The hypothalamic-pituitary-gonadal (HPG) axis is the central neuroendocrine regulator of vertebrate reproduction, governing sexual maturation, reproductive function, and endocrine homeostasis through multilevel hormonal cascades. It is also a sensitive target for environmental endocrine disruptors. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons and pituitary gonadotropes are located upstream of the HPG axis, and are indispensable for reproductive and endocrine functions. Agrochemicals represent a major class of endocrine-disrupting chemicals capable of interfering with GnRH pulsatility as well as the synthesis and release of gonadotropins through multiple pathways. This review summarized recent epidemiological and toxicological evidence concerning the effects of insecticides, herbicides, fungicides and plant growth regulators on hypothalamic GnRH neuron-pituitary gonadotropes. It surveyed the evidence linking agrochemicals exposure to abnormalities in hypothalamic GnRH pulsatility and disturbances in gonadotropin synthesis and secretion, and further examined the roles of key pathways such as the Kisspeptin/G protein-coupled receptor 54 system, neurotransmitters and signaling molecules, ion channels, as well as oxidative stress and inflammatory responses. Current research remains largely confined to insecticides, with significant limitations in simulating real-world exposure complexity and systematically elucidating underlying toxic mechanisms. Future studies should expand to other agrochemicals classes and integrate emerging approaches such as multi-omics and computational toxicology to systematically identify the integrated mechanisms disrupting upstream HPG axis functions. Such efforts will provide more comprehensive scientific evidence for assessing the reproductive toxicity of agrochemicals.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

BACKGROUND:Adipose-derived stem cells have anti-aging effects,but whether adipose-derived stem cells from donors of different ages are different needs further study. OBJECTIVE:To compare the biological properties of adipose-derived stem cells in old and young mice. METHODS:Adipose-derived stem cells were extracted from adipose tissue of C57BL mice aged 8 and 14 weeks,respectively.The differences of cell cycle,apoptosis,and proliferation of adipose-derived stem cells in old and young mice were compared.The expression levels of aging-related P21 and P27 genes and proteins of adipose-derived stem cells in old and young mice were detected by quantitative PCR and western blot assay. RESULTS AND CONCLUSION:Compared with old mouse adipose-derived stem cells,young mouse adipose-derived stem cells were more active,more regular in morphology,less apoptosis,faster proliferation,and lower in expression of age-related P21 and P27 genes and proteins.It has been proven that adipose-derived stem cells from young mice have better anti-aging effects.

Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 in-flammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the met-formin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson stai-ning was performed to observe the morphology and fi-brosis of myocardial tissue.TUNEL staining was per-formed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP and β-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleaved-caspase-1,GSDMD and GSDMD-NT in myocardial tis-sue.Results DJC could alleviate myocardial patho-logical damage,reduce collagen deposition and apopto-sis,reduce the levels of blood glucose,blood lipid,myo-cardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP and β-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,prob-ably by inhibiting the activation of NLRP3 inflamma-somes,attenuating cardiomyocyte pyroptosis,and amel-iorating the inflammatory state.

BACKGROUND:As an emerging treatment method,stem cell therapy is expected to improve the ovarian environment,delays the aging of ovarian granulosa cells,and brings new hope to older pregnant women.OBJECTIVE:To review the mechanism and research progress of stem cells against ovarian granulosa cell senescence.METHODS:CNKI and PubMed databases were retrieved for articles on stem cell therapy for ovarian granulosa cell senescence.Chinese and English search terms were"stem cells,ovary granulosa cells,aging."Finally,67 articles were included for analysis.RESULTS AND CONCLUSION:(1)This review summarizes five mechanisms of ovarian granulosa cell senescence:DNA damage and decreased repair capacity,oxidative stress,impaired mitochondrial function,inflammatory response,and changes in hormone levels.(2)This article summarizes five main mechanisms of stem cells in the treatment of ovarian granulosa cell senescence:promoting proliferation and inhibiting apoptosis,differentiation potential and regeneration ability,secreting factors,anti-oxidation,anti-inflammatory response,and immune regulation.(3)At present,there are various types of stem cells that can cooperate to treat ovarian granulosa cell senescence through a variety of ways,and stem cell therapy has broad prospects in restoring female fertility.

