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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
    Abstract2705)   HTML57)    PDF(pc) (1172KB)(256854)       Save

    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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    Influence of cathepsin S deficiency on development of communicating hydrocephalus in mice induced by kaolin#br#
    LIU Feng-di, ZHAO Rong, SHI Yan-hui, LI Ge-fei, WU Yi-lan, ZHUANG Mei-ting, YIN Jia-wen, DU Xiao-xia, ZHOU Jia-jun, LIU Jian-ren
       2017, 37 (10): 1342-.   DOI: 10.3969/j.issn.1674-8115.2017.10.006
    Abstract2029)      PDF(pc) (6744KB)(92168)       Save
     Objective · To evaluate the influence of cathepsin S(CatS) on the severity of communicating hydrocephalus in a kaolin injected mouse model.  Methods · Kaolin suspension was injected to 8 CatS knock-out (CatS -/-) mice and 12 wild type (WT) C57BL/6 mice through cisterna magna to establish communicating hydrocephalus mouse model. Cerebral magnetic resonance imaging (MRI) was used before and 1 week after kaolin injection to compare lateral ventricular volume. Lateral ventricular index was calculated to analyze the severity of hydrocephalus.  Results · One week after kaolin injection, 1 in CatS -/- group and 2 in WT group died. The mortality rate was 12.5% each and there was no significant difference (P=1.000). MRI results showed varying degrees of ventriculomegaly in both groups. Lateral ventricular index of CatS -/-group (n=8) and WT group (n=16) before kaolin injection was 0.05±0.01 and 0.04±0.01 respectively (P=0.720). One week after kaolin injection, lateral ventricular index of CatS-/- group (n=7) and WT group (n=14) was 0.13±0.02 and 0.11±0.01 respectively (P=0.950). In each group, in 71.4% of mice, lateral ventricular index enlarged twice or more.  Conclusion · One week after kaolin injection into cisterna magna, lateral ventricles enlarges obviously, indicating hydrocephalus occurs, with high success rate. CatS gene deficiency has no significant influence on the development of communicating hydrocephalus.
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    Reliability and validity of Chinese version of Working Alliance Inventory-Short Form Revised in the inpatients with schizophrenia
    CHEN Ru-meng, CHEN Jian-hua, XU Yi-feng
       2018, 38 (12): 1494-.   DOI: 10.3969/j.issn.1674-8115.2018.12.018
    Abstract2040)      PDF(pc) (6724KB)(44931)       Save
    Objective · To investigate the reliability and validity of Chinese version of Working Alliance Inventory-Short Form Revised (WAI-SR) in the hospitalized schizophrenics. Methods · A sample of 124 inpatient schizophrenics who were diagnosed according to International Classification of Diseases 10th Revision in Shanghai Mental Health Center and collectedconvenience sampling, were interviewedquestionnaire. Item analysis, internal consistency, construct validity and criterion validity were tested using total sample. Patient-Doctor Relationship Questionnaire-15 (PDRQ-15) and Chinese version of Wake Forest Physician Trust Scale (WFPTS) were used as criteria to test criterion validity. Results · Exploratory factor analysis extracted two dimensions labeled “goal and task” and “affective bond”, and the cumulative variance contribution rate was 63.99%. Confirmatory factor analysis showed that the two-factor model had higher adjusted goodness of fit index. The scores of scale and its two dimensions exhibited positive correlations with PDRQ-15 and WFPTS (r0.324-0.726, P<0.01). The internal consistency of the scale (Cronbachs α coefficient) was 0.864, and split-half reliability was 0.919. Conclusion · The Chinese version of WAI-SR is accepin reliability and validity and can be recommended for alliance assessment in the inpatients with schizophrenia.
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    Research progress of immune response regulated by epigenetic modification in pneumonia
    WANG Qing, HAN Xiao, ZHANG Xiaobo
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (7): 931-938.   DOI: 10.3969/j.issn.1674-8115.2023.07.016
    Abstract1025)   HTML26)    PDF(pc) (1688KB)(30984)       Save

