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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 Abstract （1811）      PDF（pc） （6744KB）（91238）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （1361）      PDF（pc） （6724KB）（43863）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （965）      PDF（pc） （8200KB）（23503）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （425）   HTML （23）    PDF（pc） （1688KB）（10582）       Knowledge map    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. Table and Figures | Reference | Related Articles | Metrics

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Study on relevant factors of maximum standard uptake value of 18F-FDG PET/CT for lung cancer WANG Shao-yan, WANG Hui, ZUO Chang-jing, et al    DOI: 11.3969/j.issn.1674-8115.2015.07.017

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Preliminary study of exenatide-induced pancreatic tissue injury in rats TANG Hua-yong, YU Xiao, YANG Yong-chao, et al    2011, 31 (4): 421-.   DOI: 10.3969/j.issn.1674-8115.2011.04.008 Abstract （2233）      PDF（pc） （6217KB）（9749）       Knowledge map    Save Objective To investigate the pancreatic tissue injury induced by exenatide in rats. Methods Thirty SD rats were randomly divided into exenatide-induced group and blank control group, with 15 rats in each group. Rats in exenatide-induced group were subcutaneously injected with exenatide at the dose of 5 μg/kg twice a day for 10 weeks, and those in blank control group were injected with the same amount of normal saline. Rats were then sacrificed, blood samples were obtained from inferior vena, and pancreatic tissues were harvested. Serum levels of amylase, lipase, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α and contents of myeloperoxidase (MPO) in pancreatic tissues were measured by ELISA, pancreatic wet/dry ratios were calculated, HE staining and histopathological scoring of pancreatic tissues were performed, and microstructure of pancreatic tissues were observed by electron microscopy. Results There was no significant difference in serum levels of amylase, lipase, IL-1, IL-6 and TNF-α between two groups （P>0.05）. The content of MOP in exenatide-induced group was significantly higher than that in blank control group [（0.24±0.07）U/L vs （0.18±0.05）U/L]（P<0.05）, and the pancreatic wet /dry ratio in exenatide-induced group was significantly lower than that in blank control group (0.183±0.049 vs 0.256±0.064) （P<0.05）. HE staining demonstrated that there were 5 pancreatic tissue samples with chronic inflammation in exenatide-induced group, while there were no chronic inflammatory changes in blank control group. Histopathological scoring of pancreatic tissues revealed that except for the parameter of gland atrophy, there were significant differences in the parameters of lesion area, fibrosis, inflammation and edema between two groups （P<0.05）. It was observed by electronic microscopy that there were karyopyknosis, cytoplasmic vacuolization, wide intercellular gap and infiltration of inflammatory cells for pancreatic acinar cells in exenatide-induced group, while there was no obvious abnormality in blank control group. Conclusion Long-term administration of exenatide may lead to chronic pancreatic inflammation and pancreatic tissue injury in rats. Related Articles | Metrics

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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 Abstract （1333）   HTML （43）    PDF（pc） （1837KB）（8619）       Knowledge map    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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （2550）   HTML （92）    PDF（pc） （773KB）（8105）       Knowledge map    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. Reference | Related Articles | Metrics

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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 Abstract （3930）   HTML （545）    PDF（pc） （917KB）（7040）       Knowledge map    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. Reference | Related Articles | Metrics

