Objective: To systematically evaluate the association between maternal adverse childhood experiences (ACEs) and offspring social behavior, so as to provide a theoretical basis for further research on intergenerational social behavioral development. Methods: Relevant research literature about maternal ACEs and the development of children s maladaptive social behaviors were collected, from China National Knowledge Infrastructure (CNKI), VIP, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library, Embase and SpringLink databases, covering the period from the inception of each database to May 2025. The Chinese database matched and searched through three groups of keywords: "Pregnant women" "Mothers" and "Women"; "Bad childhood experience" "Bad early experience" and "Bad adolescent experience"; "Children" "Teenagers" "Children s behavior" "Children s development" "Teenagers behavior" "Internalized behavior" and "Externalized behavior". The English database was searched by three groups of keywords: "Female" "Pregnant women" "Mothers"; "Adverse childhood experiences" "Adverse early childhood experiences" "Adverse experiences of adolescent"; "Child behavior" "Child development" "Adolescent behavior" "Internalized behaviors" "Externalized behaviors". The selected literature was evaluated for quality and data extraction, with OR and 95% CI as effect indicators. Stata 16.0 software was used for heterogeneity testing, subgroup analysis, and publication bias analysis. Results: A total of 14 studies involving 64 302 mother-child pairs were included. The Meta analysis results showed a significant correlation between maternal ACEs and both offspring maladaptive internalized behaviors ( OR=1.75, 95%CI=1.42-2.15, P <0.01) and externalized behaviors ( OR=1.82, 95%CI=1.51-2.20, P <0.01). The results of subgroup analyses showed that in different regions[internalized behaviors:domestic, foreign OR (95% CI )=2.03(1.49-2.76), 1.55(1.19-2.03); externalized behaviors: domestic, foreign OR (95% CI )=2.41(1.52-3.82), 1.65(1.36-2.01)], study type[internalized behaviors: cohort study, cross sectional study OR (95% CI )=1.64(1.34-2.00), 1.85(1.30-2.65); externalized behaviors: cohort study, cross sectional study OR (95% CI )=1.76(1.46-2.12), 2.12(1.40-3.20)], sample size [internalized behaviors: ≥4 000, <4 000 pairs OR (95% CI )=1.69(1.13-2.55), 1.77( 1.41 -2.24); externalized behaviors: ≥3 000, <3 000 pairs OR (95% CI )=1.72(1.37-2.17), 2.13(1.44-3.15)], there were significant and positive association between mothers ACEs and children s internalizing and externalizing behaviors (all P <0.05). Conclusion A substantial positive association exists between maternal ACEs and the development of offspring maladaptive internalized and externalized behaviors, but the result needs to be continued to be validated by more research.

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

Objective:To discuss the effect of azathioprine(AZA)on ferroptosis in spermatocytes of the mice induced by reduced glutathione(GSH)peroxidase 4 inhibitor RSL3,and to clarify the potential mechanism.Methods:The spermatogonia GC-2 cells of the mice were randomly divided into control group(no treatment),RSL3 group(treated with 10 nmol·L-1 RSL3 for 24 h),RSL3+ferroptosis inhibitor(Ferrostatin-1,Fer-1)group(treated with 10 nmol·L-1 RSL3 for 24 h+2 μmol·L-1 Fer-1 for 12 h),RSL3+low dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+5 μmol·L-1 AZA for 12 h),RSL3+medium dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+10 μmol·L-1 AZA for 12 h),and RSL3+high dose of AZA group(treated with 10 nmol L-1 RSL3 for 24 h+20 μmol·L-1 AZA for 12 h).The MTT method was used to detect the activities of the GC-2 cells in various groups after treated with different concentrations of AZA and RSL3;the GSH and GSSG levels in the GC-2 cells were detected by GSH and oxidized glutathione(GSSG)detection kits;the malondialdehyde(MDA)levels in the GC-2 cells in various groups were detected by MDA detection kit;Western blotting method was used to detect the expression levels of long-chain acyl-CoA synthetase 4(ACSL4),heme oxygenase-1(HO-1),and glutathione peroxidase 4(GPX4)proteins in the cells in various groups;immunofluorescence staining was used to detect the expressions of ACSL4 protein in the cells in various groups.Results:Compared with control group,the differences in activities of the GC-2 cells in 5,10,and 20 μmol·L-1 AZA groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 30 and 40 μmol·L-1 AZA groups were significantly decreased(P＜0.01);therefore,the AZA concentration was selected to be within 20 μmol·L-1.Compared with control group,the differences of the activities of the GC-2 cells in 1,5,and 10 nmol·L-1 RSL3 groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 50,100,500,and 1 000 nmol·L-1 RSL3 groups were significantly decreased(P＜0.05 or P＜0.01);therefore,the RSL3 concentration was set to be within 10 nmol·L-1.The GSH and MDA detection kits results showed that compared with control group,the levels of GSSG and MDA in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the GSH levels were significantly decreased(P＜0.05);compared with RSL3 group,the levels of GSSG and MDA in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased(P＜0.01),while the GSH levels were significantly increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of ACSL4 and HO-1 proteins in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the expression level of GPX4 protein was significantly decreased(P＜0.01);compared with RSL3 group,the expression levels of GPX4 protein in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly increased(P＜0.05),while the expression levels of ACSL4 and HO-1 proteins were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the expression amount of ACSL4 protein in the GC-2 cells in RSL3 group was significantly increased,and compared with RSL3 group,the expression amounts of ACSL4 protein in the cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased.Conclusion:AZA can alleviate the ferroptosis-induced by RSL3 in spermatocytes of the mice.

