Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Electroacupuncture (EA) may affect the severity of hot flashes (HFs) associated with natural menopause and provide additional benefits for postmenopausal women. However, the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood. OBJECTIVE: We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized sham-controlled trial involved 72 women with HFs. The participants were divided equally into the intervention and control groups. The intervention group was treated with EA, while the control group was treated with sham acupuncture. The main acupoints used were Hegu (LI4), Guanyuan (RN4), Sanyinjiao (SP6), Taixi (KI3), Fuliu (KI7) and Shenshu (BL23). All participants received 18 treatment sessions, distributed across a 6-week period. The treatment was administered on three occasions per week, adhering to a fixed weekday schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) with a minimum interval of one day between sessions. Each patient received a 12-week follow-up. MAIN OUTCOME MEASURES: The HF score was the primary outcome. Participants documented the frequency and severity of HFs in a 7-day symptom diary, which provided data for calculating the HF score. Secondary outcomes were the Menopause Rating Scale (MRS), Menopause-Specific Quality of Life Questionnaire (MENQOL), Pittsburgh Sleep Quality Index (PSQI) and Traditional Chinese Medicine Syndrome Score Scale (TCMSSS), as well as estradiol (E₂), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. RESULTS: Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up (P < 0.001). Immediately after completion of the 6-week treatment cycle and at 12 weeks post-intervention, the HF scores were similar in both groups. At week 6, the intervention group showed significantly greater improvements in MRS, MENQOL (vasomotor, psychosocial, and physical), PSQI and TCMSSS scores (P < 0.05). The improvements in the MENQOL (vasomotor, and psychosocial) and PSQI total scores persisted through the follow-up (P < 0.05). However, the results showed no significant inter- or intragroup differences in sexual scores on the MENQOL (P > 0.05). EA did not significantly decrease E₂, LH or FSH levels compared to placebo. The incidence of adverse events was similar in both groups. CONCLUSION: EA does not significantly improve HFs in early postmenopausal patients. However, it enhances the quality of sleep and decreases menopausal symptoms across vasomotor, psychosocial and physical domains. TRIAL REGISTRATION Chinese Clinical Trial Registry (http://www.chictr.org.cn); Trial ID: ChiCTR2300072002. Please cite this article as: Wang HX, Yu XT, Hu J, Chen JJ, Mei YT, Chen YF. Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial. J Integr Med. 2025; 23(5):519-527.
Humans ; Female ; Electroacupuncture ; Hot Flashes/therapy* ; Middle Aged ; Acupuncture Points ; Quality of Life ; Menopause ; Treatment Outcome ; Adult

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Prostate cancer (PCa) ranks as the second most prevalent malignancy among men worldwide. Early diagnosis, personalized treatment, and prognosis prediction of PCa play a crucial role in improving patients' survival rates. The advancement of artificial intelligence (AI), particularly the utilization of deep learning (DL) algorithms, has brought about substantial progress in assisting the diagnosis, treatment, and prognosis prediction of PCa. The introduction of the foundation model has revolutionized the application of AI in medical treatment and facilitated its integration into clinical practice. This review emphasizes the clinical application of AI in PCa by discussing recent advancements from both pathological and imaging perspectives. Furthermore, it explores the current challenges faced by AI in clinical applications while also considering future developments, aiming to provide a valuable point of reference for the integration of AI and clinical applications.
Humans ; Prostatic Neoplasms/diagnosis* ; Male ; Artificial Intelligence ; Deep Learning ; Prognosis