    Pneumonia is one of the most common infectious diseases, and although considerable progress has been made in the diagnosis and treatment of pneumonia, it is still associated with high mortality, prolonged hospitalization, and significant medical expenditures. Epigenetic modifications are heritable changes in gene expression without altering the DNA sequence, including DNA methylation, histone modification, non-coding RNA and RNA modification, which are involved in regulating gene expression at multiple levels, including DNA, histone, and transcriptional and post-transcriptional levels. A growing number of studies have suggested that epigenetic regulation may play a central role in the initiation and progression of pneumonia by regulating the immune function. Following the infection with pathogens in the lungs, epigenetic modification can affect the occurrence and progression of pneumonia in different individuals by regulating the inflammatory and immune response, including the development and differentiation of various immune cells, the recognition and transduction of infection signals, and the production of cytokines and anti-pathogen effector molecules. By summarizing recent studies on epigenetic modification of immunity in pneumonia, this review elucidates the key role that epigenetic modification of immunology plays in the initiation and progression of pneumonia, as well as its potential application to clinical diagnosis and therapeutic targets in the treatment of pneumonia, providing a sound theoretical basis for further research.

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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
    Abstract3931)   HTML146)    PDF(pc) (773KB)(26253)       Save

    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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    Research progress in the role of M1/M2 polarization of macrophages in different liver diseases
    NIU Yuanyuan, WANG Longde, XU Wenjuan, LI Zhengju, ZHANG Ruiting, WU Yuqian
    Journal of Shanghai Jiao Tong University (Medical Science)    2024, 44 (4): 509-517.   DOI: 10.3969/j.issn.1674-8115.2024.04.012
    Abstract2329)   HTML59)    PDF(pc) (1837KB)(24520)       Save

    Macrophages have strong plasticity and heterogeneity, and can undergo functional transformation in response to different signal stimuli, such as classical activation of M1 type (M1 type polarization) and selective activation of M2 type (M2 type polarization). The pathways of macrophage M1/M2 polarization are quite extensive, involving nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, interleukin-4 (IL-4)/signal transduction and activator of transcription 6 (STAT6) signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, etc. At the same time, M1/M2 polarization of macrophages is also regulated by exosomes, metabolites, non-coding RNA, electrical stimulation, probiotics, etc., and its imbalance is closely related to the occurrence and development of different types of liver disease. In this paper, the mechanism of its polarization was reviewed, and it was found that M1 polarization of macrophages played a promoting role in the process of liver tissue injury, inflammation and fibrosis, while M2 polarization of macrophages played the opposite role. Among them, hepatocellular carcinoma, as the advanced stage of chronic liver disease, was characterized by increased M2 polarization and impaired M1 polarization of macrophages. Therefore, this paper pays attention to the role of M1/M2 polarization of macrophages in different types of liver diseases, in order to better establish the targeted therapy of macrophage subsets.

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    Progress on application of echocardiography in cardiac assessment for hypertensive children
    WU Yu-jian, SUN Kun
       2018, 38 (12): 1489-.   DOI: 10.3969/j.issn.1674-8115.2018.12.017
    Abstract1218)      PDF(pc) (8200KB)(24487)       Save
    The detection rate of childhood hypertension is on the rise all over the world and the damage of hypertension to heart has been paid enormous attention for its direct influence on prognosis. Echocardiography is routinely used to evaluate cardiac structure and function. On the basis of the traditional techniques, some new ultrasound imaging techniques have continuously applied in clinic in recent years and shown their respective advantages and values. This article reviewed the application and progress of echocardiography in cardiac assessment for hypertensive children.
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    Sevoflurane inhibits the differentiation and development of neural progenitor cells into neurons in the prefrontal cortex of newborn mice
    LIU Siyu, ZHANG Lei
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (9): 1115-1130.   DOI: 10.3969/j.issn.1674-8115.2023.09.006
    Abstract839)   HTML19)    PDF(pc) (6319KB)(19414)       Save

