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 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 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.

Drawing on recent advances in modern fascial anatomy and biomechanics， this paper interprets the biomechanical implications of yin-yang balance at the physical level from the perspective of holistic force lines. It posits that holistic force lines represent the functional expression of mechanical load transmission and integration within the myofascial network； the channel sinews system and myofascial chains exhibit significant similarities in terms of their distribution， functional attributes， and principles of holistic regulation， and can thus be understood as structural-functional carriers of yin-yang balance. Accordingly， this paper provides a biomechanical interpretation of the yin-yang relationship from four aspects， including interdependence， mutual restriction， dynamic balance through waxing and waning， and mutual transformation， proposing that in a healthy state， the body relies on the continuous integration， distribution， and readjustment of the myofascial tension network to maintain overall coordination， whereas disease states are often associated with compensatory transmission of local tension abnormalities along holistic force lines， the accumulation of imbalances， and structural rigidity. The holistic force-line perspective provides a biomechanical explanatory framework for the theory of yin-yang balance and offers a new theoretical basis for clinical diagnosis and treatment to shift from empirical holistic balancing toward holistic force-line balancing based on posture， function， and tension transmission pathways.

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 explore the relationship between social media use and internalized homophobia in homosexual and bisexual persons,and the role of self-esteem and perceived social support.Methods:A total of 626 homosexual and bisexual persons were selected through online social media platforms,and the Social Media Use In-tensity Scale(SNSIS),Self-Esteem Scale(SES),Perceived Social Support Scale(PSSS)and Internalized Homo-phobia Scale(IHS)were used for measurement.Use the SPSS macro program PROCESS to test moderated media-tion effects.Results:The average SNSIS score was(3.0±1.0).The SES score played a partial mediating role in the relationship between SNSIS scores and IHS scores,and the value of mediating effect was 21.43％.The PSSS scores moderated the relationship between the SNSIS scores and the SES scores(β=-0.10,P＜0.01),and the re-lationship between the SES scores and the IHS scores(β=-0.11,P＜0.01).Conclusion:Social media use by ho-mosexual and bisexual persons is associated with internalized homophobia,self-esteem mediated the relationships,and perceived social support plays a moderating role.

Objective:To analyze the factors influencing the achievement of "textbook outcome" (TO) after pancreaticoduodenectomy (PD) and explore the relationship of postoperative prognoses with TO.Methods:The clinical and pathological data of 169 patients treated by PD between January 2021 and December 2023 at the First Affiliated Hospital of Harbin Medical University were retrospectively analyzed. The patients were divided into the TO group ( n=91) and the non-TO group ( n=78) based on whether they met the TO criteria after sugery. According to the benignity or malignancy of the tumor, patients in the two groups above were futher divided into a non-malignant tumor subgroup (benign and junctional) and a malignant tumor subgroup, of which there were 10 cases of non-malignant tumor subgroup and 81 cases of malignant tumor subgroup in the TO group, and 9 cases of non-malignant tumor subgroup and 69 cases of malignant tumor subgroup in the non-TO group. Data collected included general patient information, laboratory indices on postoperative day 3, pathological findings, intraoperative blood loss, operative duration, and the like. Patients with malignant tumors were followed up until December 2024. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for clinical data. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors affecting TO achievement. Survival curves for patients with malignant tumors in the TO and non-TO groups were plotted using the Kaplan-Meier method and compared with the Log-rank test. Results:Among the 169 patients, 91 patients (53.8%) achieved TO. There were 150 patients (88.76%) with malignant tumors, all of whom achieved R0 resection. Univariate analysis showed that a history of cardiovascular/cerebrovascular disease, main pancreatic duct diameter, white blood cell count on postoperative day 3, aspartate aminotransferase level, total bilirubin level, serum urea nitrogen level, pancreatic texture, and operative duration were factors influencing TO achievement (all P value <0.05). Multivariate analysis identified that a postoperative white blood cell count greater than 16.35×10 9/L ( OR=3.558, 95% CI 1.319-9.596), a postoperative serum urea nitrogen levels exceeding 5.42 mmol/L ( OR=2.154, 95% CI 1.070-4.334), soft pancreatic texture ( OR=2.321, 95% CI 1.035-5.203), and an operative duration exceeding 312.50 min ( OR=2.043, 95% CI 1.005-4.154) were independent risk factors that prevented the achievement of TO (all P value <0.05). Kaplan-Meier survival analysis revealed that the 1-, 2-, and 3-year survival rates for patients with malignant tumors in the TO group were 67.90%, 47.73%, and 36.84%, respectively, which were significantly higher than those in the non-TO group (57.90%, 32.00%, and 31.58%, respectively; all P value <0.05). The median survival time was 28 months in the TO group and 16 months in the non-TO group, with a statistically significant difference ( P<0.05). Conclusions:Postoperative white blood cell count, serum urea nitrogen level, pancreatic texture, and operative duration are independent risk factors affecting the achievement of TO. For patients with malignant tumors, achieving TO is beneficial for prolonging survival time and improving survival rates.

