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.

Constructing an efficient and easy-to-operate multigene expression system is currently a crucial part of plant genetic engineering. In this study, a fragment carrying three independent gene expression cassettes and the expression unit of the gene-silencing suppressor protein(RNA silencing suppressor 19 kDa protein, P19) simultaneously was designed and constructed. This fragment was cloned into the commonly used plant expression vector pCAMBIA300, and the plasmid pC1300-TP2-P19 was obtained. Each gene expression cassette consists of different promoters, fusion tags, and terminators. The target gene can be flexibly inserted into the corresponding site through enzymatic digestion and ligation or recombination and fused with different protein tags, which provides great convenience for subsequent detection. The enhanced green fluorescent protein(eGFP) reporter gene was individually constructed into each expression cassette to verify the feasibility of this vector system. The results of tobacco transient expression and laser-confocal microscopy showed that each expression cassette presented independent and normal expression. Meanwhile, the three key enzyme genes in the betanin synthesis pathway, BvCYP76AD, BvDODA1, and DbDOPA5GT, were constructed into the three expression cassettes. The results of tobacco transient expression phenotype, protein immunoblotting(Western blot), and chemical detection of product demonstrated that the three exogenous genes were highly expressed, and the target compound betanin was successfully produced. The above results indicated that the constructed multigene expression system for plants in this study was efficient and reliable and can achieve the co-transformation of multiple plant genes. It can provide a reliable vector platform for the analysis of plant natural product synthesis pathways, functional verification, and plant metabolic engineering.
Nicotiana/metabolism* ; Genetic Vectors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Genetic Engineering/methods* ; Green Fluorescent Proteins/metabolism* ; Gene Expression

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

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.

Objective:To evaluate the long-term outcomes and prognostic factors of locally advanced gastric cancer with serosa-invasion.Methods:This study is a retrospective cohort study. The clinical and pathological data of 495 patients with locally advanced gastric cancer with serosa-invasion who underwent laparoscopic radical gastrectomy in Department of General Surgery, the First Hospital Affiliated to Army Medical University from October 2012 to October 2018 was analyzed retrospectively. There were 356 males and 139 females with an age ( M(IQR)) of 59 (16) years (range: 18 to 75 years). Observation indicators included postoperative results and long-term prognosis. The survival curve was drawn by the Kaplan-Meier method. Univariate and multivariate prognostic analysis was performed using the Cox proportional hazards model. Results:Among the 495 patients, a total of 57 patients (11.5%) were lost to follow-up, with a follow-up time of 89 (40) months (range: 23 to 134 months). The 5-year disease-free survival rate (DFS) and the 5-year overall survival rate (OS) were 56.0% and 58.2%, respectively. The 5-year DFS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 60.5%, 51.6%, 33.3%, respectively. The 5-year OS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 62.2%, 54.1%, 39.3%, respectively. Multivariate analysis showed that age >65 years (DFS: HR=1.402, 95% CI: 1.022 to 1.922, P=0.036; OS: HR=1.461, 95% CI: 1.057 to 2.019, P=0.022), lymph node dissection number less than 25 (DFS: HR=1.348, 95% CI: 1.019 to 1.779, P=0.036; OS: HR=1.376, 95% CI: 1.035 to 1.825, P=0.028), pathological stage Ⅲ (DFS: HR=2.131, 95% CI: 1.444 to 3.144, P<0.01; OS: HR=2.079, 95% CI: 1.406 to 3.074, P<0.01), and no postoperative chemotherapy (DFS: HR=3.127, 95% CI: 2.377 to 4.113, P<0.01; OS: HR=3.768, 95% CI: 2.828 to 5.020, P<0.01) were independent prognostic factors for the decrease in DFS and OS rates. Conclusions:Laparoscopic radical gastrectomy for locally advanced gastric cancer with serosa-invasion could achieve satisfactory long-term oncological outcomes. More lymph node dissection and standardized postoperative adjuvant chemotherapy are expected to further improve the prognosis of patients with locally advanced gastric cancer with serous invasion after laparoscopic radical surgery.

