of hepatic fibrosis.

    Methods

    ·The literatures in PubMed were searched for statins for different chronic liver diseases from January 2010 to June 2020. Meta analysis was performed based on the occurrence of liver fibrosis, liver failure and overall patient mortality. Sixteen male C57BL/6 mice were randomly divided into control group, atorvastatin group, CCl4 injection group, and CCl4 injection combined with atorvastatin group with 4 mice in each group. The mice in the CCl4 injection group were administered intraperitoneally twice a week with 20% volume fraction of CCl4 at a dose of 1 mL/kg; the control group was administered intraperitoneally by using the same dose of corn oil; the mice in the atorvastatin group were gavaged once daily with a dose of 15 mg/kg of atorvastatin; the mice in the CCl4 injection combined with atorvastatin group were treated with a combination of CCl4 and atorvastatin. After 4 weeks, the animals were euthanized, and serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) were detected; the degree of intrahepatic fibrosis in the mice was detected by Sirius red staining; immunofluorescence staining was used to detect the expression of collagen ⅠA; the mRNA expressions of α-smooth muscle actin (α-SMA), collagen Ⅰ, collagen Ⅲ, interleukin (IL)-1b, IL-6, and transforming growth factor-β (TGF-β) were detected by real-time fluorescence quantitative PCR; the expressions of α-SMA protein and phosphorylated Smad4 (pSmad4) protein were detected by Western blotting.

    Results

    ·Finally 9 papers were selected for meta analysis, and the results showed that statins reduced the incidence of liver fibrosis, liver failure and overall mortality in patients with liver disease. In the animal experiments, the weight of mice in both the CCl4 injection group and the CCl4 injection combined with atorvastatin group decreased significantly compared with that in the control group (P=0.000); while the weight of mice in the CCl4 injection combined with atorvastatin group decreased to a lesser extent compared with that in the CCl4 injection group (P=0.040). Compared with the control group, GPT and GOT concentrations were significantly increased in both the CCl4 injection group and CCl4 injection combined with atorvastatin group (P=0.000), while liver enzymes in the CCl4 injection combined with atorvastatin group showed a smaller increase in GPT and GOT compared with that in the CCl4 injection group (P=0.020). Sirius red staining showed excessive deposition of intrahepatic fibers in the CCl4 injection group, and immunostaining suggested high expression of collagen ⅠA in the CCl4 injection group. The results of fluorescence quantitative PCR and Western blotting suggested that α-SMA protein expression increased, and mRNA expressions of α-SMA, collagen Ⅰ, and collagen Ⅲ were upregulated in the CCl4 injection group compared with the control group (P<0.05), whereas the expressions of these markers were downregulated in the CCl4 injection combined with atorvastatin group compared with the CCl4 injection group (P<0.05). The mRNA expressions of IL-1b and IL-6 were slightly upregulated and the expression of TGF-β was significantly upregulated in the CCl4 injection group compared with the control group (P<0.05). In contrast, the mRNA expressions of IL-1b and IL-6 were significantly up-regulated and the expression of TGF-β decreased in the CCl4 injection combined with atorvastatin group compared with the CCl4 injection group (P<0.05). The expression of pSmad4 protein increased in the CCl4 injection group compared with the control group, while the expression of pSmad4 protein was lower in the CCl4 injection combined with atorvastatin group compared with the CCl4 injection group.

    Conclusion

    ·Atorvastatin may attenuate the occurrence and development of liver fibrosis via manipulating TGF-β signaling pathway.

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    Research progress in the function of desmoglein-2 in digestive system tumors
    Yanqing LI, Xiaoxia WANG, Xiangdong JIA, Meng REN, Tianxiang XU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 247-252.   DOI: 10.3969/j.issn.1674-8115.2022.02.018
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    Desmoglein-2 (DSG2) is a member of the cadherin family. As an important part of desmoglein, DSG2 mainly plays a role in maintaining intercellular adhesion. Studies have found that DSG2 can also regulate cell proliferation, differentiation and apoptosis through signal transduction, and plays a key role in regulating intestinal epithelial barrier. With the deepening of research, more and more evidence shows that DSG2 is abnormally expressed in a variety of digestive system tumors, and the expression levels are different. The expression level is closely related to the prognosis of tumors. It is speculated that DSG2 plays different roles in the occurrence and development of different digestive system tumors. This article reviews the biological function of DSG2 and its role in digestive system tumors.