    Objective ·To investigate the mechanism of sevoflurane damaging neuron development in the prefrontal cortex (PFC) of the neonatal mice after single or multiple sevoflurane anesthesia based on the single-cell RNA sequencing (scRNA-seq). Methods ·The neonatal mice were divided into multiple anesthesia exposure (Sev3) group, single anesthesia exposure (Sev1) group, and control group with 3 mice each. The Sev3 group received anesthesia with 3% sevoflurane and 60% O2 on postnatal day 6, 7, and 8, and the Sev1 group received anesthesia only on postnatal day 6. The PFC from mice in the 3 groups was harvested on postnatal day 9 for scRNA-seq. PFC cell profiles and neuronal subpopulation profiles of newborn mice after sevoflurane anesthesia were obtained by UMAP (uniform manifold approximation and projection) clustering, RNA velocity analysis, and transcription factor analysis (SCENIC). Differential expression gene analysis was performed. The biological processes and pathways of the differential genes were investigated through Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database; QuSAGE analysis was used to describe the activation of the cell cycle and Hippo signaling pathway gene sets. Transcript enrichment and stemness of PFC neuronal lineage cells of neonatal mice after sevoflurane anesthesia was determined by CytoTRACE score. The differentiation trajectory of PFC neurons was determined by using pseudo-time analysis, and the developmental nodes were resolved by BEAM analysis to identify key genes that determine different cell fates. Results ·A total of 40 061 cells with 10 cell types were obtained from the PFC of newborn mice in the 3 groups by scRNA-seq. The down-regulated genes in the PFC cells after single sevoflurane anesthesia were enriched in cell differentiation, forebrain neuron differentiation, noradrenergic neuron differentiation, and cerebral cortex GABAergic interneuron differentiation. The down-regulated genes after multiple sevoflurane anesthesia were enriched in positive regulation of cell differentiation. KEGG analysis showed that the down-regulated genes after single sevoflurane anesthesia were enriched in transforming growth factor-β signaling pathway, and the down-regulated genes after multiple sevoflurane anesthesia were enriched in the Notch signaling pathway. SCENIC analysis showed that early growth response 1 (Egr1) and SRY-box transcription factor 7 (Sox7) were up-regulated after both single and multiple sevoflurane anesthesia (both P<0.01), and HES family bHLH transcription factor 6 (Hes6) and NK2 homeobox 1 (Nkx2-1) were down-regulated only after single sevoflurane anesthesia (P<0.01). Activation of the gene set of the cell cycle in radial glial cells and neurons increased after sevoflurane anesthesia, and the increase in activation was more pronounced after multiple sevoflurane anesthesia. The gene set of the Hippo signaling pathway in neurons changed from inhibition to activation after multiple sevoflurane anesthesia. Subpopulation analysis of 8 224 neurons identified 8 neuronal lineage cells, and CytoTRACE scores indicated increased neuron stemness and delayed neuron development after sevoflurane anesthesia. The PFC neurons were divided into 3 developmental stages by pseudo-time analysis, and multiple sevoflurane anesthesia receded the differentiation of PFC neurons in pseudo-time (P=0.000). The down-regulated genes in PFC neurons of newborn mice after single sevoflurane anesthesia were enriched in the regulation of cyclin-dependent protein serine/ threonine kinase activity, mitotic cell cycle phase transition, cell differentiation, long-term memory, and G1/S transition of the mitotic cell cycle. The down-regulated genes in PFC neurons after multiple sevoflurane anesthesia were enriched in the negative regulation of cell population proliferation, positive regulation of cell differentiation, forebrain neuron differentiation, positive regulation of canonical Wnt signaling pathway, and cell differentiation. Conclusion ·Both single and multiple sevoflurane anesthesia promote PFC neuron proliferation and migration, and multiple sevoflurane anesthesia inhibits the differentiation of neural progenitor cell into neuron in PFC. The underlying mechanism might be related to cell cycle transitions.

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    Effects of work stress, psychological resilience and perceived social support on compassion fatigue of nurses in assisted reproduction departments
    Yu-lian HU, Ya-qing ZHANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (12): 1565-1571.   DOI: 10.3969/j.issn.1674-8115.2021.12.004
    Abstract1569)   HTML32)    PDF(pc) (2407KB)(19176)       Save
    Objective

    ·To understand the current status of work stress, psychological resilience, perceived social support, and compassion fatigue among assisted reproduction department nurses in China, and explore their quantitative relationship model on this basis.