BACKGROUND:With the increase of age,the function of bone marrow-derived mesenchymal stem cells is gradually reduced,and delaying the aging of bone marrow-derived mesenchymal stem cells itself has become an important topic.OBJECTIVE:To explore ways to delay the aging of bone marrow-derived mesenchymal stem cells by changing the expression of telomerase Cajal body protein 1(TCAB1)gene.METHODS:Mouse bone marrow-derived mesenchymal stem cells were cultured by cell adhesion method.TCAB1 gene in bone marrow-derived mesenchymal stem cells was overexpressed and interfered by recombinant lentivirus technique.The expression of aging related genes P16,P21,P53,and P27 was detected by qPCR.The relative length of telomeres was detected by qPCR.The expression of aging proteins P16,P21,P53,and P27 was detected by western blot assay.Cell proliferation was detected by CCK-8 assay.Annexin V-PE/7-AAD apoptosis kit was used to detect the degree of cell apoptosis.RESULTS AND CONCLUSION:Bone marrow-derived mesenchymal stem cell lines overexpressing TCAB1 gene had decreased expression of senescence related genes and proteins,increased Telomere relative length,stronger cell proliferation,less apoptosis,and a youthful state.The expression of age-related genes and proteins in bone marrow mesenchymal stem cells interfering with TCAB1 gene increased,and the relative telomere length decreased;cell proliferation ability was weak;cell apoptosis was more,and cells showed senescence.These results indicate that increasing the expression of TCAB1 in an appropriate range can delay the rate of cell senescence.

Objective To explore the clinical characteristics of the patients with follicular cysts and menstrual disorders.Methods A total of 178 women with follicular cysts complicated by menstrual disorders were recruited,who were aged 23-53(38.62±6.35)years and came to the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital between August 2022 and July 2024.The participants were divided into three groups according to the age,with 27 women in the age group of 21-30 years(Group 1),77 in the age group of 31-40 years(Group 2),and 74 in the age group of>40 years(Group 3).The age and menstruation of these patients were collected,the body height,weight,follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),progesterone(Po),total testosterone(TT),prolactin(PRL),anti-müllerian hormone(AMH)and thyroid function[blood routine and blood clotting for patients with abnormal uterine bleeding(AUB)]were measured,and the diameter of ovarian cyst and the thickness of endometrium were examined.The clinical characteristics of the patients with follicular cysts complicated by menstrual disorders were described and compared with each other among the three age groups.Results ① Among 178 patients,61(34.3%)patients presented with complaints of cessation of regular menstruation or amenorrhea and 117(65.7%)with complaints of AUB.Out of 178 patients,13(7.3%)patients developed anemia due to AUB,and all the patients were treated with medication.② Follicular cysts disappeared in 1 month for 124(69.7%)patients,disappeared in 2 months for 176(98.9%)patients,and disappeared in 3 months for 178(100%)patients.A total of 177(99.4%)patients had follicular cysts with a diameter less than 5 cm,and only 1(0.6%)patient had follicular cysts with a diameter≥5 cm.③ The overall prevalence of diminished ovarian reserve(DOR)in patients with follicular cysts complicated by menstrual disorders was 82.0%,and the prevalence of DOR was 70.2%for the patients under 40 years old.The prevalence of DOR in three age groups was 37.0%(10/27),81.8%(63/77),and 98.6%(73/74),respectively.The prevalence of DOR gradually increased with age.④ The median AMH values for Group 1,Group 2,and Group 3 were 1.55,0.51,and 0.15 ng/mL,respectively.The FSH level in Group 3 was significantly higher than that in Groups 1 and 2(adjusted P<0.05),while the AMH level was significantly lower than that in Groups 1 and 2(adjusted P<0.05).The AMH level in Group 2 was lower than that in Group 1(adjusted P<0.05).Conclusion Patients with follicular cysts complicated by menstrual disorders are recommended to receive medication treatment,rather than just expecting treatment.The prevalence of DOR in patients with follicular cysts complicated by menstrual disorders is significantly higher than that in normal women,even in women younger than 40 years old.Therefore,it is essential to evaluate the ovarian reserve of these patients while treating menstrual disorders,particularly for young women with fertility needs.

Objective To explore the correlation between thyroid autoimmunity(TAI)and gestational diabetes mellitus(GDM)in Chinese euthyroid women.Methods A total of 508 euthyroid women were enrolled in the cross-sectional study,who performed their entire clinical/biological workup and oral glucose tolerance test(OGTT)from the department of Gynecology and Endocrinology of the Beijing Obstetrics and Gynecology Hospital,Capital Medical University from June 2023 to June 2024.At median 8(6-10)weeks of gestation,thyroid-stimulating hormone(TSH),free thyroxine(fT4),and thyroid peroxidase antibodies(TPOAb)were measured,baseline characteristics were recorded,and an OGTT was performed between 24 and 28 weeks of pregnancy.According to the OGTT results,they were divided into GDM group(n=169)and non GDM group(n=339).Thyroid parameters,the demographic and obstetric parameters,and the prevalence of TAI were compared with two groups.The factors associated with GDM were analyzed with multivariate Logistic regression analysis.Results The age,body mass index(BMI),and proportion of obese women before pregnancy in the GDM group were all significantly higher than those in the non-GDM group,with statistically significant differences(P<0.001).The proportion of pregnant women over 30 years old in the GDM group was significantly higher than that in the non-GDM group(59.17%vs 6.79%,χ2=168.667,P<0.001).The proportion of obese mothers(BMI≥28 kg/m2)before pregnancy in the GDM group was 24.26%,which was significantly higher than that in the non-GDM group(8.26%)(χ2=24.599,P<0.001).The incidence of TAI in the GDM group was 54.44%,while it was 15.93%in the non-GDM group.The difference between the two groups was statistically significant(χ2=81.659,P<0.001).The results of Logistic regression analysis showed that maternal age over 30 years and pre-pregnancy obesity increased the risk of GDM occurrence in TAI women by 6.08 times(OR=6.08,95%CI 3.61-10.25,P<.001).Conclusion Among early pregnancy women with normal thyroid function,as age increases during follow-up(especially over 30 years old),pre-pregnancy BMI increases(especially in obese individuals),and those with pre-pregnancy TAI,the risk of developing GDM during pregnancy significantly increases.It is necessary to explore preventive strategies for GDM in euthyroid TAI women,with a view to improving adverse pregnancy outcomes.

