OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

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.

ObjectiveTo construct a stable monoclonal human embryonic kidney 293 （HEK293） cell line expressing recombinant human coagulation factor Ⅶ （rhFⅦ） and evaluate the expression level and procoagulant bioactivity of rhFⅦ. MethodsThe plasmid pCDNA3.1-EGFP-FⅦ was transfected into HEK293 cells to verify the effectiveness of the transfection system. The plasmid pCDNA3.1-FⅦ was transfected into HEK293 cells， and monoclonal stable transfected cell lines were selected using geneticin （G418）. The transcription of the FⅦ gene was identified by reverse transcription polymerase chain reaction （RT-PCR）. The expression level of rhFⅦ in the supernatant of the monoclonal stable transfected cell line was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. The concentration of rhFⅦ was determined by enzyme-linked immunosorbent assay （ELISA）， and the procoagulant activity of rhFⅦ was measured by human coagulation factor Ⅶ potency assay. ResultsHEK293 cells transfected with pcDNA3.1-EGFP-FⅦ showed green fluorescence， indicating that rhFⅦ was successfully expressed in the supernatant of HEK293 cells after transient transfection with pcDNA3.1-FⅦ. The monoclonal stable transfected cell line was obtained by G418 screening. RT-PCR identified that the FⅦ gene was integrated into the genome of the monoclonal stable transfected cell line. The cell viability was good as detected by Cell Counting Kit-8， and a single band of rhFⅦ was obtained by purification of the cell supernatant. The highest rhFⅦ expression was （1.27±0.09） mg/L， and the highest procoagulant activity was （380.29±13.80）%. ConclusionThe monoclonal HEK293 cell lines which can express rhFⅦ protein efficiently and stably with excellent procoagulant bioactivity is successfully screened.

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.

[Objective]To analyze the prescriptions for the differentiation,treatment and application in the Treatise on Three Categories of Pathogenic Factors regarding low back pain by using data mining technology,and to explore CHEN Wuze's understanding of low back pain as well as the rules for prescribing medications.[Methods]Prescriptions that met the inclusion criteria were screened to establish a database.The IBM SPSS Modeler 18.0 software was used for association rule analysis,and the SPSS statistics 26.0 software was adopted for drug frequency statistics and cluster analysis.Combined with ancient literature records,CHEN's understanding of low back pain,treatment ideas and medication rules were analyzed.[Results]A total of 63 prescriptions were included,involving 143 types of Chinese medicinal herbs with a total frequency of 581 applications.Seventeen high-frequency herbs were identified,primarily including roasted licorice(Glycyrrhiza uralensis),poria(Poria cocos),ginger(Zingiber officinale),aconite(Aconitum carmichaelii),white peony root(Paeonia lactiflora),and cinnamon bark(Cinnamomum cassia).Common herb pairs included"Atractylodes macrocephala-Poria cocos","Poria cocos-Cinnamomum cassia"and"Cinnamomum cassia-Angelica sinensis".The predominant therapeutic effects involved tonifying and deficiency-replenishing medicinals.Medicinal properties were mainly warm,neutral and cold,with sweet,pungent and bitter flavors predominating.Herbs primarily entered the spleen,kidney and lung meridians.Cluster analysis categorized high-frequency herbs into three groups associated with functions such as dispelling wind and eliminating dampness,tonifying the liver and kidney,relaxing tendons and nourishing blood and warming Yang to resolve dampness.[Conclusion]CHEN's approach to treating low back pain emphasizes differentiation and treatment based on the three etiological factors(internal,external and non-internal/external causes),and a spleen-stomach-focused treatment strategy.Core therapeutic principles included strengthening the spleen to eliminate dampness,warming Yang to resolve dampness and warming/unblocking blood vessels.This article summarizes and extracts the medication rules and academic thoughts of CHEN from the Yongjia medical school in treating lumbago,which has reference value for the clinical treatment of lumbago.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.

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.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To investigate the status of allostatic load (AL) in patients with polycystic ovary syndrome (PCOS) and its influence on the clinical outcomes of in vitro fertilization-embryo transfer.Methods:This was a prospective study. By using convenient sampling method, 421 patients with PCOS (PCOS group) and 372 control infertility patients (control group) in the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from April 2022 to January 2024 were investigated for basic information, physical examination, laboratory examination and follow-up of clinical outcomes. The total score of AL was calculated using 16 related indicators of cardiovascular system, metabolic system and immune system, and AL>3 was used as the judgment criteria for the high level AL group and the low level AL group. The differences in general data, embryo development and clinical outcomes between the groups were compared.Results:There were 222 cases (52.7%, 222/421) in PCOS low level AL group and 199 cases (47.3%, 199/421) in PCOS high level AL group. There were 214 patients (57.5%, 214/372) in the control low level AL group and 158 patients (42.5%, 158/372) in the control high level AL group. Embryo development outcomes: number of oocytes retrieved (median: 12, 12, 19, 14, respectively; P<0.001), number of two pronuclei (median: 8, 7, 11, 8, respectively; P<0.001), number of fertilization (median: 9, 9, 13, 10, respectively; P<0.001), number of metaphase of meiosis Ⅱ oocytes (median: 9, 8, 13, 10, respectively; P<0.001), number of transferable embryos (median: 5, 5, 7, 6, respectively; P<0.001), number of high-quality embryos (median: 4, 3, 6, 5, respectively; P<0.001), gonadotropin(Gn) starting dosage (median: 150, 200, 150, 200 U, respectively; P<0.001), total dosage of Gn (median: 1 800, 2 075, 1 575, 2 025 U, respectively; P<0.001), duration of Gn used (median: 10, 10, 10, 10 days, respectively; P=0.027) in the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group were significantly different. Pairings between groups showed that number of oocytes retrieved, number of two pronuclei, number of fertilization, number of metaphase of meiosis Ⅱ oocytes and number of transferable embryos in PCOS high level AL group were lower than those in PCOS low level AL group (all P<0.05); Gn starting dosage and total dosage of Gn in PCOS low level AL group were lower than those in the other three groups (all P<0.05); duration of Gn used in PCOS high level AL group was higher than that PCOS low level AL group ( P<0.05). Clinical outcomes: the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group underwent fresh transplantation [27.4% (57/208), 24.4% (38/156), 15.1% (32/212), 17.1% (33/193), respectively; P=0.006] and the proportion of transplanted day 5 embryos [82.7% (172/208), 77.6% (121/156), 91.0% (193/212), 86.5% (167/193), respectively; P=0.018] were statistically significant. There were no significant differences in fertilization rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate and early abortion rate among the four groups (all P>0.05). Conclusion:The high level of AL in PCOS patients may affect the outcomes of embryo development, and more attention should be paid to AL in PCOS patients to reduce stress.