Abstract To clarify the relationship between sports participation and adolescent suicide risk, as well as its underlying mechanisms for preventing suicidal behaviors, the study employs a literature review approach to analyze, synthesize, and summarize relevant research. The findings reveal that physical exercise can reduce suicide rates among middle school students, with high intensity aerobic exercise performed 5-7 days per week demonstrating the most significant effect. However, daily physical activity and muscle strengthening exercises show no significant correlation with suicide related behaviors. The mechanisms through which physical activity reduces the risk of suicide among adolescents include emotional release leading to self help skills, helping adolescents build social connections, and improving physical and brain function. It is recommended that families and schools help adolescents discover the joy of participating in sports, assist in forming sports teams, and ensure at least 60 minutes of moderate to vigorous physical activity daily to reduce the risk of suicidal behavior among adolescents.

Objective CT scans combined with Mimics software were used to measure femoral offset(FO),rotation center height(RCH)and lower leg length discrepancy(LLD)following total hip arthroplasty(THA),and the relationship between FO,RCH and LLD after THA is discussed.Methods Retrospective analysis was performed on 40 patients with unilateral THA who met standard cases from October 2020 to June 2022.There were 21 males and 19 females,18 patients on the left side and 22 patients on the right side,aged range from 30 to 81 years old,with an average age of(58.90±14.13)years old,BMI ranged from 17.3 to 31.5 kg·m-2withan average of(25.3±3.4)kg·m-2.There were 30 cases of femoral head necrosis(Ficattype Ⅳ),2 cases of hip osteoarthritis(Tonnis type Ⅲ),2 cases of developmental hip dislocation combined with end-stage osteoarthritis(Crowe type Ⅲ),and 6 cases of femoral neck fracture(Garden type Ⅳ).Three-dimensional CT reconstruction of pelvis was taken preoperative and postoperative,and three-dimensional reconstruction model was established after processing by Mimics software.FO,RCH and LLD were measured on the model.The criteria for FO reconstruction were as follows:postoperative bi-lateral FO difference less than 5 mm;the standard for equal length of both lower limbs was as follows:postoperative LLD differ-ence less than 5 mm.Results Bilateral FO difference was positively correlated with LLD(r=0.744,P＜0.00l).Chi-square test was performed between the FO reconstructed group and the non-reconstructed eccentricity group:The results showed that the i-sometric ratio of lower limbs in the FO reconstructed group was significantly higher than that in the FO reconstructed group(x2=6.320,P=0.012).The bilateral RCH difference was significantly negatively correlated with LLD(r=-0.877,P＜0.001).There is a linear relationship between bilateral FO difference and bilateral RCH difference and postoperative LLD,and the lin-ear regression equation is satisfied:postoperative LLD=0.038x-0.099y+0.257(x:postoperative bilateral FO difference,y:post-operative bilateral RCH difference;Unit:cm),F=77.993,R2=0.808,P=0.009.Conclusion After THA,LLD increased with the increase of FO and decreased with the increase of RCH.The effect of lower limb isometric length can be obtained more easily by reconstruction of FO.There is a linear relationship between the bilateral FO difference and the bilateral RCH difference after THA and LLD,and the regression equation can provide a theoretical reference forjudging LLD.

The current treatment of glioma is facing drug resistance,which limits the efficacy of traditional chemotherapy drugs.This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound(KZL204)against glioma.Through the Cell Counting Kit-8(CCK-8)assay,we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells,with a 48-hour half-maximal inhibitory concentration(IC50)of 3.63±0.38 μmol/L,which is significantly better than the positive control drug temozolomide(TMZ)(IC50 value of 81.67±5.49 μmol/L).Additionally,flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase.At the same time,the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells.Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204,of which 1 320 were upregulated,and 1 115 were downregulated.KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways.Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets,with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes.Quantitative real-time PCR(RT-qPCR)experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1,CSF1,CXCL5,BCL3,and the upregulating effects on genes like FOS,LT A,PTGS2,MAP2K3.Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins,including the upregulation of Bax,cleaved Caspase-3 protein,and the downregulation ofAKT,Bcl-2,Caspase-3,and Caspase-8 protein expression.In summary,KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways,demonstrating its potential as a candidate drug against drug-resistant glioma.

Objective:To prepare mesenchymal stem cells with antioxidant capacity (AO-MSC ) from human umbilical cords and evaluate its cell biological properties.Methods:In control group,mesenchymal stem cells (MSC) were isolated by digesting human umbilical cord Wharton's Jelly tissues with 0.2％ collagenase Ⅱ,and the released cells were collected and cultured in an animal serum-free culture medium.In AO-MSC group,incompletely collagenase Ⅱ-digested tissue debris were allowed to adhere to flusk flat bottoms and the AO-MSC was harvested by adherent culture. The conventional digestion and culture method was used as control.MSC colony forming ability was evaluated by fibroblast colony forming assay (CFU-F).MSC proliferative capacity was evaluated by CCK-8 assay.The MSC surface markers were detected by using flow cytometry and immunofluorescence staining.The adipogenic and osteogenic capacity of MSC was evaluated by multi-differentiation in vitro,and the mRNA expression of genes that control adipogenic and osteogenic differentiation was detected by real-time fluorescence quantitative PCR (RT-qPCR );Moreover,the mRNA expression of antioxidant substances such as SOD-1,GSH,GAT,and NQO1 in MSC was also evaluated by RT-qPCR.Results:The AO-MSC isolated by this strategy reached a confluence of 80％-90％ at around 18 days and grew in a swirling pattern.Flow cytometry and immunofluorescence staining assays showed that CD73,CD29,CD105,CD90 were highly expressed and CD31,CD45,HLA-DR were scarcely expressed in AO-MSC.AO-MSC exhibited stronger self-renewal and differentiation ability compared to MSC.However,the in vitro adipogenic-osteogenic capacity of MSC in the control group was stronger than that of AO-MSC.RT-qPCR assay showed that AO-MSC expressed higher mRNA levels of antioxidant substances compared to MSC.Conclusion:Human AO-MSC is successfully prepared from human umbilical cord without animal serum.

