Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury.Methods From January 2016 to December 2020,the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed,includ-ing 35 males and 22 females,aged from 18 to 47 years old with an average of(32.9±7.9)years old.Knee function was evaluat-ed using the International Knee Documentation Committee(IKDC)and Lysholm scores both before the operation and at the fi-nal follow-up.Meniscus healing was evaluated according to the postoperative Barrett standard.Wound healing complications,such as vascular injury,nerve injury,and lower extremity venous thrombosis,were recorded.Results All 57 patients were fol-lowed up for 12 to 58 months with an average of(38.1±14.9)months.The incisions of the patients after the operation were all Grade A healing without infection,popliteal tendon injury,blood vessel injury,nerve injury and lower extremity venous throm-bosis.The IKDC score increased from(49.7±3.6)points preoperatively to(88.5±4.4)points in the final follow-up(P＜0.05).The Lysholm score increased from(48.8±4.9)points preoperatively to(91.9±3.9)points at the final follow-up(P＜0.05).At 3,6 months and 1 year after operation,according to Barrett's criteria,54 cases were clinically healed,the healing rate was 94.7％(54/57).Conclusion This study preliminarily confirmed that arthroscopic suture technique can result in clinical sta-bility through suture and fixation of the meniscus in the injured lateral popliteal tendon area.No adverse effects on knee joint function were found in the mid-term follow-up after the operation.

Objective To observe the effect of Baduanjin exercise on depression,sleep quality and life quality of patients with breast cancer in the rehabilitation period.Methods A total of 76 breast can-cer patients in postoperative rehabilitation were randomly divided into an intervention group of 38 with 2 dropping out,and a control group of 38 with 3 dropouts.Both groups received routine nursing and rehabilitation after breast cancer surgery,while the intervention group additionally practised Baduanjin for 6 weeks.The Beck Depression Inventory-Ⅱ(BDI-Ⅱ-C),Pittsburgh Sleep Quality Index(PSQI)and Quality of Life Questionnaire Core 30(EORTC QLQ-C30)were used to evaluate both groups be-fore,as well as 3 and 6 weeks after intervention.Results After 3-week intervention,the average BDI-Ⅱ-C score,the total PSQI score and the scores of all dimensions except for the hypnotic drug dimen-sion of the intervention group was significantly lower than before treatment(P<0.05),and the control group at the same time point(P<0.05),while the scores of physical,emotional,cognitive,social and role function in EORTC QLQ-C30 were significantly higher than the latter(P<0.05).Three weeks lat-er,the average BDI-Ⅱ-C score,the total PSQI score and the scores of all dimensions except for the hypnotic drug dimension of the intervention group was significantly lower than before treatment(P<0.05),and the control group at the same time point(P<0.05),while the various scores of EORTC QLQ-C30 were significantly higher than the latter(P<0.05).Compared with after 3-week intervention,after 6-week intervention,the average BDI-Ⅱ-C score,the total PSQI score and the scores of its all dimensions except for the sleep disorder dimension of the intervention group decreased significantly,while all dimension scores of EORTC QLQ-C30 except the cognitive function dimension increased sig-nificantly(P<0.05 for all).Conclusion Baduanjin is feasible in improving the sleep and life quality of patients in the rehabilitation period after breast cancer surgery,and relieving their depression.

Objective Based on the theory of Information-Knowledge-Attitude-Practice(IKAP),the reliability and validity of the discharge preparation scale for patients with diabetic foot(DF)was developed and tested,which is in accordance with the national conditions and disease characteristics of our country.Methods Based on the IKAP theoretical framework,articles were identified through literature analysis,qualitative interviews and Delphi method.After pre-investigation,a total of 483 patients with DF were selected from 3 general hospitals in Jiangxi province from June 2023 to February 2024.The items were screened by item analysis,and the reliability and validity were tested.Results The discharge preparation scale for patients with DF included 4 dimensions and 29 items.The Cronbach's α coefficient was 0.934;the scores of each dimension Cronbach's α coefficient ranged from 0.889 to 0.947;the overall split-half reliability was 0.966,and the split-half reliability of each dimension ranged from 0.901 to 0.952.A total of 4 common factors were extracted by exploratory factor analysis,and the cumulative contribution rate of variance was 68.074％.The x2/df value of confirmatory factor analysis was 1.906.The fitting fit of the model is suitable.The content validity was 0.973 at scale level and 0.875～1.000 at item level.Conclusion The reliability and validity of the discharge preparation scale for patients with DF are good,and it can be used as a tool to evaluate the discharge preparation for patients with DF.

Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.

Objective:To investigate the effects of naringin(NRG)on apoptosis,proliferation,migration and invasion of oral squa-mous cell carcinoma(OSCC)cells.Methods:NRG of 0,5,10,15,20,25 and 30 μmol/L was respectively used to treat OSCC CAL-27 cells,and CCK-8 assay was used to cell vitality.CAL-27 cells were divided into low,medium and high dose NRG groups(NRG-L,NRG-M and NRG-H),Compound C(AMPK inhibitor)group,NRG-H+Compound C group,and control group(NC group,normal cul-ture).Cell proliferation,apoptosis,migration and invasion were detected by CCK-8 assay,EdU staining,flow cytometry,scratch and Tr-answell assays.The expression of aspartate specific cysteine proteinase-3(Caspase-3),proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-2(MMP-2),MMP-9,p-AMPK,sirtuin 1(SIRT1)and acetylated NF-κB p65(Ac-NF-κB p65)was detected by Western blot.Results:5,10 and 20 μmol/L NRG was selected as the low,medium and high dose for the treatment of CAL-27 cells,re-spectively.Compared with NC group,in NRG-L,NRG-M and NRG-H groups EdU positive rate,scratch healing rate,A450 value,num-ber of invasive cells,the protein expression of PCNA,MMP-2,MMP-9 and Ac-NF-κB p65 in CAL-27 cells decreased,the apoptosis rate,and the protein of Caspase-3,p-AMPK,and SIRT1 increased(P＜0.05);in Compound C group EdU positive rate,scratch healing rate,A450 value,the number of invasive cells,the protein expression of PCNA,MMP-2,MMP-9 and Ac-NF-κB p65 in CAL-27 cells in-creased,apoptosis rate and the protein expression of Caspase-3,p-AMPK and SIRT1 decreased(P＜0.05).Compound C reversed the effects of high dose NRG on the proliferation,migration,apoptosis and invasion of CAL-27 cells.Conclusion:The inhibitory effects of NRG on proliferation,migration and invasion of CAL-27 cells and the promotion of apoptosis may be related to activation of AMPK and inhibition of NF-κB pathway.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.