Objective To verify whether early growth response-3(EGR3) gene is targeted by microRNA-181b using molecular biology methods so as to provide guidance for the subsequent study on microRNA-181b`s role in the molecular mechanisms of schizophrenia.Methods Bioinformatic methods predicted that EGR3 gene is targeted by microRNA-181b.PCR methods amplified the fragment in EGR3 gene 3`UTR including the putative microRNA-181b binding site.Then the sequence was cloned into the pmirGLO luciferase vector.The DNA sequences of the amplified fragments were identified by restriction enzyme digestion and sequencing, and were consistent with the reference sequence from UCSC.This constructed vector was marked as pmirGLO-EGR3 vector.Finally, the pmirGLO vector, the pmirGLO-EGR3 vector, microRNA-181b mimics and negative control (NC) were divided into 5 groups and transfected into HEK393T cells;the luciferase activity was tested by dual luciferase reporter gene assay.Results The results of restriction enzyme digestion and sequencing demonstrated that the PCR fragmentwas successfully cloned into pmirGLO vector.The transfection results showed that the recombinant plasmid was successful transfected into HEK293T under the fluorescence microscope, with transfection efficiency being about 90％.The results of dual luciferase activity assay demonstrated that microRNA-181b significantly decreased the reporter gene`s activity compared with the NC.Conclusion At the cellular level, the schizophrenia susceptibility gene EGR3 was verified to be targeted by micorRNA-181b, which provides a new clue for the subsequent study on microRNA-181b`s role in the molecular mechanisms of schizophrenia.

ObjectiveTo investigate the relationship between intramural gallstones and intraluminal gallstones. MethodsIn this present study, the control study was applied to analysis on the gallstones from 116 cholecystolithiasis patients with intramural gallstones as well as intraluminal gallstones. All the patients were from the general surgery department and accepted gallbladder-preserving cholecystolithotomy during 2009.02-2009.08. Meanwhile, 171 patients with intraluminal gallstones were investigated the clinical traits; and gallstones from them were analyzed with FT-IR and microsopic examination. ResultsThe results showed the coincidence rate of stone type was 97.4％, and it was mainly pigment gallstones and mixed gallstones in 116 cases; the coincident detection rate of clonorchis sinensis eggs was 98.3 ％, and it was much higher in the pigment gallstones and mixed gallstones than that in the cholesterol gallstones. The ratio of pigment gallstones from the 116 patients group was higher than the 171 patients group, and the detection rate of C. sinensis eggs of the two groups had no statistical difference (P＞0.05). ConclusionsThe stone type of intramural gallstones was mainly pigment gallstones and mixed gallstones. Intramural gallstones and intraluminal gallstones were homologous.

Aim To observe the effects of rapamycin (Rapa) and starvation-induced autophagy on the morphology of neuronal cells, tau protein aggregation and expression of phosphorylated tau protein, to explore the possible mechanism of cytoprotective effect of these two classical autophagy inducers on phosphorylated tau expressing cells.Methods N2a cells were transfected with GFP-tau plasmid, and equal amount of empty vector was used as control.Then cells were incubated with or without okadaic acid(OA) for 12 h, followed by treatment with autophagy inducers rapamycin(Rapa) and EBSS, autophagy inhibitor Bafilomycin A1(Baf A1) for 6 h.DAB was used to observe tau expression and cell morphology.Confocal microscopy was used to observe the intracellular tau aggregation.TUNEL assay and cleaved caspase-3 level were used to detect cell apoptosis.Immunoblot was used to detect the expression of phosphorylated tau and autophagy-related proteins.Results Our study showed that the N2a cells treated with OA exhibited small cell body, retracted processes and increased tau aggregation, compared with only tau-expressing cells.Rapa and EBSS treatment significantly improved cell morphology, decreased tau aggregation and reduced cell apoptosis.On the contrary, Baf A1 treatment induced aberrant cell shape and increased tau aggregation and cell apoptosis.In addition, Rapa significantly decreased the high molecular weight, phosphorylated tau whereas EBSS especially decreased the low molecular weight phosphorylated tau.Conclusions Rapa and EBSS is alleviate hyperphosphorylated tau-induced cytotoxicity through different mechanism.Rapamycin mainly decreases phosphorylated tau oligomers, while EBSS liable to decrease the soluble phosphorylated tau.