A middle-aged female with abnormal liver function indicators was admitted to hospital with obstructive jaundice. Urine protein of the patient was positive, and the color turned green during the retest with sulfosalicylic acid, which was relatively rare. According to the laboratory examination and other auxiliary diagnosis of the patient, the cause of the discoloration was found to be obstructive jaundice induced by choledochal adenocarcinoma, which impeded the excretion of copper ions through the bile of the patient. Copper enters the urine through the circulation of the bile, causing an increase in urinary copper. This provides a theoretical basis for the discovery of this phenomenon in clinical tests.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

International collaboration in education enables learning from advanced teaching experience and promotes the reform, optimization, and upgrading of medical education and teaching. We analyzed the difficulties and challenges in the education concept, curriculum system, and teaching language mode of infectious diseases under the condition of international cooperation in education in Chongqing Medical University. We tried to upgrade the teaching concepts, optimize the curriculum, and explore teaching language mode in the practice of teaching infectious diseases. We used the methods of deepening cooperation between departments, strengthening the communication between teachers and students, and emphasizing teacher training. We also adopted a variety of teaching methods and flexible teaching modes based on teaching content. With these methods, we explored teaching models of infectious diseases suitable in the context of international cooperation in education.

In our retrospective cohort study, we aim to explore whether Azvudine modifies the risk of death in COVID-19 patients. It was conducted on the medical records of patients, consecutively admitted for COVID-19 pneumonia to two hospitals in Chongqing, China. Based on Azvudine treatment exposure, the patients were divided into Azvudine group and non-Azvudine group. We used 1:2 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between Azvudine and non-Azvudine groups. There were 1072 patients included in our original cohort. With 1:2 ratio PSM, the Azvudine group included 195 patients and non-Azvudine group included 390 patients. The results showed that Azvudine treatment was associated with improved in-hospital mortality in overall population (OR 0.375, 95% CI 0.225-0.623, P < 0.001), severe subgroup (OR 0.239, 95% CI 0.107-0.535, P = 0.001), critical subgroup (OR 0.091, 95% CI 0.011-0.769, P = 0.028) in matched cohort with univariate analysis. And there was a significantly lower in-hospital mortality in overall population (11% vs. 24%, P＜0.001), severe sub-group (10% vs. 32%, P < 0.001) and critical sub-group (5% vs. 34%, P = 0.017) in matched cohort. These results suggest Azvudine can reduce in-hospital mortality in overall COVID-19 patients, severe, and critical subgroup population.

