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 explore the effects of parenting style on emotional and behavioral problems (EBPs) of preschool children and to provide theoretical reference for promoting children s physical and mental health. Methods: In October-November 2021, a stratified cluster random sampling method was adopted to select 3 575 preschool children aged 3-6 years from 12 kindergartens in Hefei. Data on parenting styles and children s EBPs were collected through electronic questionnaires. Binary Logistic regression model was used to explore the effects of parenting styles on children s EBPs. Results: The detection rates of emotional symptoms, conduct problems, hyperactivity, peer interaction problems, and prosocial behavior problems were 15.5% ( n =554), 23.2% ( n =830), 22.4% ( n =802), 38.2% ( n =1 367), and 29.5% ( n =1 055) in preschool children, respectively. Binary Logistic regression analysis showed that after adjusting for covariates such as child s age, sex, and preterm birth, a high authoritative parenting style reduced the risk of EBPs in children ( OR =0.29-0.78), while a high authoritarian ( OR =1.36-2.15) and high permissive ( OR =1.36-1.68) parenting style in mothers increased the risk of EBPs in children (all P <0.05). Further stratified analysis indicated that among children with fathers exhibiting high authoritative, high authoritarian, or high permissive parenting styles, a high authoritative parenting style in mothers reduced the risk of peer interaction problems and prosocial behavior problems ( OR =0.51, 0.30 ; 0.44, 0.23; 0.51, 0.29, all P <0.05). Among children with fathers exhibiting a high authoritative parenting style, a high authoritarian parenting style in mothers increased the risk of emotional problems ( OR =2.59), and both high authoritarian and high permissive parenting styles in mothers increased the risk of conduct problems ( OR =3.25, 2.09) and hyperactivity problems ( OR =2.35, 2.87) (all P <0.05). Among children with fathers exhibiting high authoritarian or high permissive parenting styles, a high authoritarian parenting style in mothers increased the risk of EBPs ( OR =1.65-2.71, 1.62-2.52, all P <0.05). Conclusion Parenting style is an important factor affecting EBPs of preschool children, and appropriate parenting style is beneficial for children s psychological development.

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare familial autosomal dominant genetic disease with primary hyperparathyroidism, jaw tumors, kidney tumors and uterine tumors caused by cell division cycle 73 (CDC73) germline mutations. A 42-year-old male patient was admitted for pancreatitis and further examination revealed elevated PTH at 54.00pmol/L and a history of jaw tumors. This patient was diagnosed as HPT-JT finally and underwent upper right, lower right, and upper left parathyroid glands resection and genetic testing. Postoperative pathology revealed that atypical adenomatous nodules of parathyroid glands with extensive atypia and nucleus division and parathyroid hyperplasia and whole exome sequencing suggested that the CDC73 mutation.

Objective To understand the distribution and antimicrobial resistance profiles of bacterial strains isolated from blood cultures at Yunyang County People's Hospital from 2019 to 2023.Methods The data of bacterial isolates from blood samples and the results of antimicrobial susceptibility testing were analyzed retrospectively from 2019 to 2023 at Yunyang County People's Hospital.Results A total of 3 789 bacterial strains were isolated from blood culture,including 1 931(51.0％)strains of Gram negative bacteria and 1 858(49.0％)strains of Gram positive bacteria.Coagulase negative Staphylococcus(33.3％),Escherichia coli(25.4％),Klebsiella pneumoniae(13.7％),Staphylococcus aureus(9.9％),and Enterobacter cloacae(1.8％)were the top five bacterial pathogens.Antimicrobial susceptibility testing showed that the prevalence of methicillin-resistant strains was 27.1％in S.aureus,34.5％in S.epidermidis,and 49.9％in other coagulase-negative Staphylococcus.Methicillin resistant strains(MRSA,MRSE,and other MRCNS)showed significantly higher resistance rates to most antibiotics than corresponding methicillin-susceptible strains(MSSA,MSSE,and other MSCNS).No staphylococcal isolates were resistant to vancomycin,teicoplanin,linezolid,or tigecycline.Enterococcus faecium showed significantly higher resistance rate to antibiotics than Enterococcus faecalis.No enterococcal strains were resistant to vancomycin,teicoplanin,linezolid,or tigecycline.No streptococcal isolates were found resistant to vancomycin or linezolid.Serratia marcescens strains had a resistance rate of 25.0％to carbapenems.All other Enterobacterales species showed a resistance rate of less than 10.0％to carbapenems.No Enterobacterales isolates were found resistant to tigecycline.The resistance rates of P.aeruginosa to imipenem and meropenem were 5.7％and 3.8％,respectively.No P.aeruginosa isolates were found resistant to colistin.The resistance rates of Acinetobacter baumannii to imipenem and meropenem were 41.4％and 38.0％,respectively.Conclusions The proportion of Gram negative bacteria is slightly higher than that of Gram positive bacteria in the bacterial isolates from blood samples at Yunyang County People's Hospital.The prevalence of MRSA and MRCNS is relatively high,while A.baumannii and S.marcescens showed high resistance rates to carbapenems.Antimicrobial resistance surveillance should be strengthened for the bacterial isolates from blood samples in order to learn the changing resistance profiles,use antibiotics reasonably,and prevent the spread of drug-resistant bacteria.

