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.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

In graduate course of"Advanced Pharmacology",problem-based learning(PBL)was used to stimulate students'initiative.To further study the advanced pharmacology knowledge,the new use of old drugs,literature re-viewing,clinical case and flipped classroom were applied in the courses to comprehensively strengthen capacity building of students'scientific thinking and reasoning.The outcomes of this course remodeling are well appreciated.

Objective:To investigate the effects of circular RNA(circRNA)hsa_circ_0081621 on the malignant biological behaviors of human laryngeal squamous cell carcinoma AMC-HN-8 and TU177 cells.Methods:AMC-HN-8 and TU177 cells were routinely cultured.si-NC,si-hsa_circ_0081621,empty vector(vector),and hsa_circ_0081621 overexpression vector(hsa_circ_0081621-OE)were transfected into AMC-HN-8 and TU177 cells,namely si-NC,si-hsa_circ_0081621,vector,and hsa_circ_0081621-OE groups,respectively.The effects of knockdown or overexpression of hsa_circ_0081621 on the proliferation,migration,and invasion of AMC-HN-8 and TU177 cells were detected by CCK-8 assay,colony formation assay,scratch wound healing assay,and Transwell chamber assay.Results:Successful knockdown or overexpression of hsa_circ_0081621 was achieved in AMC-HN-8 and TU177 cells.hsa_circ_0081621 knockdown significantly inhibited while hsa_circ_0081621 overexpression significantly promoted the proliferation,migration,and invasion of AMC-HN-8 and TU177 cells(P<0.01 or P<0.001 or P<0.0001).Conclusion:hsa_circ_0081621 promotes the malignant biological behaviors of human laryngeal squamous cell carcinoma AMC-HN-8 and TU177 cells.

AIM:To investigate the mechanism of flavonoid extract from Dracocephalum rupestre hance(DRHF)in the treatment of gouty arthritis through network pharmacology,molecular docking and animal experiment.METHODS:Literature re-trieval was used to explore the main active chemi-cal components and targets of DRHF.Gouty arthri-tis disease targets were obtained using Gene Cards and OMIM databases,and drug-disease intersect-ing targets were obtained using Wayne online tools.protein-protein interactions(PPI)and other related network diagrams were constructed using Cytoscape software.GO and KEGG enrichment analyses were performed on the shared intersect-ing targets using Metascape database.A rat model of gouty arthritis was established by Coderre meth-od;the swelling degree of ankle joint,gait behav-iour scores of rats were observed,and hematoxylin-eosin(HE)staining was performed.ELISA and real-time PCR were used to detect the key targets pre-dicted by the network pharmacology,and the ef-fects of DRHF on the molecular mechanism and key targets of gouty arthritis were observed.RESULTS:A total of 7 active compounds and 129 candidate targets for the treatment of GA were obtained,in-cluding IL-6,IL-1β,RELA,TNF,PPARG,etc.and the KEGG enrichment results suggested that DRHF may be involved in PI3K-Akt,TNF,IL-17 and other signal transduction pathways.Animal results:HE staining showed that the thickening of synovial tissue was not obvious in each administered group,and syno-vial cell proliferation and inflammatory cell infiltra-tion were significantly improved;compared with the normal group,the serum levels of TNF,IL-6,and IL-1β in the model group were significantly higher(P＜0.05),and the mRNA of PPARG,IL-6,and RELA in the synovial tissues were significantly high-er;compared with the model group,the levels of TNF,IL-6,and IL-1β were significantly lower(P＜0.05)in the low group of DRHF(0.45 g/kg)and high group of DRHF(0.9 g/kg),TNF,IL-6,IL-1β lev-els were significantly reduced(P＜0.05);PPARG,IL-6,RELA mRNA in synovial tissue were significantly reduced.CONCLUSION:DRHF inhibits IL-17/PI-3K/TNF signaling pathway by down-regulating the ex-pression of IL-6,PPARG and RELA mRNA,decreas-ing the levels of IL-6,IL-1β and TNF,and then treat-ing gouty arthritis.

