BackgroundPatients with schizophrenia experience low quality of life， and internalized stigma is considered an important indicator for quality of life， while the mediating role of self-esteem and severity of negative symptoms in the relationship between internalized stigma and quality of life remains underexplored. ObjectiveTo examine the mediating role of self-esteem and severity of negative symptoms in the relationship between internalized stigma and quality of life， so as to provide references for improving their quality of life. MethodsA total of 342 patients with schizophrenia who were hospitalized in 6 hospitals in Xiangyang City， Siping City and Changchun City from April to September 2023 were included， and all of whom met the diagnostic criteria for schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10）. Internalized Stigma of Mental Illness Scale （ISMI）， Schizophrenia Quality of Life Scale （SQLS）， Self-Esteem Scale （SES） and negative symptom subscale of Positive and Negative Symptom Scale （PANSS） were administered to all patients. Spearman correlation analysis was adopted to determine correlations between the different scales. A structural equation modeling was constructed using Amos 28.0， and Bootstrap method was employed to verify the mediating effect of self-esteem and negative symptom severity in the association between internalized stigma and quality of life. ResultsA total of 309 patients （90.35%） completed questionnaires in this study. The ISMI score of schizophrenia patients was positively correlated with both SQLS score and the PANSS negative symptom subscale score （r=0.612， 0.492， P<0.01）， while was negatively correlated with SES score （r=-0.513， P<0.01）. The SQLS score was negatively associated with the SES score （r=-0.555， P<0.01） and positively associated with PANSS negative symptom subscale score （r=0.672， P<0.01）. The SES score was negatively correlated with PANSS negative symptom subscale score （r=-0.433， P<0.01）.The total effect value of internalized stigma on quality of life was 0.746 （95% CI： 0.680~0.806）. Self-esteem and severity of negative symptoms independently mediated the relationship between internalized stigma and quality of life， and the indirect effect values were 0.151 （95% CI： 0.062~0.254） and 0.126 （95% CI： 0.047~0.205）， accounting for 20.24% and 16.89% of the total effect， respectively. In addition， a chained mediation effect of self-esteem and quality of life was also demonstrated， the indirect effect value was 0.102 （95% CI： 0.049~0.165）， accounting for 13.67% of the total effect）. ConclusionInternalized stigma in patients with schizophrenia patients can not only directly affect the quality of life， but also indirectly affect the quality of life of patients through either separate or chained mediation of self-esteem and the severity of negative symptoms. ［Funded by Hubei Provincial Undergraduate Innovation and Entrepreneurship Project （number， S202410519027）］

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective:To discuss the effects of bone marrow-derived mesenchymal stem cells(BMSCs)transplantation on mitophagy in the vascular dementia(VaD)rats through reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling,and to clarify its mechanism.Methods:Forty-five male adult SD rats were randomly divided into sham operation group,model group,unloaded group,BMSCs group,and MSCs+ML385(Nrf2 inhibitor)group(combination group),and there were 9 rats in each group.After intraperitoneal anesthesia,the VaD models were established in all groups except sham operation group.Morris water maze test was used to detect the learning and memory abilities of the rats in various groups;HE staining was used to observe the histopathological morphology of brain tissue of the rats in various groups;Nissl staining was used to observe the changes of Nissl bodies in hippocampus region of brain tissue of the rats in various groups;transmission electron microscope was used to observe the ultrastructure of hippocampus region of the rats in various groups;fluorescence probe method was used to detect the ROS levels in hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),PTEN-induced putative kinase 1(PINK1),parkin RBR E3 ubiquitin protein ligase(Parkin),Beclin-1,ubiquitin-binding protein p62(P62),and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ/LC3-Ⅰ)ratio in brain tissue of the rats in various groups.Results:The Morris water maze results showed that compared with sham operation group,the escape latency of the rats in model group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).Compared with model group,the escape latency of the rats in BMSCs group was significantly decreased(P<0.01),while the number of crossing time and residence time were significantly increased(P<0.01).Compared with BMSCs group,the escape latency of the rats in combination group was significantly increased(P<0.01),while the number of crossing time and residence time were significantly decreased(P<0.01).The HE staining results showed that hippocampus neurons of the rats in sham operation group were normal in quantity and morphology,with uniform staining and clear structure.Compared with sham operation group,the hippocampus tissue of the rats in model group showed sparse arrangement,disordered structure,reduced neuronal quantity,varied morphology,uneven staining,nuclear pyknosis,and partial neuronal necrosis.Compared with model group,the neuronal damage of the rats in hippocampus regio in BMSCs group was alleviated,with restored morphology and improved neuronal loss.Compared with BMSCs group,the neurons of the rats in hippocampus region in combination group showed irregular morphology,disordered structure,unclear cell boundaries,uneven staining,and nuclear pyknosis.The Nissl staining results showed that the hippocampal neurons in sham operation group were tightly arranged with intact morphology,obvious nucleoli,and abundant darkly stained Nissl bodies.Compared with sham operation group,the neurons in hippocampus region of the rats in model group showed pyknosis,vacuolization,and sparse Nissl bodies.Compared with model group,the BMSCs group showed reduced neuronal pyknosis,relatively intact morphology,and increased Nissl bodies.Compared with BMSCs group,the combination group showed neuronal pyknosis,loss of morphological integrity,and fragmented Nissl bodies.The transmission electron microscope results showed that mitochondria in sham operation group exhibited oval shape with intact double-membrane structure and cristae.Compared with sham operation group,the mitochondria in model group showed swelling,disrupted membranes,broken cristae,and numerous autophagosomes.Compared with model group,the BMSCs group showed improved mitochondrial structure and reduced autophagosomes.Compared with BMSCs group,the combination group showed swollen mitochondria,disrupted membranes,broken cristae,and visible autophagosomes.The fluorescence probe results showed that compared with sham operation group,the ROS levels in the hippocampus neurons in brain tissue of the rats in model group were significantly increased(P<0.01);compared with model group,the ROS levels in hippocampus neurons in brain tissue of the rats in BMSCs group were significantly decreased(P<0.01);compared with BMSCs group,the ROS levels in hippocampus neurons in brain tissue of the rats in combination group were significantly increased(P<0.01).The Western blotting results showed that compared with sham operation group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in model group were significantly decreased(P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in BMSCs group were significantly increased(P<0.01);compared with BMSCs group,the expression levels of Nrf2 and HO-1 proteins in brain tissue of the rats in combination group were significantly decreased(P<0.01);compared with sham operation group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,and LC3-Ⅱ/LC3-Ⅰ ratio of the rats in model group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01);compared with model group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in BMSCs group were significantly decreased(P<0.01),while the expression level of P62 protein was significantly increased(P<0.01);compared with BMSCs group,the expression levels of Parkin,PINK1,and Beclin-1 proteins,as well as the LC3-Ⅱ/LC3-Ⅰ ratio,of the rats in combination group were significantly increased(P<0.01),while the expression level of P62 protein was significantly decreased(P<0.01).Conclusion:BMSCs can alleviate the hippocampal neuronal pathological changes and improve cognitive function in the VaD rats,and its mechanism may be related to the regulation of ROS/Nrf2 signaling pathway to inhibit mitophagy.