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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 Abstract （2260）   HTML （81）    PDF（pc） （1625KB）（6463）       Knowledge map    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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （1879）   HTML （98）    PDF（pc） （867KB）（5782）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Research progress in the role and mechanism of lactylation in diseases GE Lingling, HUANG Hongjun, LUO Yan Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (3): 374-379.   DOI: 10.3969/j.issn.1674-8115.2023.03.014 Abstract （3192）   HTML （131）    PDF（pc） （1230KB）（5563）       Knowledge map    Save Lactic acid is a product of cell respiration. After entering into cells, glucose is metabolized to pyruvate by glycolysis. When the oxygen supply is sufficient, pyruvate is converted to acetyl coenzyme A through pyruvate dehydrogenase in the mitochondrial matrix to participate in the tricarboxylic acid cycle and provide necessary energy for cells. Pyruvate is catalysed by lactate dehydrogenase in the cytoplasm to produce lactate while cells are grown under hypoxic conditions. Lactate not only provides energy for mitochondrial respiration, but also plays important roles in inflammatory responser, wound repair, memory formation and neuroprotection as well as tumor growth and metastasis and other pathophysiological processes through autocrine, paracrine, and endocrine forms, which affects the development and prognosis of diseases. Epigenetic modification regulates gene replication, transcription and translation by covalently adding or hydrolyzing functional groups on histones and DNA through related enzymes and affects the biological effects of cells. Histones are the major structural proteins of eukaryotic chromosomes. Their post-translational modifications, such as methylation and acetylation, affect their affinity with DNA, change chromatin structures, and are widely involved in regulation of gene expression. Recent studies have found that histones can undergo lactylation, which is a new epigenetic modification by adding lactate to lysine residues on histones. As the research deepens, numerous evidences reveal that lactylation also occurs on non-histone proteins. The discovery of lactylation has expanded our understanding of lactate functions in the pathogenesis of diseases. In this review, we summarize the roles and mechanisms of lactylation in tumor, inflammatory and neural system diseases, in order to provide new ideas for the research, diagnosis and treatment of these diseases. Reference | Related Articles | Metrics

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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 Abstract （684）      PDF（pc） （798KB）（5334）       Knowledge map    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. Reference | Related Articles | Metrics

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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 Abstract （334）   HTML （14）    PDF（pc） （6319KB）（5320）       Knowledge map    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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （846）   HTML （29）    PDF（pc） （2407KB）（5224）       Knowledge map    Save ·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. ·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. ·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. ·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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （565）   HTML （19）    PDF（pc） （3954KB）（5074）       Knowledge map    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. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （1184）   HTML （219）    PDF（pc） （1279KB）（4944）       Knowledge map    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. Reference | Related Articles | Metrics

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2017, 37 (10): 1-.   Abstract （1150）      PDF（pc） （3910KB）（4828）       Knowledge map    Save Related Articles | Metrics

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Progress in metabolism of the immune cells in tumor microenvironment LIN Jiayu, QIN Jiejie, JIANG Lingxi Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 1122-1130.   DOI: 10.3969/j.issn.1674-8115.2022.08.018 Abstract （2379）   HTML （109）    PDF（pc） （2370KB）（4693）       Knowledge map    Save Metabolic reprogramming refers to cells' mechanism to change their metabolic patterns in order to meet the increased energy demand caused by growth and proliferation. By way of metabolic reprogramming such as the Warburg effect, tumor cells gain rich energy to support their own survival, growth, and metastasis. The tumor microenvironment (TME) is the internal environment in which tumor cells survive, containing not only tumor cells, but also stromal cells, immune cells, and other components that are closely related to tumor cells. Meanwhile, tumor cells regulate intercellular function and signaling via secreting cytokines, metabolites, and other molecules and shape a commonly hypoxic, acidic, and nutrient-deprived TME which contributes the most to immune resistance. However, rapidly proliferating tumor cells compete for relatively scarce nutrients with immune cells, consequently, producing an immunosuppressive metabolism microenvironment. Under the influence of immunosuppressive TME, immune cells generate tolerance phenotype-related metabolic adaptations through metabolic reprogramming to satisfy their own needs and further perform anti-tumor or immunosuppressive roles. The response of immune cells to tumor cells mainly depends on respective unique metabolic pathways, which are related to the type and function of immune cells. Moreover, the functional properties of immune cells are directly associated with the immunotherapy effects. Regulating metabolic pathways of immune cells provides a great direction for cancer therapy. In this paper, the main metabolic pathways of immune cells in TME is described, the relationship between their metabolic characteristics and immune functions is summarized, and the mechanism of metabolic pathways underlying the functions of immune cells is further discussed, providing new insights for unveiling tumor immunosuppressive microenvironment and improving the efficacy of tumor immunotherapy. Table and Figures | Reference | Related Articles | Metrics

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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 Abstract （2473）   HTML （156）    PDF（pc） （908KB）（4607）       Knowledge map    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. Reference | Related Articles | Metrics