OBJECTIVE: To explore the functional rehabilitation of patients with rheumatoid arthritis (RA) after total knee arthroplasty (TKA). METHODS: A retrospective analysis was conducted on 101 patients who needed TKA due to rheumatoid arthritis (RA) involving both knees from January 2017 to December 2020, including 16 males and 85 females, aged from 41 to 65 years old with an average of (58.13±5.53) years old;body mass index (BMI) ranged from 16.88 to 33.33 kg·m^-2 with an average of (23.16±3.49) kg·m^-2;63 patients with grade 1, 29 patients with grade 2, and 9 patients with grade 3 according to classification of American Society of Anesthesiologists (ASA). According to the latest follow-up results at 12 months after operation, 82 patients returned to work and 19 patients did not return to work. Visual analogue scale(VAS) was used to evaluate the degree of pain relief before operation and 12 months after operation, and work, osteoarthritis and joint replacement questionnaire (WORQ) was used to evaluate knee joint activity status of all patients before and after operation, and the working ability index was used to evaluate working ability of all patients before operation and 12 months after operation. For the 82 patients who returned to work, the labor time stopped before operation and within 12 months after operation was compared, and the changes in labor grades, types of work and labor hours of patients before and after operation were recorded. For the 19 patients who did not return to work, the specific reasons for their non-return to work was analyzed;the postoperative satisfaction of patients was evaluated by using Likert satisfaction scale. All patients were followed up for at least 12 months. VAS was decreased from (6.49±0.59) before operation to (1.10±0.43) at 12 months after operation (P<0.05);for WORQ questionnaire survey, scores of walking, sitting posture, standing and stair climbing were increased from (1.07±0.35), (1.05±0.29), (1.06±0.34) and (1.14±0.42) before operation to (3.00±0.00), (2.87±0.33), (2.95±0.21) and (2.95±0.21) after operation, respectively, had statistically significant (P<0.05);the labor work index of all patients increased from 1.11±0.46 before operation to 2.99±0.10 at 12 months after operation, and the difference was statistically significant (P<0.05). Among the 82 patients who returned to work after operation, regarding the time of stopping labor, 81 patients stopped working within 3 months before operation, 1 patient stopped working for 4 to 6 months after operation, and the number of patients who stopped working was 81, 1, and 0 respectively. Forty patients returned to work within 3 months after operation, 4 to 6 months after operation for 29 patients, and 12 months after operation for 13 patients. 95.1% (78/82) of patients engaged in light labor before operation, and 85.4% (70/82) of patients engaged in moderate labor after operation. At 12 months after operation, the types of jobs and working hours available to all patients increased compared with those before operation. Among 19 patients who did not return to work after TKA, 7 patients had poor control of rheumatoid arthritis, 5 patients still felt pain, swelling and numbness on knee joint, 2 patients had retired, and 5 patients had other reasons. Eighty-six patients (85%) expressed great satisfaction with the postoperative working ability, 8 patients (8%) expressed satisfaction with the postoperative working ability, 6 patients (6%) expressed acceptance of postoperative working ability, and 1 patient (1%) expressed dissatisfaction with postoperative working ability. CONCLUSION TKA is an effective treatment option for patients with RA. After undergoing TKA, patients could significantly improve pain and functional activities of knee joint, and effectively enhance the quality of life and working ability. For patients whose rehabilitation labor capacity is not fully met, postoperative management and personalized rehabilitation treatment need to be strengthened to achieve the best rehabilitation effect.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/rehabilitation* ; Arthritis, Rheumatoid/physiopathology* ; Middle Aged ; Aged ; Retrospective Studies ; Adult

OBJECTIVES: To explore the application of the colloidal gold method and chemiluminescence method in detecting gonadotropin (Gn) in morning urine for assessing pubertal development status in children. METHODS: A total of 132 children diagnosed with central precocious puberty (CPP), early and fast puberty (EFP), and premature thelarche (PT) at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2021 to December 2022 were included, along with 685 healthy children who underwent routine health examinations at the hospital's pediatric health care department during the same period. All 132 patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test. Both patients and healthy children had their urinary Gn levels measured using the colloidal gold method and chemiluminescence method, including levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The correlation between serum Gn and urinary Gn detected by the two methods, as well as the correlation between Tanner stages of healthy children and urinary Gn, was analyzed. RESULTS: Urine Gn levels detected by both the colloidal gold method and chemiluminescence method showed a positive correlation with serum LH baseline values, LH peak values, baseline LH/FSH ratios, and peak LH/FSH ratios (P<0.05). In healthy children, urinary LH levels detected by the chemiluminescence method gradually increased from Tanner stage Ⅰ to Ⅳ (P<0.05), while urinary FSH levels were lower in Tanner stage I than in stages Ⅱ, Ⅲ, and IV (P<0.05). Urinary LH levels detected by the colloidal gold method were lower in Tanner stage I compared to stages Ⅱ, Ⅲ, and IV, with the highest levels observed in Tanner stage Ⅳ (P<0.05). Additionally, urinary FSH levels in Tanner stage Ⅲ were higher than in stages Ⅰ and Ⅱ (P<0.05). The area under the receiver operating characteristic curve for evaluating Tanner stages I and II in healthy children using urinary LH and FSH levels by the chemiluminescence method and urinary LH levels by the colloidal gold method were 0.730, 0.699, and 0.783, respectively. CONCLUSIONS The colloidal gold method and chemiluminescence method for detecting Gn in morning urine show good correlation with serum Gn levels. As a non-invasive and convenient detection method, the colloidal gold method can serve as a useful tool for screening the onset of pubertal development in children.
Humans ; Child ; Male ; Female ; Gold Colloid ; Luminescent Measurements/methods* ; Gonadotropins/urine* ; Puberty ; Luteinizing Hormone/urine* ; Child, Preschool ; Adolescent ; Follicle Stimulating Hormone/urine*

This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.

Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.