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.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Objective:To preliminarily evaluate the lumen gain of sonodynamic therapy (SDT) mediated by sinoporphyrin sodium at carotid and femoral atherosclerotic plaque sites, and to assess whether concomitant statin use, lesion location, plaque echogenicity/type, and baseline stenosis severity modify the therapeutic response.Methods:This single-center, prospective, exploratory pilot clinical study enrolled patients with peripheral artery disease who attended the outpatient cardiology clinic of the First Affiliated Hospital of Harbin Medical University between February and September 2016. All enrolled patients received optimized oral medical therapy in combination with a single session of SDT. Vascular evaluation was performed using color Doppler ultrasound before treatment and 1 and 4 weeks after treatment. The primary efficacy endpoint was the percent change from baseline in luminal diameter stenosis at the site of the atherosclerotic plaque (%Δ) at week 4, while the secondary efficacy endpoint was %Δ at week 1. Subgroup analyses were conducted according to prior statin use, plaque location, plaque characteristics, and baseline degree of luminal stenosis.Results:A total of 24 patients, aged (70.7±2.2) years were enrolled. There were 20 (83%) males. Compared to baseline, luminal diameter stenosis at the plaque site reduced by week 4 ((50.1±1.2)% vs. (57.2±1.1)%, P<0.001), %Δ was(12.32±1.05)%; and luminal diameter stenosis also reduced by week 1 ((51.7±1.2)% vs. (57.2±1.1)%, P<0.001)), %Δ was(9.61±0.85)%. In subgroup analyses, the treatment effect on diameter stenosis was independent of prior statin use; SDT reduced stenosis in both carotid and femoral plaques; with superior efficacy observed in hypoechoic and mixed-echo plaques; and efficacy was observed across mild, moderate, and severe baseline stenosis categories (all P<0.05). Conclusion:In this single-center pilot study, SDT demonstrates therapeutic efficacy across mild, moderate, and severe stenoses, as well as in hypoechoic and mixed-echo plaques, showing potential to rapidly promote luminal gain at carotid and femoral atherosclerotic plaque sites.

Aim To predict and verify the potential mechanism of the compatibility of"ginseng-astragalus-pueraria"in protecting islet morphology and improving insulin resistance by using network pharmacology.Methods The active ingredients and targets of the horn medicine were obtained from three platforms:TC-MSP,TCMIP,and BATMAN.The targets of type 2 dia-betes mellitus(T2DM)were obtained from three plat-forms:TTD,OMIM,and disgeNET.The PPI network was constructed by using the STRING database and Cy-toscape 3.9.1;GO and KEGG analysis were per-formed;POCASA 1.1 was used to predict protein binding sites,and AutoDock Vina1.1.2 was used for docking and experimental verification.Results"Gin-seng-astragalus-pueraria"screened out 2 021 targets,of which 152 were closely related to T2DM,and 10 key genes and the AGE-RAGE signaling pathway were i-dentified.Molecular docking showed that quercetin had good binding to RAGE,INS,and PI3K.Experi-ments showed that the horn drug increased insulin binding rate and secretion index and reduced serum in-sulin level and insulin resistance index.These data benefited from"ginseng-astragalus-pueraria"reducing the expression of AGE-RAGE,activating PI3K-Akt,in-hibiting NF-κB,and reducing the expression of IL-6,IL-1β and TNF-α.Conclusion The study suggests that"ginseng-astragalus-pueraria"regulates the AGE-RAGE/PI3K-Akt/NF-κB signaling pathway,repairs damaged islet morphology,and improves insulin resist-ance.

Objective To establish an expert consensus on the management of low anterior resection syndrome(LARS)in patients with rectal cancer post-surgery(hereinafter referred to as"consensus"),aiming to standardize the related work of medical institutions in the context of post-operative LARS.Methods A comprehensive search of domestic and international databases was conducted to collect guidelines,expert consensuses,systematic reviews,evidence summaries,and original research related to post-operative LARS in rectal cancer published from the establishment of the databases until August 2024.Based on clinical practice experience,a preliminary draft of the"consensus"was formed.From September to November 2024,22 experts were invited to participate in 2 rounds of expert consultations,during which the draft content was revised and improved,and the final version of the"consensus"was determined through expert validation.Results A total of 22 experts responded,achieving a response rate of 100％.The effective recovery rate of the consultation questionnaires in both rounds was 100％,with an expert authority coefficient of 0.89,a judgment coefficient of 0.97,and a familiarity degree of 0.84.The Kendall harmony coefficients for the 2 rounds of expert consultations were 0.122 and 0.136,respectively(P＜0.001).This consensus covers 5 main aspects:definition,assessment,prevention,treatment,and follow-up management of LARS.Conclusion This consensus demonstrates a high level of scientific rigor and can provide a strong reference for clinical nursing personnel in the specialized care of rectal cancer patients with post-operative LARS.

Objective:To evaluate the effect of baicalein on acute myocardial injury in rats with high-level spinal cord injury (SCI) and the role of nuclear factor E2-related factor 2 (Nrf2).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SCI group, SCI+ baicalein group (SCI+ Bai group) and SCI+ baicalein+ ML385 group (SCI+ Bai+ ML385 group). The high-level SCI rat model was established by the modified Allens method. In Sham group, the 7th cervical vertebra (C 7) was only exposed, but the spinal cord was not hit. In SCI group, C 7 was exposed and the spinal cord was hit. In SCI+ Bai group, baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. In SCI+ Bai+ ML385 group, Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before SCI, and baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. The rats were anesthetized at 24 h after SCI and sacrificed after the blood samples from the abdominal aorta were collected and the hearts were taken for microscopic examination of the pathological changes (by HE staining) which were scored and the ultrastructure of cells (with a transmission electron microscope) and for determination of the serum cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay), content of ferrous ion (Fe 2+ ) in myocardial tissues (by colorimetry), contents of malondialdehyde(MDA) and glutathione (GSH) and activity of superoxide dismutase(SOD) in myocardial tissues (by biochemical method) and expression of glutathione peroxidase 4 (GPX4), acyl CoA synthase long chain family member 4 (ACSl4) and Nrf2 protein and mRNA in myocardial tissues (by Western blot and fluorescent quantitative polymerase chain reaction). The mitochondrial Flameng score was assessed and recorded. Results:Compared with Sham group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 was down-regulated, and the expression of ACSL4 and Nrf2 was up-regulated in SCI group ( P<0.05). Compared with SCI group, the pathological score, mitochondrial Flameng score and serum cTnI concentration were significantly decreased, the contents of Fe 2+ and MDA in myocardial tissues were decreased, the contents of GSH and SOD activity were increased, the expression of GPX4 and Nrf2 was up-regulated, and the expression of ACSL4 was down-regulated in SCI+ Bai group ( P<0.05). Compared with SCI+ Bai group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 and Nrf2 was down-regulated, and the expression of ACSL4 was up-regulated in SCI+ Bai+ ML385 group ( P<0.05). Conclusions:Baicalein can alleviate acute myocardial injury in rats with high-level SCI, and Nrf2 is involved in this process.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.