Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.

This study aimed at investigating the effects of the extract of Chinese herb,Nansheteng (C.orbiculatus Thunb.),on human HepG2 cells through the overexpression of mTOR.The GV238-mTOR recombinant plasmids were transfected into HepG2 cells using molecular biological technology.The expression level of mTOR was evaluated by means of relative activity of luciferase and western blot.Human hepatic carcinoma HepG2/mTOR++ cells were treated with C.orbiculatus extract in different concentrations (20,40,80,160 and 320 tg·mL-1) for 24 h.The mTOR protein expression was detected by western blot.It was found that the protein expression of mTOR in transfected HepG2 cells was significantly enhanced.C.orbiculatus extract significantly inhibited the proliferation of HepG2/mTOR++ cells.Simultaneously,C.orbiculatus extract inhibited mTOR at its protein level in a dose-dependent manner.In conclusion,we successfully constructed recombinant mTOR cloning vectors,and established the stable HepG2 cell line with the overexpression of mTOR.Besides,C.orbiculatus extract significantly inhibited mTOR protein expression in human hepatic carcinoma HepG2 cells.

This study was aimed to investigate the effect of Nan-She-Teng (Celastrus orbiculatus) extract on epithe-lial-mesenchymal transition(EMT) in HepG2 cells. Except the control group, human hepatocellular carcinoma HepG2 cells in other groups were treated with Celastrus Orbiculatus extract in different concentrations (10, 20, 40, 80, and 160 μg·mL-1). The protein expression levels related to EMT were detected by western blotting. At 48 h after fertiliza-tion, the zebrafish embryos were randomly assigned to 7 groups as follows: untreated control group (E3 buffer), DMSO group (E3 buffer with 1% DMSO), and different dosages treatment of C.orbiculatus extract (10, 20, 40, 80, and 160μg·mL-1) for 24 h. The protein expressions of mTOR signaling pathways were detected by western blotting. The re-sults showed that compared with the control group, C.orbiculatus extract significantly increased E-cadherin protein expression. Simultaneously, C.orbiculatus extract inhibited vimentin and mTOR signaling pathways at protein levels. It was concluded that to a certain extent, C.orbiculatus extract prevented EMT in HepG2 cells by modulating the mTOR signaling pathway. Therefore, it suggested that mTOR can be chosen as a new therapeutic target for clinical treatment of hepatic carcinoma.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. The main clinical manifestation of SCA2 is progressive cerebellar syndrome, but a wide range of extracerebellar and non-motor symptoms can be observed clinically. The non-motor symptoms and extra-cerebellar signs in SCA2 patients are reviewed to provide a better understanding in cognition, diagnosis and treatment of the disease.

Objective:To develop a questionnaire on knowledge, attitude and practice of Helicobacter pylori (Hp) infection among physical examination population, and to verify its reliability and validity.Methods:This study was a cross-sectional survey. Based on the theory of knowledge, attitude and practice, the first draft of the questionnaire on knowledge, attitude and practice of Hp infection in physical examination population was designed by means of retrospective literature research, qualitative interview, discussion in the research group. The structure and items of the questionnaire were consulted and revised by the expert consultation method (Delphi method). Through pre investigation of 186 physical examination personnel from May to June in 2021, the final version of the "knowledge, attitude and practice questionnaire on Helicobacter pylori infection among physical examination population" was formed after adjustment and verification of the reliability and validity of the questionnaire.Results:The questionnaire of knowledge, attitude and practice of Hp infection in physical examination population included 3 dimensions and 28 items, and the cumulative variance contribution rate was 56.271%. The content validity index of each item level of the questionnaire was 0.75-1.00, and the content validity index of the total questionnaire was 0.94. The Cronbach alpha of knowledge, attitude and practice dimensions in this questionnaire were 0.862, 0.901 and 0.798 respectively. The overall Cronbach alpha of the questionnaire was 0.890, and the half reliability was 0.698. The test-retest reliability of the questionnaire was 0.919, and the test-retest reliability of each dimension was 0.924, 0.917 and 0.845.Conclusions:The questionnaire has good reliability and validity, and can be used to measure the level of knowledge, attitude and practice of Hp infection in physical examination population.