    Methods

    ·Using a convenience sampling method, 511 assisted reproduction department nurses from 32 tertiary hospitals in 17 provinces and cities in the eastern, central and western economic regions of China were surveyed from September to December 2020 with using a general information questionnaire, the Nurses' Work Stressor Scale, the Mental Toughness Scale, the Appreciative Social Support Scale and the Compassion Fatigue Scale. Through basic statistics and structural equation modeling, we constructed a quantitative relationship model among work stress, psychological resilience, perceived social support, and compassion fatigue, and analyzed the relationships among these variables and their effects on compassion fatigue among assisted reproduction department nurses in China.

    Results

    ·The mean item scores of the dimensions of compassion fatigue among nurses in our assisted reproduction departments were compassion satisfaction (3.68±0.63), job burnout (2.39±0.52), and secondary traumatic stress (2.46±0.56), all of which were at moderate levels; there was a correlation between work stress, psychological resilience, perceived social support, and compassion fatigue among nurses in assisted reproduction departments (all P=0.000).The results of structural equation modeling showed that job stress had a direct negative effect on compassion satisfaction (β=-0.34, P=0.000), a direct positive effect on compassion fatigue symptoms (β=0.25, P=0.000); psychological resilience had a direct positive effect on compassion satisfaction (β=0.53, P=0.000), and a direct negative effect on compassion fatigue symptoms (β=-0.29, P=0.000); psychological resilience mediated the effect between job stress and compassion fatigue symptoms and between job stress and compassion satisfaction, and appreciating the role of social support in compassion fatigue symptoms and compassion satisfaction was not significant.

    Conclusion

    ·Compassion fatigue of nurses in our assisted reproduction departments is affected by a variety of factors, among which the role of psychological resilience is significant in improving compassion satisfaction. It is recommended to start from enhancing the psychological resilience of nurses, take effective measures to improve the psychological resilience of nurses, reduce the incidence of compassion fatigue of nurses, and thus improve the quality of care.

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    Research progress on the neural circuit of pain emotion mediated by amygdala
    MA CUI, YE Yujuan, YAN Xingke
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (10): 1304-1310.   DOI: 10.3969/j.issn.1674-8115.2023.10.012
    Abstract1833)   HTML32)    PDF(pc) (1243KB)(19156)       Save

    The occurrence of pain emotion is closely related to the functional and structural changes of specific central nervous circuit. When pain is accompanied by depression, anxiety, pain aversion memory and other emotional states, it activates or inhibits different neural circuits. The amygdala (AMY) of the limbic system participates in the regulation of pain, anxiety, depression, aversive memory and other emotions, and has extensive connections with brain nuclei related to pain and emotion, jointly regulating pain, anxiety, depression, aversive memory and other responses. This article summarizes the main circuits related to pain emotions mediated by AMY. It is concluded that the neural circuits related to depression include central amygdala → parafascicular nucleus of thalamus (CeA GABA → PF Glu), dorsal raphe nucleus → central amygdala (DRN 5-HT → CeA SOM), central amygdala → ventrolateral periaqueductal gray (CeA GABA → vlPAG GABA). Nerve circuits related to anxiety include ventral tegmental area → central amygdala (VTA→CeADA), locus coeruleus → basolateral amygdala (LCNE→BLA). The neural circuit related to pain aversion memory is lateral parabrachial nucleus → central amygdala (lPBN CGRP→CeA CGRP). Among them, activating the CeA GABA→PF Glu circuit can lead to depression accompanied by pain, activating the CeA GABA→vlPAG GABA circuit can alleviate pain sensitivity caused by depression, and activating the DRN 5-HT→CeA SOM circuit can alleviate pain perception and depressive emotions; activating the VTA→CeA DA loop can alleviate pain sensitivity and anxiety like behavior, inhibiting LC NE→BLA loop can alleviate anxiety caused by pain; activating the lPBN CGRP→CeA CGRP loop can generate pain aversion memory.

