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

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

OBJECTIVE: To compare early graft healing between over-the-top (OTT) and anatomic single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. METHODS: A clinical data of 40 patients underwent ACL reconstruction, who admitted between June 2021 and October 2022 and met the selective criteria, was retrospectively analyzed. Among them, 20 patients were treated with OTT reconstruction (OTT group) and 20 with SB reconstruction (SB group). There was no significant difference between groups ( P>0.05) in the gender, age, affected side, disease duration, degree of meniscus injury, body mass index, and preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, pain visual analogue scale (VAS) score, and KT-2000 measurement. At 3, 6, and 12 months, MRI was performed to measure the signal noise quotient (SNQ) of the proximal end, middle, and distal end of the graft in the two groups, as well as at the corner of the graft with lateral femoral condyle and 1 cm around the femoral fixation point in the OTT group, to observe the degree of graft healing. Before operation and at 3, 6, and 12 months, the knee function and pain were evaluated by IKDC score, Lysholm score, and VAS score. Before operation and at 12 months after operation, the KT-2000 measurement was taken to evaluation the knee joint stability. RESULTS: All operations were successfully completed in both groups and the incisions healed by first intention. All patients were followed up 12-15 months (mean, 12.9 months), with no significant difference in the follow-up time between groups ( P>0.05). After operation, the IKDC score, VAS score, and Lysholm score improved gradually over time in both groups, with significant differences between different time points ( P<0.05). The differences between groups at 3, 6, and 12 months after operation were not significant ( P>0.05). The anterior and posterior stability of the knee joint improved significantly in both groups at 12 months after operation, and the difference in KT-2000 measurements was significant when compared with the preoperative value ( P<0.05), but the difference of pre- and post-operation between groups was not significant ( P>0.05). At 3, 6, and 12 months after operation, MRI showed that the differences in the SNQ of the proximal end and middle of the grafts between the two groups were not significant ( P>0.05), and the SNQ of distal end was significantly higher in the SB group than in the OTT group ( P<0.05). At each time point, grafts in the OTT group had the highest SNQ at the corner and the lowest at the fixation point, and the differences were significant compared to the other sites ( P<0.05). In the two groups, except for the fixation point, the SNQ of the remaining sites were highest at 6 months and lowest at 12 months ( P<0.05). In addition, there were significant differences in SNQ between the different sites of grafts ( P<0.05), and the SNQ was lowest at proximal end and highest at distal end. At last follow-up, the knee grafts in both groups were in good shape and no graft necrosis or loosening of the internal fixation was observed. CONCLUSION The knee joint function and graft healing after OTT reconstruction of ACL are similar to those of SB reconstruction, but it should be noted that the healing at the corner of the graft is slower.
Retrospective Studies ; Treatment Outcome ; Anterior Cruciate Ligament Reconstruction/rehabilitation* ; Follow-Up Studies ; Tibial Meniscus Injuries/surgery* ; Patient Positioning/methods* ; Recovery of Function ; Pain Measurement ; Knee Joint/surgery* ; Humans ; Male ; Female ; Adult ; Wound Healing

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Objective:To investigate exercise fear condition and its influencing factors in patients with coronary heart dis-ease(CHD)involving in phase Ⅱ cardiac rehabilitation after percutaneous coronary intervention(PCI).Methods:Conven-ience sampling was performed among cardiac rehabilitation patients from a Shanxi grade-A tertiary hospital between Janu-ary 2023 and June 2023.General data questionnaire,Tampa Scale for Kinesiophobia-Short Version for Heart patients(TSK-SV H),the Multidimensional Scale of Perceived Social Support(MSPSS)and the Post Percutaneous Coronary In-tervention Health Literacy Scale(PPCIHLS)were used for assessment.Pearson and Spearman rank correlation analyses were applied to investigate the relationships between social support factors and health literacy factors with patients'fear of exercise;multivariate linear regression models and quantile regression models were used to analyze the influencing factors of fear of exercise.Results:Among the 118 patients,average TSK-SV H score was(33.78±3.79)points;10.2％patients showed significant fear.The correlation analysis showed that PPCIHLS score was negatively correlated with TSK-SV H score(r=-0.423,P＜0.001).Results from multivariate regression analysis indicated that health literacy,cardiac func-tion class and drinking status affected the average score of exercise fear(P＜0.05 all).The quantile regression model pro-vided additional insights,showing that the impact of factors such as living situation,drinking status,cardiac function class and health literacy on exercise fear varied across different quantiles.Notably,cardiac function class had a consistently posi-tive effect on TSK-SV H score at various quantiles.Conclusion:Improving health literacy and tailored rehabilitation plans are vital to reduce exercise fear and improve cardiac rehabilitation effect.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

In the context of"Artificial Intelligence(AI)+Education"era,this study introduces the teaching reform and devel-opment path of the course"Fundamentals of Immunology and Pathogenic Biology"by Professor Lu Fangguo's team at Hunan University of Traditional Chinese Medicine.After twenty years of exploration,the course has successfully transitioned from traditional teaching to intelligent teaching,achieving a comprehensive upgrade in educational concepts,teaching methods,and resources.The reform process is divided into three stages:Early exploration,comprehensive reform,and deepening development.It encompasses the construction of a smart teaching platform,the development and promotion of new forms of digital teaching resources,and the deep integration of ideological and political education.This reform has significantly enhanced teaching quality and students'overall competencies,showcasing the innovative spirit of educators.It has gained nationwide recognition and promotion,providing valuable references for the innovation of medical education in the new era.

