OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective: To explore the relationship between snack consumption and depressive symptoms in first year junior high school students with different left behind experiences in Yunnan Province, so as to provide a basis for improving depressive symptoms among first year junior high school students with different left behind experiences. Methods: From October to December 2022,a cluster random sampling method was used to select 8 500 first year junior high school students from 11 ethnic minority areas (Fugong County, Longling County, Longyang District, Luchun County, Mojiang County, Nanjian County, Qiaojia County, Shuangjiang County, Tengchong City, Yuanmou County, Zhenyuan County) in Yunnan Province for a questionnaire survey. The Chinese version of Depression Anxiety Stress Scale-21 was applied to assess depressive symptoms in first year junior high school students, and snack consumption was collected by employing food frequency questionnaire. The generalized linear model was used to analyze the association between first year junior high school students snack consumption and depressive symptoms, and the analysis was stratified according to left behind experience. Results: The detection rates of depressive symptoms among firstyear junior high school students with and without left behind experience were 36.25% and 26.91%, respectively. After controlling for confounding variables, the generalized linear model analysis showed that sweet snacks ( β=0.16, 95%CI =0.07-0.25), fast food ( β=0.14, 95%CI =0.04-0.23) and carbonated drinks ( β=0.09, 95%CI =0.01-0.17) of first year junior high school students with left behind experience (all P <0.05). Compared with those without such behavior, the risk of depressive symptoms was higher in consumption of fast food ( β=0.13, 95%CI =0.07-0.18) and carbonated drinks ( β=0.10, 95%CI =0.06-0.15)among first year junior high school students without left behind experience (both P <0.05). Conclusion Snack consumption among first year junior high school students in Yunnan may increase the risk of developing depressive symptoms, while first year junior high school students with left behind experience may have a greater risk of developing depressive symptoms.

Objective: To investigate the prevalence and associated factors of depressive symptoms among junior and senior high school students in Beijing from 2019 to 2023, in order to provide a scientific basis for interventions targeting high risk groups. Methods: From 2019 to 2023, a stratified cluster random sampling method was used to select 88 927 junior and senior high school students from 16 districts in Beijing. The Center for Epidemiologic Studies Depression Scale(CES-D) was conducted to assess depressive symptoms. The Chi square test was used to compare the detection rates of depressive symptoms among different student groups, and the trend Chi square test was employed for trend analysis of detection rates across the years. Multivariate Logistic regression analysis was applied to examine the association between the detection of depressive symptoms and related factors among junior and senior high school students. Results: From 2019 to 2023, the prevalence rates of depressive symptoms among junior and senior high school students in Beijing were 20.45%, 18.19%, 16.64%, 17.89% and 18.17%, respectively, with an overall downward trend ( χ 2 trend =27.51, P <0.01). Multivariate Logistic regression analysis revealed that after adjusting for gender, monitoring year, educational stage,family structure,boarding status and has taken a medical leave of absence in the past year unhealthy dietary behaviors ( OR=1.80, 95%CI =1.73-1.87), physical inactivity ( OR=1.24, 95%CI =1.19-1.29), try smoking ( OR=1.46, 95%CI =1.35-1.58), try alcohol( OR=1.96, 95%CI =1.88-2.05), Internet addiction ( OR=3.88, 95%CI =3.57-4.22), and adverse ear related behavior ( OR=1.82, 95%CI =1.71-1.93) were all associated with an increased risk of depressive symptoms among junior and senior high school students (all P <0.05). Conclusions The prevalence depression symptoms among middle school students in Beijing showed a fluctuating downward trend from 2019 to 2023. Targeted interventions should be adopted to reduce the occurrence of depression symptoms among junior and senior high school students.

