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.

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective To analyze the value of abdominal CT images combined with serological indicators in predicting the ureteral involvement in idiopathic retroperitoneal fibrosis(IRF). Methods The CT images of 79 IRF patients were analyzed retrospectively,including the involved sites and enhancement characteristics of the lesions.According to the inclusion and exclusion criteria,43 patients with complete serological data were selected and assigned into a ureteral involvement group(n=29)and a non-ureteral involvement group(n=14) according to whether ureters were involved in IRF.Logistic regression analysis was performed to select independent risk factors for ureteral involvement in IRF.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of the CT arterial phase enhancement magnitude and serum cystatin C(CysC)for ureteral involvement in IRF. Results The CT images of IRF usually showed a soft tissue density lesion encompassing the abdominal aorta,iliac arteries,ureters,and retroperitoneal tissue,with a wide range of distribution.The ureteral involvement group and the non-ureteral involvement group showed differences in gender(P=0.031),CT arterial phase enhancement amplitude(P=0.014),CT venous phase enhancement amplitude(P=0.032),and serum CysC(P=0.036).Logistic regression analysis showed that gender(P=0.034),CT arterial phase enhancement amplitude(P=0.046),and serum CysC(P=0.041)were independent risk factors for ureteral involvement in IRF.The area under the curve for CT arterial phase enhancement combined with serum CysC to predict ureteral involvement in IRF was 0.776.Ten patients had lower levels of erythrocyte sedimentation rate(P<0.001),C-reactive protein(P=0.021),and IgG4(P<0.001)in the follow-up period than before treatment. Conclusion The combination of abdominal CT images with serological indicators demonstrates high accuracy in predicting the ureteral involvement in IRF,providing reference for early clinical diagnosis.
Humans ; Male ; Female ; Retroperitoneal Fibrosis/pathology* ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed ; Aged ; Adult ; Ureter/diagnostic imaging* ; Predictive Value of Tests ; Cystatin C/blood*

Objective:To investigate the protective effect of a composite hydrogel against hydrogen peroxide(H2O2)-induced oxidative stress injury in the cardiomyocytes,and to clarify its possible mechanism.Methods:The mice were subcutaneously injected with 100 μL of hydrogel.After normal feeding for 1,14,and 28 d,the mice were sacrificed.Tissue samples were collected and subjected to HE staining to observe the histocompatibity of the hydrogel.The primary cardiomyocytes isolated from 1-day-old SD rats were used to establish an oxidative stress injury model.The primary cardiomyocyties were divided into control,H2O2 and H2O2+Hydrogel groups.The primary cardiomyocytes in control group were cultured normally,the primary cardiomyocytes in H2O2 group were treated with 200 μmol·L-1 H2O2 for 24 h,and the primary cardiomyocytes in H2O2+Hydrogel group were incubated with 1 g·L-1 composite hydrogel and 200 μmol·L-1 H2O2 for 24 h.The viabilities of cardiomyocytes in various groups were assessed by cell counting kit-8(CCK-8)method.Dihydroethidium(DHE)and 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining were used to assess the reactive oxygen species(ROS)levels in the cells.The expressions of filamentous actin(F-actin)in the cells in various groups were detected by phalloidin fluorescence staining;the expressions of connexin 43(Cx43)and cardiac troponin T(cTnT)proteins in the cardiomyocytes in various groups were detected by immunofluorescence method.The apoptotic rates of cardiomyocytes in various groups were assessed with TUNEL staining method.The expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in the cardiomyocytes in various groups were assessed by Western blotting method.Results:The HE staining results showed that the inflammatory cells around the implanted hydrogel were less infiltrated,and the inflammatory reaction of subcutaneous implantation was less.Compared with control group,the viability of cardiomyocytes in H2O2 group was significantly decreased(P＜0.05),the level of ROS in the cells was increased(P＜0.05),the expression levels of Cx43,cTnT and F-actin proteins in the cells were decreased(P＜0.001),the apoptosis rate of cardiomyocytes were decreased(P＜0.01),the expression level of Bcl-2 protein in the cells was increased(P＜0.001),and the expression level of Bax protein was decreased(P＜0.01).Compared with H2O2 group,the viability of cardiomyocytes was significantly increased(P＜0.05),the level of ROS in the cells was decreased(P＜0.01),the expression levels of cTnT,Cx43 and F-actin proteins were increased(P＜0.01),the apoptotic rate of cardiomyocytes were significantly decreased(P＜0.001),the expression level of Bcl-2 protein in the cells were decreased(P＜0.01),and the expression level of Bax protein was increased(P＜0.01).Conclusion:Hydrogel may promote the expression of cardiomyocyte-related proteins by scavenging ROS in the environment and inhibit the cardiomyocyte apoptosis to achieve the protective effect on the cardiomyocytes under oxidative stress.

Objective To analyze the status quo of exercise compliance in patients with chronic heart failure and its influencing factors.Methods Using convenient sampling method,425 patients with chronic heart failure in General Hospital of Ningxia Medical University from August 2022 to February 2023 were se-lected as the study objects.General data questionnaire,exercise compliance scale,exercise self-efficacy scale,heart-activity fear tampa scale,Pittsburgh sleep quality index,perceptive social support scale and psychological experience scale were used to investigate and analyze the results.Results 415 effective questionnaires were collected,with a recovery rate of 97.65%.The total score of exercise compliance in patients with chronic heart failure was 88.94±17.12.The results of multiple linear regression analysis showed that BMI,hospitalization times and fear of cardiac activity negatively affected patients'exercise compliance,while education level,exer-cise self-efficacy,perceptive social support and retirement positively affected patients'exercise compliance(P＜0.05).Conclusion The overall level of exercise compliance of patients with chronic heart failure is poor,and timely intervention measures should be taken.