Objective To investigate the effect of ergothioneine(EGT)on tissue metabolism in middle-aged and aged mice.Methods Nine-month-old middle-aged and aged C57BL/6J mice were selected to be gavaged with EGT aqueous solution at the dose and frequency of 35 mg EGT per kg body weight every two days.The control group was gavaged with the same amount of water.Both groups were fed with EGT-free diet.After 7 weeks,the liver,kidney,and small intestine of mice were collected,and untargeted metabolomics analysis was performed using ultra-per-formance liquid chromatography-mass spectrometry(UHPLC-MS).The differential metabolites were selected for KEGG metabolic pathway enrichment analysis.Results Compared with the control group,the abundances of me-tabolites related to redox balance in liver,kidney and small intestine of middle-aged and aged mice treated with EGT did not change significantly.However,taurine and hypotaurine metabolism in liver(P＜0.01),purine metabo-lism in kidney(P＜0.01),and cysteine and methionine metabolism in small intestine(P＜0.001)were affected.Conclusions Non-redox-related metabolic changes in the liver,kidney and small intestine of middle-aged and aged mice by ergothioheine.

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Objective:To develop and evaluate a rapid and sensitive point-of-care chemiluminescent assay(POC-CLIA)for β-human chorionic gonadotropin(β-HCG).Methods:POC-CLIA was constructed based on alkaline phosphatase(Alp)-AMPPD lumi-nescence system and magnetic particles(Mps)carrier.Performance of POC-CLIA,including sensitivity,precision,accuracy,linear dilution,specificity,stability,hook effect and clinical application were evaluated.Results:Detection limit of β-HCG was 0.71 mU/ml,linear detection range was 0.710～1.092×104 mU/ml,and was no hook effect up to 1.7×105 mU/ml.Intra and inter batch coefficients of variation were less than 10％,and could be stored stably at 37℃ for 10 days.Accuracy deviation was within±10％,so results were reliable.There was no cross-reactivity between interfering substances and anti-β-HCG antibdies.For detecting β-HCG in 100 clinical serum samples,results were highly correlated with those that were tested by clinical standard methods(R2=0.997 0).Turnaround time for single sample was less than 15 min and throughput could reach 200 T/h.Conclusion:This method is adequate that can be widely used in grassroots communities to help large-scale screening of pregnancy and related diseases.

