AIM:This study aimed to investigate the mechanism by which celoside I enhances mitophagy in a model of optic nerve injury through regulation of reactive oxygen species(ROS)-mediated c-Jun N-terminal kinase(JNK)/c-Jun signaling pathway.METHODS:Twenty-four New Zealand white rabbits were randomly divided into four groups:sham surgery,model,mecobalamin,and experimental group.Optic nerve injury was induced in the model,mecobala-min,and experimental groups,while the sham surgery group underwent a sham procedure.The mecobalamin group re-ceived mecobalamin,the experimental group received celoside I,and the sham surgery and model groups received saline.Interventions were administered daily for 28 d.Various techniques including endoscopy,hematoxylin-eosin(HE)stain-ing,TUNEL method,immunofluorescence staining and Western blot were used to assess fundus condition,retinal mor-phology,apoptosis,ROS expression,and protein levels in the retina.RESULTS:Fundus examination revealed im-proved blood flow in the mecobalamin and experimental groups compared to the model group.Retinal morphology showed enhanced retinal ganglion cells(RGCs)in the mecobalamin and experimental groups.Apoptosis index was lower in the mecobalamin group compared to the experimental group.Immunofluorescence staining indicated reduced ROS and P62 ex-pression and increased parkin and microtubule-associated protein light chain 3(LC3)expression in the experimental group compared to the mecobalamin group.Protein analysis showed decreased JNK,c-Jun,and P62 levels,and increased parkin and LC3 levels in the mecobalamin and experimental groups compared to the model group.CONCLUSION:Celo-side I reduces ROS expression,inhibits the JNK/c-Jun pathway,enhances mitophagy,reduces apoptosis,and protects RGCs in optic nerve injury models.

BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.

This paper discussed the current education status on medical ethics and styles and the assessment condition in the examination of doctors' qualification， as well as the existing problems and potential solutions by reviewing domestic and foreign literature and summarizing the practice experience. Traditionally， medical ethics and styles have always been integrated into clinical medical practice in China. However， under the modern medical education system， it is challenged to integrate traditional education on medical ethics and styles with the rules of modern medical knowledge. By summarizing the education and assessment status of medical ethics and styles in the examination of doctors' qualification， it is found that the current examination is relatively poor in the evaluation content， and the way of evaluation is not diverse， with lack of curriculum of medical humanities. The solutions suggested are enriching relevant examination content， introducing more and comprehensive evaluation method， and establishing more medical humanities-related courses.

