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.

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

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 optimize the platelet enrichment method,and to analyze the concentration changes of key molecules in platelet-rich plasma(PRP)before and after activation,as well as the impact of its activated products on the proliferation of rat endothelial progenitor cells.Methods The tube double-centrifu-gation method was employed to optimize platelet enrichment,and the platelet count in the enriched PRP was measured.ELISA was used to detect the concentration changes of vascular endothelial growth factor(VEGF),endostatin(ES),and P-selectin(CD62P)in PRP before and after activation.The PRP was activated by using liquid nitrogen freeze-thaw method,and the effect of its activated products on the proliferation of rat endothelial progenitor cells was evaluated by using the methyl thiazolyl tetrazolium(MTT)assay.Results The optimal enrichment coefficient of platelets achieved by the double-centrifugation method was 4.63.After low-speed,long-duration double centrifugation,the platelet count was highest in the upper layer of the buffy coat.For PRP with a platelet count of 500× 109/L obtained by machine collection,the VEGF con-centrations before and after activation were(3 418.12±488.80)pg/mL and(4 530.04±308.30)pg/mL,re-spectively,the ES concentrations were(6 168.98±253.22)pg/mL and(6 594.65±82.47)pg/mL,respec-tively,the CD62P concentrations were(6 678.23±324.15)pg/mL and(17 630.53±746.24)pg/mL,respec-tively,statistically significant differences were observed in the above indicators before and after activation(P＜0.01).The activated PRP was diluted in a gradient manner by using a specialized culture medium for en-dothelial progenitor cells.MTT assay results indicated that,in the basal medium,the optimal volume fraction for promoting endothelial progenitor cell proliferation was 0.25％after 48 hours of culture;in the complete medium,the optimal volume fractions for promoting endothelial progenitor cell proliferation were 0.062 5％after 24 hours and 0.125％after 48 hours.Conclusion The concentrations of VEGF,ES,and CD62P in the optimized,enriched PRP exhibited significant changes before and after activation.The optimal volume fraction for promoting endothelial progenitor cell proliferation in the basal medium was 0.25％.

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:This study aimed to analyze the prognostic risk factors for hepatoid adenocarcinoma of the stomach (HAS) and construct two nomogram-based clinical prediction models to predict overall survival (OS) and recurrence-free survival (RFS) in patients with HAS.Methods:Data were retrospectively collected from 82 patients (64 males, 18 females; mean age 60.3 ± 9.4 years) who underwent radical gastrectomy and were pathologically diagnosed with gastric hepatoid adenocarcinoma at the First Medical Center of the PLA General Hospital between February 2006 and September 2023. Statistical analyses were conducted using SPSS 25.0 and R 4.3.2. Survival analyses were performed using the Kaplan-Meier method, and univariate analyses were used to identify clinical and pathological factors associated with prognosis. Variables with P<0.05 in the univariate analysis were included in multivariate Cox regression models to identify independent risk factors for OS and RFS. These factors were incorporated into the prediction models to construct nomograms. The discriminatory power of the models was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) analyses, while calibration curves, decision curve analysis (DCA), and comparisons with the 8th edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) were employed to evaluate model performance. Results:Among the 82 patients, 36 (43.9%) exhibited vascular infiltration, 61 (74.4%) had nerve infiltration, and lymph node metastasis was observed in 60 cases (73.2%). Pathological stages I, II, III, and IV were distributed as 11 (13.4%), 26 (31.7%), 44 (53.7%), and 1 (1.2%) cases, respectively. Inflammatory markers included neutrophil-to-lymphocyte ratio (NLR) ≥ 4.33 in 22 cases (26.8%), platelet-to-lymphocyte ratio (PLR) ≥ 142.2 in 50 cases (61.0%), monocyte-to-lymphocyte ratio (MLR) ≥ 0.411 in 22 cases (26.8%), α-fetoprotein (AFP) ≥ 2.48 μg/L in 64 cases (78.0%), and C-reactive protein (CRP) ≥ 7.506 mg/L in 12 cases (14.6%). Among the 82 patients, 3 cases (3.6%) were lost to follow-up. The median follow-up time was 52 (range: 8–147) months, with a median OS of 61(2–147) months. The 1-year and 3-year OS rates were 78.5% and 58.5%, respectively, while the 1-year and 3-year RFS rates were 77.3% and 60.3%, respectively. Multivariate analysis identified several independent risk factors influencing OS in patients with HAS: advanced pathological stage, MLR ≥ 0.411, AFP ≥ 2.545 μg/L, and CRP ≥ 7.51 mg/L. The hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: 5.218 (1.230–22.143), 2.610 (1.287–5.294), 2.950 (1.013–8.589), and 2.594 (1.145–5.877), respectively (all P < 0.05). For RFS, advanced pathological stage, PLR ≥ 152.0, and MLR ≥ 0.411 were independent risk factors, with HRs (95% CIs) of 4.735 (1.080–20.760), 3.759 (1.259–11.226), and 2.714 (1.218–6.048), respectively (all P < 0.05). The AUC values for OS prediction at 1 year, 3 years, and 5 years were 0.7765, 0.7525, and 0.7702, respectively. For RFS, the AUC values were 0.7304, 0.8137, and 0.8307 at 1 year, 3 years, and 5 years, respectively. The calibration curves demonstrated strong agreement between nomogram- predicted outcomes and observed survival data. DCA indicated that both TNM staging and the nomogram-based clinical prediction models provided a net positive benefit in predicting OS and RFS in HAS patients, with the nomogram model demonstrating superior performance. Conclusion:The nomogram-based clinical prediction models developed in this study demonstrated robust performance in predicting long-term OS and RFS in patients with HAS.

Aortic aneurysm(AA)and aortic dissection(AD)are critical cardiovascular disease emergencies that seriously threaten human life and health.Due to various factors,the progressive reduction of various types of cells,such as smooth muscle cells and endothelial cells in the aortic wall,is an essential mechanism for developing AA and AD.On this basis,AD is induced by mechanical stresses such as hypertension,leading to damaged endothelial rupture or hemor-rhage within the aortic wall.However,AA causes the aortic wall to thin and expand outward in response to stimuli such as prolonged blood flow impingement.At present,increasing evidence shows that various programmed cell death,such as apoptosis,necroptosis,pyroptosis,ferroptosis,copper death,poly ADP-ribose polymerase 1(PARP-1)-dependent cell death,and immunogenic cell death,play essential roles in the pathogenesis of AA and AD.Therefore,understanding the key molecules and pathways in the pathogenesis of AA and AD from the perspective of programmed cell death and searching for inhibitors of various types of programmed death is essential to prevent aortic destruction and disease progression.The review summarizes the roles and research progress of different types of programmed cell death modalities in the development of AA and AD,clarifies the central position of programmed cell death in forming AA and AD,and searches for new thera-peutic methods for the clinic.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.