Objective To compare the influence between self-monitoring of blood gluocose(SMBG)combined with digital diabetes management and traditional management mode on the related clinical indexes in the patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM treated in the endocrinology and metabolism outpatient department of this hospital from January 2022 to June 2022 and meeting the inclusion criteria of this study were successively included.They were divided into the experimental group and control group.The experimental group was managed by SMBG combined with digital diabetes man-agement mode,while the control group adopted the traditional management mode,the outpatient clinic follow up once a month.After 6 months of follow-up,fasting blood glucose,glycosylated hemoglobin(HbA1c),low density lipoprotein cholesterol(LDL-C)and urinary microalbumin/creatinine ratio(UACR)were compared between the two groups.Results The FBG,HbA1c,LDL-C,and UACR of the experimental group decreased after intervention when compared with baseline.Compared with the control group,the FBG[8.7(7.7,9.2)mmol/L vs.10.8(8.8,12.7)mmol/L,Z=-4.660,P＜0.001],HbA1c[6.3％(5.3,7.8)％vs.8.5％(7.2,10.0)％,Z=-5.130,P＜0.001],LDL-C[2.6(1.8,3.1)mmol/L vs.3.3(2.6,4.0)mmol/L,Z=-4.112,P＜0.001],UACR[16.1(3.5,46.5)mg/g vs.58.4(11.9,108.0)mg/g,Z=-2.220,P=0.026]for patients in the expriemental group after intervention were significantly decreased.Conclusion SMBG combined with digital diabetes management model can significantly improve the clinical indicators of patients.

Objective To analyze the effects of down-regulation+hormone replacement therapy(HRT)endometrial preparation regimen on the pregnancy outcomes of advanced age women(≥35 years old)undergoing frozen-thawed embryo transfer.Methods The clinical data of 329 patients with frozen-thawed em-bryo transfer in this hospital from June 2020 to June 2022 were analyzed retrospectively.Among them,149 pa-tients receiving gonadotropin-releasing hormone analogue(GnRHa)down-regulation+HRT endometrial preparation were included in the group A,and the other 180 patients with HRT endometrial preparation were included in the group B.The basic situation,endometrial transformation day situation and clinical outcome were compared between the two groups.The group A and group B were further divided into the two sub-groups according to age:group A1(35-＜40 years old,n=101),group A2(≥40 years old,n=48),group B1(35-＜40 years old,n=99)and group B2(≥40 years old,n=81).The effects of two endometrial prepara-tion regimens were compared among the different age groups.Results There were no significant differences in the age,infertility years,BMI,anti-Mullerian hormone level,as well as basal hormones levels such as estra-diol,progesterone,follicle-stimulating hormone,luteinizing hormone(LH),prolactin and testosterone between the two groups(P＞0.05).The levels of estradiol and LH on the endometrial transformation day in the group A were significantly lower than those in the group B(P＜0.05),the endometrial thickness,proportion of the patients with endometrial thickness ≥8 mm and proportion of the patients with type Ⅲ blood intima in the group A were significantly higher than those in the group B(P＜0.05).There was no significant difference in the number of transplanted embryos and the number of transplanted excellent embryos between the two groups(P＞0.05).The clinical pregnancy rate and embryo implantation rate in the group A were significantly higher than those in the group B(46.31％vs.35.56％;33.33％vs.25.18％,P＜0.05),and there was no significant difference in the early miscarriage rate between the two groups(P＞0.05).The further subgroup analysis showed that the clinical pregnancy rate and embryoimplantation rate in the group A2 were significant-ly higher than those in the group B2(35.42％vs.18.52％;21.43％vs.12.40％,P＜0.05),while there was no significant difference between the group A1 and group B1(P＞0.05).Conclusion The advanced age pa-tients undergoing frozen-thawed embryo transfer could select GnRHa down-regulation+HRT regimen to a-chieve better pregnancy outcomes,especially for those age ≥40 years old.

Objective To investigate the relationship between the central foveal thickness(CFT),ellipsoid zone(EZ)interruption ratio and best corrected visual acuity(BCVA)in patients with idiopathic epiretinal membranes(iERM).Methods A retrospective case-control study was conducted.The cluster sampling method was used to select 336 iERM patients(500 eyes)who underwent physical examinations in 9 community hospitals of the Kailuan Group from 2014 to 2018.Among them,215 were male(64.0％)and 121 were female(36.0％),with an average age of 31-89(66.4±8.8)years.According to the gass classification,these patients were divided into three groups:gass 0 group(201 patients,305 eyes),gass 1 group(75 patients,101 eyes),and gass 2 group(60 patients,94 eyes).Pearson correlation analysis was used to evaluate the correlation between BCVA(converted to logMAR visual acuity)and gass classification,EZ interruption ratio,CFT.Results The average BCVA(logMAR)and CFT of 500 eyes were 0.45±0.28 and(337.6±101.8)μm,re-spectively,with EZ interruption in 86 eyes(17.2％).There were statistically significant differences in BCVA(logMAR)(0.62±0.29,0.48±0.23,0.26±0.32),CFT[(283.20±79.30)μm,(335.50±84.50)μm,(394.00±135.60)μm],and EZ interruption ratio(2.6％,20.8％,60.6％)among gass 0,gass 1 and gass 2 groups(all P＜0.05).Pearson correlation analysis showed that there was no correlation between age and BCVA among different groups(r2=0.021,P=0.314);BCVA was positively correlated with CFT(r2=0.531,P=0.000),EZ interruption ratio(r2=0.304,P=0.000),and gass classification(r2=0.587,P=0.000).Conclusion The EZ interruption may occur in the early stage of iERM.BCVA is correlated with CFT,EZ interruption ratio and gass classification;the incidence of EZ interruption in gass 2 iERM signifi-cantly increases.

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.