Objective: To understand the trends of classroom lighting and illumination of primary and secondary schools in Beijing from 2016 to 2023, so as to provide a scientific basis for targeted improvement measures. Methods: A sampling survey was conducted on the lighting and illumination indicators of 8 390 classrooms in primary and secondary schools in Beijing from 2016 to 2023. The survey included classroom daylight factor, window to floor area ratio, average illuminance and illuminance uniformity on the desks, average illuminance and illuminance uniformity on blackboards, as well as classroom lighting and blackboard illumination sources. Intergroup comparisons were performed using the Kruskal-Wallis H test and the Chi square test, and Spearman correlation analysis was used to examine the trend of classroom lighting and illumination changes. Results: Except the window to floor area ratio, the measured values and compliance rates of all lighting and illumination indicators showed an overall upward trend from 2016 to 2023 (daylight factor r = 0.27, χ 2 trend =206.80, average illuminance on the desk surface r =0.30, χ 2 trend =87.97, illuminance uniformity on the desk surface r =0.14, χ 2 trend =73.59, average illuminance on the blackboard r =0.33, χ 2 trend =477.43, illuminance uniformity on the blackboard r = 0.09, χ 2 trend =50.76) (all P ＜0.01). The lighting and illumination indicators of classrooms (included classroom daylight factor, average illuminance and illuminance uniformity on the desks, average illuminance and illuminance uniformity on blackboards) in urban schools, primary schools, and secondary schools from 2016 to 2023 showed an upward trend (urban r =0.23-0.40, χ 2 trend =88.66-392.18; primary school r =0.12-0.36, χ 2 trend =39.50-281.44; secondary schools r =0.06-0.31, χ 2 trend =11.79-213.73) (all P ＜ 0.01 ). The illuminance uniformity on the blackboard in suburban schools showed a downward trend ( r = -0.09, χ 2 trend =31.53, both P ＜0.01). The illuminance uniformity on the desk surface in suburban schools showed no significant change ( r =0.03, χ 2 trend =1.23, both P ＞0.05). The other indicators showed an upward trend (daylight factor r =0.28, χ 2 trend =40.69, average illuminance on the desk surface r =0.24, χ 2 trend =16.35, average illuminance on the blackboard r =0.25, χ 2 trend =118.05, all P ＜0.01). The trends of classroom and blackboard illumination sources were that fluorescent lamps decreased year by year and LED lamps increased by year (classroom illumination sources χ 2 trend =1 059.82, blackboard illumination sources χ 2 trend =1 070.25, both P ＜0.01). Conclusions The classroom lighting and illumination in primary and secondary schools in Beijing has shown an overall improving trend from 2016 to 2023. However, problems remain, such as limited improvement of illuminance uniformity indicators, late start and poor effect of reconstruction in suburban schools. Further improvements are still needed.

Objective:To explore the clinical application value of serum N-glycan profiles for evaluating the severity of liver tissue inflammation in patients with chronic hepatitis B (CHB).Methods:A total of 221 CHB patients who underwent liver biopsy at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2018 to December 2020 were retrospectively enrolled. The Scheuer scoring system was used to assess the histological inflammation grade of the liver tissue. Serum N-glycan levels were measured using DNA sequencer-assisted N-glycan fingerprinting (NGFP). Using the upper limit of the alanine aminotransferase (ALT) reference value (40 U/L) as a cutoff, logistic regression models were developed to construct diagnostic models under two scenarios: normal ALT or abnormal ALT. Models based on serum N-glycan levels and serum N-glycan levels combined with routine laboratory indicators, were used to non-invasively evaluation of various pathological grades of liver tissue inflammation in CHB patients. The DeLong test was used to compare the diagnostic efficacy of the models by analyzing the areas under the receiver operating characteristic curve (AUC). Glycosylation-related gene expression differences associated with varying degrees of liver inflammation were analyzed using the Gene Expression Omnibus (GEO) database.Results:In CHB patients with normal ALT level, the relative abundances of N-glycan structure peak 1 (NGA2F) and peak 2 (NGA2FB) increased with higher liver inflammation grades, while the relative abundance of peak 5 (NA2) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G A) and its enhanced version (HIS-G A Plus) for identifying significant inflammation and necrosis (≥G2, indicating the initiation of antiviral therapy) were 0.805 (95% CI 0.690-0.899) and 0.904 (95% CI 0.821-0.960), respectively. In CHB patients with ALT>40 U/L, the relative abundances of peaks 1 (NGA2F), 2 (NGA2FB), and 3 (NG1A2F) increased with higher liver inflammation grades, while the relative abundances of peaks 8 (NA3) and 11 (NA4) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G B) and its enhanced version (HIS-G B Plus) for identifying significant inflammation (≥G2) were 0.810 (95% CI 0.727-0.889) and 0.838 (95% CI 0.754-0.901), respectively. With increasing liver inflammation grades, the expression levels of four glycosyltransferase genes (CHST4, FUT8, SLC51B, and ST8SIA4) were significantly upregulated ( P<0.05). Conclusions:Serum N-glycan biomarker models can be used to assist in evaluating the severity of liver tissue inflammation in CHB patients with both normal and abnormal ALT levels.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

