BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

OBJECTIVES: To explore the toxic mechanism of Clostridium perfringens Beta1 toxin mediated by P2X7 receptor-induced calcium dyshomeostasis. METHODS: Ten-day-old BALB/c mice were randomly divided into control group, recombinant Beta1 toxin (rCPB1) group, PD151746 group, and PD151746+rCPB1 group, and all the treatment agents were administered by gavage. The changes in expressions of inflammatory factors in the jejunum of the mice were detected using antibody chip technology to explore the regulatory role of calcium dyshomeostasis in Beta1 toxin-induced inflammatory injury level. In the cell experiment, THP-1 cells were transfected with a si-RNA targeting P2X7 receptor and treated with rCPB1, and the changes in cell survival rate, levels of Ca²⁺, ROS and ATP, and expressions of pyroptosis and ferroptosis markers were determined. RESULTS: Oral administration of rCPB1 significantly increased the levels of inflammatory cytokines in the jejunal tissue of the neonatal mice, but their levels were significantly decreased after treatment with PD151746. In THP-1 cells, rCPB1 treatment significantly decreased cell survival and increased the levels of Ca²⁺, ROS, ATP and the expressions of pyroptosis and ferroptosis markers, and these changes were obviously attenuated by P2X7 receptor knockdown. CONCLUSIONS P2X7 receptor-mediated functional pore formation by Beta1 toxin can further lead to calcium dyshomeostasis, thereby triggering excessive accumulation of ROS to subsequently induce the co-occurrence of pyroptosis and ferroptosis.
Animals ; Pyroptosis/drug effects* ; Receptors, Purinergic P2X7/metabolism* ; Mice ; Mice, Inbred BALB C ; Ferroptosis/drug effects* ; Humans ; Calcium/metabolism* ; Macrophages/drug effects* ; Bacterial Toxins/toxicity*

Objective:To investigate the role of platelet-rich fibrin (PRF) membrane tamponade combined with silicone oil filling in the treatment of high myopia macular hole (HMMH) with retinal detachment (RD).Methods:A randomized controlled study was conducted.A total of 52 patients (52 eyes) with HMMH with RD were enrolled at the Eye Center, Renmin Hospital of Wuhan University from September 2021 to April 2023.The patients were randomly divided into three groups according to the random number table method.All patients in the three groups underwent standard three-channel 23-gauge pars plana vitrectomy.In the internal limiting membrane (ILM) peeling group including 18 cases (18 eyes), the ILM was peeled intraoperatively.In the ILM tamponade group including 16 cases (16 eyes), the ILM flap was inverted and filled into the macular hole (MH).In the PRF tamponade group including 18 cases (18 eyes), the MH was filled with PRF.Intraocular pressure measurement, best corrected visual acuity (BCVA) measurement, and central macular thickness (CMT) measured by optical coherence tomography were performed preoperatively and 1 week, 1 month, 3 months, and 6 months postoperatively.Superficial retinal vessel density (SVD) and deep retinal vessel density (DVD) were determined by optical coherence tomography angiography before surgery and 6 months after surgery.The efficacy of the procedure was determined at six months postoperatively, and the rates of MH closure and retinal reattachment were compared among the three groups.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.2022-1-X-53).Written informed consent was obtained from each subject before any medical examination.Results:At 6 months postoperatively, the MH closure rates in the ILM peeling, ILM tamponade, and PRF tamponade groups were 83.3%(15/18), 87.5%(14/16), and 94.4%(17/18), respectively, without significant differences among them (fit χ2=1.180, P>0.05).Furthermore, the retinas of all groups were reattached.The postoperative BCVA of ILM peeling, ILM tamponade, and PRF tamponade groups were elevated compared with before surgery, and the differences were statistically significant (all at P<0.05).At 6 months after surgery, the CMT of the PRF tamponade group was significantly thicker than that of the ILM peeling and ILM tamponade groups (both at P<0.05).The CMT of the three groups at different time points after surgery was significantly decreased compared with before surgery, with statistically significant differences (all at P<0.05).SVD and DVD of the three groups at 6 months postoperatively were higher compared with before surgery, with statistically significant differences (all at P<0.05).No serious complications such as endophthalmitis and vitreous haemorrhage occured during treatment and follow-up.Müller cell gliosis was observed in 4 eyes in the ILM tamponade group, and no Müller cell gliosis eyes were seen in the remaining two groups. Conclusions:PRF tamponade combined with silicone oil filling can promote MH healing and retinal reattachment, improve visual acuity and blood flow density in patients suffering from HMMH with RD, and is a safe and effective surgical procedure.

