BackgroundLow medication compliance among patients with severe mental disorders increases the disease burden on both the patients' families and the society. Medication adherence is influenced by numerous factors. Traditional methods such as Logistic regression struggle to quantify the importance of these factors. By introducing Extreme Gradient Boosting （XGBoost） combined with Shapley Additive Explanations （SHAP）， enables the quantification of the relative contribution weights of each factor， providing support for identifying the core influencing factors. ObjectiveTo explore the influencing factors of medication adherence among patients with severe mental disorders in Zhuhai， aiming to provide references for optimizing patient management strategies. MethodsExtract the data of patients with severe mental disorders who were registered on the mental health system platform in Zhuhai City from January 1， 2023 to March 31， 2025. A total of 9 329 patients were finally included for analysis. Influencing factors were screened using univariate analysis and multivariate logistic regression analysis， and an XGBoost model combined with the SHAP algorithm was constructed to quantify the importance of each influencing factor. ResultsAmong 9 329 patients， 8 446 demonstrated medication adherence， yielding an adherence rate of 90.53%. Multivariable analysis identified several risk factors significantly associated with medication non-adherence， being unmarried （OR=1.237， 95% CI： 1.019–1.502） or divorced （OR=1.389， 95% CI： 1.038–1.832）， a diagnosis of mental retardation with psychiatric disorders （OR=3.025， 95% CI： 2.402–3.796） or paranoid psychosis （OR=5.117， 95% CI： 3.086–8.299）， a disease duration of 2–4 years （OR=1.355， 95% CI： 1.085–1.696）， 4–6 years （OR=2.143， 95% CI： 1.671–2.747）， or >6 years （OR=1.681， 95% CI： 1.365–2.079）， lack of guardian subsidies （OR=1.412， 95% CI： 1.099–1.801）， absence of a disability certificate （OR=1.900， 95% CI： 1.588–2.282）， not being enrolled in care and support groups （OR=1.384， 95% CI： 1.183–1.617） or community services （OR=1.313， 95% CI： 1.042–1.645）， and not cohabiting with a guardian （OR=1.257， 95% CI： 1.048–1.501）. Conversely， the enrollment in special outpatient disease programs （OR=0.716， 95% CI： 0.609–0.842） and a family history of mental illness （OR=0.713， 95% CI： 0.503–0.982） were identified as protective factors. The XGBoost model exhibited robust predictive performance， with a sensitivity of 0.433， specificity of 0.944， accuracy of 0.891， Area Under the Curve （AUC） of 0.837， and F1 value of 0.449. Feature importance ranking indicated that the top three factors were disease duration， diagnosis， and the acquisition of disability certificates. ConclusionPolicy-based support （acquisition of disability certificates， special outpatient disease enrollment） and clinical disease characteristics （disease duration， diagnosis type） are key factors affecting medication adherence among patients with severe mental disorders in Zhuhai City. ［Funded by Zhuhai Medical Research Project （number， 2220009000281）］