Objective To investigate the risk factors of postoperative pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP),establish a quantitative risk prediction model,and conduct external validation.Methods The clinical data of patients with ERCP were analyzed.Among them,603 ERCP patients From January 2017 to January 2021 were selected as the modeling group,and 205 ERCP patients from March 2021 to March 2022 were selected as the validation group.Pancreatitis was diagnosed according to Atlanta standards.There were 45 cases in the modeling group and 23 cases in the validation group developed pancreatitis after ERCP.Compare the clinical data and biochemical indicators of patients with and without pancreatitis in the modeling group,and screen for risk factors of pancreatitis through multivariate Logistic regression analysis.Then,establish a risk prediction model and validate it.Results Univariate analysis showed that there were statistically significant differences in age,history of gastectomy,calculus of common bile duct,papillary foramen nodule type,pancreatic wire channel,sphincterotomy,serum total bilirubin and albumin between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that the history of gastrectomy(O(R) = 6.417,95%CI:1.900～21.675,P = 0.000),calculus of common bile duct(O(R) = 3.442,95%CI:1.496～7.917,P = 0.000),papillary foramen nodule type(O(R) = 2.447,95%CI:1.072～5.585,P = 0.018),pancreatic wire channel(O(R) = 3.673,95%CI:1.609～8.383,P = 0.000),sphincterotomy(O(R) = 1.758,95%CI:1.140～2.711,P = 0.004),elevated total bilirubin(O(R) = 1.415,95%CI:1.084～1.847,P = 0.008)and decreased albumin(O(R) = 1.239,95%CI:1.016～1.510,P = 0.010)were independent risk factors for post ERCP pancreatitis.Establish a risk prediction model Y =-1.023 + 1.859×(history of gastrectomy)+ 1.236×(calculus of common bile duct)+ 0.895×(papillary foramen nodule type)+ 1.301×(pancreatic wire channel)+ 0.564×(sphincterotomy)+ 0.347×(elevated total bilirubin)+ 0.214×(decreased albumin).The receiver operator characteristic curve(ROC curve)showed that the area under the curve(AUC)of the model predicting pancreatitis in the modeling and validation groups were 0.895 and 0.864,respectively.After assigning values to each variable in the model,it was divided into low risk(0～5 points),medium risk(5～10 points),and high risk(≥10 points).The actual incidence of high-risk pancreatitis in the modeling and validation groups was significantly higher than that of low-risk patients,and the actual incidence of high-risk pancreatitis was significantly higher than that of medium risk patients,with statistical significance(P＜0.05).Conclusion The history of gastrectomy,calculus of common bile duct,papillary foramen nodule type,pancreatic wire channel,sphincterotomy,elevated total bilirubin and decreased albumin were independent risk factors for post ERCP pancreatitis.We have developed a quantitative risk prediction model with good predictive efficacy for pancreatitis,which has important clinical application value.

Parkinson′s disease (PD) is a common neurodegenerative disease. Its main pathological feature is the progressive loss of substantia nigra and other catecholaminergic neurons containing neuromelanin (NM). Therefore, NM may be closely related to the pathogenesis of PD. The content of NM can be detected by NM magnetic sensitive sequence imaging, and then it can be applied to the study of the neuropathological mechanism of NM and PD. This paper focuses on the physiological significance of NM, its role in the pathogenesis of PD and the prospect of NM as a biomarker to assist diagnosis and disease monitoring of PD.

Objective:To investigate the changes of mitochondria in the substantia nigra pars reticulata(SNr)in a mouse model of acute hepatic encephalopathy(AHE),and the effects of mitochondrial division inhibitor Mdivi-1 on the motor function and mitochondrial function of SNr in AHE mice.Methods:The mouse model of AHE was established by intraperitoneal injection of thioacetamide(TAA)and treated with Mdivi-1.The changes of serum aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT),and blood ammonia were detected by biochemical detection kits.Open field test,rotor-rod fatigue test and elevated plus maze test were performed to observe the motor function of AHE mice.Mitochondrial membrane potential(MMP),cellular reactive oxygen species(ROS)and ATP of SNr were detected by commercial kits.Results:Compared with the control group,the levels of AST,ALT and blood ammonia in AHE mice were increased.The total movement distance of the mice in the open field was reduced,and the movement time of the rotor-rod fatigue test and the elevated plus maze test were shortened.In SNr,mitochondria became smaller and rounder,mitochondrial fission increased,MMP decreased,cellular ROS increased,and ATP production decreased.After treat-ment with Mdivi-1,the levels of AST,ALT and blood ammonia in AHE mice were decreased.In the open field,the total movement distance of mice increased,the movement time of rotorrod fatigue test and elevated plus maze test increased,the mitochondria of SNr were larger,with decreased roundness,decreased mitochondrial division,increased MMP,decreased cellular ROS,and increased ATP production.Conclusion:Mdivi-1 can improve movement disorders in AHE mice by repairing mitochondrial in the SNr.

