To explore the callsal association between intrahepatic cholestasis of pregnancy (ICP) and offspring attention-deficit hyperactivity disorder (ADHD) and Tourette’s syndrome (TS) and its potential mechanisms.

Genome wide association study (GWAS) in public datasets was used to extract data. Among them, exposure was ICP (n=123 579), which stems from FinnGen dataset. Outcome was defined as ADHD, TS and other tic disorders (n=23 918), which is extracted from GWAS Catalog. Among mediators, total cholesterol in high-density lipoprotein (TC in HDL) were from the genetic map of the human plasma proteinome (n=21 558), and Obg-like ATPase 1 was from whole-genome study of circulating metabolites (n=3 301). In this study, we chose instrumental variables (IVs) that meets the Mendelian randomization (MR) hypothesis. When using two-sample MR, inverse variance weighted (IVW) was adopted as the primary method, and MR-Egger regression, weighted median, weighted mode, and simple mode were also utilized to analyse the robustness. Cochran’s Q test, MR-Egger intercept test and leave-one-out sensitivity analysis were performed to verify the reliability. Significant threshold was set up as P<0.05. When using two-step MR, the first step is two-sample MR from exposure to mediator, and the second step is multivariable MR (MVMR), which is from mediator to outcome. At this time, conditional F-statistic was adopted to test the strength of IVs. At last, product distribution test was applied to determine the significance of mediation effects.

ICP was significantly related to ADHD and TS as well as other tic disorders in offspring (IVW: OR=1.003, 95%CI: 1.000~1.006, P=0.035), and sensitivity analysis verified the robustness of the results. The potential positive mediators included TC in HDL [total effect (TE) =2.855×10^-3; mediated effect (ME) =8.628×10^-4; mediated proportion (MP) =30.217%, 95%CI: 0.878%~73.954%], and Obg-like ATPase 1 (TE=2.855×10^-3; ME=1.216×10^-3; MP=42.572%, 95%CI: 6.356%~90.195%).

ICP is possible to elevate the incidence rate of ADHD and TS and other tic disorders via reducing TC in HDL and Obg-like ATPase 1.

To investigate the role of p300 in lipid metabolism disorders.

Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes. Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease (NAFLD). A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet (HFD) for 12 weeks. Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice. A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid (FFA). The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol (TC) and triglyceride (TG), lipid deposition, and production of reactive oxygen species (ROS).

Clinically, p300 was highly expressed in lipid metabolism disorders, and its level was positively correlated with NAFLD severity (P<0.05). Gene Set Enrichment Analysis (GSEA) revealed that p300 expression was significantly associated with fatty acid metabolism, cholesterol homeostasis, lipogenesis, PPAR signaling pathway, and peroxisome pathway. In vivo, p300 was significantly up-regulated in the livers of HFD-fed mice (P<0.01). In vitro, FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells (P<0.01), whereas p300 knockdown significantly reduced intracellular TG and TC levels (P<0.01), attenuated lipid droplet accumulation, and reversed FFA-induced ROS elevation (P<0.01). Furthermore, p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.

p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes, thereby affecting lipid synthesis and oxidative stress. These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

Investigate the expression level of discs large homolog associated protein 5 (DLGAP5) in oral squamous cell carcinoma (OSCC) and analyze its effects on cell proliferation, migration, invasion capacity, and the Warburg effect.

Bioinformatics analysis was performed to identify the potential therapeutic targets for OSCC. A total of 72 OSCC tissue samples and 40 adjacent non-cancerous tissue samples collected in the First Affiliated Hospital of Shihezi University from 2013 to 2024 were included, and the clinical pathological and prognostic data were collected from patients. Immunohistochemistry assay was applied to detect the protein expression of DLGAP5, and its association with clinical pathological features was analyzed. Kaplan-Meier survival curve was plotted for survival analysis, and Cox regression model was employed to analyze the prognostic factors. The expression of DLGAP5 at mRNA and protein levels was detected in HOK, SCC-9, SCC-15, SCC-25, and CAL-27 cell lines with RT-qPCR and Western blotting, respectively. Four small interfering RNAs (siRNAs) were designed to target the DLGAP5 sequence, and then based on the transfection efficiency, the sequence with optimal silencing effect was selected for subsequent functional studies. After DLGAP5 was silenced in the CAL-27 and SCC-15 cells, Western blotting was applied to detect the expression of hexokinase 2 (HK2) and enolase 1 (ENO1), CCK-8, scratch healing and Transwell assays were conducted to assess cell proliferation, migration, and invasion capabilities, and glucose, lactate, and ATP detection kits were utilized to determine the glycolytic metabolic levels in OSCC cells.