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    Application of Quality-of-Life Assessment Scales and psychological assessment tools to people with dry eye disease
    Yu-ying CAI, Yan LIU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1252-1255.   DOI: 10.3969/j.issn.1674-8115.2021.09.018
    Abstract1175)      PDF(pc) (798KB)(17681)       Save

    Dry eye disease (DED) is a common disease with multiple etiologies. It can affect the daily activities of patients to reduce their quality of life and interfere with their mental state. At present, for DED patients, the clinical application of Quality-of-Life Assessment Scales are more, but the summary research of professional psychological assessment tools is less. On the basis of extensive review at home and abroad, this paper summarizes and explores the application of Quality-of-Life Assessment Scales and psychological assessment tools to DED patients, in order to provide suggestions and guidance for the clinical diagnosis and treatment and nursing work of DED.

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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
    Abstract5703)   HTML571)    PDF(pc) (917KB)(17243)       Save

    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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    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
    Abstract3391)   HTML118)    PDF(pc) (1625KB)(16351)       Save

    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 cell wall structure and Candida albicans-host interaction
    Yi-kun MEI, Jing-cong TAN, An-jun WANG, Hui WANG, Ning-ning LIU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1246-1251.   DOI: 10.3969/j.issn.1674-8115.2021.09.017
    Abstract1893)      PDF(pc) (948KB)(16215)       Save

    Candida albicans is an opportunistic human fungal pathogen. The mortality rate of blood infection caused by Candida albicans is as high as 40% while that of the cancer patients can even reach to 70%, which greatly increases the burden of human health. The cell wall of Candida albicans is the frontline of defense against external stress and the first contact point between fungi and host. Therefore, the cell wall is very important for fungi-host interaction and immune recognition, and is the most attractive target for antifungal therapy. Once the balance of synthesis and remodeling of cell wall of Candida albicans is broken, the molecular integrity of cell wall will be disturbed, which will finally lead to cell lysis and death. This paper reviews the characteristics of cell wall components of Candida albicans and their functions on fungi-host interaction and immune recognition mechanism, in order to provide novel research clues and theoretical basis for identification of specific antifungal targets and development of more economic and effective antifungal drugs.

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    Research progress of the role of non-canonical Wnt signaling pathway in ovarian cancer and its potential therapeutic implications
    ZHOU Wanzhen, TENG Yincheng
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (8): 1056-1063.   DOI: 10.3969/j.issn.1674-8115.2023.08.015
    Abstract1091)   HTML29)    PDF(pc) (1663KB)(15029)       Save

    Ovarian cancer is a malignant tumor of the female reproductive system with the highest mortality, and involves the aberrant regulation of multiple molecular signaling pathways. As a highly conserved molecular pathway, Wnt signaling pathway plays an important role in embryonic development, tissue homeostasis, and tumorigenesis. Wnt signaling pathway includes canonical Wnt/β-catenin pathway and non-canonical pathway, and the latter mainly includes Wnt/planar cell polarity (Wnt/PCP) pathway and Wnt/Ca2+ pathway. Previous studies have mainly focused on the relationship between the canonical Wnt pathway and tumor progression. Recently, the non-canonical Wnt pathway has gradually received attention, and related researches have enriched the understanding of the non-canonical Wnt pathway in physiological and pathological processes such as tissue development and tumorigenesis. The existing studies suggest that the nonclassical Wnt pathway is abnormally regulated in ovarian cancer and is closely related to the staging and prognosis of ovarian cancer. Non-classical Wnt pathway plays an important role in many biological processes such as proliferation, migration and invasion of ovarian cancer cells, and the changes of this pathway are also related to chemotherapy resistance of ovarian cancer. This article reviews the role of the non-canonical Wnt pathway in ovarian cancer, and discusses the research progress of targeted therapy based on the non-canonical Wnt pathway, aiming to provide new ideas for the development of novel targeted drugs.