Objective:To evaluate the long-term outcomes and prognostic factors of locally advanced gastric cancer with serosa-invasion.Methods:This study is a retrospective cohort study. The clinical and pathological data of 495 patients with locally advanced gastric cancer with serosa-invasion who underwent laparoscopic radical gastrectomy in Department of General Surgery, the First Hospital Affiliated to Army Medical University from October 2012 to October 2018 was analyzed retrospectively. There were 356 males and 139 females with an age ( M(IQR)) of 59 (16) years (range: 18 to 75 years). Observation indicators included postoperative results and long-term prognosis. The survival curve was drawn by the Kaplan-Meier method. Univariate and multivariate prognostic analysis was performed using the Cox proportional hazards model. Results:Among the 495 patients, a total of 57 patients (11.5%) were lost to follow-up, with a follow-up time of 89 (40) months (range: 23 to 134 months). The 5-year disease-free survival rate (DFS) and the 5-year overall survival rate (OS) were 56.0% and 58.2%, respectively. The 5-year DFS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 60.5%, 51.6%, 33.3%, respectively. The 5-year OS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 62.2%, 54.1%, 39.3%, respectively. Multivariate analysis showed that age >65 years (DFS: HR=1.402, 95% CI: 1.022 to 1.922, P=0.036; OS: HR=1.461, 95% CI: 1.057 to 2.019, P=0.022), lymph node dissection number less than 25 (DFS: HR=1.348, 95% CI: 1.019 to 1.779, P=0.036; OS: HR=1.376, 95% CI: 1.035 to 1.825, P=0.028), pathological stage Ⅲ (DFS: HR=2.131, 95% CI: 1.444 to 3.144, P<0.01; OS: HR=2.079, 95% CI: 1.406 to 3.074, P<0.01), and no postoperative chemotherapy (DFS: HR=3.127, 95% CI: 2.377 to 4.113, P<0.01; OS: HR=3.768, 95% CI: 2.828 to 5.020, P<0.01) were independent prognostic factors for the decrease in DFS and OS rates. Conclusions:Laparoscopic radical gastrectomy for locally advanced gastric cancer with serosa-invasion could achieve satisfactory long-term oncological outcomes. More lymph node dissection and standardized postoperative adjuvant chemotherapy are expected to further improve the prognosis of patients with locally advanced gastric cancer with serous invasion after laparoscopic radical surgery.

Objective:To discuss the changes in the levels of chemokine ligand 19(CCL19)and soluble CD163(sCD163)in serum of the patients with systemic lupus erythematosus(SLE)during pregnancy,and to clarify their effects on the maternal and infant outcomes.Methods:A total of 180 pregnant SLE patients were selected as SLE group and then divided into successful pregnancy group(n=132)and pregnancy failure group(n=48)based on the maternal and infant outcomes.A total of 180 healthy pregnant women underwent prenatal checks during the same period were randomly selected as control group.The general data of the patients in two groups were collected,and the serum levels of CCL19 and sCD163,along with related serum factors,were detected by kits.Multivariate Logistic regression analysis was used to detect the risk factors for pregnancy failure in the SLE patients,and receiver operating characteristic(ROC)curve was used to evaluate the effectiveness of serum CCL19 and sCD163 levels in predicting the pregnancy outcomes of the patients in SLE group.Results:Compared with control group,the levels of complements C3 and C4 in the serum of the patients in SLE group were significantly decreased(P<0.05),and the levels of erythrocyte sedimentation rate(ESR),creatinine(CR),anti-cardiolipin antibody(ACA)-IgG,anti-β2 glycoprotein Ⅰ(anti-β2GPⅠ),CCL19,and sCD163 of the patients were significantly increased(P<0.01).Compared with successful pregnancy group,the levels of complement C3 and C4 pregnancy of the patients in failure group were significantly decreased(P<0.01),and the levels of ESR,CR,ACA-IgG,anti-β2GPⅠ,CCL19,and sCD163 were significantly increased(P<0.01).The serum levels of CCL19,sCD163,ESR,CR,ACA-IgG,and anti-β2GPⅠ were the risk factors for pregnancy failure of the SLE patients(P<0.05 or P<0.01),while the levels of complement C3 and C4 were the protective factors(P<0.01).The area under the ROC curve(AUC)of the serum CCL19 level for predicting the pregnancy failure of the SLE patients was 0.726,and the AUC of serum SCD163 level for predicting the pregnancy failure of the SLE patients was 0.789;the AUC of combination of both markers for predicting the pregnancy failure of the SLE patients was 0.835.The predictive performance of CCL19 and sCD163 for pregnancy outcomes of the SLE patients was superior to either marker alone(Zcombined-CCL19=3.066,P=0.002;Zcombined-sCD163=2.087,P=0.037).Conclusion:The serum levels of CCL19 and sCD163 in the SLE patients during pregnancy are significantly increased,which may cause the poor outcomes in the patients.

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 develop a portable field infusion kit for first aid to meet the treatment requirements in field conditions.Methods The infusion kit had its frame made of third-generation carbon fiber material and was composed of a lid and a body.The lid was equipped with embedded handles on the outer surface,a medicine module consisting of 12 mesh bags on the inner surface and LED lights on the inner and outer front side walls.The kit body had three storage layers in its upper,middle and lower parts,of which the upper layer was for supplies of infusion and hemostatic dressing,the middle layer was for medical instruments and soft bags of liquid for first aid,and the lower layer was for medical waste and sharp instruments,and the bottom of the kit was provided with telescopic drawbars and invisible rollers.Results The first-aid infusion kit facilitated the storage and utilization of kinds of infusion supplies,and lowered time consumption and workloads for transport.Conclusion The first-aid infusion kit gains advantages in reasonable layout,comprehensive functions and convenient operation,and thus is worhty promoting for casualty treatment in field conditions.[Chinese Medical Equipment Journal,2024,45(7):115-117]

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.