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

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

Objective:To explore the correlation between post-traumatic stress disorder(PTSD),resilience and quality of life of front-line medical staff in public health emergencies.Methods:From Nov to Dec 2020,the medical staff of 4 COVID-19 designated hospitals in Wuhan were investigated with the general demographic questionnaire,10-item Connor-Davidson Resilience Scale,PTSD Checklist for DSM-5 and Simplify Qualify of Life Scale.Spearman correlation analysis and hierarchical regression analysis were used to investigate the correlation between PTSD,resilience and quality of life.Results:A total of 545 questionnaires were collected in this survey and the valid effective rate was 97.8% (533/545).The score of psychological resilience,PTSD and quality of life of medical staff were 26(20,30),17(8,25),and 20(18,23),respectively.And 13.1% (70/533)of medical staff had obvious PTSD symptoms.There were significant differences in the score of quality of life among medical staff with different genders,occupations and PTSD levels.Spearman correlation analysis results showed that the score of PTSD was negatively correlated with quality of life and psychological resilience(r=-0.488 and-0.464,P＜0.01).The score of psychological resilience was positively correlated with the score of quality of life(r =0.578,P＜0.01).Psychological resilience and PTSD were important predictors of quality of life,with an explanatory capacity of 37.0% .Conclusions:PTSD is a risk factor for quality of life,and psychological resilience is a protective factor for quality of life.In public health emergencies,improving psychological resilience,preventing and treating PTSD can improve the quality of life of medical staff.

Objective To analyze the efficacy of sintilizumab combined with paclitaxel(albumin-bound)and nedaplatin(TN chemotherapy regimen)in patients with advanced non-small cell lung cancer(NSCLC)and its effects on serum tumor markers and immune cell levels.Methods The patients were divided into control group and treatment group according to random number table method.In the control group,80 mg·m-2 nedaplatin and 260 mg·m-2 paclitaxel(albumin-bound type)were injected intravenally on the 1st day for 21 days.The etreatment group was given sindilizumab 200 mg intravenously on the basis of the control group,21 days a cycle for 4 cycles.The anti-tumor efficacy,tumor markers,lung function,immune cytokines and adverse drug reactions of the two groups were compared after 4 cycles of treatment,and the 1-year survival of the two groups was statistically analyzed.Results A total of 7 cases fell off during treatment.Finally,98 patients in the treatment group and 96 patients in the control group were included in the analysis.After treatment,the objective response rate(ORR)of treatment group and control group were 43.88％(43 cases/98 cases)and 29.17％(28 cases/96 cases);the disease control rate(DCR)were 77.55％(76 cases/98 cases)and 60.42％(58 cases/96 cases),the difference was statistically significant(all P＜0.05).After treatment,carbohydrate antigen 125(CA125)in treatment group and control group were(39.03±5.97)and(42.15±6.35)U·mL-1;squamous cell carcinoma antigen(SCCA)were(4.58±0.63)and(5.29±0.84)ng·mL-1;forced vital capacity(FVC)were(2.96±0.52)and(2.71±0.49)L;forced expiratory volume in the first second(FEV1)/FVC were(68.47±11.39)％and(64.92±10.43)％;Th1/Th2 were 5.01±0.63 and 5.36±0.74;Th17/Treg were 1.04±0.15 and 1.20±0.19;CD4+/CD8+were 1.36±0.19 and 1.23±0.17,respectively.The differences were statistically significant(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 25.51％(25 cases/98 cases)and 22.92％(22 cases/96 cases),respectively,the difference was not statistically significant(P＞0.05).There was no significant difference in 1-year overall survival curves between the two groups(P＞0.05).Conclusion Sindilizumab combined with TN chemotherapy regimen in the treatment of advanced NSCLC can enhance the anti-tumor efficacy,reduce the level of tumor markers,improve lung function and immune function,and has good safety.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:To analyze the dynamic changes of neutrophil percentage-to-albumin ratio (NPAR) during treatment with bortezomib-lenalidomide-dexamethasone (VRD) in patients with multiple myeloma (MM),and explore the relationship between NPAR value and short-term prognosis of MM patients. Method:The data of 80 MM patients who underwent VRD chemotherapy at Tangshan Workers Hospital from January 2019 to April 2021 were retrospectively analyzed. NPAR levels were measured before VRD chemotherapy (T0),and on the first day of the third (T1),sixth (T2),and eighth (T3) chemotherapy cycles. All patients were followed up for 1 year,with the recurrence,progression,or death occurring within 1 year after the completion of VRD treatment as the endpoint event. The patients were divided into a good prognosis group and a poor prognosis group based on the follow-up results. The changes in NPAR at T0,T1,T2,and T3 in the two groups were statistically analyzed. The restricted cubic spline method was used to analyzed the relationship between NPAR and adverse short-term prognosis in MM patients undergoing VRD chemotherapy. Results:Among the 80 MM patients,25 cases (31.25％) had poor short-term prognosis,including 19 cases (23.75％) of progression or recurrence,and 6 cases (7.50％) of all-cause mortality. The levels of neutrophils and NPAR in the poor prognosis group at T0,T1,T2 and T3 were higher than those in the good prognosis group at the same period,while the albumin levels in the poor prognosis group at T0,T1,and T2 were lower than those in the good prognosis group at the same period (P<0.05);There was no significant difference in albumin levels between the poor prognosis group and the good prognosis group at T3 (P>0.05). Within the poor prognosis group and the good prognosis group,the levels of neutrophils and NPAR decreased sequentially at T0,T1,T2,and T3,while the levels of albumin increased sequentially,and the differences between each stage were statistically significant (P<0.05). The restricted cubic spline model showed an approximate J-shaped curve between the risk of poor short-term prognosis and the pre-treatment NPAR level in MM patients (P<0.05). If the pre-treatment NPAR>0.52,the risk of poor short-term prognosis in MM patients increased with the increase of NPAR value. Conclusion:After VRD treatment,the NPAR value of MM patients gradually decreases,and there is a correlation between the NPAR value before VRD treatment and the risk of poor prognosis after treatment. If NPAR>0.52 before treatment,the higher the NPAR value,the higher the risk of poor short-term prognosis in MM patients.