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases. Methods:The two-sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P＜5×10-8).Causal effect estimates were generated using the inverse-variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed. Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease(OR=1.444,95％CI 1.199 to 1.738,P＜0.001)and ulcerative colitis(OR=1.002,95％CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema. Conclusion:Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

In the context of high-quality development in medical institutions, the supply-processing-distribution(SPD) management mode has gradually been widely applied. The authors described in detail the procurement, supply, inventory, distribution, and settlement management of medical consumables and in vitro diagnostic reagents in a certain hospital under the SPD mode. It was found that SPD was conducive to strengthening the supervision of medical consumables and in vitro diagnostic reagents in the hospital, ensuring quality and safety of use, reducing hospital operating costs, and improving hospital′s competitiveness. However, attention should be paid to preventing data security risks, strengthening operational management, and improving the cost-benefit analysis of in vitro diagnostic reagents.

Objective To explore the dynamics of carers'caregiving dilemmas during different stages of disease progression in patients with diabetic foot ulcers,and to provide a basis for giving precise intervention strategies.Methods Based on the theory of Timing It Right,the phenomenological study was adopted.A purposive sampling method was used to select carers of patients with diabetic foot ulcers who were hospitalised in the Wound Repair Unit of a tertiary hospital in Beijing from March 2023 to February 2024 to conduct semi-structured interviews,and the data were analysed using the Colaizzi 7-step analysis method.Results Combined with the theory of Timing It Right,5 stages of diabetic foot ulcer development were formed,and 5 themes were extracted(①diagnostic period:mixed emotions,facing the dilemma of being unable to do anything;②therapeutic period:lack of knowledge of the disease,and the difficulties of bedside care;③recovery period:contradictions of the desire for rapid healing and the lack of caregiving ability;④transition period:poor patient adherence,and the hope for professional support;⑤adaptation period:the accumulation of negative emotions,and the persistence of caregiving difficulties),and 12 sub-themes.Conclusion At different stages of disease development in patients with diabetic foot ulcers,the caregiving dilemma of caregivers changes dynamically,and healthcare professionals should provide professional,personalised,and high-quality professional support according to their caregiving experience and needs at different stages to improve their quality of care and promote patients'recovery.

Objective:To investigate the utility of 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-04 PET imaging in assessing the therapeutic response in pressure overload-induced heart failure. Methods:Rat models of pressure overload-induced heart failure were established by abdominal aortic constriction (AAC). Thirty rats were categorized into AAC group, 7 days reverse AAC (rAAC) group, and sham operation (sham) group ( n=10 per group) using completely random grouping method. All rats underwent 68Ga-FAPI-04 PET/CT imaging at 4 and 8 weeks after the ACC operation, while echocardiography, pathological examination, and immunohistochemical analysis were performed at 8 weeks postoperation. One-way analysis of variance, independent-sample t test and Pearson correlation analysis were used for data analysis. Results:68Ga-FAPI-04 PET/CT imaging showed that the target-to-background ratios of the heart and liver had significant differences among three groups both at 4 and 8 weeks postoperation ( F values: 2 547.12, 2 041.71, 462.65, 1 210.97, all P<0.001). Echocardiography revealed left ventricular ejection fraction (LVEF), left ventricular internal diameter at end-diastole (LVIDd), and left ventricular internal diameter at end-systole (LVIDs) in three groups at 8 weeks postoperation were significantly different ( F values: 118.92, 9.11, 10.63, all P<0.01). Rats were sacrificed at 8 weeks postoperation, and Masson staining showed that the fibrosis in the heart and liver of the rAAC group was significantly improved compared with that of the AAC group, and immunohistochemical analysis revealed significantly lower FAP levels in the heart and liver of the rAAC group compared with those of the AAC group ( t values: from -11.27 to -4.16, all P<0.01). FAPI uptake in the heart of the AAC group and rAAC group at 8 weeks postoperation were significantly positively correlated with FAPI uptake in the liver, LVIDd and LVIDs, FAPI uptake in the heart was significantly negatively correlated with LVEF, and FAPI uptake in the heart and liver were significantly positively correlated with fibrosis degree and FAP levels of corresponding organs ( r values: -0.89, -0.88, 0.72-0.97, all P<0.05). Conclusions:68Ga-FAPI-04 PET/CT can show the improvement process of cardio-liver fibrosis following the unloading of excessive pressure in heart failure. Myocardial FAPI uptake is closely related to the extent of heart failure improvement.