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    Inhibitory effect of sanguinarine on proliferaton and invasion of gastric cancer cells by upregulating m 6A methyltransferase 14
    Ming CHEN, Jing ZHANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 135-141.   DOI: 10.3969/j.issn.1674-8115.2022.02.001
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    Objective

    ·To investigate the effect of sanguinarine (SAG) on the proliferation and invasion of gastric cancer cells MGC-803 and AGS, and the relationship between the mechanism and N6-methyladenosine (m6A) methyltransferase 14 (METTL14).

    Methods

    ·After the gastric cancer cell lines (MGC-803 and AGS) were exposed to different concentrations of SAG (0, 10, 20 μmol/L) for 48 h, quantitative PCR and Western blotting analysis were used to detect the effect of SAG on the expression of METTL14. Then, MGC-803 and AGS cells transfected with lentiviruses-mediated small interfering RNA of METTL14 (si-METTL14) or control (si-NC) were treated with 10 μmol/L SAG or PBS for 48 h, and thus the two cell lines were divided into si-METTL14+SAG group, si-NC+SAG group and si-NC+PBS group, respectively. Quantitative PCR and Western blotting were used to verify the expression levels of METTL14 after it was transfected with si-METTL14 in gastric cancer cells. The proliferation level, number of clones formed and invasion potential of the 3 groups in both MGC-803 cells and AGS cells were observed by MTT proliferation assay, cell clone formation test and Transwell invasion assay, respectively. Independent samples t test was used for comparison between two groups of data, and one-way ANOVA was used for comparison between more than two groups of data.

    Results

    ·Compared with the control group (0 μmol/L), 10 μmol/L SAG and 20 μmol/L SAG up-regulated METTL14 mRNA and protein expression levels (P<0.05), showing a certain concentration dependence. Quantitative PCR and Western blotting results confirmed that the expression levels of METTL14 in gastric cancer cells were significantly reduced after transfection of si-METTL14 in both MGC-803 cells and AGS cells. MTT cell proliferation assay showed that the cell proliferation rate of the si-NC+SAG group was significantly lower than that of the si-NC+PBS group in each cell line (P=0.000). The cell clone formation test showed that the number of cell clones of the si-NC+SAG group was significantly smaller than that of the si-NC+PBS group in each cell line (P<0.01). The Transwell invasion assay showed that the cells crossing Matrigel gel in the si-NC+SAG group was significantly less than that in the si-NC+PBS group in each cell line (P<0.01). si-METTL14 could partially reverse the inhibitory effects of SAG on gastric cancer cells.

    Conclusion

    ·SAG can inhibit the proliferation activity, clonal formation and invasion potential of gastric cancer cells, which may be realized by upregulating METTL14 expression level.

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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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    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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    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
    Abstract222)   HTML32)    PDF(pc) (4932KB)(83)       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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    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
    Abstract218)   HTML16)    PDF(pc) (853KB)(66)       Save

    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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    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
    Abstract216)   HTML17)    PDF(pc) (893KB)(41)       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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    Effects of Pcsk9 gene interference on high fat-induced nonalcoholic fatty liver disease with atherosclerosis in rats
    Xiaowen ZHANG, Yi WANG, Chan ZHANG, Di ZHANG, Hang YUN, Di HUANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 150-157.   DOI: 10.3969/j.issn.1674-8115.2022.02.003
    Abstract215)   HTML1004)    PDF(pc) (2405KB)(205)       Save
    Objective

    ·To investigate the effects of proprotein convertase subtilisin kexin 9 (Pcsk9) gene knockdown on non-alcoholic fatty liver disease (NAFLD) and atherosclerotic lesions in rats induced by high fat.