Bioinformatics analysis indicates that DLGAP5 is a potential key therapeutic target for OSCC. Experimental validation demonstrated that DLGAP5 was highly expressed in both OSCC tissues and cells (P<0.05). Analysis of clinical pathology and prognostic data revealed that DLGAP5 expression level was significantly correlated with tumor TNM stage, lymph node metastasis, and differentiation grade in OSCC patients, and high DLGAP5 expression was associated with poor prognosis (P<0.05). DLGAP5 silencing resulted in significantly reduced expression of HK2 and ENO1, markedly decreased levels of glycolytic metabolites (P<0.05), and notably declined cell proliferation, migration, and invasion capabilities (P<0.05).

DLGAP5 is highly expressed in OSCC. Silencing DLGAP5 may inhibit OSCC cell proliferation, migration, and invasion by indirectly regulating the Warburg effect, and the molecule is associated with poor prognosis in the OSCC patients.

To determine whether an intelligerct cloud platform follow-up model demonstrates superiority over conventional methods in enhancing follow-up quality, reducing costs, and improving functional recovery following total knee arthroplasty(TKA).

A retrospective cohort study was conducted on 260 patients undergoing TKA at our hospital from October 2022 to September 2023. According to the different postoperative follow-up methods, they were divided int a cloud platform group (n=130) and a traditional group (n=130). The baseline data, pre- and postoperative knee function scores, and follow-up costs were collected and compared between the 2 groups.

The cloud platform group exhibited significantly higher rate of follow-up satisfaction, reduced resource utilization, shorter per-follow-up duration, fewer accompanying persons per visit, lower total follow-up expenditures, and decreased cumulative follow-up time when compared with the traditional group (P<0.05). At 6 weeks, 3, 6, and 12 months postoperatively, better range of motion (ROM) was observed in the cloud-based group than the traditional group (P<0.05), but no intergroup differences were seen in other knee function scores.

Cloud platform follow-up enhances early postoperative ROM (6 weeks to 12 months) and demonstrates marked cost-effectiveness when compared to the conventional mode. It represents a viable alternative for post-TKA rehabilitation surveillance.

To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index (BMI), overweight BMI, and different CYP3A4/5 enzyme genotypes.

The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study. Before the operation, the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit. Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes, the patients were divided into groups I (3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation), II (3A4 heterozygous mutation + 3A5 heterozygous mutation), and III (3A4 wild type or 3A4 heterozygous mutation + 3A5 wild type). According to their BMI, they were also assigned into a normal body weight group (18.5~24.0 kg/m²) and an overweight group (24~<28 kg/m²), and the differences in drug metabolism parameters were statistically analyze between the 2 groups. After routine general anesthesia induction (sufentanil 0.5 μg/kg), venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.

Among the 90 participants completing the blood drug concentration test, 8 patients had their blood samples contaminated (including 1 case with an anesthesia duration of <2 h), and 3 were excluded due to low weight or overweight. Eventually, 79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group. Compared with the normal body weight group, the central compartment volume of distribution in the overweight group was significantly reduced (P<0.05), while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution, total clearance rate, peripheral compartment clearance rate, distribution half-life, clearance half-life, and area under the blood concentration-time curve. In group Ⅰ (n=26), the overweight patients (n=13) had significantly reduced central compartment volume of distribution, peripheral compartment volume of distribution, and peripheral compartment clearance rate when compared with the normal body weight patients (n=13) (P<0.05), while no differences were observed in other pharmacokinetic parameters. In groups Ⅱ (n=25) and Ⅲ (n=28), the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.