Objective:To investigate the significance of metronomic therapy against Helicobacter pylori (HP) in the prevention of delayed emesis caused by chemotherapy of gastric cancer compared with the routine therapy. Methods:HP infection was confirmed by carbon 14 breath test in 69 patients. Combined chemotherapy was employed for the first time in the patients, who were divided into groups A and B. Metronomic therapy was administered to group A (n=33). Briefly, triplex medication against Helicobacter bacil i triplex was oral y ad-ministered:20 mg of omeprazole and 0.5 g of amoxicillin twice daily, with 200 mg of tinidazole once daily. Oral administration in group A was performed for 14 days from the start of chemotherapy. Simultaneously, 5-HT3 antagonists were applied. By contrast, group B (n=36) was treated with the oral triplex medication against Helicobacter bacilli:20 mg of omeprazole and 1 g of amoxicillin twice daily, with 400 mg of tinidazole once daily. Oral administration in group B was performed for 7 days from the beginning of chemotherapy with simultaneous application of 5-HT3 antagonists. Both groups were simultaneously treated with the 5-HT3 antagonist granisetron at 3 mg once daily during the administration of anti-HP therapy. HP infection was evaluated by immunohistochemistry before and after treatment. Results:The total effective rate for emesis in group A was 84.85%, which was significantly higher than that in group B (55.56%). Among the patients in group A, 15.15%demonstrated delayed emesis, compared with 44.44%of the patients in group B;the number of individuals was significantly lower in group A than in group B. The average number of chemotherapy cycles in group A was significantly higher than that in group B at 3.1 cycles;the difference between groups was statistically significant (P<0.05). In addition, the HP infection in group B was significantly lower than that in group A (P<0.05). Conclusion:Compared with one week of treatment with the conventional dose, two weeks of low-dose metronomic therapy against HP during chemotherapy can significantly reduce chemotherapy induced delayed emesis and can significantly reduce the degree of HP infection in patients with gastric cancer with HP infection.

ObjectiveTo investigate the distribution of thethymidylate synthase (TS) gene polymorphisms inChinese femaleHan-nationality breast cancer patients,including tandemrepeat polymorphisms in the enhancer region ( ER), 6 bp deletion/insertion (del6/ins6) polymorphism in the 3′untranslated region (3′-UTR) and G→C single-nucleotide polymorphism (SNP). The association of TS gene polymorphism with pathological results was retrospectively analyzed.MethodsThis study included 83 breast cancer patients who received no preoperative chemotherapy. The polymorphisms of TS, ER and TS 3′2UTR were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.Results ( 1 ) Of the 83 patients, the frequencies of the TSER 3R/3 R, 2R/3 R and 2R/2R were 68.7％ ,27. 7％ and 3. 6％, respectively; (2) Due to existence of the G→C single nucleotide polymorphism,TSER genotypes were divided into 2R/2R, 2R/3C, 2R/3G, 3G/3G,3C/3C and 3G/3C,their frequencies were 3. 6％, 19. 3％, 8.4％, 19. 3％, 37. 3％ and 12. 1％, respectively; ( 3 ) Of the 83 patients, the frequencies of the TS 3′-UTR ins6/ias6、ins6/del6 and del6/del6 were 8.4％ 、50.6％ and 41.0％, respectively; (4) TSER polymorphisms were correlated with lymph node metastasis ( P = 0.019 ),Ki67 ( P = 0.022 ) and histological grade ( P = 0.042 ). The TS 3′-UTR polymorphisms were correlated with age ( P = 0.002) and histological grade (P = 0.042). G→C SNP were correlated with lymph node metastasis ( P = 0.021 ) and histological grade ( P = 0.028 ).ConclusionsChinese female Han-nationality breast cancer patients have more genotypes frequencies of the TSER 3R/3R and 3′-UTR del6/del6; The TS polymorphisms are correlated with pathological factors of breast cancer.

With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification(PTM)has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on dis-eases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in mod-ification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing fac-tors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the re-search progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.

Objective To explore the strategies of using psychological crisis intervention in public emergencies.Methods In the early stage,psychological crisis intervention concepts and behavioral responses were formed through literature research and qualitative research methods.Use three rounds of Delphi for expert advice.Three indexes including positive coefficient,authority and coordination were used to test the reliability of expert consultation.Results Overall,it passed 239 out of 269 entries.The first round passed item 210,modified item 18,no consensus item 41;In the second round,8 new entries were added,and 22 entries were deleted through 24 entries.In the third round,there were 5 entries and 16 entries were deleted.The authority coefficient was 0.859,indicating that the experts were very familiar with the items.The coordination coefficient of three rounds of consultations were 0.464,0.696,and 0.407 (P＜0.001)respectively,showing that the coordination degree of experts was excellent,the credibility of feedback was high,and results were highly reliable.Conclusions The strategies of field psychological crisis intervention for public emergencies developed in this study received the consensus by domestic psychological crisis intervention experts,it is will provide a basis for systematic,comprehensive and effective guidance for this work.

Background:Patients with primary biliary cholangitis(PBC)may develop gastroesophageal varices at an early stage.It is of great significance to prevent variceal bleeding for the long-term outcome of PBC.Aims:To assess the risk factors for clinically significant portal hypertension(CSPH)among PBC patients and develop a predictive model.Methods:The clinical data of PBC patients admitted from January 2018 to January 2022 in the Division of Gastroenterology and Hepatology,Renji Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively collected and analyzed.Patients were divided into CSPH and non-CSPH groups according to the diagnostic criteria of CSPH.Multivariate Logistic regression and Lasso regression were used to identify the risk factors and construct CSPH predictive model which was presented as nomogram and internally validated.Results:Of the 458 subjects enrolled in this study,140 cases were in CSPH group while 318 cases in non-CSPH group.Multivariate analysis identified that male gender(OR=2.89),positive for anti-centromere antibody(ACA;OR=2.18)and anti-gp210 antibody(OR=1.75),high baseline total bilirubin(OR=1.01)and IgA(OR=1.27),and low baseline albumin(OR=0.91)and platelet count(OR=0.98)were independent risk factors for CSPH.These variables were selected to form the predictive model and nomogram ultimately.Favorable stability and predictive performance of the model were confirmed by ROC curve analysis(AUC=0.891)and bootstrap method(C-index=0.891).Conclusions:The predictive model constructed in this study has certain reference value for risk stratification of CSPH among PBC patients.Intensive follow-up is recommended for ACA-positive PBC patients in clinical practice for avoidance of gastroesophageal variceal bleeding.