ObjectiveTo explore the characteristics and associated risk factors of diabetes in patients with schizophrenia living in communities, and to provide a basis for the prevention of diabetes comorbidity in this population. MethodsA stratified cluster sampling was used to randomly select patients with schizophrenia in Shanghai who participated in the free health examination provided by the National Basic Public Health Services in 2020. Statistical methods were employed to analyze the general demographic data, clinical characteristics, and laboratory test results of the study subjects. ResultsThe study included 3 374 individuals with schizophrenia, among which the prevalence of diabetes was 17.01%. Statistically significant differences were observed in terms of age, education level, urban area type, marital status, employment status, duration of illness, blood pressure, body mass index, total cholesterol, and triglyceride levels (all P<0.05). Multivariate logistic regression analysis revealed that living in non-central urban areas (OR=1.76, 95%CI: 1.33‒2.32), disease duration of 6‒ years (OR=2.60, 95%CI: 1.07‒6.32), disease duration of 11‒ years (OR=2.72, 95%CI: 1.17‒6.35), disease duration of 16‒ years (OR=3.38, 95%CI: 1.54‒7.42), hypertension(OR=1.73, 95%CI: 1.27‒2.36), obesity (OR=1.52, 95%CI: 1.15‒2.00), and elevated triglyceride levels (OR=2.78, 95%CI: 2.22‒3.49) were risk factors for diabetes in patients with schizophrenia. ConclusionThe prevalence of diabetes in community-dwelling patients with schizophrenia is higher than that in the general population. It is recommended that appropriate health education and rehabilitation guidance be provided as part of community-based mental health services.

Objective:To understand the reinfection rate of 2019-nCoV in the previously infected population in Suzhou and compare the illness severity and prognosis of the reinfection cases with the first-time infection cases.Methods:A questionnaire survey was conducted in the persons with previous 2019-nCoV infection reported in Suzhou from January 22, 2020 to November 8, 2022 to collect the information about the incidence of reinfection of 2019-nCoV in this population from December 8, 2022 to January 18, 2023. The persons who were infected with 2019-nCoV for the first time were selected by marching the residence, age and gender at ratio of 1∶2 from 2019-nCoV infection community follow-up cohort of Suzhou. By χ2 test, the clinical symptoms and prognosis of the reinfection case and the first-time infection cases were compared. Results:The reinfection rate of 2019-nCoV was 13.01% (147/1 130) in Suzhou. No reinfection was found within 1-6 months after the first-time infection, the rate of reinfection was 10.59% (95/897) in those with interval of 7-12 months between the reinfection and the first-time infection and 45.61% (52/114) in those with the interval ≥24 months. The lowest reinfection rate was 9.09% (1/11) in those who had completed 4 doses of 2019-nCoV vaccination. The main symptoms of the reinfection cases were similar to those of the first-time infection cases. Except for dry cough, nausea/poor appetite and other symptoms, there were significant differences in other clinical symptoms between the two groups ( P<0.05). In the reinfection cases, fever had shorter duration with lower body temperature. The hospital visit rate in the reinfection cases was 4.08% (6/147), lower than that in the cases with the first-time infection (11.56%, 34/294). The time for negative nucleic acid (antigen) test result and recovery from illness after the reinfection were shorter than those after the first-time infection. Conclusions:Reinfection occurred in some people who had been infected with 2019-nCoV. The interval between the reinfection and the first-time infection and the completion of the 4 doses of booster vaccination were the factors influencing the reinfection rate. The hospital visit rate in the reinfection cases was lower than that in the cases with the first-time infection. The reinfection had similar symptoms and shorter illness duration compared with the first-time infection.