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    In vitro therapeutic effects and molecular mechanisms of targeted inhibition of CDK12/13 in high-grade gliomas
    MEI Yanqing, HAN Yujie, WENG Wenyun, ZHANG Lei, TANG Yujie
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (5): 545-559.   DOI: 10.3969/j.issn.1674-8115.2023.05.005
    Abstract1170)   HTML25)    PDF(pc) (3954KB)(14744)       Save

    Objective ·To find novel and common targeting strategies for high-grade gliomas (HGGs) from the perspective of epigenetic and transcriptional modulators, test the therapeutic effect in vitro and investigate the related molecular mechanisms. Methods ·Glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) cell lines with high malignancy and mortality in HGGs were selected for screening of targeted small molecule drug library related to epigenetic transcription and for functional genome screening based on the CRISPR-Cas9 technology. The effect of selected targeted epigenetic transcriptional modulators on growth, proliferation, and apoptosis of GBM and DIPG cell lines were then measured either by CRISPR-Cas9 knockout or treatment with targeted small molecule inhibitors of genes in vitro. Anti-tumor molecular mechanisms of the modulators in corresponding small molecule inhibitors-treated GBM and DIPG cells were explored via RNA-seq transcriptome analysis and further verified by real time quantitative PCR (RT-qPCR), Western blotting and flow cytometry. Results ·Targeted small molecule drug library combined with functional genome screening for epigenetic transcriptional modulators identified CDK12/13 as the novel therapeutic targets for both GBM and DIPG. Knockout out of CDK12 by CRISPR-Cas9 in multiple GBM and DIPG cell lines significantly reduced their in vitro cellular activity. CDK12/13 inhibitors SR-4835 and THZ531 also significantly inhibited the growth of these two types of HGGs cell lines in vitro by antagonizing cell proliferation and promoting cell apoptosis. RNA-seq transcriptome analysis of GBM and DIPG cell lines after SR-4835 treatment showed that genes significantly down-regulated by CDK12/13 inhibitors in HGGs cells were mainly enriched in transcriptional regulation, DNA damage response (DDR) pathway, ubiquitin-proteasome pathway, and cell cycle. Furthermore, a series of experiments demonstrated that targeted inhibition of CDK12/13 significantly down-regulated the transcription of DDR-related genes, resulting in the accumulation of DNA damage, and induced G2-M cell cycle arrest. Conclusion ·CDK12/13 is a common potential therapeutic target of these two types of HGGs, providing theoretical support for the follow-up in vivo verification and combination therapy test. The research also lays the foundation for further clinical application.

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    Application of Montreal Cognitive Assessment Scale to the elderly in Chinese community
    An-qi XIA, Jun LI, Ling YUE, Bo HONG, Feng YAN, Ning SU, Shi-fu XIAO, Yuan-yuan LIU, Tao WANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (12): 1662-1667.   DOI: 10.3969/j.issn.1674-8115.2021.12.017
    Abstract2472)   HTML44)    PDF(pc) (2168KB)(14430)       Save
    Objective

    ·To update the cut-off value of the normal elderly (NE) and mild cognitive impairment (MCI) elderly in urban areas of China according to the Montreal Cognitive Assessment (MoCA) scores and analyze the sections of MoCA.

    Methods

    ·A cross-sectional study was conducted to investigate the elderly over 60 years old in ten cities of China. Mini-Mental State Examination (MMSE) and MoCA (Beijing version) were used to assess cognitive function. Data was statistically analyzed by SPSS 19.0.

    Results

    ·There were 2 367 NE, 553 MCI patients, 1 319 males and 1 601 females, with an average age of (70.6±7.5) years and an average length of education of (8.7±5.2) years. There were significant difference in age and length of education between MCI and NE groups (t=12.3, P=0.000; t=-13.5, P=0.000). Female was more likely to have MCI (χ2=13.5, P=0.000). By analyzing the score of MoCA of the NE, it was found that the MoCA score of males, high education level and low age group were higher. Rhinoceros and camel in naming, church and face in delayed memory, alternating connection test and pointer position in clock drawing were more difficult. The sections' scores of MoCA showed that the subjects performed better in the orientation and attention tests, while the scores of visuospatial functions, delayed recalling, sentence repetition and abstract ability were lower. The best cut-off value of MoCA was 20 (sensitivity = 63.7%, specificity = 75.7%). The area under the curve was 0.76.