Objective:To screen the differentially expressed genes (DEG) related to inflammatory response associated with the prognosis of colon cancer based on the bioinformatics approach, and to construct and validate a prognostic model for colon cancer.Methods:RNA sequencing and clinical data of 472 colon cancer patients and normal colon tissues of 41 healthy people were retrieved from the Cancer Genome Atlas (TCGA) database. Gene expression related to prognosis of colon cancer and clinical data were retrieved from the International Cancer Genome Consortium (ICGC) database. The retrieval time was all from the establishment of library to November 2022. A total of 200 genes associated with inflammatory response obtained from the Gene Set Enrichment Analysis (GSEA) database were compared with the RNA sequencing gene dataset of colon cancer and normal colon tissues obtained from the TCGA database, and then DEG associated with inflammatory response were obtained. The prognosis-related DEG in the TCGA database were analyzed by using Cox proportional risk model, and the inflammatory response-related DEG were intersected with the prognosis-related DEG to obtain the prognosis-related inflammatory response-related DEG. The prognostic model of colon cancer was constructed by using LASSO Cox regression. Risk scores were calculated, and colon cancer patients in the TCGA database were divided into two groups of low risk (< the median value) and high risk (≥the median value) according to the median value of risk scores. Principal component analysis (PCA) was performed on patients in both groups, and survival analysis was performed by using Kaplan-Meier method. The efficacy of risk score in predicting the overall survival (OS) of colon cancer patients in the TCGA database was analyzed based on the R software timeROC program package. Clinical data from the ICGC database were applied to externally validate the constructed prognostic model, and patients with colon cancer in the ICGC database were classified into high and low risk groups based on the median risk score of patients with colon cancer in the TCGA database. By using R software, single-sample gene set enrichment analysis (ssGESA), immunophenotyping difference analysis, immune microenvironment correlation analysis, and immune checkpoint gene difference analysis of immune cells and immune function were performed for prognosis-related inflammation response-related DEG in the TCGA database.Results:A total of 60 inflammatory response-related DEG and 12 prognosis-related DEG were obtained; and 6 prognosis-related inflammatory response-related DEG (CCL24, GP1BA, SLC4A4, SRI, SPHK1, TIMP1) were obtained by taking the intersection set. LASSO Cox regression analysis showed that a prognostic model for colon cancer was constructed based on 6 prognosis-related inflammatory response-related DEG, and the risk score was calculated as = -0.113×CCL24+0.568×GP1BA+ (-0.375)×SLC4A4+(-0.051)×SRI+0.287×SPHK1+0.345×TIMP1. PCA results showed that patients with colon cancer could be better classified into 2 clusters. The OS in the high-risk group was worse than that in the low-risk group in the TCGA database ( P < 0.001); the area of the curve (AUC) of the prognostic risk score for predicting the OS rates of 1-year, 3-year, 5-year was 0.701, 0.685, and 0.675, respectively. The OS of the low-risk group was better than that of the high-risk group in the ICGC database; AUC of the prognostic risk score for predicting the OS rates of 1-year, 2-year, 3-year was 0.760, 0.788, and 0.743, respectively. ssGSEA analysis showed that the level of immune cell infiltration in the high-risk group in the TCGA database was high, especially the scores of activated dendritic cells, macrophages, neutrophils, plasmacytoid dendritic cells, T helper cells, and follicular helper T cells in the high-risk group were higher than those in the low-risk group, while the score of helper T cells 2 (Th2) in the high-risk group was lower compared with that in the low-risk group (all P < 0.05); in terms of immune function, the high-risk group had higher scores of antigen-presenting cell (APC) co-inhibition, APC co-stimulation, immune checkpoint, human leukocyte antigen (HLA), promotion of inflammation, parainflammation, T-cell stimulation, type Ⅰ interferon (IFN) response, and type ⅡIFN response scores compared with those in the low-risk group (all P < 0.05). The results of immunophenotyping analysis showed that IFN-γ-dominant type (C2) had the highest inflammatory response score, and the differences were statistically significant when compared with trauma healing type (C1) and inflammatory response type (C3), respectively (all P < 0.05). Immune microenvironment stromal cells and immune cells were all positively correlated with prognostic risk scores ( r values were 0.35 and 0.21, respectively, both P < 0.01). The results of immune checkpoint difference analysis showed there was a statistically significant difference in programmed-death receptor ligand 1 (PD-L1) expression level between high-risk group and low-risk group ( P = 0.002), and PD-L1 expression level was positively correlated with prognostic risk score ( r = 0.23, P < 0.01). Conclusions:Inflammatory response-related genes may play an important role in tumor immunity of colon cancer and can be used in the prognostic analysis and immunotherapy of colon cancer patients.

Hepatitis B virus （HBV） has the characteristics of wide transmission， a high chronic infection rate， and a low cure rate， and improving the cure rate of HBV may help to improve the long－term prognosis of patients. Heat shock protein 90 （Hsp90） is a chaperone protein widely present in organisms. In recent years， more and more studies have shown that Hsp90 is associated with HBV infection and plays an important role in HBV replication. It can not only interact with specific proteins of the virus to promote its replication， but also interact with the host’s own proteins to perform its function. This article reviews the role of Hsp90 in HBV replication in recent studies， so as to provide new theoretical guidance and directions for the development of new anti－HBV drugs targeting Hsp90 and the prevention and treatment of HBV infection in the future.

Objective:To investigate the risk factors of early neurological deterioration (END) in patients with minor ischemic stroke caused by large vessel occlusion (LVO) and the impact of rescue endovascular thromboectomy (REVT) on clinical outcomes of patients with END at discharge.Methods:Consecutive patients with acute minor ischemic stroke caused by LVO within 24 h of onset in the Third Affiliated Hospital, Soochow University from January 2021 to March 2023 were retrospectively enrolled. Minor ischemic stroke was defined as baseline National Institute of Health Stroke Scale (NIHSS) score ≤5 at admission. END was defined as an increase of ≥4 in the NIHSS score within 24 h after the best medical management. The modified Rankin Scale was used to evaluate the clinical outcomes of patients with END at discharge. 0-2 was defined as a good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for END and the impact of REVT on clinical outcomes in patients with END. Results:A total of 75 patients with minor ischemic stroke caused by LVO were included, of which 31 (41.3%) developed END and 13 (41.9%) underwent REVT after END. Multivariate logistic regression analysis showed that internal carotid artery occlusion was an independent risk factor for END (odds ratio 4.304, 95% confidence interval 1.213-15.270; P=0.024), and REVT was an independent protective factor for good outcomes in patients with END (odds ratio 0.068, 95% confidence interval 0.006-0.774; P=0.030). Conclusions:The incidence of END is higher in patients with minor ischemic stroke caused by LVO, and internal carotid artery occlusion is an independent risk factor for the occurrence of END. Providing REVT after END may improve the clinical outcomes of patients with END at discharge.