Among the patients with the same genotype combination of CYP3A4/5 mutations, there was no difference in the metabolism of sufentanil between the overweight and normal weight patients. Additionally, in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation, the overweight patients have smaller peripheral distribution range of sufentanil, and weakened metabolic process.

To investigate the predictive role of transcranial Doppler (TCD) ultrasound combined with invasive intracranial pressure (ICP) monitoring in the early outcomes for patients with moderate-to-severe traumatic brain injury (msTBI) after ICP probe insertion surgery.

A retrospective case-control analysis was conducted on the clinical data of 65 msTBI patients who underwent invasive ICP probe insertion surgery within 24 h after injury and routine TCD examination postoperatively in No. 904 Hospital of Joint Logistic Support Force of Chinese PLA between January 2021 and March 2025. Based on whether disease progression met the indications for craniotomy, they were divided into a failed conservative treatm ent group (n=28) and a successful conservative treatment group (n=37). Baseline clinical data, and parameters of TCD and ICP monitoring were collected in both groups. Univariate analysis was used for comparing differences in various parameters between the groups. The variables related to ICP and TCD were denoted as Model 1, and variables that significantly affected the outcome were incorporated as potential confounding factors into Model 2 based on clinical experience. Multivariate logistic regression analysis was performed to screen for independent predictors of conservative treatment failure. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic efficacy of each predictive factor.

Statistical differences were observed between the 2 groups in terms of Glasgow Coma Scale (GCS) score at admission, postoperative mean intracranial pressure (ICPm), postoperative mean cerebral perfusion pressure (CPPm), and pulsatility index (PI) of the ipsilateral internal carotid artery extracranial segment (ICAt), and mean flow velocity (Vm) and pulsatility index (PI) of the ipsilateral middle cerebral artery (MCA) (all P<0.01). After adjusting for age, GCS score at admission, hematoma volum, and mean postoperative brain temperature, multivariate logistic regression analysis revealed that ICPm (OR=1.248, 95%CI: 1.044~1.491, P=0.015), ipsilateral MCA.Vm (OR=0.964, 95%CI: 0.933~0.997, P=0.034), and ipsilateral MCA.PI (OR=1.612, 95%CI: 1.026~2.533, P=0.038) were independent predictors of failure in conservative treatment in msTBI patients. After adjustment, ROC curve analysis demonstrated that the combined model of ipsilateral MCA.PI, ipsilateral MCA.Vm, and ICPm achieved a predictive efficacy of 0.931 (95%CI: 0.873~0.988), which was obviously higher than that of the single model of ICPm (0.875, 95%CI: 0.791~0.959).

Combined monitoring of TCD and ICP can provide a more accurate prediction of the early outcomes for msTBI patients after ICP probe insertion, providing a more effective assessment for clinical diagnosis and treatment.

To stratify the estrogen receptor (ER) positive while human epidermal growth factor receptor 2 (HER2) negative breast cancer patients by the expression level of ER, providing new evidence for prognostic prediction and guiding precision endocrine therapy (ET) for those with different ER expression levels.

A retrospective cohort study was conducted on 1 962 ER-positive/HER2-negative breast cancer patients treated in our department from January 1, 2013 to December 31, 2018. X-tile was used to calculate the optimal cutoff point of ER expression level, and then based on the results, they were divided into low (1%~10%), moderate (11%~30%), and high expression (31%~100%) groups. After propensity score matching (PSM) was performed to balance baseline characteristics, their prognostic outcomes were compared and the responses to ET were analyzed in the groups. Cox proportional risk regression model was applied to analyze the prognostic factors, and subgroup analysis was further performed.