Objective To explore effects and action mechanism of Fu Fang Ku Shen Zhu She Ye on adverse reactions of 5-fluorouracil(5-FU)chemotherapy in rats with liver cancer.Methods The rat model of liver cancer was constructed by diethylnitrosamine(DEN).Model rats were divided into the liver cancer group,the chemotherapy group and the chemotherapy+Fu Fang-L/M/H groups.At 24 h after modeling,the chemotherapy group and the chemotherapy+Fu Fang groups were given intraperitoneally injection of 5-FU(100 mg/kg,once/week),and the chemotherapy+Fu Fang-L/M/H groups were given intraperitoneally injection of Fu Fang Ku Shen Zhu She Ye[0.7,1.4 and 2.8 mL/kg,once/d]for 8 weeks.The cardiac function,myocardial injury markers and pathological changes of myocardial tissue were compared between different groups.Serum levels of brain natriuretic peptide(BNP),cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)were detected by enzyme-linked immunosorbent assay.The expression levels of glucose-regulating protein 78(GRP78),activating transcription factor 6(ATF6)and endoplasmic reticulum stress-related protein(CHOP)in myocardial tissue were detected by Western blot assay.Changes of immune function indexes were compared between different groups.Results Compared with the liver cancer group,left ventricular ejection fraction(LVEF)and left ventricular anterior wall thickness in systole(LVAWs)were decreased in the chemotherapy group(P＜0.05),left ventricular end diameter in systole(LVEDs),levels of BNP,cTnI and CK-MB were increased(P＜0.05),levels of tumor necrosis factor α(TNF-α),interleukin(IL)-1β and IL-6 in myocardial tissue,expression levels of GRP78,ATF6 and CHOP were increased(P＜0.05).Levels of CD3+,CD4+,CD4+/CD8+,IgG,IgM and IgA were decreased in the chemotherapy group(P＜0.05).The myocardial tissue was disordered,vacuolated and infiltrated by inflammatory cells.Compared with the chemotherapy group,the above indexes and pathological changes of myocardial tissue were significantly improved in the chemotherapy+Fu Fang-L/M/H groups,and the improvement was more significant in the chemotherapy+Fu Fang-H group.Conclusion Fu Fang Ku Shen Zhu She Ye injection can alleviate cardiotoxic injury induced by 5-FU in rats with liver cancer,which may be related to alleviating endoplasmic reticulum stress.It can also alleviate immunosuppression.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare familial autosomal dominant genetic disease with primary hyperparathyroidism, jaw tumors, kidney tumors and uterine tumors caused by cell division cycle 73 (CDC73) germline mutations. A 42-year-old male patient was admitted for pancreatitis and further examination revealed elevated PTH at 54.00pmol/L and a history of jaw tumors. This patient was diagnosed as HPT-JT finally and underwent upper right, lower right, and upper left parathyroid glands resection and genetic testing. Postoperative pathology revealed that atypical adenomatous nodules of parathyroid glands with extensive atypia and nucleus division and parathyroid hyperplasia and whole exome sequencing suggested that the CDC73 mutation.