[Objective]To evaluate the efficacy of different traditional Chinese medicine(TCM)appropriate techniques on patients with coronary heart disease and insomnia by network Meta-analysis.[Methods]A computer-based search of China National Knowledge Infrastructure(CNKI),WanFang,China Science and Technology Journal Database(VIP),China Biology Medicine disc(CBM),PubMed,CINAHL,Web of Science,Embase and the Cochrane Library was conducted to retrieve the literature on the improvement of the efficacy of TCM appropriate technology in patients with coronary heart disease and insomnia.The retrieval time limit was from the establishment date of the database to December 2023.Two researchers independently screened the literature,evaluated the quality of the literature and extracted the information.The Cochrane bias assessment tool was used to evaluate the quality of the literature,Review Manager 5.3 was used for traditional Meta-analysis,and Stata 17 software was used for network Meta-analysis.[Results]A total of 31 studies involving 2 977 patients and 14 TCM appropriate techniques were included.Network Meta-analysis showed that in terms of the total effective rate of insomnia,acupoint massage+five-tone therapy[odds ratio(OR)=7.61,95％confidence interval(CI)(2.05,28.30),P＜0.05]was superior to conventional treatment,and had the best effect compared with other TCM appropriate techniques.In terms of sleep quality score,acupoint application[mean difference(MD)=0.51,95％CI(0.04,8.23),P＜0.05]was superior to conventional treatment,and had the best effect compared with other TCM appropriate techniques.[Conclusion]Existing studies have shown that acupoint massage+five-tone therapy can effectively improve the total effective rate of insomnia.Acupoint application can effectively improve the sleep quality of patients.Medical staff can select appropriate TCM appropriate techniques according to the patient's own situation.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Objective:To construct of a computed tomography (CT) based radiomics model for predicting the prognosis of patients with gastric neuroendocrine neoplasm (GNEN) and inves-tigate its application value.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 182 patients with GNEN who were admitted to 2 medical centers, including the First Affiliated Hospital of Zhengzhou University of 124 cases and the Affiliated Cancer Hospital of Zhengzhou University of 58 cases, from August 2011 to December 2020 were collected. There were 130 males and 52 females, aged 64(range, 56-70)years. Based on random number table, all 182 patients were divided into the training dataset of 128 cases and the validation dataset of 54 cases with a ratio of 7:3. All patients underwent enhanced CT examination. Observation indicators: (1) construction and validation of the radiomics prediction model; (2) analysis of prognostic factors for patients with GNEN in the training dataset; (3) construction and evaluation of the prediction model for prognosis of patients with GNEN. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and the chi-square test, corrected chi-square test or Fisher exact probability were used for comparison between groups. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. The R software (version 4.0.3) glmnet software package was used for least absolute shrinkage and selection operator (LASSO)-COX regression analysis. The rms software (version 4.0.3) was used to generate nomogram and calibration curve. The Hmisc software (version 4.0.3) was used to calculate C-index values. The dca.R software (version 4.0.3) was used for decision curve analysis. Results:(1) Construction and valida-tion of the radiomics prediction model. One thousand seven hundred and eighty-one radiomics features were finally extracted from the 182 patients. Based on the feature selection using intra-group correlation coefficient >0.75, and the reduce dimensionality using LASSO-COX regression analysis, 14 non zero coefficient radiomics features were finally selected from the 1 781 radiomics features. The radiomics prediction model was constructed based on the radiomics score (R-score) of these non zero coefficient radiomics features. According to the best cutoff value of the R-score as -0.494, 128 patients in the training dataset were divided into 64 cases with high risk and 64 cases with low risk, 54 patients in the validation dataset were divided into 35 cases with high risk and 19 cases with low risk. The area under curve (AUC) of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the training dataset was 0.83[95% confidence interval ( CI ) as 0.76-0.87, P<0.05], 0.84(95% CI as 0.73-0.91, P<0.05), 0.91(95% CI as 0.78-0.95, P<0.05), respectively. The AUC of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the validation dataset was 0.84(95% CI as 0.75-0.92, P<0.05), 0.84 (95% CI as 0.73-0.91, P<0.05), 0.86(95% CI as 0.82-0.94, P<0.05), respectively. (2) Analysis of prognostic factors for patients with GNEN in the training dataset. Results of multivariate analysis showed gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression were independent factors influencing prognosis of patients with GNEN in the training dataset ( P<0.05). (3) Construction and evaluation of the prediction model for prognosis of patients with GNEN. The clinical prediction model was constructed based on the independent factors influen-cing prognosis of patients with GNEN including gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression. The C-index value of clinical prediction model in the training dataset and the validation dataset was 0.86 (95% CI as 0.82-0.90) and 0.80(95% CI as 0.72-0.87), respectively. The C-index value of radiomics prediction model in the training dataset and the validation dataset was 0.80 (95% CI as 0.74-0.86, P<0.05) and 0.75(95% CI as 0.66-0.84, P<0.05), respectively. The C-index value of clinical-radiomics combined prediction model in the training dataset and the validation dataset was 0.88(95% CI as 0.85-0.92) and 0.83 (95% CI as 0.77-0.89), respectively. Results of calibration curve show that clinical prediction model, radiomics prediction model and clinical-radiomics combined prediction model had good predictive ability. Results of decision curve show that the clinical-radiomics combined prediction model is superior to the clinical prediction model, radiomics prediction model in evaluating the prognosis of patients with GNEN. Conclusions:The predection model for predicting the prognosis of patients with GNEN is constructed based on 14 radiomics features after selecting. The prediction model can predict the prognosis of patients with GNEN well, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Objective To understand the barriers of surrogate decision-makers participating in the advanced care planning(ACP)for patients with advanced cancer,and to provide references for the construction and intervention of educational programs.Methods Under the guidance of ternary reciprocal determinism,qualitative research method was used to conduct semi-structured interviews with 12 surrogate decision makers of advanced cancer patients in 2 tertiary hospitals of Zhejiang Province,and the data was analyzed using targeted content analysis.Results Based on the theory,the influencing factors of participating in ACP of the surrogate decision-makers of patients with advanced cancer were summarized into 3 themes:individual level-dual restriction of subjective thought and objective ability(value restriction,cognitive understanding deviation,economic condition restriction,patient's situation control),environment level-synergistic influence of medical environment and social environment(limited medical conditions,pressure from public moral opinion,insufficient policy guarantee,lack of family consensus),behavior level-interaction of external guidance and internal feedback(lack of guidance of medical staff,experience support of medical decision-making).Conclusion Surrogate decision-makers of patients with advanced cancer face many pressures before participating in the ACP.Under the guidance of the theory of knowledge,belief and practice,medical staff can give them pre-established medical care knowledge to correct their cognitive bias.Medical staff can guide the realization of"family-centered"decision-making mode to strengthen the family support of surrogate decision-makers.Medical staff also can lead the establishment of a surrogate decision-makers support group to share decision-making experience and provide medical decision-making assistance.