AIM:To investigate the mechanism of flavonoid extract from Dracocephalum rupestre hance(DRHF)in the treatment of gouty arthritis through network pharmacology,molecular docking and animal experiment.METHODS:Literature re-trieval was used to explore the main active chemi-cal components and targets of DRHF.Gouty arthri-tis disease targets were obtained using Gene Cards and OMIM databases,and drug-disease intersect-ing targets were obtained using Wayne online tools.protein-protein interactions(PPI)and other related network diagrams were constructed using Cytoscape software.GO and KEGG enrichment analyses were performed on the shared intersect-ing targets using Metascape database.A rat model of gouty arthritis was established by Coderre meth-od;the swelling degree of ankle joint,gait behav-iour scores of rats were observed,and hematoxylin-eosin(HE)staining was performed.ELISA and real-time PCR were used to detect the key targets pre-dicted by the network pharmacology,and the ef-fects of DRHF on the molecular mechanism and key targets of gouty arthritis were observed.RESULTS:A total of 7 active compounds and 129 candidate targets for the treatment of GA were obtained,in-cluding IL-6,IL-1β,RELA,TNF,PPARG,etc.and the KEGG enrichment results suggested that DRHF may be involved in PI3K-Akt,TNF,IL-17 and other signal transduction pathways.Animal results:HE staining showed that the thickening of synovial tissue was not obvious in each administered group,and syno-vial cell proliferation and inflammatory cell infiltra-tion were significantly improved;compared with the normal group,the serum levels of TNF,IL-6,and IL-1β in the model group were significantly higher(P＜0.05),and the mRNA of PPARG,IL-6,and RELA in the synovial tissues were significantly high-er;compared with the model group,the levels of TNF,IL-6,and IL-1β were significantly lower(P＜0.05)in the low group of DRHF(0.45 g/kg)and high group of DRHF(0.9 g/kg),TNF,IL-6,IL-1β lev-els were significantly reduced(P＜0.05);PPARG,IL-6,RELA mRNA in synovial tissue were significantly reduced.CONCLUSION:DRHF inhibits IL-17/PI-3K/TNF signaling pathway by down-regulating the ex-pression of IL-6,PPARG and RELA mRNA,decreas-ing the levels of IL-6,IL-1β and TNF,and then treat-ing gouty arthritis.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.

Objective To analyze the blood concentration monitoring results of 7 new antiepileptic drugs levetiracetam(LEV),oxcarbazepine(OXC),lamotrigine(LTG),topiramate(TPM),lacosamide(LCM),zonisamide(ZNS)and perampanel(PER)and provide a basis for clinical rational drug use.Methods Aretrospective analysis was conducted on the blood concentration monitoring results of 7 new antiepileptic drugs in a grade-A tertiary hospital in Beijing from November 2021 to March 2023,with a total of 6 537 valid concentration data collected.The patients were grouped according to age,gender and concomitant medication,and the blood drug concentration levels and compliance rates among the groups were analyzed and compared.Results The male to female patient ratio was 1.35∶1.There were statistically significant differences in the blood concentration distribution of OXC,LEV,LCM and TPM between genders(P<0.05).The blood concentration of LEV showed statistically significant differences between the pediatric group and the elderly group,as well as between the young adult group and the elderly group(P<0.05).The blood concentrations of OXC,ZNS and TPM showed statistically significant differences between the pediatric group and the young and middle-aged group,between the young and middle-aged group and the elderly group,and between the pediatric group and the young and middle-aged group,respectively(P<0.05).The highest and lowest overall compliance rates of blood concentration were observed for OXC and LCM,respectively.The compliance rates of OXC and TPM in the pediatric group were significantly higher than those in the young-middle-aged group,with statistically significant differences(P<0.05),while the compliance rate of LEV in the elderly group was significantly higher than that in the pediatric group and the young-middle-aged group,with a statistically significant difference(P<0.05).There were a total of 2 133 cases with combined drug use.LEV,OXC and LTG are frequently used and have good efficacy and weak interactions when added to treatment.Conclusion New antiepileptic drugs show a promising prospect in treatment,and therapeutic drug monitoring can further improve the effectiveness of individualized clinical treatment.