Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective To observe the value of machine learning(ML)models based on brain functional network features combining clinical indicators for predicting postoperative outcomes of patients with drug-resistant mesial temporal lobe epilepsy(DR-mTLE).Methods Totally 84 patients with unilateral DR-mTLE who underwent surgery were retrospectively enrolled and classified into seizure free(SF)group(n=55)and non-seizure free(NSF)group(n=29)according to one-year postoperative follow-up.Clinical data were analyzed to screen independent predictors of postoperative outcomes.Based on brain preoperative resting-state functional MRI,brain functional networks were constructed using graph theory analysis,and 587 features were extracted.Five-fold cross validation was used to divide the data into training set and test set,then the optimal brain functional network features related to postoperative outcomes of DR-mTLE patients were selected.Combining with clinically relevant independent predictors,ML models were constructed using classifiers including Gaussian process(GP),logistic regression(LR),support vector machine(SVM)and quadratic discriminant analysis(QDA),respectively,and the prediction efficacy,calibration and clinical value of each ML model were evaluated.Results Both course of disease and lesion location were clinically relevant independent predictors of postoperative outcome of DR-mTLE patients(OR=0.928,5.710,P=0.010,0.016).Four optimal brain function network features were selected,including betweenness centrality of the third zone of cerebellar vermis,degree centrality of right globus pallidus,nodal efficiency of temporal left inferior temporal gyrus and nodal clustering coefficient of left inferior parietal lobule.The average area under the curve(AUC)of GP,LR,SVM and QDA models in test set was 0.868,0.864,0.875 and 0.870,respectively.Calibration curves and decision curve analysis indicated that each ML model had good calibration and high clinical net benefit.Conclusion ML models based on brain functional network features combining with clinical indicators could be used to effectively predict postoperative outcomes in DR-mTLE patients.

Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) in bus drivers in Zhuhai City, analyze the ergonomic factors, and explore the prevention and control measures of WMSDs.Methods:From March to May 2023, 1675 active bus drivers from 5 branches of a bus group in Zhuhai were selected by stratified sampling method. The incidence of WMSDs among bus drivers in the past 12 months was investigated by using the modified Chinese Version of Musculoskeletal Disorders Questionnaire. The influencing factors of WMSDs were analyzed by χ2 test and generalized linear model. Results:The total incidence of WMSDs in bus drivers in the past 12 months was 47.2% (790/1675) , and the incidence of WMSDs in neck and shoulder and lower back was 36.9% (618/1675) and 31.7% (531/1675) , respectively. The χ2 test showed that there were statistically significant differences in the incidence of WMSDs among bus drivers with different individual factors such as body mass index (BMI) , physical exercise and looking down at mobile phones ( P<0.05) . There were significant differences in the incidence of WMSDs in the neck and shoulder of bus drivers with different years of service and number of stops on their routes ( P<0.05) . There were statistically significant differences in the incidence of WMSDs in the lower back of bus drivers with different one-way driving time, shift patterns, and rest breaks during work ( P<0.05) . Abnormal BMI, professional working years >12 years, uncomfortable working posture, frequent turning, slightly forward neck posture, large forward neck posture and long shoulder posture were the risk factors for WMSDs of bus drivers ( P<0.05) , and comfortable seat was the protective factor ( P<0.05) . One-way driving time >70 min, shift work schedules, uncomfortable working posture, slightly forward back posture, and frequent turning were the risk factors leading to lower back WMSDs ( P<0.05) , and physical exercise, comfortable driving cabin space, and seat comfort were the protective factors ( P<0.05) . Conclusion:The total incidence of WMSDs in bus drivers is higher, and ergonomic factors are related to the occurrence of WMSDs. In the implementation of bus driving space comfort, human-computer interaction interface friendliness and seat comfort, employers should be reasonable allocation of fitness facilities, regular training, reasonable shift organization and other measures to prevent and control the occurrence of bus drivers WMSDs.

Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective To observe the value of machine learning(ML)models based on brain functional network features combining clinical indicators for predicting postoperative outcomes of patients with drug-resistant mesial temporal lobe epilepsy(DR-mTLE).Methods Totally 84 patients with unilateral DR-mTLE who underwent surgery were retrospectively enrolled and classified into seizure free(SF)group(n=55)and non-seizure free(NSF)group(n=29)according to one-year postoperative follow-up.Clinical data were analyzed to screen independent predictors of postoperative outcomes.Based on brain preoperative resting-state functional MRI,brain functional networks were constructed using graph theory analysis,and 587 features were extracted.Five-fold cross validation was used to divide the data into training set and test set,then the optimal brain functional network features related to postoperative outcomes of DR-mTLE patients were selected.Combining with clinically relevant independent predictors,ML models were constructed using classifiers including Gaussian process(GP),logistic regression(LR),support vector machine(SVM)and quadratic discriminant analysis(QDA),respectively,and the prediction efficacy,calibration and clinical value of each ML model were evaluated.Results Both course of disease and lesion location were clinically relevant independent predictors of postoperative outcome of DR-mTLE patients(OR=0.928,5.710,P=0.010,0.016).Four optimal brain function network features were selected,including betweenness centrality of the third zone of cerebellar vermis,degree centrality of right globus pallidus,nodal efficiency of temporal left inferior temporal gyrus and nodal clustering coefficient of left inferior parietal lobule.The average area under the curve(AUC)of GP,LR,SVM and QDA models in test set was 0.868,0.864,0.875 and 0.870,respectively.Calibration curves and decision curve analysis indicated that each ML model had good calibration and high clinical net benefit.Conclusion ML models based on brain functional network features combining with clinical indicators could be used to effectively predict postoperative outcomes in DR-mTLE patients.

Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) in bus drivers in Zhuhai City, analyze the ergonomic factors, and explore the prevention and control measures of WMSDs.Methods:From March to May 2023, 1675 active bus drivers from 5 branches of a bus group in Zhuhai were selected by stratified sampling method. The incidence of WMSDs among bus drivers in the past 12 months was investigated by using the modified Chinese Version of Musculoskeletal Disorders Questionnaire. The influencing factors of WMSDs were analyzed by χ2 test and generalized linear model. Results:The total incidence of WMSDs in bus drivers in the past 12 months was 47.2% (790/1675) , and the incidence of WMSDs in neck and shoulder and lower back was 36.9% (618/1675) and 31.7% (531/1675) , respectively. The χ2 test showed that there were statistically significant differences in the incidence of WMSDs among bus drivers with different individual factors such as body mass index (BMI) , physical exercise and looking down at mobile phones ( P<0.05) . There were significant differences in the incidence of WMSDs in the neck and shoulder of bus drivers with different years of service and number of stops on their routes ( P<0.05) . There were statistically significant differences in the incidence of WMSDs in the lower back of bus drivers with different one-way driving time, shift patterns, and rest breaks during work ( P<0.05) . Abnormal BMI, professional working years >12 years, uncomfortable working posture, frequent turning, slightly forward neck posture, large forward neck posture and long shoulder posture were the risk factors for WMSDs of bus drivers ( P<0.05) , and comfortable seat was the protective factor ( P<0.05) . One-way driving time >70 min, shift work schedules, uncomfortable working posture, slightly forward back posture, and frequent turning were the risk factors leading to lower back WMSDs ( P<0.05) , and physical exercise, comfortable driving cabin space, and seat comfort were the protective factors ( P<0.05) . Conclusion:The total incidence of WMSDs in bus drivers is higher, and ergonomic factors are related to the occurrence of WMSDs. In the implementation of bus driving space comfort, human-computer interaction interface friendliness and seat comfort, employers should be reasonable allocation of fitness facilities, regular training, reasonable shift organization and other measures to prevent and control the occurrence of bus drivers WMSDs.

Objective::Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) filled an important data gap by showing a significant reduction of ischemic cardiovascular events in a ticagrelor plus aspirin cohort compared with placebo plus aspirin cohort among patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) but without a history of myocardial infarction. This study aims to evaluate the applicability of the THEMIS results in a real-world clinical setting in China.Methods::This retrospective, observational cohort study used data from the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study which enrolled participants who were hospitalized between November 2012 and December 2013. The 24-month cumulative incidence of major adverse cardiovascular event (MACE), major bleeding, and all-cause death in patients with T2DM and CAD (T2DM-CAD), T2DM and stable CAD (SCAD)(T2DM-SCAD), and T2DM and SCAD without prior myocardial infarction or stroke (THEMIS-like) were analyzed.Results::Data from 13,296 patients with CAD were included; the T2DM-CAD, T2DM-SCAD, and THEMIS-like cohorts comprised 3,344 (25.2%), 949 (7.1%), and 509 (3.8%) patients, respectively. The corresponding 24-month cumulative incidence of major bleeding was 38 (1.1%), 16 (1.7%), and 8 (1.6%), and that of MACEs was 250 (7.5%), 87 (9.2%), and 29 (5.7%), and all-cause death was 181 (5.4%), 84 (8.9%), 29 (5.7%), respectively. The risk of MACE in the THEMIS-like cohort was approximate to that in the THEMIS trial (7.7% vs. 8.5% in ticagrelor and placebo group, respectively). Conclusion::The incidence of MACE was substantial in the THEMIS-like cohort, suggesting that cardiovascular risk for future events correlates with the presence of cardiovascular disease across the CAD risk continuum.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