Objective:To identify the potential pathogenic genes for perioperative neurocognitive disorder (PND) in the patients with digestive system tumors.Methods:The gene expression data of esophageal cancer, gastric cancer, colon cancer, rectal cancer and liver cancer in The Cancer Genome Atlas database were analyzed by bioinformatics analysis method, and the differentially expressed genes in tumor tissues in above-mentioned disease samples were identified compared with para-carcinoma tissues.Secretory proteome differential genes with the same expression trend in digestive system tumors were obtained by comparing with human secretory proteome genes.The correlation between secretomics and PND was determined by comparing with the GeneCards database.Hub genes were identified through PPI network construction and calculation, and the functions and signaling pathways of the above-mentioned differential genes were identified through GO and KEGG enrichment analysis.Results:Compared with para-carcinoma tissues, the expression of 2 640 genes was significantly up-regulated and the expression of 1 423 genes was down-regulated in esophageal cancer tissues; the expression of 3 748 genes was up-regulated and the expression of 908 genes was down-regulated in gastric cancer samples; the expression of 2 684 genes was up-regulated and the expression of 2 678 genes was down-regulated in colon cancer samples; the expression of 2 876 genes was up-regulated and the expression of 2 945 genes was down-regulated in rectal cancer samples; the expression of 1 484 genes was up-regulated and the expression of 723 genes was down-regulated in hepatocellular carcinoma samples.Among them, the expression of the encoding genes of 53 secreted proteins was uniformly up-regulated and the expression of the encoding genes of 20 secreted proteins was uniformly down-regulated in the above tumors.Twenty up-regulated genes and 3 down-regulated genes were associated with PND.PPI network analysis showed that MMP9 was the hub gene.The results of GO and KEGG analysis suggested that differentially expressed genes were mainly related to receptor-ligand activity, cytokine activity and chemokine activity, and were mainly enriched in signaling pathways related to cell cycle and cellular senescence.Conclusions:About 23 differentially expressed genes in digestive system tumors are potentially related to PND, of which MMP9 and other genes may be the hub genes, mainly acting on receptor-ligand binding, regulation of cytokine and chemokine activity, cell cycle, cellular senescence and other related signaling pathways.

ObjectiveTo study the regulatory effect of microRNA-124（miR-124） on the expression of Apelin（APLN） in epileptic neurons and its effect on neuronal injury. Methods Epileptic model of neurons was established by low magnesium extracellular medium. Dual-luciferase reporter gene system was used to verify the regulatory effect of miR-124 on APLN. Quantitative real-time PCR（qRT-PCR） was used to examine mRNA expression of miR-124 and APLN gene. Western blotting was employed to detect the expression of APLN，Bax，Bcl-2，and Caspase 3 proteins. Flow cytometry was utilized to determine the apoptosis of neurons. 〖WTHZ〗Results〖WTBZ〗Although no significant difference was reached，the luciferase activity was lower in miR-124+APLN gene wide-type group than that in control group. Both qRT-PCR and western blotting showed that up-regulation of miR-124 could promote the expression of APLN，and down-regulating miR-124 expression could inhibit APLN mRNA expression. Furthermore，up-regulating miR-124 expression could promote the apoptosis of epileptic neurons. The underlying mechanisms involved up-regulation of pro-apoptotic protein Bax and caspase 3，and down-regulation of anti-apoptotic protein Bcl-2. Conclusion The results of this study suggested that miR-124 might positively regulate APLN expression，and miR-124 might lead to neurons deaths by regulating other gene expression other than APLN gene.

Objective To investigate the effect of section of pancreatic envelope combined with vacuum sealing drainage under laparoscopy on inflammatory mediators of patients with early severe acute pancreatitis (SAP). Methods Forty-two SAP patients were admitted to Foshan Hospital of Traditional Chinese Medicine in Guangdong Province from January 2008 to December 2016. That 22 patients underwent pancreatic membrane incision and vacuum sealing drainage under laparoscopy was in the experimental group, and that 20 patients underwent the routine pancreatic membrane incision and double tube drainage was in the control group. The venous blood was collected, the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured before and after operation for 1, 3, 7 and 14 days, and the clinical therapeutic effects were observed in the two groups. Results With the prolongation of therapy, the levels of CRP, IL-6 and TNF-α were decreased continuously in both groups, the degrees of decrease of above indexes in experimental group were more significant than those in the control group, and the differences in these indexes between the two groups were statistically significant [CRP (mg/L): 1 day was 203.80±25.12 vs. 271.79±60.41, 3 day was 117.26±19.70 vs. 174.53±42.37; IL-6 (ng/L): 1 day was 40.63±3.38 vs. 57.10±11.46, 3 days was 23.14±3.51 vs. 46.87±10.69; TNF-α (ng/L): 1 day was 23.91±10.42 vs. 36.73±15.90, 3 days was 19.13±8.34 vs. 32.58±15.81, all P < 0.05]. There were no statistical significant differences in the levels of above indexes on 7 days and 14 days after treatment between the two groups (all P > 0.05). The therapeutic efficacy of the experimental group was significantly higher than that of the control group [95.45% (21/22) vs. 90.0% (18/20), P < 0.05]. Conclusion Under laparoscopy, pancreatic envelope incision combined with vacuum sealing drainage performed for early SAP patients can control the body inflammation more rapidly, reduce complications and shorten the disease course.