    Methods

    ·The SD rat model of NAFLD was established. Rats were randomly divided into 4 groups: control group, model group (high fat), shRNA-negative control (NC) interference model group (high fat+shRNA-NC) and Pcsk9-shRNA interference model group (high fat+ Pcsk9-shRNA). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect Pcsk9 gene interference efficiency. Fasting serum insulin was determined by radioimmunoassay. Automatic biochemical analyzer was used to detect levels of blood lipid in rats. Hematoxylin-eosin staining (H-E staining) was used to observe the injury of liver tissue and aorta tissue. Apoptosis of liver tissue was detected by TUNEL staining. The levels of interleukin-1β (IL-1β), IL-6 and inducible nitric oxide synthase (iNOS) in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA). The expression of PCSK9, Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) P65 and tumor necrosis factor α (TNF-α) were detected by Western blotting.

    Results

    ·Compared with the control group, obesity index and insulin level in the model group were significantly increased (all P=0.000); the apoptosis rate of liver cells was significantly increased (P=0.000); the level of high density lipoprotein cholesterol (HDL-C) was significantly decreased, while the levels of low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triacylglycerol (TAG) were significantly increased (all P=0.000); the levels of IL-1β, IL-6 and iNOS were significantly increased (all P=0.000); TLR4, NF-κB P65 protein activation and TNF-α expression were significantly increased (all P=0.000); the liver tissue and aorta tissue were significantly damaged. After interference of Pcsk9 gene expression, compared with the model group, obesity index and insulin level in the high fat+Pcsk9-shRNA group were significantly reduced (P=0.007, P=0.000); the apoptosis rate of liver cells was significantly reduced (P=0.000); the level of HDL-C was significantly increased while the levels of LDL-C, TC and TAG were significantly decreased (all P=0.000); the levels of IL-1β, IL-6 and iNOS were significantly decreased (all P=0.000); TLR4, NF-κB P65 protein activation and TNF-α expression were significantly decreased (all P=0.000); the histopathological lesions of liver tissue and aorta tissue were improved.

    Conclusion

    ·Knockdown of Pcsk9 gene can reduce obesity index, insulin level, blood lipid index and inflammatory response in the rats with NAFLD and atherosclerosis, and inhibit the activation of TLR4 and NF-κB P65 protein, thereby improving the injury of liver and aortic tissue in rats.

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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
    Abstract211)   HTML13)    PDF(pc) (811KB)(50)       Save

    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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    Effect of ferroptosis on regeneration after muscle injury
    DU Yuting, ZHANG Jing, HUANG Ying, ZHANG Jing
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (3): 298-306.   DOI: 10.3969/j.issn.1674-8115.2022.03.006
    Abstract211)   HTML0)    PDF(pc) (2816KB)(63)       Save
    Objective

    ·To investigate the role of ferroptosis in muscle regeneration after injury induced by cardiotoxin (CTX).

    Methods

    ·CTX was injected into the tibialis anterior (TA) of fifteen 8-week-old male C57BL/6J mice at the upper, middle and lower points. After injection, TA tissue of the mice was collected at 0 d, 3 d and 7 d respectively (n=5) to detect injury by hematoxylin-eosin (H-E) staining. Meanwhile, quantitative real-time PCR (qPCR) and Western blotting were used respectively to detect the expression levels of muscle regeneration-related indexes and ferroptosis-related genes from RNA and protein levels, respectively. At the same time, forty-five 8-week-old C57BL/6J male mice were divided into 3 groups before CTX injection: saline control group, iron chelator deferoxamine (DFO) treatment group and ferroptosis inhibitor UAMC-3203 treatment group (n=15). CTX was injected into TA, and muscle tissue was collected at 0 d, 3 d and 7 d respectively. RNA sequencing (RNA-seq) technology and bioinformatics were used to analyze the effect of ferroptosis inhibitor pretreatment on muscle injury and regeneration after CTX injection. H-E staining and qPCR were utilized to analyze the effect of ferroptosis inhibitor on the expression levels of muscle regeneration-related genes.