After PAM, 129 (11.5%) were assigned into a low ER expression group, 151 (13.5%) and 840 (75%) into moderate and high ER expression groups, respectively. Statistical differences were observed in disease-free survival (DFS) and overall survival (OS) among the 3 groups (P=8e-6, P=8e-14). In the low ER expression group, the patients treated with selective estrogen receptor modulators (SERMs) showed no significant differences in DFS and OS than those treated with aromatase inhibitors (AIs) (P>0.05). However, the patients from the moderate and high ER expression groups demonstrated significantly better DFS when treated with AI than with SERM (P=0.02, P=0.03). Multivariate analysis showed that compared with the moderate ER expression group, the high ER expression group exhibited significantly lower risk of disease recurrence/metastasis (HR=0.62, 95%CI: 0.43~0.88, P=0.009) and risk of death (HR=0.49, 95%CI: 0.26~0.93, P=0.03). Subgroup analysis revealed that when compared with the high ER expression group, the moderate ER expression group exhibited notably worse DFS in the following subgroups: oral SERM, non-breast-conserving surgery, lymph node metastasis, TNM stage Ⅱ, and chemotherapy, and shorter OS in the subgroups of oral SERM, non-breast-conserving surgery, lymph node metastasis, TNM stage Ⅱ subgroup, and chemotherapy.

Taking ER expression of 11%~30% as an independent stratification criterion can guide more accurate prognostic assessment and more rational ET selection in ER-positive/HER2-negative breast cancer patients.

To investigate the effect of gender on prognosis after transcatheter patent foramen ovale (PFO) closure in patients with cerebral infarction or transient ischemic attack.

A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack (TIA) who underwent PFO closure at our hospital between January 2013 and December 2023. The patients were grouped by gender, and related data were collected, including age, comorbidities, Risk of Paradoxical Embolism (RoPE) score, laboratory results, findings of transthoracic/transesophageal echocardiography (TTE/TEE), and post-procedural complications, such as device-related thrombosis (DRT), recurrent stroke, bleeding, and atrial fibrillation (AF).

A total of 112 patients were enrolled, including 59 males and 53 females, at a mean age of 42.47±12.35 years. The females had significantly higher preoperative RoPE score than the males (6.6±1.4 vs 6.0±1.5, P=0.046), and a statistical difference was observed in the distribution of infarction sites between them (Chi-square=10.25, P=0.006), indicating that the males were prone to posterior circulation infarction. Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females (9.3±2.4 mm vs 7.6±2.0 mm, P<0.001). During a median follow-up of 4 years, the male group had 1 case of myocardial infarction, 1 cerebral hemorrhage, 1 paroxysmal AF, 2 gingival bleeding episodes, and 1 skin ecchymosis. In the female group, 1 case experienced pulmonary embolism, 1 paroxysmal atrial fibrillation, 3 gingival bleeding episodes, 2 skin ecchymoses, 2 recurrent cerebral infarctions, and 2 recurrent TIAs. There was no statistical difference in overall adverse events between gender (P=0.291). Although the females had higher rates of recurrent cerebral infarction and TIA, this difference lacked statistical significance (P=0.222). Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors, such as RoPE score, age, hypertension, coronary heart disease, and other factors, gender was not an independent predictor of composite endpoint events after surgery.

Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA. However, females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

To investigate the correlation between thyroid hormone levels and cognitive function in schizophrenia (SCZ) patients with metabolic syndrome (MetS), as well as the mediating role of thyroid hormones in the relationship between MetS-related indicators and cognitive function.

A cross-sectional trial was conducted on 120 SCZ inpatients and outpatients (40 cases of MetS and 80 cases of non-MetS) and 80 healthy controls admitted in the Chongqing Mental Health Center from August 2023 to December 2024. Thyroid function indicators [Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4)], MetS-related parameters [blood glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and waist circumference], Positive and Negative Syndrome Scale (PANSS) score, and Montreal Cognitive Assessment (MoCA) scores were collected. One-way ANOVA or Kruskal-Wallis rank sum test was applied to analyze the differences among the 3 groups, and LSD test or Bonferroni correction was performed for post hoc analysis. Pearson correlation analysis was conducted to assess the relationship between thyroid hormone levels and metabolic parameters as well as cognitive/clinical scale scores (MoCA, PANSS) in the MetS group.