    Conclusion

    ·MoCA (Beijing version) has a good distinction between NE and MCI, and 20 can be used as a cut-off value in MCI subjects screening in urban areas of China. MoCA score is influenced by age, gender and education level. Based on difficulty analysis, some words that evaluate memory could be replaced (replacing “face” with “hand” and replacing “church” with “factory”).

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    Aptamer-drug conjugates (ApDCs): new trend for cancer precision therapy
    HAN Yongqi, HAN Da, XIA Qian, JI Dingkun, TAN Weihong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1176-1181.   DOI: 10.3969/j.issn.1674-8115.2022.09.003
    Abstract1792)   HTML227)    PDF(pc) (1279KB)(14418)       Save

    Cancer is a worldwide medical issue that seriously threatens human health. Precision molecular medicine provides a new strategy for cancer theranostics. As excellent targeting recognition molecules and drug delivery platforms, aptamers and aptamer drug-conjugates (ApDCs) have provided a series of useful molecular tools for cancer precision therapy. In this paper, the properties and the selection techniques of aptamers, the construction of ApDCs and their applications to clinical tumor-targeting therapy are reviewed. Additionally, the challenges and perspective of ApDCs in precision molecular medicine for cancers are presented. This review may provide new horizons for molecular-targeted anti-tumor drugs in the therapy of clinical malignant tumors.

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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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    Ameliorative effects on osteoporosis of small extracellular vesicles derived from bone marrow mesenchymal stem cells
    LI Xuran, TAO Shicong, GUO Shangchun
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (4): 406-416.   DOI: 10.3969/j.issn.1674-8115.2023.04.002
    Abstract1238)   HTML396)    PDF(pc) (7654KB)(12921)       Save

    Objective ·To investigate the effects of small extracellular vesicles (sEVs) derived from human bone marrow mesenchymal stem cells (BMSCs) on the regulation of osteoclast differentiation and macrophage polarization in mice, and mouse model of osteoporosis. Methods ·BMSCs were cultured and sEVs were isolated through differential centrifugation. The isolated sEVs were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RAW264.7 cells were cultured and stimulated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) to differentiate the cells into osteoclasts. Tartrate-resistant acid phosphatase (TRAP) staining and phalloidin staining were performed to assess the effect of sEVs on osteoclast formation. The expression levels of osteoclast marker genes, i.e., cAMP-response element binding protein (CREB), cathepsin K (CTSK), and Jun proto-oncogene (c-Jun) were examined by real-time quantitative PCR. To polarize RAW264.7 cells to M1 phenotype, they were cultured with lipopolysaccharides; to polarize them to M2 phenotype, they were cultured with interleukin-4 (IL-4) and IL-13. Flow cytometry was performed to detect the effect of sEVs on macrophage polarization. Micro-computed tomography (micro-CT) and TRAP staining were performed to investigate the effect of sEVs on the bone tissues of lumbar vertebrae in osteoporosis mouse models. Results ·TEM and NTA demonstrated that the isolated sEVs had a typical globular structure with a diameter ranging from 30?150 nm. TRAP staining and phalloidin staining showed that BMSC-derived sEVs inhibited the fusion of RAW264.7 cells to form osteoblasts. PCR revealed that sEVs could decrease the expression of CREB, CTSK, and c-Jun (all P<0.05). Flow cytometry analysis indicated that BMSC-derived sEVs inhibited RAW264.7 macrophages polarization to M1 phenotype and induced RAW264.7 macrophages polarization to M2 phenotype. Micro-CT indicated that the number of trabeculae and the bone volume fraction of lumbar vertebrae were significantly higher in the sEV-intervened group than those in the control group (both P<0.05). TRAP staining revealed a reduction of osteoclast number in the lumbar vertebrae after intervention with sEVs. Conclusion ·The sEVs from human BMSCs can delay bone loss in osteoporosis mice, which may be related to its effects of inhibiting osteoclast differentiation and promoting the polarization of M2 type macrophages.

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