ObjectiveTo explore the mechanism of total saponins of Dioscoreae Nipponicae Rhizoma （TSDN） in treating gouty arthritis （GA） by regulating cyclooxygenase-2 （COX-2）-mediated M1 macrophage reprogramming by in vivo and in vitro experiments. MethodsIn vivo experiment： 24 male SD rats were randomly allocated into blank， model （GA）， TSDN， and celecoxib groups， with 6 rats in each group. After 7 days of administration， pathological changes in the ankle synovial tissue were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to quantify the mRNA levels of NOD-like receptor protein 3 （NLRP3） inflammasome， apoptosis-associated speck-like protein （ASC）， Caspase-1， COX-2， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of inducible nitric oxide synthase （iNOS）， IL-1β， CD86， CD80， CD206， and arginase-1 （Arg-1）. In vitro experiment： The GA model was established by lipopolysaccharide （LPS） + MSU induction， and the inhibitor concentration was screened by the methyl thiazolyl tetrazolium （MTT） assay. RAW264.7 cells were allocated into blank， model， TSDN， dexamethasone， COX-2 inhibitor （celecoxib）， and TSDN + COX-2 inhibitor groups. The levels of iNOS， IL-1β， CD86， CD80， CD206， and Arg-1 in the cell supernatant of each group were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in each group were determined by Real-time PCR and Western blot， respectively. ResultsIn vivo experiment： compared with the model group， TSDN reduced the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in the synovial tissue （P<0.05， P<0.01）. ELISA results showed that TSDN lowered the serum levels of iNOS， IL-1β， CD86， and CD80 （P<0.01） while increasing the serum levels of CD206 and Arg-1 （P<0.01）. In vitro experiment： compared with the model group， TSDN and inhibitor down-regulated the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α and the protein levels of NLRP3 inflammasome， COX-2， cleaved IL-1β， and TNF-α （P<0.01）. Compared with TSDN alone， TSDN + COX-2 inhibitor further reduced the mRNA and protein levels of the markers above （P<0.01）. Compared with the model group， TSDN and COX-2 inhibitor decreased the levels of IL-1β， iNOS， CD80， and CD86 （P<0.01） and increased the levels of CD206 and Arg-1 （P<0.01） in cells. Compared with TSDN alone， TSDN + COX-2 inhibitor reduced IL-1β， iNOS， CD80， and CD86 levels （P<0.05， P<0.01） and elevated CD206 and Arg-1 levels （P<0.01） in cells. ConclusionTSDN can alleviate GA by downregulating COX-2-mediated M1 macrophage reprogramming and suppressing the inflammatory factors.

ObjectiveTo explore the mechanism of total saponins of Dioscoreae Nipponicae Rhizoma （TSDN） in treating gouty arthritis （GA） by regulating cyclooxygenase-2 （COX-2）-mediated M1 macrophage reprogramming by in vivo and in vitro experiments. MethodsIn vivo experiment： 24 male SD rats were randomly allocated into blank， model （GA）， TSDN， and celecoxib groups， with 6 rats in each group. After 7 days of administration， pathological changes in the ankle synovial tissue were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to quantify the mRNA levels of NOD-like receptor protein 3 （NLRP3） inflammasome， apoptosis-associated speck-like protein （ASC）， Caspase-1， COX-2， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of inducible nitric oxide synthase （iNOS）， IL-1β， CD86， CD80， CD206， and arginase-1 （Arg-1）. In vitro experiment： The GA model was established by lipopolysaccharide （LPS） + MSU induction， and the inhibitor concentration was screened by the methyl thiazolyl tetrazolium （MTT） assay. RAW264.7 cells were allocated into blank， model， TSDN， dexamethasone， COX-2 inhibitor （celecoxib）， and TSDN + COX-2 inhibitor groups. The levels of iNOS， IL-1β， CD86， CD80， CD206， and Arg-1 in the cell supernatant of each group were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in each group were determined by Real-time PCR and Western blot， respectively. ResultsIn vivo experiment： compared with the model group， TSDN reduced the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in the synovial tissue （P<0.05， P<0.01）. ELISA results showed that TSDN lowered the serum levels of iNOS， IL-1β， CD86， and CD80 （P<0.01） while increasing the serum levels of CD206 and Arg-1 （P<0.01）. In vitro experiment： compared with the model group， TSDN and inhibitor down-regulated the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α and the protein levels of NLRP3 inflammasome， COX-2， cleaved IL-1β， and TNF-α （P<0.01）. Compared with TSDN alone， TSDN + COX-2 inhibitor further reduced the mRNA and protein levels of the markers above （P<0.01）. Compared with the model group， TSDN and COX-2 inhibitor decreased the levels of IL-1β， iNOS， CD80， and CD86 （P<0.01） and increased the levels of CD206 and Arg-1 （P<0.01） in cells. Compared with TSDN alone， TSDN + COX-2 inhibitor reduced IL-1β， iNOS， CD80， and CD86 levels （P<0.05， P<0.01） and elevated CD206 and Arg-1 levels （P<0.01） in cells. ConclusionTSDN can alleviate GA by downregulating COX-2-mediated M1 macrophage reprogramming and suppressing the inflammatory factors.

