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.

OBJECTIVES: With the accelerating aging of the population and the rising prevalence of chronic diseases, the number of patients with pressure injuries (PIs) has increased markedly, prolonging the period of disease-related care. Informal caregivers play a critical role in the daily care of patients with pressure injuries, and their care burden has become increasingly prominent. This study aims to investigate the current status and influencing factors of care burden among informal caregivers of patients with PIs, providing evidence for targeted intervention strategies. METHODS: A total of 170 informal caregivers of patients with PIs were selected by convenience sampling from the Third Xiangya Hospital of Central South University. General demographic and clinical data of both patients and caregivers were collected. The Zarit Caregiver Burden Inventory (ZBI), Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, General Self-Efficacy Scale (GSES), and Family Caregiver Task Inventory (FCTI) were used to assess caregiving burden, knowledge-attitude-practice level, self-efficacy, and caregiving ability, respectively. Pearson correlation analysis was conducted to evaluate relationships among ZBI, Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, GSES, and FCTI scores. Stepwise multiple linear regression analysis was used to identify factors influencing caregiving. RESULTS: Among the 170 patients with pressure injuries, the age was (65.52±15.88) years; 118 (69.41%) were male and 52 (30.59%) were female. The duration of PIs was less than 1 month in 108 (63.53%) cases and 1 to 6 months in 40 cases (23.53%). Stage II injuries were predominant (135 cases, 79.41%). A total of 193 pressure injury sites were recorded, most commonly located at the sacrococcygeal region (127 sites, 65.80%), followed by the head (3 sites, 1.55%), shoulder and back (9 sites, 4.66%), feet (24 sites, 12.44%), and other regions (30 sites, 15.55%). Informal caregivers were 48.82% aged 46 to 59 years, 54.71% female, 41.77% primarily spouses and 47.06% children of the patients, and 77.06% lived with the patients. Caregivers who received assistance from others or had higher family per-capita monthly income reported significantly lower caregiver burden scores than those without assistance or with lower income (all P<0.001). The total ZBI score was 50.89±14.95, indicating a moderate burden. The total scores of the Knowledge-Attitude-Practice Scale for Informal Caregivers, GSES, and FCTI were 50.61±7.22, 26.03±7.11, and 14.76±8.70, respectively. Pearson correlation analysis revealed that ZBI scores were correlated with scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs (r=-0.543, P<0.001), GSES scores (r=-0.545, P<0.001), and FCTI scores (r=0.800, P<0.001). The scores on Knowledge-Attitude-Practice Scale for Informal Caregivers of patients with PIs were correlated with GSES scores (r=0.500, P<0.001) and FCTI scores (r=-0.461, P<0.001); GSES scores was negatively correlated with FCTI scores (r=-0.415, P<0.001). Stepwise multiple linear regression analysis showed that assistance availability, family per-capita monthly income, total scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, total GSES score, and total FCTI score were the main influencing factors of caregiver burden, jointly explaining 79.38% of its variance. CONCLUSIONS The main factors influencing the caregiving burden of informal caregivers of patients with PIs include the availability of assistance, family per-capita monthly income, total score on the Knowledge-Attitude-Practice Scale for Informal Caregivers of PI patients, total score on the GSES, and total score on the FCTI. Developing targeted intervention strategies addressing these factors may help alleviate the caregiving burden among informal caregivers of patients with PIs.
Humans ; Caregivers/psychology* ; Pressure Ulcer/nursing* ; Female ; Male ; Middle Aged ; Cost of Illness ; Adult ; Aged ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice ; Self Efficacy ; Caregiver Burden ; China

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans ; High-Throughput Nucleotide Sequencing ; Metagenomics ; Rickettsia/isolation & purification* ; Spotted Fever Group Rickettsiosis/microbiology*

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.

Objective:To establish a practical patient-based internal quality control method for valproic acid drug concentration monitoring.Methods:Observational Study. A PBRTQC model based on the exponentially weighted moving average (EWMA) method was established using Python. All results of a total of 28, 757 valproic acid concentration data from February 1, 2023 to January 31, 2024 were collected and split into training set and validation set at a ratio of 80% and 20% respectively. The truncation limit (TL) was optimized by using the winsorized mean method and the trimmed mean method. Different weighting coefficients λ were set. Different TL and different λ were combined with the EWMA algorithm into different patient-based real-time quality control (PBRTQC) models. The optimized models were verified by introducing simulated constant errors (CE) and proportional errors (PE) respectively. The false positive alarm rate (FAR) was used to evaluate specificity, and the average number of patients before error detection (ANPed) was used to evaluate sensitivity. According to the daily test volume and quality target requirements, we comprehensively judged whether the performance evaluation indicators of FAR and ANPed meet the laboratory requirements. Bias detection curve was used for determination of the best model.Results:The parameters of the best PBRTQC model for valproic acid drug concentration monitoring are: trimmed mean method with 1.5 standard deviations (i.e., truncating data outside 1.5 standard deviations of the data mean), λ=0.01. The performance verification result shows that ANPed of CE and PE of this model are both less than 100. The comparison between the EQA results and the EWMA results show that the EWMA method results are comparable to the EQA results.Conclusion:A PBRTQC model for the valproic acid drug concentration monitoring project based on the EWMA method has been successfully established. It is comparable with both IQC and EQA results, which means PBRTQC may be used as a supplement to the quality control of daily quality control products.

Objective To analyze risk factors of acute cardio-cerebrovascular accidents in elderly patients with lower extremity fracture,and to construct a risk prediction diagram model.Methods A retrospective analysis was conducted on the clinical data of 510 elderly patients with lower extremity fractures,and the patients were divided into the occurrence group and the non-occurrence group based on the occurrence of acute cardiovascular and cerebrovascular accidents during the postoperative hospitalization.Univariate and multivariate Logistic regression analysis was used to analyze risk factors affecting acute cardiovascular and cerebrovascular accidents in elderly patients with lower extremity fracture,and the risk prediction model was constructed and verified.Results A total of 52 cases of acute cardio-cerebrovascular accidents occurred during hospitalization in 510 patients(10.20%).Age,ASA grade Ⅲ ratio,preoperative concurrent cerebrovascular disease,postoperative pneumonia ratio and postoperative bed time≥5 days ratio were higher in the occurrence group than those in the non-occurrence group(P＜0.05).Multivariate Logistic regression analysis showed that age,ASA grade Ⅲ,preoperative concurrent cardiovascular and cerebrovascular disease,and postoperative pneumonia were risk factors for acute cardio-cerebrovascular accidents in elderly patients with lower limb fracture(P＜0.05).Multivariate Logistic regression analysis was used to screen risk factors as predictive variables to build a risk early warning histogram model for acute cardio-cerebrovascular accidents.The total score ranged from 103 to 168 points,corresponding to a risk range of 0.1 to 0.9 points.Receiver operating characteristic curve(ROC)curve results showed that the area under the curve(AUC)of this model for predicting acute cardiovascular and cerebrovascular accidents was 0.980(95%CI:0.964-1.000),and discrete choice approach(DCA)showed that when the risk threshold was 0.2-0.6,the prediction model of this column graph had a good clinical advantage.Conclusion The risk diagram model constructed based on risk factors has good predictive value for the occurrence of acute cardio-cerebrovascular accidents after lower extremity fracture in elderly patients.

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.