Objective To investigate the effects of different dialysis modalities on hormonal profiles and menstrual disorders in childbearing-age women with uremia.Methods From March 2020 to July 2024,102 childbearing-age women with uremia treated in the Department of Nephrology of Tianmen First People's Hospital were enrolled and divided into hemodialysis group(n=52)and peritoneal dialysis group(n=50),and 50 healthy women undergoing physical examinations were selected as the control group.Sex hormone lev-els and menstrual patterns were compared among three groups at baseline and 6 months post-dialysis.Results Pre-treatment levels of follicle-stimulating hormone(FSH),prolactin(PRL),and luteinizing hormone(LH)in both hemodialysis and peritoneal dialysis groups were significantly higher than those in healthy controls,while progesterone(P)levels were lower(P＜0.05).Post-treatment,hemodialysis and peritoneal dialysis groups showed decreased FSH and increased LH,PRL,and P compared to baseline(P＜0.05).Estradiol(E2)and P levels in hemodialysis group were slightly lower than those in the peritoneal dialysis group without statistical significance(P＞0.05).No significant intergroup differences existed in FSH,LH,P,or PRL between hemodi-alysis and peritoneal dialysis groups post-treatment(P＞0.05).Menstrual normalization and disorder rates in hemodialysis group were nonsignificantly lower than peritoneal dialysis group(P＞0.05),whereas amenor-rhea incidence was significantly higher in hemodialysis group(P＜0.05).Menstrual resumption rate after a-menorrhea showed no statistical difference between groups(P＞0.05).Conclusion Both peritoneal dialysis and hemodialysis effectively ameliorate hormonal dysregulation in female uremia patients,while peritoneal dialysis demon-strates superior efficacy in improving menstrual disorders.

Objective:This study aims to explore the ability of three assessment tools,namely mPG-SGA,PG-SGA,and GLIM,to evaluate malnutrition in patients with head/neck tumors undergoing radiotherapy.Additionally,it intends to investigate the correlation between mPG-SGA and calf circumference,grip strength,as well as traditional laboratory indicators in assessing malnutrition in this patient population.Methods:Prospectively,patients with head/neck tumors undergoing radiotherapy in West China Hospital,Sichuan University from January 1,2025 to March 20,2025 were selected as the research subjects.Baseline data and traditional nutritional indicators of the patients were collected,and malnutrition assessment was conducted using three tools:mPG-SGA,PG-SGA,and GLIM.Spearman correlation coefficient was used for analysis to explore the correlation between mPG-SGA scores and traditional nutritional indicators.Results:A total of 106 patients were initially included in this study,with 6 cases excluded,resulting in 100 eligible head and neck tumor patients.The average age of the enrolled patients was(51.62±11.97)years,among whom 74 were male(74%).The incidence rates of malnutrition assessed by mPG-SGA,PG-SGA,and GLIM were 41%,45%,and 23%,respectively.With PG-SGA as the gold standard reference,the sensitivity of mPG-SGA and GLIM in detecting malnutrition was 100.00%and 28.89%,respectively,and the specificity was 93.22%and 81.82%,respectively,with AUC values of 0.956 and 0.554.Results of correlation analysis showed that left calf circumference,right calf circumference,dominant hand grip strength,non-dominant hand grip strength,hemoglobin,and red blood cells were positively correlated with mPG-SGA[correlation coefficients were 0.307(P=0.002),0.294(P=0.003),0.395(P<0.001),0.360(P<0.001),0.226(P=0.028),and 0.267(P=0.009),respectively].Conclusion:mPG-SGA exhibited comparable diagnostic efficacy to PG-SGA and GLIM for malnutrition assessment in head and neck cancer patients undergoing radiotherapy,while offering simplified operational procedures.This tool shows potential as a rapid nutritional evaluation alternative,though multicenter validation across various cancer types remains necessary.

Objective To establish and verify a mature and stable glioblastoma(GBM)organoid model,so as to provide an accurate and personalized preclinical model for the research and treatment of GBM.Methods Fresh GBM tissues obtained through surgical procedures were initially processed,and then GBM stem cells(GSCs)were isolated using stem cell culture medium and were identified.Subsequently,GSCs were cultured in organoid culture medium for 3D cultivation,and GBM organoids were successfully obtained.The histological morphology of GBM organoids was observed by hematoxylin-eosin(H-E)staining;the stemness and similarity to the parental tumor were identified by immunofluorescence staining;and the in vivo tumorigenic ability of GBM organoids was identified by orthotopic tumorigenesis experiments in nude mice.Results A total of 7 GBM organoids were constructed from 9 human GBM samples,with a morphology resembling"neurosphere",and the average duration for organoid formation was 1 week.H-E staining results showed that the histological morphology of GBM organoids under high-power microscope was very similar to that of GBM tumor tissues;immunofluorescence staining results indicated that the GBM organoids possessed stemness characteristics and histological cellular similarity;and GBM organoids had a stronger tumorigenic ability compared to ordinary GBM cells in nude mice.Conclusion This study presents a stable and reliable method for constructing GBM organoids retaining the histological characteristics of the original GBM tissue,which providing new insights for future GBM research and clinical practice.