Objective To compare ovulation recovery rate and metabolic indicators between ethinyl-estradiol/drospirenone(EE/DRSP)combined with orlistat and EE/DRSP alone in overweight/obese patients with polycystic ovary syndrome(PCOS).Methods This study was a randomized controlled clinical trial conducted based on the 2004 Rotterdam criteria.From October 2020 to December 2023,180 overweight/obese PCOS patients aged 20-40 were recruited from the Department of Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients were randomly divided into two groups in a 1∶2 ratio.Among them,60 patients received treatment with EE/DRSP(EE20 μg,DRSP 3 mg),while 120 patients received a combination treatment of EE/DRSP and orlistat(360 mg/d).The height,weight,waist circumference,hip circumference,and blood pressure of the patients were measured before treatment and after 12 weeks of treatment.Laboratory tests included measurements of follicle-stimulating hormone(FSH),luteinizing hormone(LH),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),free androgen index(FAI),alanine transaminase(ALT),aspartate transaminase(AST),gamma-glutamyl transferase(GGT),fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),lipoprotein(a)[Lp(a)],sex hormone-binding globulin(SHBG),total testosterone(T),and free testosterone(FT).After 12 weeks of treatment,the medication was discontinued,and natural ovulation was observed.Results After 12 weeks of treatment,the ovulation rate of the EE/DRSP combined with orlistat group reached 70.8%,while the natural ovulation rate of the EE/DRSP group alone was only 35%,indicating that the ovulation rate was significantly increased after EE/DRSP combined with orlistat treatment.After 12 weeks of treatment,both groups showed a significant decrease in total testosterone,free testosterone,and low-density lipoprotein levels(all P<0.05),and the decrease in BMI,waist circumference,fasting insulin,and HOMA-IR in the EE/DRSP combined with orlistat group was greater than that in the EE/DRSP group alone(P<0.05).After treatment,both groups showed a significant increase in high-density lipoprotein and triglyceride levels(all P<0.05),with no significant changes in total cholesterol and fasting blood glucose(all P>0.05).Conclusion After 12 weeks of treatment,EE/DRSP combined with orlistat can significantly improve the ovulation rate of PCOS patients.It is superior to EE/DRSP alone in reducing androgen levels,body weight,insulin resistance,and low-density lipoprotein levels.

Objective To investigate the effect of individualized lifestyle intervention on sexual function in obese patients with polycystic ovarian syndrome(PCOS).Methods The study was conducted on obese patients with PCOS in the Department of Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University from October 2022 to December 2023.There were 160 cases in both the experimental group and the control group,progesterone was administered to both groups for 3 months to regulate menstruation.For women in the experimental group received individualized comprehensive lifestyle intervention combining diet,exercise,and behavior modifications,along with dedicated follow-up and weight management.The control group received routine clinical education for lifestyle intervention aimed at weight loss.Female Sexual Function Index(FSFI)and 12-item Short-Form Health Survey(SF-12)scale were applied to evaluate the sexual function and quality of life.The clinical data that may affect sexual function were collected and sex hormone levels were measured,including anthropometric indicators,estradiol,sex hormone-binding globulin,total testosterone,bioactive testosterone,and dehydroepiandrosterone sulfate in serum.Results After 3 months of intervention,the body mass index,waist circumference,body fat percentage,insulin resistance index,total testosterone,bioactive testosterone and dehydroepiandrosterone sulfate in experimental groups were significantly lower(P<0.05),and the sex hormone binding globulin level was significantly higher(P<0.001),compared with the control group.SF-12 mental health scores,FSFI total scores,sexual desire,orgasm and sexual satisfaction scores were significantly increased in experimental groups(P<0.05),however,there were no significant differences in SF-12 physical health scores,as well as the scores of sexual arousal,vaginal lubrication,and coital pain.Conclusions Individualized lifestyle intervention can better improve the sexual function and mental health of obese patients with PCOS.