Objective:To investigate the magnetic resonance imaging (MRI) features of pediatric and adolescent mediastinal T-lymphoblastic lymphoma (T-LBL) and to evaluate their predictive value for early treatment response.Methods:A retrospective, multicenter case series study was conducted on 49 pediatric and adolescent patients diagnosed with mediastinal T-LBL between September 2020 and May 2024 at the Fifth Affiliated Hospital of Zhengzhou University, Beijing Gaobo Boren Hospital, and Henan Cancer Hospital.All patients underwent chest MRI, including conventional MRI sequences and diffusion-weighted imaging.Tumor imaging characteristics were analyzed, and quantitative parameters such as minimum apparent diffusion coefficient (ADCmin), maximum ADC (ADCmax), and mean ADC (ADCmean) were measured.Treatment response was evaluated 15 days post-treatment.The patients were divided into a response group (complete or partial response, 26 cases) and a non-response group (progressive disease or minor response, 23 cases).The relationship between MRI features and treatment response was analyzed.The intraclass correlation coefficient was used to assess inter-reader agreement, and independent sample t-tests and chi-square tests were employed to compare differences between groups.Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of imaging parameters. Results:Significant differences were observed between the response and non-response groups in ADC values [ADCmin (0.80±0.41)×10 -3 mm 2/s vs.(1.23±0.70)×10 -3 mm 2/s, ADCmax (1.14±0.48)×10 -3 mm 2/s vs.(1.92±0.77)×10 -3 mm 2/s, ADCmean (0.98±0.42)×10 -3 mm 2/s vs.(1.56±0.74)×10 -3 mm 2/s] and the maximum tumor diameter was [(11.92±3.61) cm vs.(8.17±2.46) cm] (all P<0.05).ROC curve analysis showed that ADCmax had the highest predictive efficiency for treatment response, with an area under the curve (AUC) of 0.853 (95% CI: 0.790-0.910), sensitivity of 92.3%, and specificity of 65.2%.The AUC for the maximum tumor diameter was 0.814, demonstrating its excellent predictive performance. Conclusions:MRI features, particularly ADC values and the maximum tumor diameter, can effectively predict treatment response in pediatric and adolescent mediastinal T-LBL.