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

Objective:To investigate the epidemiological characteristics and morbidity trends of hypertensive disorders of pregnancy (HDP) in Shenzhen, China.Methods:This study was a cross-sectional study. Data were based on the Shenzhen Birth Cohort. Pregnant women who gave birth from January 1, 2018 to March 31, 2023 were included. Incidence and change trends of HDP and its different pathological types were analyzed. The enrolled pregnant women were divided into the HDP group and the non-HDP group according to whether HDP occurred. General clinical data and pregnancy outcomes were collected from both groups. The incidence of adverse pregnancy outcomes among pregnant women with different pathological types of HDP was analyzed, and subgroup analyses were performed based on age and body mass index (BMI).Results:A total of 90 117 pregnant women were enrolled, aged (31.6±4.4) years. There were 4 117 cases in the HDP group and 86 000 in the non-HDP group. The overall incidence of HDP in the whole study population was 4.57% (4 117/90 117). From 2018—2023, the incidence of HDP in Shenzhen showed an increasing trend year by year, from 2.88% (523/18 155) to 7.04% (271/3 851). Specifically, the incidence of gestational hypertension increased from 0.93% (168/18 155) to 3.09% (119/3 851), the incidence of preeclampsia-eclampsia increased from 1.78% (323/18 155) to 3.17% (122/3 851), the incidence of chronic hypertension increased from 0.01% (1/18 155) to 0.42% (16/3 851), and the incidence of chronic hypertension with superimposed preeclampsia increased from 0.17% (31/18 155) to 0.36% (14/3 851). The age ((32.8±4.8) years vs. (31.5±4.3) years, P<0.05) and BMI in the first trimester ((23.37±3.77) kg/m 2 vs. (21.35±2.91) kg/m 2, P<0.05) of HDP group were higher than those of the non-HDP group. Subgroup analysis showed that the incidence of HDP in pregnant women aged≥50.0 years was the highest in all age subgroups (42.86% (6/14)). The incidence of HDP in pregnant women with BMI≥30.0 kg/m 2 in the first trimester was the highest among all BMI subgroups (20.44% (241/1 179)). The proportions of preterm birth, gestational diabetes, fetal growth restriction, small for gestational age, placental abruption, and late abortion in HDP group were 30.82% (1 269/4 117), 30.46% (1 254/4 117), 6.80% (280/4 117), 4.86% (200/4 117), 3.59% (148/4 117), and 0.80% (33/4 117), respectively. Conclusions:The incidence of HDP among pregnant women has been increased year by year in Shenzhen, China. With the increase in age and BMI during early pregnancy, the incidence of HDP showed an overall upward trend.

Objective To investigate the clinical characteristics,treatment strategies,and prognostic factors of adenoid cystic carcinoma(ACC)of the external auditory canal(EAC),and to provide evidence for optimizing surgical extent and adjuvant therapy.Methods A retrospective cohort study was conducted on 58 patients with pathologically confirmed ACC of the EAC treated in Department of Otorhinolaryngology Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University,between January 2001 and December 2021.All patients underwent surgical treatment,with some receiving adjuvant radiotherapy.The primary outcome was local recurrence,while secondary outcomes included overall survival(OS)and local recurrence-free survival(LRFS).Survival analysis was performed by the Kaplan-Meier method,and Cox regression models were used to identify risk factors for recurrence.Results The median follow-up time for the entire cohort was 6.27(3.25,11.30)years.The 1-year,3-year,and 5-year OS rates were 96.55％,91.37％,and 89.66％.43.10％of cases were classified as T4 stage at diagnosis,indicating advanced local progression.Local recurrence occurred in 23 patients(39.66％),and distant metastasis was observed in 28 patients(48.28％),with pulmonary metastasis accounting for 92.86％of cases.Multivariate analysis revealed that the solid histological pattern(HR=2.729,95％CI:1.025-7.226,P=0.044)and perineural invasion(PNI)(HR=9.891,95％CI:3.525-27.752,P＜0.01)were independent risk factors for local recurrence.Conclusion ACC of the EAC is characterized by a high propensity for local recurrence and distant metastasis.The solid histological pattern and perineural invasion are critical prognostic determinants.Multimodal therapy(surgery combined with adjuvant radiotherapy)may improve clinical outcomes,and early diagnosis and intervention are pivotal for enhancing survival rates.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

Based on the concept of"two-stage,four-phase,and three-phase treatments"of in vitro fertilization and embryo transfer(IVF-ET)assisted the whole-course management of TCM by national TCM master You Zhaoling,this article analyzed the treatment strategy assisted by acupuncture in five aspects:principle,method,prescription,acupoint,and technique.Principle:syndrome differentiation and treatment follow different cases;method establish guiding methods based on principles,while following stage diagnoses and treatments;prescription:determine the prescriptions based on therapeutic principles within the context of overall regulation;acupoint:precise acupoint taking and rational acupoint matching;technique:the primary method is acupuncture,supported by various therapeutic modalities,providing a comprehensive framework and evidence-based support for the clinical application of acupuncture and moxibustion in IVF-ET.