The integration of ideological and political education into medical courses is an important part of China's medical education reform in the new era.The construction of ideological and political education in clinical research curriculum is of great significance for the cultivation of clinical research talents with both ability and political integrity.Based on the clinical research curriculum offered by the Second Clinical College of Wuhan University,this paper introduced the necessity of ideological and political curriculum in clinical research curriculum.Through the learning situation analysis of the eight-year program students majoring in clinical medicine,the ideological and political teaching objectives were formulated,and the ideological and political elements and cases were selected in combination with the teaching content of clinical research curriculum.Combined with the characteristics of the medical professional methodology course,the diversified,innovative student-centered teaching methods were designed integrating the theoretical teaching,flipped classroom,scenario simulation teaching,problem-based learning,case-based learning and team based learning,and added the consideration of moral education dimension in the teaching evaluation,to carry out the ideological and political teaching design of clinical research curriculum.These measures promoted the organic integration of knowledge teaching,ability training and value building,and provided reference for the ideological and political education in clinical research curriculum.

OBJECTIVES: To investigate the synergistic inhibitory effects of AKBA and doxorubicin on malignant phenotype of triple-negative breast cancer (TNBC) MDA-MB-231 cells. METHODS: CCK-8 assay was used to determine the 48-h IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells, and SynergyFinder was employed to calculate the synergistic index and the optimal concentrations of the two agents. MDA-MB-231 cells treated with AKBA (22.5 μmol/L), doxorubicin (0.84 μmol/L) or their combination were examined for changes in cell proliferation, migration, invasion and apoptosis using Transwell migration, scratch assay, clone generation, RT-qPCR and Western blotting. Network pharmacology analysis was conducted to identify the downstream targets of AKBA in TNBC. In nude mouse models bearing subcutaneous MDA-MB-231 cell xenografts, the effects of normal saline, AKBA (50 mg/kg), doxorubicin (2.5 mg/kg), and AKBA combined with doxorubicin on xenograft growth and histopathology were observed. RESULTS: The IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells at 48 h was 45.15±0.97 μmol/L and 0.42±0.99 μmol/L, respectively. SynergyFinder confirmed the synergistic effect of AKBA and ADR with a ZIP>10. The combined treatment with AKBA and doxorubicin significantly inhibited the proliferation, migration and invasion, promoted apoptosis of MDA-MB-231 cells, and effectively suppressed xenograft growth in nude mice. Network pharmacology analysis predicted that AKBA affects the progression of TNBC through its downstream target AKBA. CONCLUSIONS AKBA combined with doxorubicin inhibits proliferation, migration and invasion, promotes apoptosis of MDA-MB-231 cells and suppresses MDA-MB-231 cell xenograft growth in nude mice. The combined use of AKBA can attenuate the toxic effects of doxorubicin in nude mice.
Animals ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/pathology* ; Mice, Nude ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Humans ; Female ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Drug Synergism ; MDA-MB-231 Cells