Objective:To investigate the clinical efficacy of open arthrolysis in the treatment of posttraumatic elbow stiffness.Methods:A retrospective analysis was conducted on the data of 407 patients with post-traumatic elbow stiffness treated by open arthrolysis surgery in Shandong Provincial Hospital from January 2010 to January 2024. The cohort included 303 males and 104 females, with a mean age of 38.98±10.90 years (range, 18-72 years) and mean body mass index (BMI) of 24.32±3.29 kg/m 2 (range, 17.91-33.41 kg/m 2). There were 230 patients with right-sided elbow stiffness, 159 patients with left-sided elbow stiffness, and 18 patients with bilateral elbow stiffness. Initial injuries included 21 patients of isolated elbow dislocation; 25 patients of soft tissue injury; and 361 patients of initial intra-articular elbow fractures, among which there were 200 patients of multiple fractures, 87 patients of single distal humerus fracture, 43 patients of single proximal ulna fracture, and 31 patients of single radial head fracture. Initial injuries were treated non-surgically in 69 cases and surgically in 338 cases, among which 177 cases were retained with internal fixation. There were 334 preoperative patients complicated with heterotopic ossification and 73 patients without heterotopic ossification, with 99 patients undergoing early release (stiffness duration <6 months) and 308 patients undergoing late release (stiffness duration ≥6 months). Record the range of motion (ROM) of the elbow joint, forearm rotational range (FRR), visual analogue scale (VAS), Mayo elbow performance score (MEPS), modified Broberg-Morrey score (MBS), Oxford elbow score (OES), and disability of arm, shoulder and hand (DASH) score before and after surgery, and conduct comparative analysis. Results:All patients were followed up for an average of 41.86±10.27 months (range, 13-119 months). At 12 months postoperatively, elbow ROM improved from preoperative 33.7°±26.5° to 101.2°±24.0°, elbow FRR improved from preoperative 101.4°±53.5° to 138.9°±38.7°, the MEPS increased from 60.1±14.7 to 91.5±10.1, the BMS increased from 57.5±12.8 to 83.7±11.0, the OES decreased from 31.6±7.3 to 16.0± 4.6, the DASH score decreased from 38.8±13.9 to 10.1±9.5, and the VAS decreased from 3.0±2.3 to 0.9±1.1, with all changes showing statistical significance ( P<0.05). In patients with preoperative heterotopic ossification, postoperative mean flexion range was 120.1°±15.5° and elbow ROM was 102.6°±23.4°. In patients without preoperative heterotopic ossification, postoperative mean flexion range was 113.9°±15.6° and elbow ROM was 93.4°±26.4°. Statistically significant differences were observed between the two groups in postoperative flexion range and flexion-extension ROM. There were no statistically significant differences in the postoperative above-mentioned indicators between early and late release patients ( P>0.05). The supination range and elbow FRR in patients with multiple fractures were lower than those in patients with distal humerus fractures and proximal ulna fractures; the DASH score in patients with multiple fractures was higher than that in patients with proximal ulna fractures and radial head fractures; the OES score in patients with multiple fractures was higher than that in patients with proximal ulna fractures, and all differences were statistically significant ( P<0.05). Among 407 patients, complications included new-onset postoperative ulnar neuropathy in 61 cases, new heterotopic ossification in 11 cases, recurrent heterotopic ossification in 96 cases, elbow instability in 6 cases, and superficial surgical site infection in 2 cases. Conclusions:Open arthrolysis is an effective treatment option for post-traumatic elbow stiffness. Patients with preoperative heterotopic ossification have a greater postoperative flexion range and elbow flexion-extension range of motion. The surgical timing exerts no significant influence on the ultimate functional outcome of treatment in patients with post-traumatic elbow stiffness. Patients with different initial fracture sites exhibited significant differences in postoperative functional outcomes, including supination, DASH scores, and OES.

Exosome play a crucial role in human immunodeficiency virus（HIV）infection. They share high similarities with HIV virions in physicochemical properties and secretion mechanisms：both the formation and secretion of exosome and the budding of HIV depend on the endosomal sorting complex required for transport（ESCRT）complex and VPS4 protein，with their membrane structures being phospholipid bilayers and comparable ranges of diameter and density. These similarities pose challenges to related research. Exosome participate in HIV infection through multiple mechanisms，including promoting HIV entry，inhibiting HIV replication，activating HIV latent reservoirs，and engaging in host antiviral immune responses. In terms of clinical applications，the potential of exosome as biomarkers or vaccine carriers has attracted attention，showing translational prospects. In summary，exosome influence the progression of HIV infection through complex mechanisms，and their application prospects in diagnostic markers，vaccine development，and therapeutic targets merit in-depth exploration.