Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

Objective To analyze the incidence rate and risk factors of atrial fibrillation (AF) in elderly patients with chronic obstructive pulmonary disease (COPD). Methods A total of 392 patients with COPD in the hospital were selected from December 2020 to December 2024. Patients' data (medical history, echocardiographic data, etc.) were recorded. The incidence rate of AF in patients was recorded and the patients were grouped according to whether or not they developed AF. The differences were compared between the two groups, and the risk factors of AF occurrence in elderly patients with COPD were analyzed. Results Among the 392 patients with COPD, 127 cases (32.40%) met the diagnostic criteria of AF. There were statistically significant differences in age, pulmonary infection, heart failure, diabetes, smoking history, disease duration, LAD, severe renal insufficiency and coronary heart disease between the AF group and the non-AF group (P<0.05). Multivariate logistic regression analysis suggested that age, pulmonary infection, heart failure, diabetes mellitus, smoking history, disease course, LAD, severe renal insufficiency and coronary heart disease were all risk factors for elderly patients with COPD (OR=1.129, 4.246, 3.955, 4.125, 2.038, 1.112, 1.102, 4.397, and 3.865, P<0.05). Conclusion The incidence rate of AF is high in elderly patients with COPD. Age, pulmonary infection, heart failure, diabetes mellitus, smoking history, course of disease, LAD, severe renal insufficiency, and coronary heart disease are all risk factors for AF.

Objective: To understand the current status and related factors of oral health behavior in preschool children, so as to provide scientific basis for improving parents oral health care abilities. Methods: From March 5 to 12, 2024, using a stratified cluster sampling method, an online questionnaire survey was conducted among parents of 1 381 preschool children aged 3-6 from 6 selected kindergartens of a district in Beijing. A structural equation model (SEM) was constructed based on the Theory of Planned Behavior framework to analyze the factors associated with preschool children s oral health behaviors. Results: The rates of parental assistance in brushing teeth, regular oral examination, and postprandial rinsing were 44.4%, 18.6% and 23.6%, respectively. Attitude, subjective norms were positively correlated with oral health behavior intention ( r =0.61, 0.55); attitude, perceived behavioral control, and behavioral intention were positively correlated with oral health behavior ( r =0.14, 0.13, 0.16) (all P < 0.01 ). The results of the SEM showed that attitude and subjective norms had a significant direct effect on oral health behavior intention ( β = 0.42 , 0.40), and the direct effect of perceived behavioral control on oral health behavior was statistically significant ( β =0.42) (all P <0.01). Conclusions The overall level of oral health behavior among preschool children needs to be improved. Perceived behavioral control is the most direct positive related factor of oral health behavior. In the future, intervention measures should focus on perceived behavioral control as the entry point and provide systematic intervention guidance in combination with planned behavior theory.

Objective: To determine the potential genetic causal relationship between sleep related phenotypes and female pubertal onset using the two sample Mendelian randomization approach. Methods: Genetic instrumental variables for sleep and age at menarche were sourced from FinnGen, IEU Open GWAS and GWAS Catalog three publicly available Genome Wide Association Study databases. Causal effects were estimated using the inverse variance weighted method, supplemented by sensitivity analyses and tests for heterogeneity, pleiotropy, and direction. Results: Genetically predicted sleep duration was positively associated with age at menarche ( β =0.61, 95% CI =0.30-0.91, P <0.01). Conversely, overall sleep problems ( β =-0.13, 95% CI =-0.20 to -0.07 ), two specific types of sleep disorders (sleep apnea: β =-0.10, 95% CI =-0.16 to -0.03; insomnia: β =-0.40, 95% CI = -0.69 to -0.11) were causally associated with earlier age at menarche (all P <0.01). Sensitivity analyses confirmed the robustness of these findings with consistent effect directions and no evidence of significant directional pleiotropy. Conclusions The study reveales a genetic causal relationship between sleep and pubertal onset. Adequate sleep duration appears to have a protective effect. These findings suggest that sleep may have a critical regulatory role in the initiation of pubertal development.

Objective The clinical characteristics of 21 cases of nocardiosis were reviewed and antimicrobial resistance of Nocardia strains was analyzed in order to improve the accuracy of clinical diagnosis and treatment of nocardiosis.Methods Clinical data of patients diagnosed with nocardiosis in Zhoukou Central Hospital from 2019-2023 and the corresponding results of antimicrobial susceptibility testing were retrospectively analyzed to summarize the clinical characteristics and outcomes of patients.Results Overall,the 21 cases of nocardiosis included 9 males and 12 females,aged 2-91 years.Underlying disease was reported in 15 patients.Most common type of nocardiosis was pulmonary nocardiosis in 15 cases,followed by skin and soft tissue infection,pleurisy,lymphadenitis,and disseminated nocardiosis.Laboratory tests showed increased levels of WBC,neutrophils percentage,erythrocyte sedimentation rate,C-reactive protein,and procalcitonin.The 21 strains of Nocardia included 4 strains of Nocardia cyriacigeorgica,2 strains each of Nocardia brasiliensis,Nocardia abscessus,Nocardia asiatica,Nocardia otitidiscaviarum and Nocardia beijingensis,and 1 strain each of Nocardia puris,Nocardia asteroides,Nocardia farcinica,Nocardia pneumoniae,Nocardia amamiensis,and 2 strains of unclassified Nocardia.All of the Nocardia strains(100％)were susceptible to linezolid,amikacin,and trimethoprim-sulfamethoxazole,followed by various levels of susceptibility to cefotaxime,moxifloxacin,imipenem and ceftriaxone,and lower susceptibility rate to cefepime,minocycline,ciprofloxacin and clarithromycin.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Of the 21 patients,two were referred to other hospitals,another two died,two patients received unknown treatment,and the remaining 15 patients were improved after antibiotic treatment,including sulfonamides combined with other antibiotics in 11 cases,other antibiotics in 4 cases.Conclusions Immunocompromised patients or those with underlying diseases are more susceptible to nocardiosis.The clinical features are complex and diverse.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Accurate identification and antimicrobial susceptibility test are essential for prescribing effective antibiotic treatment.