The MetS group exhibited significantly lower FT4 level (P<0.05) and MoCA score (P=0.001), but higher TSH level (P<0.05) and PANSS negative symptom score (P<0.001) when compared to the non-MetS group. Correlation analysis indicated that in the MetS group, TSH level was positively correlated with TG (r=0.672, P<0.001) and PANSS negative symptom score (r=0.458, P<0.05), and negatively with HDL-C (r=-0.377, P=0.017) and MoCA score (r=-0.667, P<0.001); FT4 level was positively correlated with MoCA score (r=0.534, P<0.001). In the non-MetS group, TSH level was positively correlated with PANSS negative symptom score (r=0.267, P=0.017) and negatively with HDL-C (r=-0.236, P=0.036), T3 was positively with waist circumference (r=0.268,P=0.017). No correlation was observed in FT4 level with HDL-C (r=-0.207, P=0.067) or MoCA score (r=0.216, P=0.055). Mediation analysis revealed that TSH partially mediated the association between TG and MoCA score, with a mediation effect accounting for 29.91% of the total effect. The mediating effect was not significant in the non-MetS group.

Abnormal elevation of TSH may serve as a critical link between MetS and cognitive impairment in SCZ patients, which providing novel insights into the mechanisms underlying cognitive dysfunction in the patients.

To analyze the burden of atherosclerotic cardiovascular disease (ASCVD) attributable to lifestyle and metabolic factors in China from 1990 to 2021 and predict its future trends, providing evidence for public health prevention and control.

Based on the Global Burden of Disease (GBD) 2021 database, we extracted disability-adjusted life years (DALYs) of ASCVD attributable to 7 key risk factors: dietary, low physical activity, smoking, high body mass index (BMI), high fasting blood glucose, high low-density lipid cholesterol (LDL-C), and hypertension. Age-standardized DALY rates (ASDR) were also calculated to account for variations in age structure, and an ARIMA model was applied to predict future trends.

① Overall trend analysis showed the leading risk factor for ischemic heart disease (IHD) shifted from dietary risks in 1990 to hypertension in 2021, while hypertension and smoking remained the primary risk factors for ischemic stroke (IS) and peripheral artery disease (PAD), respectively. ② In BRICS nations, hypertension was the dominant risk factor for both IHD and IS, whereas in China, smoking and high fasting blood glucose continued to be the major drivers of PAD burden. ③ Sex-specific analysis revealed that hypertension was the leading risk factor for IHD and IS in both males and females. For PAD, smoking was the main risk factor in males, while high fasting blood glucose was for females. Age-stratified analysis revealed that in the 15-49 age group, dietary, high LDL-C and smoking were the primary factor for IHD, IS and PAD, respectively; in the 50-69 group, dietary predominated IHD risk, hypertension IS, and smoking PAD; and among those aged ≥70 years, hypertension was the leading risk factor for both IHD and IS, and high fasting blood glucose was for PAD. ④ ARIMA model forecasted that by 2035, DALYs for IHD, IS, and PAD will increase to 82.816 million, 46.808 million, and 0.192 million person-years, respectively.

The ASCVD burden attributable to lifestyle and metabolic factors continues to rise in China from 1990 to 2021, and is projected to further increase by 2035. Countermeasures　We suggest that current prevention and control priorities are enhanced management of metabolic factors, tailored interventions by sex and age, promotion of healthy lifestyles and tobacco control, and establishment of an integrated system of prevention-treatment-rehabilitation-research.

To explore the early detection value of estimated glucose disposal rate (eGDR) for non-alcoholic fatty liver disease (NAFLD), providing a simple tool for precise clinical intervention.

A cross-sectional analysis was conducted on totally 3 262 participants with complete data from the National Health and Nutrition Survey Database of the United States from 2007 to 2018. Univariate regression and multivariate logistic regression analyses were used to explore the correlation between the estimated glucose treatment rate and the incidence of non-alcoholic fatty liver disease. Subgroup analysis, restricted cubic spline and threshold effect analysis were conducted to investigate the potential factor influences and nonlinear relationships.

Among all the included populations, 948 cases (25.29%) were diagnosed with NAFLD, and the number gradually decreased with the increase of the estimated glucose treatment rate (P<0.001). Multivariate logistic regression showed that the estimated grape processing rate was negatively correlated with non-alcoholic fatty liver disease (OR=0.86, 95%CI:0.83~0.88, P<0.001), and when the estimated glucose processing rate was ≥10.246, it could significantly reduce the risk of non-alcoholic fatty liver disease (OR=0.20, 95%CI:0.10~0.39, P<0.001), and stratified analysis further confirmed this result.

