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）］

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.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

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

In 2024, notable progress was made in the clinical treatment of Parkinson′s disease (PD). These advancements encompass key areas such as novel drugs like glucagon-like peptide-1 receptor agonists, pralidoxime, and levodopa subcutaneous injection, novel neuroregulatory therapies like closed-loop adaptive deep brain stimulation, bilateral magnetic resonance imaging-guided focused ultrasound ablation, and fecal microbiota transplantation, all of which have propelled the precision treatment of PD. The significant advancements in the clinical treatment of PD published in major international academic journals in 2024 were systematically reviewed in this article.

OBJECTIVE: To evaluate the effectiveness of correcting post-traumatic equinovarus deformity using Ilizarov external fixation technique combined with limited osteotomy. METHODS: A retrospective analysis was conducted on clinical data from 29 patients with post-traumatic equinovarus deformity treated between July 2018 and March 2023. The cohort included 18 males and 11 females, with ages ranging from 15 to 57 years (mean, 24.3 years). All patients exhibited ankylosed ankle joints with equinovarus deformity. During surgery, external fixators were installed according to Ilizarov pinning principles, and minimally invasive osteotomy was performed at the ankle joint. Concurrently, soft tissue release was achieved via minimally invasive Achilles tendon lengthening. Postoperatively, multiplanar deformity correction was accomplished through gradual adjustment of the external fixator. The fixator was removed after bony union at the osteotomy site, followed by bracing. The surgical duration, intraoperative blood loss, fixator wear time, and complications were recorded. Postoperative outcomes included assessment of deformity correction and bony union at the osteotomy site. Functional improvement and pain relief were evaluated using pre- and post-operative scores from the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) score. RESULTS: All 29 patients were followed up 12-24 months (mean, 18 months). The mean surgical duration was 85.6 minutes, with a mean intraoperative blood loss of 110 mL. Full deformity correction was achieved within 26-80 days (mean, 40.7 days) through progressive fixator adjustments. At correction completion, all ankles restored to a neutral or 5°-10° dorsiflexed position with plantigrade foot function. Superficial pin tract infections occurred in 3 patients (10.3%), resolved with local wound care, enhanced nursing, and oral antibiotics. No deep or systemic infections was observed. One patient sustained a calcaneal half-pin fracture due to a fall during fixator wear, but no bone fragment displacement occurred. No vascular or neurological complication was reported. Complete bony union was achieved at all osteotomy sites without nonunion. At last follow-up, the AOFAS ankle-hindfoot score improved from preoperative 42.7±8.7 to postoperative 65.7±9.3, and the VAS score decreased from preoperative 4.5±1.3 to postoperative 2.5±1.1, with significant differences ( P<0.05). Functional outcomes were rated as excellent in 14 cases, good in 13 cases, fair in 1 case, and poor in 1 case, with an excellent and good rate of 93.1%. CONCLUSION The progressive correction strategy combining Ilizarov external fixation technique with limited foot osteotomy effectively corrects post-traumatic equinovarus deformity while preserving soft tissue integrity. This method is associated with minimal, largely controllable complications and achieves alignment stability and fusion outcomes comparable to traditional open surgery, making it an effective treatment for complex foot and ankle deformities.
Humans ; Male ; Female ; Osteotomy/methods* ; Adult ; Retrospective Studies ; Ilizarov Technique ; Middle Aged ; Adolescent ; External Fixators ; Young Adult ; Treatment Outcome ; Ankle Joint/surgery* ; Clubfoot/etiology* ; Minimally Invasive Surgical Procedures/methods*

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.