Objective:To explore the safety and efficacy of camrelizumab combined with tegafur gimeracil oteracil potassium (S-1) and albumin-bound paclitaxel in the treatment of initially unresectable cholangiocarcinoma.Methods:From October 2022 to August 2024, 17 patients with unresectable intrahepatic cholangiocarcinoma and 4 patients with hilar cholangiocarcinoma were admitted to Xiangyang Central Hospital. They received treatment with camrelizumab combined with S-1 and nab-paclitaxel. Their short-term efficacy and adverse reactions were evaluated, and their long-term survival was followed up.Results:Of the 21 patients, 2 were in complete remission, 6 were in partial remission, 12 had stable disease, and 1 had progressive disease. The objective remission rate was 38.10% (8/21), and the disease control rate was 95.23% (20/21). Five patients were converted to resectable cholangiocarcinoma, with a conversion success rate of 23.81%,2 patients had complete postoperative pathological remission, and 3 patients had major pathological remission. The median progression-free survival time was 11 months (95% CI: 8.37-13.62), and the 1-year progression-free and overall survival rates were 28.57% and 95.23%, respectively. The overall adverse event rate was 90.48% (19/21), and the grade 3 adverse event rate was 28.57% (6/21). Conclusion:The combination of camrelizumab with S-1 and nab-paclitaxel for initially unresectable cholangiocarcinoma has favorable short-term efficacy, tolerable adverse reactions, and improved long-term survival for patients.

Neuronal intranuclear inclusion disease（NIID）is a rare hereditary neurodegenerative disorder that can affect multiple systems. However，it is uncommon for urinary dysfunction to be the initial symptom. This article reports five cases. The five patients began to experience voiding dysfunction such as frequent urination，weak urination，and incomplete urination at the mean ages of 55.4（47 - 65）years old. Four months to twelve years after urinary onset，neurological symptoms such as headache，memory decline，transient loss of consciousness，and unsteady gait began to appear. Four of the five cases had a family history. Brain MRI revealed the “ribbon sign” or “crest sign” in all cases. Skin biopsy revealed eosinophilic inclusions in the cell nuclei，and NOTCH2NLC gene testing identified abnormal GGC mutations. Three of the five patients underwent cystostomy due to secondary hydronephrosis，while the other two received no special treatment. After a follow-up of 18 to 35 months since diagnosis，the patients who underwent cystostomy had normal renal function. Neurological symptoms in all five patients worsened to varying degrees.

Objective To investigate the expression of serum exosomal long non-coding RNA X chromo-some inactivation specific transcript(LncRNA XIST)and microRNA(miR)-130a-3p in gestational diabetes mellitus(GDM)patients and its relationship with pregnancy outcome.Methods A total of 149 GDM patients(GDM group)and 149 healthy pregnant women(control group)admitted to the hospital from January 2021 to January 2024 were selected.Serum exosomal LncRNA XIST,miR-130a-3p and glucose and lipid metabolism indexes of the two groups were detected and compared.The correlation of LncRNA XIST and miR-130a-3p levels with glycolipid metabolism indexes was analyzed by Pearson method.Univariate and multivariate Logis-tic regression models were used to analyze the influencing factors of pregnancy outcomes in GDM patients.Re-ceiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of serum exosomal Ln-cRNA XIST and miR-130a-3p levels alone and in combination for pregnancy outcomes in GDM patients.Results Serum exosomal LncRNA XIST levels,fasting insulin(FINS),fasting blood glucose(FBG),insulin resistance index(HOMA-IR),2-hour postprandial glucose(2 hPG),total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)levels in GDM group were higher than those in control group(P＜0.05),and the levels of miR-130a-3p and high density lipoprotein cholesterol(HDL-C)were lower than those in the control group(P＜0.05).LncRNA XIST was positively correlated with FINS,FBG,HOMA-IR,2 hPG,TC,TG and LDL-C,and negatively correlated with HDL-C(P＜0.05).miR-130a-3p was negatively correlated with FINS,FBG,HOMA-IR,2 hPG,TC,TG and LDL-C,and positively correlated with HDL-C(P＜0.05).Among the 149 GDM patients,43 cases showed adverse pregnancy outcome,accounting for 28.86％.The increase level of FBG,the increase level of LncRNA XIST and the increase of HOMA-IR were risk factors for adverse pregnancy outcome in GDM patients,while the increase of miR-130a-3p was a protec-tive factor.The ROC curve analysis showed that the predictive efficacy of combined detection was superior to that of single indicator detection.Conclusion The serum exosomal LncRNA XIST of GDM patients is highly expressed,and miR-130a-3p is lowly expressed,and the combined detection of the above indexes has a high predictive value for pregnancy outcome.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis