BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

Intracranial atherosclerosis has been regard as the most common cause of ischemic stroke.The information of the types and degree of vascular wall lesions is important basis for the diagnosis and treatment of ischemic stroke.High-resolution MR vessel wall imaging can directly display the lumen and wall of intracranial vessels,evaluate the characteristics of atherosclerotic plaque qualitatively and quantitatively,including intra-plaque hemorrhage,plaque enhancement,and plaque distribution.Thus,high-resolution MR vessel wall imaging may play an important role in risk stratification,pathogenesis,treatment and prognosis evaluation in ischemic stroke patients.This review summarizes the progress of high-resolution MRI vessel wall imaging in the evaluation of intracranial atherosclerosis,especially the pathogenesis of plaque features and treatment-related information.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective: An isochronous substitution model was established to explore the association and substitution effect between college students 24 hour activity behavior and physical health, so as to provide specific activity behavior suggestions for college students to improve their physical health. Methods: A stratified random cluster sampling method was used to conduct physical fitness tests and 24 hour activity behavior surveys among 2 794 college students in 12 colleges and universities in Tianjin.Time spent on sedentary behavior(SB), light intensity physical activity(LPA), moderate to vigorous physical activity(MVPA) and sleep(SLP) time. The isochronous method of components was used to explore the relationship between 24 h activity behavior and physical health. Results: Except for 50 m running, MVPA was negatively correlated with BMI Z ( β =-0.62, P <0.05), but positively correlated with other physical fitness indexes ( β =0.34~274.23, P <0.05). LPA was not associated with lung capacity, sitting forward flexion and 50 m running, and negatively correlated with other physical fitness indexes ( β =-14.30- -0.19, P <0.05). SB was negatively correlated with most physical fitness indexes ( β =-11.57- -0.33, P <0.05), but positively correlated with BMI Z ( β =0.45, P < 0.05 ). In addition to lung capacity, SLP was positively correlated with BMI Z , total physical fitness score,1 minute sit-ups, pull ups, 800/1 000 m running, sitting forward flexion, and 50 m running ( β =0.27-11.21, P <0.05), but negatively correlated with long jump ( β =-0.10, P <0.05）. Isochronous substitution showed that the adverse effects of 30 min/d SB and LPA substitution of MVPA were much greater than the beneficial effects of MVPA substitution for corresponding behaviors (total physical score: SB, -0.58 vs 0.47 points; LPA, -0.50 vs 0.38 points). Conclusion MVPA and SLP have been found to have a positive effect on physical fitness among college students. Therefore, in the process of improving the physical health of college students, ensuring adequate sleep, improving MVPA and reducing SB as much as possible may be one of the effective methods.

Objective: To explore the relationship between isochronous substitution and BMI, waist circumference (WC), and body fat rate (FAT) among physical activity (PA), sedentary (SB), and sleep (SLP), so as to provide effective measures for obesity control in adolescents. Methods: A total of 193 adolescents aged 12-15 (90 males and 103 females) was randomly selected, and their height, weight, and BMI were measured using routine testing methods from May to August 2022. The PA, SB and SLP of the participants were measured using a 3D accelerometer (ActiGraph GT3X+). Results: The arithmetic mean value overestimated SLP (40.8%) and SB (39.6%) to some extent, and underestimated LPA (16.1%) and MVPA (3.5%) to some extent. Based on the ISM at 15 min, MVPA was substituted for other activity, BMI Z decreased by 0.17-0.22 units, WC Z decreased by 0.16-0.20 units, and FAT Z decreased by 0.17-0.22 units. The substitution between MVPA and for other activity exhibited significant asymmetry. The effects of MVPA substitutions for SB was the largest, followed by the effects of MVPA substitutions for SLP, and the effects of MVPA substitutions for LPA was the lowest. As MVPA substitutions for other behaviors, it reached its maximum (0.06-0.08 units ) when the MVPA time increased by 5 minutes. Conclusions MVPA plays an irreplaceable role in the control of adolescent obesity . While reducing SB time, MVPA duration should be increased to ensure that the daily MVPA duration is not less than 55 minutes in order to effectively control obesity.

Objective:To investigate effects of metformin and rosiglitazone in non-obese polycystic ovary syndrome (PCOS) women with insulin resistance.Methods:Totally 200 non-obese PCOS women with insulin resistance in West China Second Hospital of Sichuan University were enrolled into this study from Sep. 2013 to Jun. 2016, and were randomly divided into two treatment groups: metformin group (1 500 mg/d) and rosiglitazone group (4 mg/d). The treatment lasted for 6 months. Their clinical and biochemical parameters were collected and compared.Results:In both groups, menstrual cycles [metformin group (37±4) days, rosiglitazone group (35±4) days] were shorter after treatment for 6 months (both P<0.01). After treatment for 6 months, body mass index [metformin group (21.6±1.6) kg/m 2, rosiglitazone group (21.7±1.7) kg/m 2] decreased in both groups (both P<0.01); decreased LH/FSH ratio (metformin group 1.67±0.80, rosiglitazone group 1.70±0.83) was also observed (both P<0.05). After treatment for 6 months, fasting insulin level [metformin group (13.5±5.1) mU/L, rosiglitazone group (12.7±5.6) mU/L] and homeostasis model assessment-insulin resistance index (metformin group 3.0±1.2, rosiglitazone group 2.8±1.2) were decreased in both groups (all P<0.01). Conclusions:For non-obese PCOS insulin resistance patients, screening of anthropometric and metabolic parameters is necessary. For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.

Ischemic stroke is one of the most important causes of death and disability in humans,but the effective methods for treating brain injury after stroke are quite limited.Sphingosine 1-phosphate (S1P) is a pleiotropic lipid.There is certain interdependence between its metabolism and regulation and the molecular mechanisms involved in important biological events following cerebral ischemia.Membrane lipid therapy with S1P as the core may be an effective neuroprotective strategy of ischemic stroke.