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 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:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

Objective To observe the effects of Tongqiao Pingchuan Decoction on miR-155 and NF-κB-HIF-1α signaling pathway in mice with combined allergic rhinitis and asthma syndrome(CARAS);To explore its potential mechanisms in the treatment of chronic inflammation of respiratory tract in CARAS.Methods Totally 60 female BALB/c mice were divided into blank group,model group,miR-155 inhibitor NC group,miR-155 inhibitor group,dexamethasone group and Tongqiao Pingchuan Decoction group using a random number table method,with 10 mice in each group.Except for the blank group,all other groups were sensitized by intraperitoneal injection of ovalbumin combined with aluminum hydroxide gel on days 0 and 7.From days 14 to 30,5%ovalbumin was administered intranasally every other day,followed by continuous nebulization with 5%ovalbumin from days 31 to 37.The miR-155 inhibitor NC group and the miR-155 inhibitor group received intranasal administration of miR-155 inhibitor NC and miR-155 inhibitor solution,respectively,3 hours before nebulization.The blank group was given an equivalent volume of normal saline via intraperitoneal injection,intranasal administration and nebulization.The administration groups were gavaged with the corresponding drug solution 1 hour after nebulization,while the other groups received an equivalent volume of normal saline via gavage.HE staining was used to observe morphology of nasal mucosa and lung tissue,ELISA was used to detect the contents of interleukin(IL)-4,IL-5,and γ-interferon(IFN-γ)in bronchoalveolar lavage fluid,RT-qPCR was used to detect the expression of miR-155,T-bet,GATA-3,NF-κB p65 and HIF-1α mRNA in nasal mucosa and lung tissue,Western blot was used to detect the expressions of T-bet,GATA-3,NF-κB p65 and HIF-1α proteins in lung tissue.Results Compared with the blank group,the model group mice showed shedding of nasal mucosal cilia,tissue congestion and edema,significant glandular hyperplasia and inflammatory cell infiltration,bronchial lumen stenosis,smooth muscle thickening and a large amount of inflammatory substance exudation,the contents of IL-4 and IL-5 increased,while IFN-γ content decreased(P<0.01),the mRNA expression of miR-155,GATA-3,NF-κB p65,HIF-1α in nasal mucosa and lung tissue were increased(P<0.01),while T-bet mRNA expression was decreased(P<0.01),the protein expression of GATA-3,NF-κB p65 and HIF-1α in lung tissue increased(P<0.01),while T-bet protein expression decreased(P<0.01).Compared with the model group,the miR-155 inhibitor group,dexamethasone group and Tongqiao Pingchuan Decoction group showed reduced inflammatory cell infiltration and pathological changes in nasal mucosa and lung tissue of mice,the contents of IL-4 and IL-5 in bronchoalveolar lavage fluid were reduced,while the content of IFN-γ was increased(P<0.01),the expressions of miR-155,GATA-3,NF-κB p65 and HIF-1α mRNA in nasal mucosa and lung tissue were reduced(P<0.05,P<0.01),while the expression of T-bet mRNA increased(P<0.05,P<0.01),the expressions of GATA-3,NF-κB p65 and HIF-1α protein in lung tissue were reduced(P<0.05,P<0.01),the expression of T-bet protein in dexamethasone group and Tongqiao Pingchuan Decoction group mice increased(P<0.05).Conclusion Tongqiao Pingchuan Decoction can effectively inhibit the expression of miR-155,suppress the abnormal activation of NF-κB-HIF-1α signaling pathway,correct the imbalance of Th1/Th2 immunity,and play a therapeutic role in alleviating airway inflammation in CARAS.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To observe the effects of Tongqiao Pingchuan Decoction on miR-155 and NF-κB-HIF-1α signaling pathway in mice with combined allergic rhinitis and asthma syndrome(CARAS);To explore its potential mechanisms in the treatment of chronic inflammation of respiratory tract in CARAS.Methods Totally 60 female BALB/c mice were divided into blank group,model group,miR-155 inhibitor NC group,miR-155 inhibitor group,dexamethasone group and Tongqiao Pingchuan Decoction group using a random number table method,with 10 mice in each group.Except for the blank group,all other groups were sensitized by intraperitoneal injection of ovalbumin combined with aluminum hydroxide gel on days 0 and 7.From days 14 to 30,5%ovalbumin was administered intranasally every other day,followed by continuous nebulization with 5%ovalbumin from days 31 to 37.The miR-155 inhibitor NC group and the miR-155 inhibitor group received intranasal administration of miR-155 inhibitor NC and miR-155 inhibitor solution,respectively,3 hours before nebulization.The blank group was given an equivalent volume of normal saline via intraperitoneal injection,intranasal administration and nebulization.The administration groups were gavaged with the corresponding drug solution 1 hour after nebulization,while the other groups received an equivalent volume of normal saline via gavage.HE staining was used to observe morphology of nasal mucosa and lung tissue,ELISA was used to detect the contents of interleukin(IL)-4,IL-5,and γ-interferon(IFN-γ)in bronchoalveolar lavage fluid,RT-qPCR was used to detect the expression of miR-155,T-bet,GATA-3,NF-κB p65 and HIF-1α mRNA in nasal mucosa and lung tissue,Western blot was used to detect the expressions of T-bet,GATA-3,NF-κB p65 and HIF-1α proteins in lung tissue.Results Compared with the blank group,the model group mice showed shedding of nasal mucosal cilia,tissue congestion and edema,significant glandular hyperplasia and inflammatory cell infiltration,bronchial lumen stenosis,smooth muscle thickening and a large amount of inflammatory substance exudation,the contents of IL-4 and IL-5 increased,while IFN-γ content decreased(P<0.01),the mRNA expression of miR-155,GATA-3,NF-κB p65,HIF-1α in nasal mucosa and lung tissue were increased(P<0.01),while T-bet mRNA expression was decreased(P<0.01),the protein expression of GATA-3,NF-κB p65 and HIF-1α in lung tissue increased(P<0.01),while T-bet protein expression decreased(P<0.01).Compared with the model group,the miR-155 inhibitor group,dexamethasone group and Tongqiao Pingchuan Decoction group showed reduced inflammatory cell infiltration and pathological changes in nasal mucosa and lung tissue of mice,the contents of IL-4 and IL-5 in bronchoalveolar lavage fluid were reduced,while the content of IFN-γ was increased(P<0.01),the expressions of miR-155,GATA-3,NF-κB p65 and HIF-1α mRNA in nasal mucosa and lung tissue were reduced(P<0.05,P<0.01),while the expression of T-bet mRNA increased(P<0.05,P<0.01),the expressions of GATA-3,NF-κB p65 and HIF-1α protein in lung tissue were reduced(P<0.05,P<0.01),the expression of T-bet protein in dexamethasone group and Tongqiao Pingchuan Decoction group mice increased(P<0.05).Conclusion Tongqiao Pingchuan Decoction can effectively inhibit the expression of miR-155,suppress the abnormal activation of NF-κB-HIF-1α signaling pathway,correct the imbalance of Th1/Th2 immunity,and play a therapeutic role in alleviating airway inflammation in CARAS.