    Results

    ·The muscle injury and regeneration model was successfully established by CTX injection, as revealed by H-E staining. The increase of ferroptosis-related genes including acyl-CoA synthetase long chain family member 4 (Acsl4) and heme oxygenase-1 (Hmox-1) at both RNA and protein levels was observed, suggesting the occurrence of ferroptosis during muscle injury. There was severe muscle injury at day 3, which was detected by the up-regulation of myogenic differentiation antigen (Myod), myogenin (Myog), and tenascin-c (Tnc), followed by declines at day 7. According to the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of RNA-seq differential genes, it was found that UAMC-3203 treatment group had significant changes in neutrophil degranulation, production of reactive oxygen species (ROS) and phospholipids in phagocytosis compared with CTX injection alone. And the expression of cathepsin S (Ctss) was much higher in the UAMC-3203 treatment group. More importantly, the expression of muscle regeneration-related genes were dramatically inhibited by both UAMC-3203 and DFO injection.

    Conclusion

    ·Inhibition of ferroptosis slows down the process of muscle regeneration to a certain degree, suggesting that ferroptosis may play a key role in facilitating muscle regeneration.

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    Analysis of clinicopathologic features and prognosis of eight children with granulosa cell tumor of ovary
    Zhengwen XING, Ying WU, Xueli WANG, Qingyu WANG, Wenting WANG, Zhi LI, Bin ZHANG, Jing JIN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 192-196.   DOI: 10.3969/j.issn.1674-8115.2022.02.009
    Abstract210)   HTML60)    PDF(pc) (3077KB)(208)       Save
    Objective

    ·To investigate the clinicopathological features and prognosis of ovarian granulosa cell tumor (GCT) in children.

    Methods

    ·The clinicopathologic and follow-up data of 8 patients with ovarian GCT in Shanghai Children's Hospital from June 2008 to June 2018 were collected and retrospectively studied to summarize the clinicopathological features and analyze the prognosis.

    Results

    ·The age of onset in this group ranged from 2 to 12 years with median age of 6.5 years. Two cases were adult granulosa cell tumor (AGCT) and six cases were juvenile granulosa cell tumor (JGCT). The first symptoms were abdominal pain or abdominal mass. Six patients were complicated with symptoms of precocious puberty, including 5 cases of true precocious puberty and 1 case of pseudo precocious puberty. The levels of peripheral blood sex hormones changed to varying degrees. Gross examination showed that the tumor masses ranged from 4 to 22 cm in the greatest dimension (average 12.8 cm). All of the 8 tumors were mixed solid-cystic in appearance. Under light microscope, AGCT showed obvious nuclear sulcus and microfollicular structure, containing eosinophilic substances, namely characteristic Call-Exner bodies. JGCT had follicular structures of different sizes, containing basophilic secretions. The inner layer of the follicular wall was composed of granular cells, which could be surrounded by follicular membrane cells. No Call-Exner bodies were found, and nuclear sulcus were rare. The results of immunohistochemistry showed that α-inhibin and CD99 were positive, and epithelial membrane antigen (EMA) were negative in all the cases. In 5 cases calretinin were positive, and in 5 cases cytokeratin (CK) were positive. Ki-67 proliferation index was 5%?50%. There were 3 estrogen receptor (ER) positive cases and 6 progesterone receptor (PR) positive cases. Forkhead transcription factor 2 (FOXL2) was highly expressed in 2 cases of AGCT and 6 cases of JGCT. SRY-box transcription factor 9 (SOX9) positive cells were scattered in 2 cases of AGCT and 3 cases of JGCT. All the cases were treated with standard surgery. Tumor rupture or metastasis was found in 5 cases, and ascites was suspiciously positive in 1 case. Eight children with ovarian GCT were followed up for 19?155 months, and all of them survived in good health.

    Conclusion

    ·The clinical features of AGCT and JGCT in children's ovaries are similar and have typical histopathological features respectively. The selection of suitable immunohistochemical detection method is helpful for differential diagnosis of ovarian tumors in children. The prognosis of ovarian GCT in children is good even with tumor rupture after radical surgery.

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