The eGDR is significantly associated with the incidence risk of NAFLD. A higher eGDR indicates a lower risk of NAFLD. This implies that in clinical practice, the risk of disease detection can be quantified through this indicator, thereby identifying potential patients earlier and initiating intervention. Countermeasures　As decision-makers, they should strengthen public health education on non-alcoholic fatty liver disease, reduce health risks by promoting healthy diets and lifestyle interventions, and pay attention to the cardiovascular health of high-risk groups for non-alcoholic fatty liver disease. At the same time, promote the research and application of drugs, and dynamically adjust policies through continuous disease monitoring to comprehensively reduce the burden of non-alcoholic fatty liver disease.

To investigate the association between the variability of remnant cholesterol inflammatory index (RCII), a novel composite biomarker, and the risk of stroke, in order to provide a theoretical basis for stroke prevention.

A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006, 2008, and 2010. These subjects were grouped based on the quartiles of RCII variability, which was represented by standard deviation (SD) and average real variability (ARV), and were followed up every 2 years, with the occurrence of stroke (including ischemic and hemorrhagic strokes), death, or the end of follow-up on December 31, 2022 as the endpoints. Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups, and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group. Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.

Among the 38 659 participants, a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years. After adjusting confounding factors, when the participants were grouped by the quartiles of RCII-SD, the hazard ratio (HR) for stroke was 1.034 (95%CI: 0.917~1.167, P=0.584), 1.146 (95%CI: 1.018~1.290, P=0.025), and 1.209 (95%CI: 1.066~1.370, P=0.003), respectively in the Q2, Q3, and Q4 groups, when compared with the Q1 group (P_trend <0.05). When they were grouped by the quartiles of RCII-ARV, the HR for stroke was 1.008 (95%CI: 0.894~1.136, P=0.901), 1.109 (95%CI: 0.986~1.248, P=0.085), and 1.152 (95%CI: 1.018~1.303, P=0.025), respectively, in the Q2, Q3, and Q4 groups, when compared with the Q1 group. Furthermore, both sensitivity and stratified analyses yielded similar results.

RCII variability is significantly associated with stroke, and the risk of stroke is gradually increasing with increment of the variability. Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism, strengthening lifestyle interventions, and standardizing dietary, exercise, and weight management in order to suppress the index fluctuations. The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

To develop a personalized recommendation strategy for tranexamic acid administration during the perioperative period of orthopedic surgery based on machine learning, aiming to reduce perioperative bleeding and related complications and improving clinical outcomes.

A total of 11 727 patients undergoing orthopedic surgery from the INSPIRE database were subjected in this study. Missing data were handled using multiple imputation methods, and relevant feature variables were screened using Boruta analysis. We constructed various machine learning models, including Gradient Boosting Machine (GBM), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost), K-Nearest Neighbors (KNN), Neural Network (NNET), Naive Bayes (NB), and Random Forest (RF), to evaluate their performance in predicting intraoperative bleeding and prolonged postoperative length of hospital stay. The optimal model was then selected and further integrated using a weighted ensemble, aiming to achieve the best prognosis by recommending usage strategies for tranexamic acid. The predictive performance of the constructed model was then verified against the testing set, and compared with the physician decision-making to complete the evaluation.

In predicting intraoperative bleeding, the RF model achieved an area under the receiver operating characteristic curve (AUC) of 0.73, which was significantly better than other models. In predicting the prolonged postoperative length of hospital stay, the XGBoost model performed the best, with an AUC value of 0.84. Based on the above best-performing models, an ensemble strategy was implemented. The patients who followed the recommended strategy had reduced intraoperative bleeding and shorter postoperative length of hospital stay.

The use of tranexamic acid is associated with intraoperative bleeding and postoperative length of hospital stay. Personalized decision-making recommendation based on our constructed model can effectively improve the outcomes of the patients undergoing orthopedic surgery.