Cultural confidence is an important part of nurturing"confidence in the path,theory,system,and culture of social-ism with Chinese characteristics"students,as well as the important direction of ideological and political courses,and play an impor-tant role for establishing the core values of Chinese socialism.This paper summarized the reform exploration and practical experience of the Basic Immunology and Pathogen Biology through deeply excavating the core ideas of Chinese medicine culture based on the course content for improving the cultural confidence.The object of this paper is to improving the effectiveness of education.

BACKGROUND:For patients with anterior cruciate ligament re-rupture after reconstruction with abnormally increased posterior slope of the tibial plateau,anterior cruciate ligament reconstruction combined with anterior closing-wedge high tibial osteotomy was performed.However,there is a lack of precise tools for osteotomy.OBJECTIVE:To investigate the effectiveness of three-dimensional(3D)printed accurate osteotomy template in anterior cruciate ligament revision for patients with excessive posterior slope.METHODS:The medical records of 30 patients who underwent anterior cruciate ligament revision combined with anterior closing-wedge high tibial osteotomy were retrospectively collected and divided into two groups according to the operation method.The trial group(n=15)was assisted by 3D printing osteotomy guide plate.The control group(n=15)was conventional surgery.The osteotomy time,fluoroscopy times,intraoperative and 24 hours postoperative blood loss,preoperative and 3 months postoperative tibiofemoral anatomical angle,medial proximal tibial anatomical angle,posterior slope,the difference between planned posterior slope correction angle and actual correction angle,and KT-2000 side-to-side difference before operation,3 and 24 months after operation were compared between the two groups.Lachman test and Pivot shift test were performed before operation,immediately after operation,and 24 months after operation.International Knee Documentation Committee score and Lysholm score were performed before operation,3 and 24 months after operation.RESULTS AND CONCLUSION:(1)The osteotomy time,fluoroscopy times,and blood loss during operation and 24 hours after operation in the trial group were significantly less than those in the control group(P＜0.05).(2)The posterior slope of the two groups decreased significantly after operation.There was no significant change in tibiofemoral anatomical angle and medial proximal tibial anatomical angle after operation.The difference between preoperative planned and postoperative actual posterior slope degree in the trial group(0.64±0.41)° was smaller than that in the control group(2.18±0.54)°,and the difference was statistically significant(P＜0.001).(3)The KT-2000 side-to-side difference was significantly reduced in both groups after surgery(P＜0.05).At 3 and 24 months after operation,there was no significant difference in KT-2000 side-to-side difference between the two groups(P＞0.05).The Lachman test and Pivot shift test of the two groups were negative immediately after operation,3 and 24 months after operation.(4)The International Knee Documentation Committee and Lysholm scores of the two groups increased significantly after surgery(P＜0.05).At 3 months after operation,the International Knee Documentation Committee score and Lysholm score of the trial group were significantly higher than those of the control group(P＜0.05).At 24 months after operation,there was no significant difference in International Knee Documentation Committee score and Lysholm score between the two groups(P＞0.05).(5)In conclusion,with the assistance of 3D printing accurate osteotomy guide plate,anterior cruciate ligament reconstruction combined with anterior closing-wedge high tibial osteotomy is easier to operate,with shorter operation time,fewer fluoroscopy times,less intraoperative and postoperative blood loss,and faster recovery of knee joint function after operation,which has high clinical application value.

Based on the viewpoints of turbidity and toxin and years of clinical experience,professor Wei Aisheng proposed that spleen qi deficiency leading to internal retention of turbidity and toxin contributes to the key pathogenesis of patients with type 2 diabetes mellitus(T2DM)characterized by obesity or metabolic disorders.For T2DM patients with obesity or metabolic disorders in the middle and end stages,long-term retention of turbidity and toxin leads to unsmooth qi movement of triple energizer and damage of viscera.Therefore,Professor Wei put forward the viewpoint of cutting off the toxin in the early stage,and established the therapy of replenishing qi,respectively expelling pathogens and eliminating turbidity from triple energizer.Professor Wei formulated Sanhuang Yinchen Wuling San as the primary prescription for T2DM.The prescription is derived from the classical formula Yinchen Wuling San with the herbs of Astragali Radix,Coptidis Rhizoma and Ephedrae Herba added,having the actions of replenishing qi and supporting healthy qi,respectively expelling pathogens from triple-energizer to resolve phlegm-damp and stagnated heat.The application of Sanhuang Yinchen Wuling San for T2DM can invigorate spleen qi,smooth qi movement of triple energizer,and eliminate turbidity and toxin,and enhance the efficacy for T2DM.