BACKGROUND:It has been found in recent observational studies that assessing localized fat mass is crucial in the evaluation of disc degeneration.Although obesity has been recognized as a risk factor for disc degeneration,the causal relationship between fat mass,which is a key factor in obesity,and intervertebral disc degeneration has been unclear in previous studies. OBJECTIVE:To investigate the causal risk factors of intervertebral disc degeneration associated with different distributions of fat mass,thereby enhancing the understanding of the pathogenesis of intervertebral disc degeneration and contributing to the development of preventive,therapeutic,and prognostic strategies. METHODS:Genetic markers associated with trunk and lower limb fat mass were extracted as instrumental variables from the publicly available IEU Open GWAS under the conditions of strong correlation and fulfillment of linkage disequilibrium.These markers were combined with the Mendelian randomization analysis to investigate the relationship between body fat and intervertebral disc degeneration.We used the latest version 9 database of FinnGen and assessed the results using several regression models,including inverse variance weighting,MR-Egger regression,simple mode,weighted mode,and weighted median estimator.We also assessed the heterogeneity of the genetic markers using Cochran's Q test,and multiplicity was assessed using the MR-Egger intercept test.Additionally,we used the leave-one-out method to determine the sensitivity of individual genetic markers to the causal effect of the exposure and outcome.The results were presented as odds ratios(OR)and 95%confidence intervals(CI). RESULTS AND CONCLUSION:The results from the inverse variance weighting method revealed that there was a positive causal relationship between trunk fat mass and the risk of developing intervertebral disc degeneration(OR=1.25,95%CI:1.15-1.35,P＜0.001).Additionally,there was an inverse causal relationship between bilateral lower limb fat mass and the risk of developing intervertebral disc degeneration(OR=0.7,95%CI:0.63-0.78,P＜0.001;OR=0.69,95%CI:0.62-0.76,P＜0.001).Furthermore,the MR-Egger intercept analysis did not detect any potential horizontal pleiotropy.No bias single nucleotide polymorphisms were detected,while heterogeneity tests were present,and the leave-one-out sensitivity analysis suggested reliable results.The results above demonstrate a positive causal relationship between trunk fat mass and intervertebral disc degeneration.As trunk fat mass increases,the risk of intervertebral disc degeneration rises.With an increase in both lower limb fat mass,the risk of intervertebral disc degeneration decreases.Fat content and distribution affects the risk of developing intervertebral disc degeneration and should be given more attention.

Objective:To design a set of assessment tool for the effectiveness of internal performance management in public hospitals, so as to provide reference for optimization hospital internal systems and multi-institutional comparison.Methods:From September 2022 to April 2023, literature review and expert group discussion were used to initially construct an index system for evaluating the effectiveness of performance management in public hospitals, based on the " structure-process-outcome" model. Index quantitative scoring rules and standardized staff questionnaire for supporting use were developed by drawing on the World Management Survey Hospital Edition and Chinese Hospital Management Survey. Two rounds of Delphi consultation were made to rate the importance and measurement feasibility of each index. The analytic hierarchy process was used to determine the relative importance of the finalized indexes. Results:The effective recovery rate of expert consultation questionnaire was 100%, and the authority coefficient was 0.882. The index system consisted of 3 first-level indexes (structure, process, and result), 9 second-level indexes, and 27 third-level indexes. The weights of structure, process and result were 0.307, 0.406 and 0.287, respectively. The second-level indexes with the highest weight were internal effectiveness, informationization, and performance tracking and evaluation, with values of 0.180, 0.156 and 0.115, respectively. The third-level indexes with the highest weight were the construction level of performance management information integration platform, the incentive degree of hospital performance management system to employees, and the scope of performance tracking and evaluation, with values of 0.156, 0.075 and 0.073. The third-level index quantitative scoring rules covered the management activity points that were easy to collect via investigation. Among them, the feasibility of 22 scoring rules were recognized by all the 15 experts, 5 rules were recognized by 14 experts, and 2 rules were recognized by 13 experts. A standardized survey questionnaire covering 25 questions was established based on four third-level indexes: the level of understanding, recognition, satisfaction, and motivation of employees towards the hospital performance management system. The importance scores of each question ranged from 7.43 to 8.71.Conclusions:This study developed a comprehensive suite of assessment instruments, including an index system, a set of quantitative scoring rules, and a standardized staff questionnaire, which could provide reference for hospitals to upgrade their internal performance management levels.