Objective::Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) filled an important data gap by showing a significant reduction of ischemic cardiovascular events in a ticagrelor plus aspirin cohort compared with placebo plus aspirin cohort among patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) but without a history of myocardial infarction. This study aims to evaluate the applicability of the THEMIS results in a real-world clinical setting in China.Methods::This retrospective, observational cohort study used data from the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study which enrolled participants who were hospitalized between November 2012 and December 2013. The 24-month cumulative incidence of major adverse cardiovascular event (MACE), major bleeding, and all-cause death in patients with T2DM and CAD (T2DM-CAD), T2DM and stable CAD (SCAD)(T2DM-SCAD), and T2DM and SCAD without prior myocardial infarction or stroke (THEMIS-like) were analyzed.Results::Data from 13,296 patients with CAD were included; the T2DM-CAD, T2DM-SCAD, and THEMIS-like cohorts comprised 3,344 (25.2%), 949 (7.1%), and 509 (3.8%) patients, respectively. The corresponding 24-month cumulative incidence of major bleeding was 38 (1.1%), 16 (1.7%), and 8 (1.6%), and that of MACEs was 250 (7.5%), 87 (9.2%), and 29 (5.7%), and all-cause death was 181 (5.4%), 84 (8.9%), 29 (5.7%), respectively. The risk of MACE in the THEMIS-like cohort was approximate to that in the THEMIS trial (7.7% vs. 8.5% in ticagrelor and placebo group, respectively). Conclusion::The incidence of MACE was substantial in the THEMIS-like cohort, suggesting that cardiovascular risk for future events correlates with the presence of cardiovascular disease across the CAD risk continuum.

OBJECTIVE To explain the material basis and biological mechanism of Astragali Radix’s “invigorating Qi” effect to regulate energy metabolism. METHODS The TCMSP database and literature search collected potential active components of Astragali Radix, the SEA database performed target prediction based on structural similarity, and the GeneCards, OMIM, and TTD databases obtained energy metabolism targets. Cytoscape software was used to construct protein-protein interaction network maps of Astragali Radix regulated energy metabolism targets, and GO and KEGG enrichment analyses were performed. Molecular docking and hierarchical cluster analysis were performed to evaluate the target-component affinity between the whole constituents of Astragali Radix and key targets, and the effects of representative compounds of Astragali Radix on the energy metabolism of H9C2 cardiomyocytes and GES-1 gastric epithelial cells were detected, and the binding mode analysis was conducted. RESULTS Network pharmacology results showed that there were 126 potential targets of Astragali Radix regulating energy metabolism. GO and KEGG enrichment analysis showed that Astragali Radix regulating energy metabolism might be related to gene expression of oxidation-reduction process, protein and enzyme synthesis. Among them, SIRT1 and PPARγ were key targets involved in the regulation of energy metabolism. Molecular docking and hierarchical clustering showed that Astragali Radix components had superior targeting to SIRT1 and PPARγ, and three representative compounds were selected for in vitro experimental verification in combination with molecular docking scores. Quercetin and kaempferol could promote energy metabolism in H9C2 cardiomyocytes and GES-1 gastric epithelial cells. The binding mode analysis showed that quercetin and kaempferol had preferable binding ability to SIRT1 and PPARγ. CONCLUSION In this study, the material basis and biological mechanism of Astragali Radix regulating energy metabolism are preliminarily explained by traditional Chinese medicine chemo-bio informatics methods, which provide a scientific basis for the connotation of Astragali Radix exerting the effect of stagnation and arthralgia through “invigorating Qi” in traditional Chinese medicine.