Objective To understand the distribution and antimicrobial resistance profiles of bacterial strains isolated from blood cultures at Yunyang County People's Hospital from 2019 to 2023.Methods The data of bacterial isolates from blood samples and the results of antimicrobial susceptibility testing were analyzed retrospectively from 2019 to 2023 at Yunyang County People's Hospital.Results A total of 3 789 bacterial strains were isolated from blood culture,including 1 931(51.0％)strains of Gram negative bacteria and 1 858(49.0％)strains of Gram positive bacteria.Coagulase negative Staphylococcus(33.3％),Escherichia coli(25.4％),Klebsiella pneumoniae(13.7％),Staphylococcus aureus(9.9％),and Enterobacter cloacae(1.8％)were the top five bacterial pathogens.Antimicrobial susceptibility testing showed that the prevalence of methicillin-resistant strains was 27.1％in S.aureus,34.5％in S.epidermidis,and 49.9％in other coagulase-negative Staphylococcus.Methicillin resistant strains(MRSA,MRSE,and other MRCNS)showed significantly higher resistance rates to most antibiotics than corresponding methicillin-susceptible strains(MSSA,MSSE,and other MSCNS).No staphylococcal isolates were resistant to vancomycin,teicoplanin,linezolid,or tigecycline.Enterococcus faecium showed significantly higher resistance rate to antibiotics than Enterococcus faecalis.No enterococcal strains were resistant to vancomycin,teicoplanin,linezolid,or tigecycline.No streptococcal isolates were found resistant to vancomycin or linezolid.Serratia marcescens strains had a resistance rate of 25.0％to carbapenems.All other Enterobacterales species showed a resistance rate of less than 10.0％to carbapenems.No Enterobacterales isolates were found resistant to tigecycline.The resistance rates of P.aeruginosa to imipenem and meropenem were 5.7％and 3.8％,respectively.No P.aeruginosa isolates were found resistant to colistin.The resistance rates of Acinetobacter baumannii to imipenem and meropenem were 41.4％and 38.0％,respectively.Conclusions The proportion of Gram negative bacteria is slightly higher than that of Gram positive bacteria in the bacterial isolates from blood samples at Yunyang County People's Hospital.The prevalence of MRSA and MRCNS is relatively high,while A.baumannii and S.marcescens showed high resistance rates to carbapenems.Antimicrobial resistance surveillance should be strengthened for the bacterial isolates from blood samples in order to learn the changing resistance profiles,use antibiotics reasonably,and prevent the spread of drug-resistant bacteria.

Objective:To compare the efficacy of Wnt3a factor and small molecule compound CHIR99021 in culturing colorectal cancer organoid, and to explore the feasibility of replacing Wnt3a with CHIR99021.Methods:The organoids were cultured using 2 culture systems containing Wnt3a or CHIR99021, based on the colorectal cancer cell line HCT116 and rectal cancer tissue from one patient (surgical specimen from the Department of Gastrointestinal Surgery, Zhongshan Hospital Affiliated to Dalian University), including Wnt3a cell organoid, CHIR99021 cell organoid, Wnt3a tissue organoid, and CHIR99021 tissue organoid. The growth of organoids was observed under the optical microscope. The pathological characteristics of organoids and the rectal cancer tissue were analyzed by hematoxylin-eosin (HE) staining and immunohistochemical (IHC) staining, which included cytokeratin(CK) 7, CK20, Ki-67, and stemness marker CD133. The expression of β-catenin (a key Wnt pathway protein) was analyzed by Western blotting (WB) method. The half maximal inhibitory concentration (IC50) values of Wnt3a and CHIR99021 cell organoids were analyzed by drug susceptible test and GraphPad Prism 9.0 software. Independent sample- t test was used for statistical analysis. Results:Under the optical microscope, the size of CHIR99021 cell organoid was relatively uniform, while the size of the Wnt3a cell organoid was uneven, compact and dense spherical structure was formed in both organoids. HE staining showed tumor features including increased nuclear-cytoplasmic ratio and obvious nuclear atypia in the Wnt3a and CHIR99021 cell organoids. The results of IHC staining showed that CK7 was negative, and CK20 and Ki-67 were positive in the Wnt3a and CHIR99021 cell organoids. The results of WB method showed that the relative expression level of β-catenin of the CHIR99021 cell organoid was higher than that of the Wnt3a cell organoid (0.89±0.09 vs. 0.26±0.04), and the difference was statistically significant ( t=13.80, P<0.001). The results of drug susceptible test demonstrated that the IC50 value of the Wnt3a and CHIR99021 cell organoid was 10.91 and 14.55 μmol/L, respectively. Further IHC staining showed that CD133 was positive in the Wnt3a and CHIR99021 cell organoids, with stronger intensity in the CHIR99021 cell organoid. The pathological characteristics of Wnt3a and CHIR99021 tissue organoid were consistent with those of the rectal cancer tissue of the patient, with all CK7 being negative and CK20 and Ki-67 being positive. Conclusions:Both Wnt3a and CHIR99021 can successfully establish colorectal cancer organoids with consistent pathological characteristics. The IC50 value of the CHIR99021 cell organoid is high, which is related to the increased stemness of organoids. The pathological characteristics of Wnt3a and CHIR99021 tissue organoid are consistent with those of the rectal cancer tissue from the patient.