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.

Prostate cancer (PCa) ranks as the second most prevalent malignancy among men worldwide. Early diagnosis, personalized treatment, and prognosis prediction of PCa play a crucial role in improving patients' survival rates. The advancement of artificial intelligence (AI), particularly the utilization of deep learning (DL) algorithms, has brought about substantial progress in assisting the diagnosis, treatment, and prognosis prediction of PCa. The introduction of the foundation model has revolutionized the application of AI in medical treatment and facilitated its integration into clinical practice. This review emphasizes the clinical application of AI in PCa by discussing recent advancements from both pathological and imaging perspectives. Furthermore, it explores the current challenges faced by AI in clinical applications while also considering future developments, aiming to provide a valuable point of reference for the integration of AI and clinical applications.
Humans ; Prostatic Neoplasms/diagnosis* ; Male ; Artificial Intelligence ; Deep Learning ; Prognosis

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

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*

Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective: To understand the association of maternal emotional symptoms and parent-child relationship with emotional and behavioral problems (EBPs) in primary school students, so as to provide a reference for the prevention of EBPs in primary school students. Methods: In May 2023, a convenient cluster sampling method was used to select 1 324 students from two primary schools in Hefei City, Anhui Province as the study subjects. The Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9), Family Adaptation and Cohesion Evaluation ScalesⅡ (FACES Ⅱ), and Strengths and Difficulties Questionnaire (SDQ) of parental version were used to investigate maternal emotional symptoms, parent-child relationship, and EBPs of primary school students, respectively. Multivariate Logistic regression analysis model was used to analyze the association of different maternal emotional symptoms and parent-child relationship with EBPs of primary school students. Results: The abnormal detection rates of emotional symptoms, conduct problems, hyperactivity disorder, peer problems, prosocial behavior and total difficulties in primary school students were 13.6%, 19.4%, 20.2%, 36.5%, 20.9% and 51.9%, respectively. Multivariate Logistic regression analysis showed that the detection rates of EBPs in primary school students whose mothers had anxiety and depression symptoms with low level of parent-child relationship increased ( OR=1.52-6.97, P <0.01). The combined effect of mothers who had anxiety and depression symptoms with low level of parent-child relationship increased the risk of EBPs in all dimensions of primary school students ( OR=4.07-10.14, P <0.01). After gender stratification, the combined effect of mothers who had anxiety and depression symptoms with low level of parent-child relationship increased the risk of EBPs in all dimensions of boys and girls ( OR=3.71- 10.95 , P <0.01). Conclusions Maternal emotional symptoms and parent-child relationship are associated with EBPs in primary school students. Reducing maternal anxiety and depression symptoms, and improving parent-child relationship are beneficial to reduce the incidence of EBPs problems in primary school students.

BACKGROUND:The basic principle of the design of the robot system used for total knee arthroplasty is to combine three-dimensional surgical planning,early warning of danger areas during surgery,real-time data feedback,robot arm assisted osteotomy and other technologies to achieve precision and personalization of total knee arthroplasty,which is exactly its biggest advantage.Therefore,it has become a hot topic in the field of joint surgery in recent years and attracted much attention. OBJECTIVE:To summarize the development status of robotic-assisted total knee arthroplasty in the field of joint surgery and the comparison of advantages and disadvantages with conventional total knee arthroplasty and to prospect the future development of robotic-assisted total knee arthroplasty. METHODS:Relevant articles were searched from PubMed,CNKI,Wanfang and VIP databases by computer.English key words were"robot OR robotic OR robotics OR robotically OR computer,total knee arthroplasty OR total knee replacement,TKA OR TKR".Chinese key words were"robotic-assisted,computer navigation,total knee arthroplasty".Finally,64 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The robot system used to assist total knee arthroplasty is divided into active,semi-active and passive according to its degree of freedom.The semi-active system,currently widely used in robotic systems,effectively enhances the accuracy and personalization of total knee arthroplasty.However,its high implementation cost and relatively steep learning curve remain key factors to be balanced when promoting its adoption in joint surgery field.(2)Robotic-assisted total knee arthroplasty can achieve precise osteotomy and correct placement of prosthesis in local three-dimensional space of the knee joint.It has been widely proven that it can provide better accuracy of prosthesis implantation,reduce imaging abnormalities,obtain good soft tissue balance during the operation,and ultimately improve the motion and functional status of the knee joint after the operation.(3)However,the current robotic-assisted system still has objective shortcomings,including the problem of learning curve between different robot devices and operators,additional installation and maintenance costs,and potential complications related to robot surgery.Therefore,whether it can truly benefit the medical system and patients still needs to be proven by long-term research,and the robotic-assisted system also needs to be further improved substantially.(4)Robotic-assisted total knee arthroplasty technique is still in the preliminary research stage in clinical practice and has not been widely applied.To better define the usage of robotic-assisted total knee arthroplasty and enhance its clinical procedural standards and safety,refining these aspects will become a focal point of future research on robotic-assisted total knee arthroplasty.

Objective To study the mechanism of the treatment of metabolism associated steatohepatitis(MASH)in rats with Xiaoyao Wan.Methods Twenty-four SD male rats were randomly divided into control group(CON group,n=8)and model group(n=8).The model group was given high-fat diet,carbon tetrachloride(CCl4)subcutaneous injection,hunger and satiety disorder and tail clamping for four weeks to establish the MASH model,and the rats were randomly divided into the MOD group and the Xiaoyao Wan group(XYW group),with 8 rats in each group.The rats of the XYW group were given Xiaoyao Wan,the other two groups were given normal saline.Four weeks after administration,the serum biochemical indexes and oxidative stress indexes of rats in different groups were detected.The pathological sections of rat liver tissue were observed by hematoxylin-eosin(HE)stai-ning and oil red O staining.The expression of cytochrome P450 2E1(CYP2E1),factor-related apoptosis ligand(FasL),tumor necrosis factor-α(TNF-α)and tumor growth factor-β1(TGF-β1)in rat liver were detected by Western blot method.The relative contents of CYP2E1,FasL,TNF-α and TGF-β1 mRNA in liver tissue were de-tected by RT-qPCR.Results The general condition of rats in the XYW group was significantly improved compared with the MOD group;the level of hepatic index was significant decrease compared with the MOD group(P＜0.01)and the level of body mass index was significant increase compared with the MOD group(P＜0.01);the serum levels of triglyceride,total cholesterol,low-density lipoprotein cholesterol,aspartate aminotransferase,alanine aminotransferase,malondialdehyde,monocyte chemotactic protein-1,TNF-α,and interleukin(IL)-18 were signif-icantly reduced compared with the MOD group(all P＜0.05),and the levels of high-density lipoprotein choles-terol,superoxide dismutase,and IL-10 were significantly elevated compared with the MOD group(all P＜0.05);the content of lipid droplets in hepatocytes of rats was significantly reduced compared with the MOD group under light microscope;the protein levels of CYP2E1,FasL,TNF-α and TGF-β1 in liver tissues were significantly re-duced compared with the MOD group(all P＜0.05),and the relative contents of CYP2E1,FasL,TNF-α and TGF-β1 mRNA were significantly reduced compared with the MOD group(all P＜0.05).Conclusion Xiaoyao Wan can regulate the expression of CYP2E1,FasL,TNF-α and TGF-β1 in the liver tissue of MASH rats by reduc-ing the accumulation of fat in the liver,so as to achieve the purpose of treating MASH.