Objective:To assess the efficacy of parent training (PT) on attention deficit hyperactivity disorder (ADHD) symptoms, behavioral problems, and parenting stress in child with ADHD or ADHD symptoms.Methods:Randomized controlled trials of the effect of PT on ADHD symptoms in Chinese children with ADHD or ADHD symptoms were collected by PsychINFO, PubMed, EMBASE, Web of science, Scopus, China National Knowledge database, WanFang database, the China Science and Technology Journal Database and the China Biology Medicine disc. The quality of the included studies was evaluated by version 2 of the Cochrane tool for assessing risk of bias in randomized trial. Forest plots were drawn using Review Manager 5.4.1, sensitivity analyses of results were performed using Stata 18.0 to assess the stability of the results, and publication bias was assessed using funnel plots and Egger's test.Results:A total of 10 studies containing 571 subjects in the experimental group and 562 subjects in the control group met the inclusion exclusion criteria. Significant differences were observed in various measures, including overall ADHD symptoms (MD=-2.43, 95% CI: -3.95--0.91), inattention (MD=-1.10, 95% CI: -1.94--0.26), hyperactivity/impulsivity (SMD=-0.58, 95% CI: -0.87--0.28), overall conduct problems (SMD=-0.80, 95% CI: -1.05--0.55), conduct problem (SMD=-1.34, 95% CI: -2.31--0.37), learning problem (SMD=-0.81, 95% CI: -1.40--0.23), impulsivity/hyperactivity (SMD=-0.53, 95% CI: -0.78--0.29), hyperactivity index (SMD=-1.27, 95% CI: -1.99--0.55), parenting stress index (SMD=-0.69, 95% CI: -1.12--0.26), difficult child (MD=-1.96, 95% CI: -3.44--0.48), dysfunctional interaction (MD=-3.10, 95% CI: -4.43--1.78), and parenting distress (MD=-3.35, 95% CI: -4.59--2.12)(all P<0.05). However, no significant differences were observed in oppositional-defiant disorder, anxiety, or somatic problem. Conclusions:The initial findings suggested that PT was effective for Chinese children with ADHD or ADHD symptoms.The addition of PT appeared to improve core symptoms of ADHD (inattention and hyperactivity/impulsivity), conduct problems, and parental stress more effectively than routine care alone.