Objective To develop a combined model integrating radiomics and 3D deep learning features for improving the predictive efficacy of overall survival in non-small cell lung cancer(NSCLC)patients undergoing radiotherapy,thereby providing a foundation for optimizing individualized radiotherapy strategies.Methods A retrospective analysis was conducted on 522 NSCLC patients from 3 centers.Radiomics features were extracted from the tumor region of interest on radiotherapy planning CT scans,and a 3D-SE-ResNet was constructed to extract deep learning features.Following feature extraction,features were selected via univariate Cox analysis and Lasso-Cox regression,and a combined model was established by fusing the two feature types through principal component analysis.The discriminative ability of the model was evaluated using the concordance index(C-index)and the area under the receiver operating characteristic curve(AUC),while the risk stratification efficacy was verified by Kaplan-Meier survival analysis.Results The predictive performance of deep learning features was significantly superior to that of radiomics features(C-index:0.73 vs 0.65).The combined model achieved the highest predictive performance in the training set,internal test set,and external test set(C-index:0.74,0.69,0.72 respectively),with higher AUC values for predicting 1-year,2-year,and 3-year OS than either single model.Kaplan-Meier analysis showed significant differences in survival between the high-and low-risk groups(Log-rank test,P<0.001),and calibration curves indicated good consistency between predicted and actual survival outcomes.Conclusion The combined model integrating radiomics and 3D deep learning features can accurately predict survival outcomes in NSCLC patients undergoing radiotherapy.The multi-center validation results support its potential application in prognosis stratification for individualized radiotherapy.

Objective:To investigate the effect of circular RNA bromodomain PHD finger transcription factor (circBPTF) targeting microRNA (miR)-224-3p on the damage of human retinal vascular endothelial cells (HRECs) induced by high glucose.Methods:HRECs were divided into control group and high glucose group, which were cultured with medium containing 5.5 mmol/L glucose and 30 mmol/L glucose for 48 hours, respectively.HRECs were transfected with siRNA negative control (si-NC), siRNA of circBPTF (si-circBPTF), miRNA mimic control (miR-NC), and miR-224-3p by Lipofectamine 2000, followed by cultured in 30 mmol/L glucose medium for 48 hours and were recorded as si-NC group, si-circBPTF group, miR-NC group and miR-224-3p group, respectively.HRECs were transfected with si-circBPTF and anti-miR-NC or si-circBPTF and anti-miR-224-3p by double transfection method, and then treated with 30 mmol/L glucose medium for 48 hours and were recorded as anti-miR-NC group and anti-miR-224-3p group, respectively.The expression of circBPTF and miR-224-3p was detected by real-time fluorescence quantitative PCR.Cell apoptosis was detected by flow cytometry.Reactive oxygen species (ROS) level was determined by 2′, 7′-dichlorodihydrofluorescein diacetate probe.Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric method.Expression of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9 proteins was detected by Western blot.The interaction between circBPTF and miR-224-3p was identified by the dual luciferase reporter method.Results:Compared with the control group, the apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, ROS level, MDA content, and circBPTF relative expression were significantly increased and SOD activity and miR-224-3p expression were decreased in the high glucose group (all P<0.05).Compared with the si-NC group, circBPTF relative expression, ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, and cell apoptosis rate were significantly reduced and SOD activity was significantly increased in the si-circBPTF group (all P<0.05).Compared with the miR-NC group, miR-224-3p relative expression and SOD activity were significantly enhanced and ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression and cell apoptosis rate were significantly reduced in the miR-224-3p group (all P<0.05).The relative luciferase activity of HRECs after co-transfection of wild type circBPTF and miR-224-3p mimic was 0.43±0.04, which was significantly decreased compared with 0.99±0.06 after co-transfection of wild type circBPTF and miR-NC ( t=23.297, P<0.05).Compared with anti-miR-NC group, the relative expression of miR-224-3p and SOD activity were significantly decreased and ROS level, MDA content, cell apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, and cleaved-caspase-9/caspase-9 protein expression were significantly increased in the anti-miR-224-3p group (all P<0.05). Conclusions:Interfering with circBPTF can inhibit high glucose induced HRECs apoptosis and oxidative stress damage by targeting miR-224-3p.