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

BACKGROUND:High tibial osteotomy results in massive blood loss during the perioperative period.Tranexamic acid can effectively reduce perioperative blood loss.However,the method of tranexamic acid application has not been unified. OBJECTIVE:To investigate the effect and safety of different methods of tranexamic acid on perioperative blood loss in the high tibial osteotomy. METHODS:A total of 160 patients who underwent primary unilateral high tibial osteotomy in the Binzhou Medical University Hospital from January 2019 to December 2021,including 69 males and 91 females,were randomly divided into four groups(n=40 per group).Among them,40 patients were given an intravenous infusion of saline containing 2 g tranexamic acid 10 minutes before tourniquet release(venous group);40 patients were given an intravenous infusion of 1 g tranexamic acid and 1 g tranexamic acid was injected through a drainage tube after the closure of the incision(combined group);40 patients were given 2 g tranexamic acid infusion into drainage tube after the closure of the incision(perfusion group);an additional 40 patients were given an intravenous infusion of the same amount of normal saline(blank group).The general information was compared among the four groups of patients.The hemoglobin,hematocrit,intraoperative blood loss,drainage volume,blood transfusion rate,incision complication,and the incidence of deep vein thrombosis were recorded on days 1,3 and 5 after operation in the four groups.The total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in general information among the four groups.(2)No significant difference was found in intraoperative blood loss among the four groups.(3)The maximum decreased values of hemoglobin and hematocrit on days 1,3 and 5 after operation,drainage volume,total blood loss and hidden blood loss were all ranked as the combined group

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective:To investigate the correlation between triglyceride-glucose (TyG) index on admission and unfavorable outcomes of patients with moderate-to-severe traumatic brain injury (msTBI) at 6 months postinjury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 277 patients with msTBI admitted to Affiliated Jiangyin Hospital of Nantong University from January 2019 to December 2022, including 208 males and 69 females, aged 18-88 years [(57.0±15.1)years]. Glasgow Coma Scale (GCS) scores on admission were 3-8 points in 168 patients and 9-12 points in 109. According to the Glasgow Outcome Scale-Extended (GOSE) assessment at 6 months after injury, there were 121 patients with unfavorable outcomes (GOSE≤4 points) and 156 with favorable outcomes (GOSE≥5 points). The following indicators of the patients were recorded, including gender, age, history of diabetes, cause of injury, admission GCS, GCS motor score (GCSM), pupillary light reflex, worst Marshall CT classification within the first 24 hours after admission, admission TyG index, Mean Amplitude of Glycemic Excursions (MAGE) within 24 hours after admission, GCSM decline≥2 points within 72 hours after admission, craniotomy or not after admission, and prognosis, etc. TyG index served as the exposure variable focused in this study, which was calculated with fasting triglycerides and fasting blood glucose within 24 hours after admission. The 6-month prognosis of the patients was designated as the outcome variable of the study. After the patients were divided into different groups according to the three quantiles of the TyG index and unfavorable or favorable outcomes, the univariate analysis was conducted on watch variables, and variables with statistically significant differences were included in directed acyclic graphs (DAGs) for further identification of confounding variables. Factors which were found with no statistical significance in the univariate analysis but might affect insulin resistance after injury according to the authors′ previous researches were also included in the DAGs analysis. Three Logistic regression models were designed (Model 1 without correction, Model 2 with core variables of International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) corrected, and Model 3 with confounding variables screened by DAGs corrected) to analyze whether the TyG index was an independent risk factor for the prognosis of msTBI patients. The optimal Logistic regression model was selected and then restricted cubic spline (RCS) was employed to investigate the relationship between the TyG index and the unfavorable outcomes.Results:The univariate analysis suggested that there were significant differences in gender, history of diabetes, MAGE, GCSM decline, and prognosis among the three quantiles of the TyG index ( P<0.05 or 0.01). Significant differences in age, history of diabetes, GCSM, pupillary light reflex, Marshall CT classification, TyG index, MAGE and GCSM decline were observed between unfavorable and favorable outcome groups ( P<0.05 or 0.01). The results of Logistic regression analysis that identified the confounding variables that influenced the correlation between the TyG index and unfavorable prognosis with DAGs suggested that a high TyG index level was significantly correlated with unfavorable outcomes in msTBI patients. Moreover, Model 3 that was corrected with confounding variables screened by DAGs had an optimal goodness-of-fit and adaptability. Model 3-based further RCS analysis indicated that the risk of unfavorable outcomes following msTBI may increase approximately linearly with the increase in TyG index within a certain range (TyG index<9.79). Conclusions:A high TyG index level on admission is the identified as an independent risk factor for unfavorable outcomes of patients with msTBI at 6 months postinjury. As the TyG index level increases, the risk of unfavorable outcomes also rises and may show a linear increasing trend within a certain range (TyG index<9.79).

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.