Objective To explore the changes and influencing factors in patients' gastrointestinal symptoms and food tolerance before and after laparoscopic sleeve gastrectomy(LSG),and to provide a reference for the development of targeted gastrointestinal symptoms management program.Methods A convenience sampling method was used to select 125 patients who underwent LSG in the bariatric and metabolic surgery department of a tertiary-level hospital in Xuzhou City from June to November 2023 for a prospective observational study.The general information questionnaire,food tolerance questionnaire and Gastrointestinal Symptom Rating Scale(GSRS)were used to investigate at preoperative,3 months after surgery,and 6 months after surgery.Two-factor repeated measures variance analysis and generalized linear mixed model(GLMM)was used to analyze the influencing factors of gastrointestinal symptoms.Results 116 valid questionnaires were collected,and the GSRS scores of LSG patients at 3 time points were 21.67±5.80,23.28±4.33,and 21.22±3.18 respectively;the incidence rates of food intolerance were 0,32.75％,and 28.45％respectively.The patients' symptoms of bowel sounds,dysphagia,constipation,and dry stool were worse after surgery than before surgery(all P＜0.05),and the symptoms of bad breath,diarrhea,loose stools,and the need to defecate immediately were alleviated compared with symptoms before surgery(all P＜0.05).GLMM results showed that short meal times,poor food tolerance,and high school/technical secondary school education were risk factors for increasing gastrointestinal symptoms(all P＜0.05).Conclusion LSG could increase the prevalence of gastrointestinal symptoms such as dysphagia,dyspepsia,constipation and food intolerance.Medical staff should pay attention to the assessment of gastrointestinal symptoms in LSG patients,especially for patients with short meal time and poor food tolerance,strengthen postoperative follow-up,build targeted treatment and care plan,and prevent and reduce such uncomfortable symptoms.

Objective:To evaluate the efficacy of almonertinib,a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI),as a first-line treatment for patients with EGFR-mutated advanced non-small cell lung cancer(NSCLC)in the real-world clinical practise,and to systematically analyze the independent risk factors influencing their prognosis.Methods:This retrospective cohort study enrolled 73 patients with EGFR-mutated advanced NSCLC who received first-line treatment with aumolertinib from April 1,2020 to December 31,2021.Survival curves were generated by using the Kaplan-Meier method,and intergroup comparisons were performed via log-rank test.Univariate and multivariate analyses of prognostic factors were conducted by using the COX proportional hazards regression model,with a focus on identifying prognostic factors in the subgroup of baseline brain metastases.Results:Among 73 patients,the median progression-free survival(mPFS)was 19.4 months,and the disease control rate(DCR)was 93.2%.Multivariate COX regression analysis revealed that central nervous system(CNS)metastasis status,EGFR mutation subtype,ECOG performance status(PS)score,and gender might be independent risk factors for PFS.Among 33 patients with baseline brain metastases,combined almonertinib with radiotherapy or bevacizumab,maximum diameter of brain metastases(≥3 cm),and ECOG PS score might be independent risk factors of PFS.Conclusion:This first real-world study confirms that aumolertinib demonstrates favorable efficacy as first-line treatment for EGFR-mutated locally advanced or metastatic NSCLC patients,aligning with findings from phase Ⅲ clinical trials.For patients in subgroup of baseline brain metastases,combining almonertinib with radiotherapy or bevacizumab is recommended to optimize outcomes.