With the global trend of delaying childbearing, the decline in female fertility has emerged as a critical public health concern. While previous research predominantly focused on ovarian failure, recent studies have revealed that endometrial aging and impaired endometrial receptivity are closely associated, serving as significant contributors to reproductive failures such as embryo implantation failure and recurrent miscarriage. This review aims to explore the impact of age-related and pathological endometrial epithelial cell senescence on the impairment of endometrial receptivity, with a focus on key factors including the senescence-associated secretory phenotype, oxidative stress, cellular-level alterations (e.g., abnormalities in cilia proportion and function), and the endometrial microenvironment. By elucidating the molecular mechanisms and signaling pathways underlying endometrial epithelial senescence, this review seeks to advance the development of effective interventions, offering novel therapeutic strategies to enhance endometrial receptivity and improve fertility outcomes among advanced-age women.

AIM:Regulatory T cells(Tregs)are a specialized subset of CD4+T cells primarily involved in im-munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen-tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un-explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1fl/fl)mice and Treg-specific AMPKα1 knockout mice(AMPKα1fl/flFoxp3cre mice).RESULTS:Compared to AMPKα1fl/fl mice,the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significant-ly reduced.Additionally,while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure,both its size and the ra-tio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduc-tion in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4+T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice.Importantly,the proportion of Siglec-F+CD11b+eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+T cells in peripheral blood,alongside a decrease in the proportion of mature CD8+T cells.Similar-ly,the proportion of CD4+T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice.In lymph nodes,the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1fl/fl mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3+T cell population,particularly the CD8+T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice,the percentage of CD4+T cells was markedly in-creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice.CONCLUSION:The populations of mature Tregs,CD8+T cells and eosinophils in various im-mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.

As one of the major diseases threatening human health,the early accurate diagnosis and localization of tumors are crucial for formulating effective treatment plans.In recent years,molecular probes(MPs)have made significant progress in the field of biological imaging.With advantages such as high sensitivity,high specificity,and non-invasiveness,they have become a research hotspot in the field of tumor diagnosis and treatment.This paper systematically reviews the applications of MPs in tumor diagnosis and treatment,covering their classifications(such as fluorescent,photoacoustic,chemiluminescent,bioluminescent,and multimodal probes),design strategies(including active/pas-sive targeting mechanisms and the synergistic construction of identification units,imaging units,signal conversion units and treatment units),as well as detection principles.It also focuses on elabo-rating the research progress of MPs based on enzymes,receptors,reactive substances,and tumor microenvironment.Meanwhile,this paper emphasizes the advantages of multifunctional integration and multimodal imaging,and analyzes the challenges faced by MPs in clinical translation(such as biocompatibility and optimization of supporting equipment).It aims to provide ideas for the develop-ment of high-performance MPs and promote the advancement of precise and personalized tumor di-agnosis and treatment.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

AIM:Regulatory T cells(Tregs)are a specialized subset of CD4+T cells primarily involved in im-munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen-tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un-explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1fl/fl)mice and Treg-specific AMPKα1 knockout mice(AMPKα1fl/flFoxp3cre mice).RESULTS:Compared to AMPKα1fl/fl mice,the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significant-ly reduced.Additionally,while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure,both its size and the ra-tio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduc-tion in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4+T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice.Importantly,the proportion of Siglec-F+CD11b+eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+T cells in peripheral blood,alongside a decrease in the proportion of mature CD8+T cells.Similar-ly,the proportion of CD4+T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice.In lymph nodes,the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1fl/fl mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3+T cell population,particularly the CD8+T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice,the percentage of CD4+T cells was markedly in-creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice.CONCLUSION:The populations of mature Tregs,CD8+T cells and eosinophils in various im-mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.

With the global trend of delaying childbearing, the decline in female fertility has emerged as a critical public health concern. While previous research predominantly focused on ovarian failure, recent studies have revealed that endometrial aging and impaired endometrial receptivity are closely associated, serving as significant contributors to reproductive failures such as embryo implantation failure and recurrent miscarriage. This review aims to explore the impact of age-related and pathological endometrial epithelial cell senescence on the impairment of endometrial receptivity, with a focus on key factors including the senescence-associated secretory phenotype, oxidative stress, cellular-level alterations (e.g., abnormalities in cilia proportion and function), and the endometrial microenvironment. By elucidating the molecular mechanisms and signaling pathways underlying endometrial epithelial senescence, this review seeks to advance the development of effective interventions, offering novel therapeutic strategies to enhance endometrial receptivity and improve fertility outcomes among advanced-age women.

As one of the major diseases threatening human health,the early accurate diagnosis and localization of tumors are crucial for formulating effective treatment plans.In recent years,molecular probes(MPs)have made significant progress in the field of biological imaging.With advantages such as high sensitivity,high specificity,and non-invasiveness,they have become a research hotspot in the field of tumor diagnosis and treatment.This paper systematically reviews the applications of MPs in tumor diagnosis and treatment,covering their classifications(such as fluorescent,photoacoustic,chemiluminescent,bioluminescent,and multimodal probes),design strategies(including active/pas-sive targeting mechanisms and the synergistic construction of identification units,imaging units,signal conversion units and treatment units),as well as detection principles.It also focuses on elabo-rating the research progress of MPs based on enzymes,receptors,reactive substances,and tumor microenvironment.Meanwhile,this paper emphasizes the advantages of multifunctional integration and multimodal imaging,and analyzes the challenges faced by MPs in clinical translation(such as biocompatibility and optimization of supporting equipment).It aims to provide ideas for the develop-ment of high-performance MPs and promote the advancement of precise and personalized tumor di-agnosis and treatment.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective:Ventricular septal defect(VSD)is a prevalent congenital cardiac anomaly.By enhancing the occluder design and optimizing procedural approaches,the indications for VSD closure can be broadened while minimizing associated complications.The utilization of fully biodegradable occluder holds promising potential in resolving conduction block issues encountered during VSD closure.This study aims to compare the results of the fully biodegradable occluder with the metal occluder in transoesophageal echocardiography-guided VSD closure via lower sternal level minor incision at the interim follow-up,and to find risk factors for the occurrence of electrocardiographic and valvular abnormalities postoperatively. Methods:We reviewed the postoperative and 3-year follow-up data of all patients who underwent the randomized controlled study of VSD closure from January 1 to November 7,2019 in the Second Xiangya Hospital of Central South University.The safety and efficacy of the procedure were assessed and compared between the 2 groups by electrocardiogram and echocardiography results,and the risk factors for the occurrence of postoperative electrocardiogram and valve abnormalities were studied with Logistic regression analysis. Results:Twelve and fifteen patients underwent VSD closure with the metallic occluder and the fully biodegradable occluder,respectively.All patients survived during the follow-up period without major complications such as atrioventricular block,significant residual shunt,too rapid absorption of the occluder,and significant valvular regurgitation.There were no significant differences in the results of electrocardiograph and color Doppler ultrasonography the metal occluder group and the fully biodegradable occluder group 1,2,and 3 years after operation(all P>0.05).The size of the occluder were risk factors for tricuspid regurgitation at 2 and 3 years postoperatively,and the difference between the occluder size and the VSD defect size were risk factors for tricuspid regurgitation at 2 years postoperatively(P<0.05). Conclusion:This study adequately demonstrates the safety and efficacy of fully biodegradable occluders in small VSD closure and shows the same postoperative effects as conventional nitinol occluders.

Objective: To explore the gene lifestyle interaction of ATP2B1-eNOS pathway gene polymorphisms on blood pressure. Methods: Using the convenient cluster sampling method, a total of 872 junior middle school students from 3 school in July to August 2019, were included in the final analysis. The survey included questionnaire investigation, anthropometry measurement and blood sample collection. After DNA was extracted from peripheral blood samples, the gene polymorphisms ( ATP2B1 gene rs 17249754 and rs 2070759, eNOS gene rs 1799983 and rs 2070744) were genotyped. Logistic regression model was used to analyze the association between gene polymorphism and blood pressure phenotypes. Results: The prevalence of high blood pressure was 9.52 % in adolescents(9.15% in boys and 9.87% in girls),with no significant sex difference ( χ 2=0.13, P =0.72). There were statistically significant differences between boys and girls in age, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) classification, birth weight, daily school physical exercise time and daily playing video games time ( P <0.05). Logistic regression analysis showed that, eNOS gene rs 2070744 polymorphism was associated with high blood pressure (HBP) under the recessive model, and the risk of HBP in CC genotype carriers were higher than that TT/TC genotype carriers ( OR=3.88, 95%CI =1.00-15.02, P < 0.05 ). The results of gene lifestyle interaction showed that ATP2B1 gene rs 2070759 polymorphism gene had an interaction with the time of physical exercise in school ( P interaction =0.05). In the subgroup with daily physical exercise time at sch ool ＜1 hour , the TT/TG genotype carriers were associated with increased risk of HBP compared with GG genotype carriers( OR= 2.65 , 95%CI =1.11-6.30, P <0.05). But in the subgroup with daily physical exercise time in school ≥1 hour, rs 2070759 was not significantly associated with HBP. Conclusion eNOS/rs 2070744 polymorphisms are associated with risk of HBP among adolescents. There is significant interaction between ATP2B1 gene rs 2070759 polymorphism and physical exercise time in school on HBP. Adolescents should spend more time on physical activity in school, which will help to maintain normal blood pressure level.