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 explore the association between interpregnancy weight change and the recurrence of gestational diabetes mellitus(GDM).Methods This study included women who had two delivery records and a history of GDM during their previous pregnancy at the Guangdong Women and Children Hospital between January 2017 and July 2022.Interpregnancy weight change was defined as the difference between the prepregnancy BMIs of two consecutive pregnancies.Interpregnancy weight change was categorized into four groups(＜-1,-1 to＜1,1 to＜3,≥3 kg/m2),with the-1 to＜1 kg/m2 group serving as the reference.Logistic regression analyses were used to assess the associations of interpregnancy weight changes with GDM recurrence and changes in glucose values during two consecutive pregnancies.Results Among 703 participants,326 individuals(46.4％)experienced GDM recurrence.Compared with the groups with an interpregnancy BMI change of-1 to＜1 kg/m2,the groups with a BMI change of 1 to＜3 or ≥3 presented an increased risk of GDM recurrence,with odds ratio(OR)[95％confi-dence intervals(CI)]of 2.16(1.52-3.08)and 2.56(1.44-4.56),respectively.The risk of GDM recurrence significantly in-creased with increasing interpregnancy weight gain(P for trend＜0.01).However,there was no significant association between a BMI change＜-1 kg/m2 and GDM recurrence,with an OR(95％CI)of 0.95(0.57-1.57).An increase of 1 kg/m2 in the in-terpregnancy BMI was associated with a higher risk of elevated fasting blood glucose and 1 h plasma glucose,with OR(95％C1)of 1.15(1.05-1.26)and 1.21(1.10-1.33),respectively.Conclusion Women with a history of GDM are at a high risk of GDM recurrence,and interpregnancy weight gain is associated with an increased risk of GDM recurrence.These findings under-score the importance of health education among women with a history of GDM who plan to conceive again and emphasize the im-portance of weight management in reducing the recurrence of GDM.

OBJECTIVE To observe the auxiliary analgesic effect of electroacupuncture at Hegu and Neiguan combined with in-domethacin suppository in patients undergoing transvaginal ultrasound-guided oocyte retrieval(TUGOR and its effect on the outcome of in vitro fertilization(IVF.METHODS 64 IVF-ET patients undergoing TUGOR were randomly divided into a treatment group and a control group,32 cases in each group.One case dropped out of the treatment group during the treatment.The control group was given indomethacin suppository rectal administration,and the treatment group was given electroacupuncture at Hegu and Neiguan in addition to the treatment of the control group.The patients'tenderness threshold,VAS score,pain grade score,respiratory rate,and pulse rate were evaluated before and after TUGOR operation.The number of oocytes obtained,the rate of two pronuclei(2PN,embryo utiliza-tion rate,and high-quality embryo rate were evaluated after TUGOR operation.The adverse reactions of the two groups were monitored during and after operation.RESULTS After TUGOR operation,the VAS score and pain grade of the treatment group were signifi-cantly lower than those of the control group(P<0.01;the tenderness threshold of the two groups was significantly reduced after opera-tion(P<0.05,P<0.01,and the treatment group was better than the control group(P<0.05;the incidence of nausea during opera-tion,abdominal distension and nausea 48 h after operation in the treatment group were better than those in the control group(P<0.05;the high-quality embryo rate in the treatment group was better than that in the control group(P<0.05.CONCLUSION Electroacupuncture at Hegu and Neiguan combined with indomethacin suppository can effectively assist in analgesia,and can reduce the incidence of adverse reactions during and after TUGOR to varying degrees,and may have certain advantages in improving the rate of high-quality embryos.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m 6A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m 6A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m 6A.

Polycythemia vera (PV) is a chronic clonal myeloproliferative disorder involving hematopoietic stem cells. This article provides a brief review of the mechanisms of erythroid abnormal amplification in PV, including the effects of JAK2 V617F and JAK2 Ex12 mutations on erythropoiesis and abnormal changes in non-specific regulation.

Cervical cancer is the fourth most common cancer among women worldwide,and several screen-ing methods are currently available,with DNA testing for human papillomavirus(HPV)considered to be the most effective technique compared to other screening methods.However,due to the lack of organized screen-ing programs and facilities in developing countries,effective screening of cervical cancer is difficult to imple-ment,thereby delaying disease prediction and contributing to the high incidence of cervical cancer.In order to improve cervical cancer screening coverage in women,a simple,time-saving and non-invasive screening method is needed.At present,more and more evidence supports the validity and practicability of self-sampling as an al-ternative method for primary HPV screening.In this paper,we reviewed the application progress of HPV self-sampling in cervical cancer screening from three aspects:vaginal self-collection,initial urine sample self-collec-tion and menstrual blood sample self-collection.

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.

Objective:To analyze the effect of comprehensive rehabilitation intervention on the physical functioning of frail elderly persons.Methods:A total of 318 frail elderly persons were randomly divided into a control group ( n=164) and an observation group ( n=154) to test different interventions. Propensity score matching was used to balance the baseline information between the two groups 1∶1. A total of 200 cases were successfully matched, with 100 cases in each group. Both groups received drug treatment and routine nursing, while the observation group was additionally provided with comprehensive rehabilitation. Before and after 4 weeks of the treatment, both groups were evaluated using visual analogue scale (VAS) scoring for their perception of pain intensity, hand grip strength, gait speed, 6-minute walking distance (6MWD), 5 sit-up time, and the timed up and go test (TUGT). Results:There were no significant differences between the groups in any of the measurements before the experiment. Afterward, all of the outcome measures except gait speed were significantly better among the experimental group than among the controls, on average.Conclusions:Comprehensive rehabilitation can relieve pain, improve the walking, handgrip strength and exercise endurance of the frail elderly.