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

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To explore the clinical characteristics, therapeutic responses and prognostic features of E2A-PBX1 fusion gene for childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 837 pediatric patients with ALL who were initially diagnosed in our hospital from July 2010 to November 2017 were retrospectively analyzed, 48 children with positive E2A-PBX1 fusion gene were detected by the real-time quantitative PCR techniques and their data were retrospectively collected for analysis. RESULTS: Among 48 cases with positive E2A-PBX1 fusion gene, there were 26 males and 22 females, with onset ages ranging from 9 months to 13 years old. There were 2 cases (4.2%) in the low-risk group, 32 cases (66.7%) in the intermediate-risk group, and 14 cases (29.1%) in the high-risk group at initial diagnosis. The white blood cell (WBC) counts of 25 cases (53.2%) at initial diagnosis were <50×10⁹/L, 11 cases (23.4%) were (50-100)×10⁹/L, and 11 cases (23.4%) ≥100×10⁹/L. The main immunophenotype was common-B ALL (44 cases, 91.7%). Other leukemia fusion genes such as BCR-ABL1, MLL-AF4, and TEL-AML1 were not observed in this cohort of patients. All patients received the treatment of NPCLC-ALL2008 protocol, and 5 cases (10.4%) occurred poor prednisone response. All the 48 cases achieved complete remission (CR) after the induction treatments. The last follow-up date was April 30, 2023. A total of 5 children relapsed, including 1 case with intermediate risk and 4 cases with high risk. The recurrence rate in the high-risk group was significantly higher than that in the intermediate- and low-risk groups (both P < 0.05). Most relapsed children had elevated WBC counts at initial diagnosis. Among them, WBC counts ≥100×10⁹/L was observed in 4 cases. The recurrence rate among children with WBC counts ≥100×10⁹/L was significantly higher than that with WBC counts <100×10⁹/L (P < 0.01). Four deaths occurred in this cohort, of which 3 died of leukemia recurrence. The 10-year event-free survival rate and 10-year overall survival rate of the 48 children with positive E2A-PBX1 fusion gene were 87.5%±4.8% and 91.7%±4.0%, respectively. CONCLUSION In ALL children with positive E2A-PBX1 fusion gene, those with elevated WBC counts and high risk stratification at initial diagnosis are more likely to experience recurrence. Recurrence is the main cause of death in this group. It is suggested that such kind of children receive more intensive chemotherapy or undergo hematopoietic stem cell transplantation as early as possible to further improve prognosis.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Oncogene Proteins, Fusion/genetics* ; Prognosis ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Retrospective Studies ; Infant ; Homeodomain Proteins

Objective To observe the therapeutic effects of different doses of methylprednisolone(MP)on smoke inhalation-induced acute lung injury(SI-ALI)in rats,and to explore the changes in the expression of aquaporins(AQPs)and the underlying mechanisms for alleviating lung injury.Methods A total of 86 healthy adult male Sprague-Dawley(SD)rats were randomly divided into five groups:control group(n=6),smoke inhalation injury(SI)group(n=20),low-dose MP group(LMP,SI+0.4 mg/kg MP,n=20),medium-dose MP group(MMP,SI+4 mg/kg MP,n=20),and high-dose MP group(HMP,SI+40 mg/kg MP,n=20).A model of smoke inhalation-induced lung injury was established.The survival status of the rats in each group was monitored.Lung tissues were collected 24 hours after injury to determine the wet-to-dry(W/D)ratio of the lung tissues,arterial oxygen partial pressure(PaO2),and the expression levels of inflammatory cytokines TNF-α and IL-6.The degree of lung injury was evaluated using HE staining,and the mRNA and protein expression levels of AQP1 and AQP5 in the lung tissues were detected.Results Compared with control group,the survival rate of the rats in SI group was significantly decreased(P<0.05);compared with SI group,the survival rates of the rats in MMP and HMP groups were significantly increased(P<0.05).Compared with control group,the PaO2 of the Rats in SI group was significantly decreased(P<0.05),and the wet-to-dry(W/D)ratio and lung injury scores were significantly increased(P<0.05).Compared with SI group,the PaO2 of the rats in LMP,MMP,and HMP groups(P<0.05)was significantly increased(P<0.05),and the lung W/D ratio and injury scores in MMP and HMP groups were significantly decreased(P<0.05).ELISA results showed that compared with control group,the serum concentrations of TNF-α and IL-6 in SI group were significantly increased(P<0.05);compared with SI group,the concentrations of TNF-α and IL-6 in MMP and HMP groups were significantly decreased(P<0.05).HE staining revealed that the alveolar structure of the rats in SI group was severely damaged;compared with SI group,the damage to the alveolar structure in MMP and HMP groups was alleviated.Real-time PCR and Western blotting analysis results showed that compared with control group,the mRNA and protein expression levels of AQP1 and AQP5 in lung tissues in SI group were significantly decreased(P<0.05);however,compared with SI group,these levels in LMP,MMP,and HMP groups were significantly increased(P<0.05).Conclusions Smoke inhalation can induce acute lung injury in rats and down-regulate the expression levels of AQP1 and AQP5 in the lung tissues.Methylprednisolone can alleviate pulmonary edema and tissue damage in rats caused by smoke inhalation,and induce the up-regulation of the expression of AQP1 and AQP5.

Fibrosis is characterized as an aberrant reparative process involving the direct replacement of damaged or deceased cells with connective tissue, leading to progressive architectural remodeling across various tissues and organs. This condition imposes a substantial burden, resulting in considerable morbidity and mortality. Ginseng (Panax ginseng C. A. Meyer), renowned for its medicinal properties, has been incorporated as a key component in Chinese patent medicines to mitigate fibrotic diseases. Ginsenosides, the primary bioactive compounds in ginseng, have garnered significant attention. Over the past five years, extensive research has explored the pharmaceutical potential of ginsenosides in diverse organ fibrosis conditions, including liver, myocardial, renal, and pulmonary fibrosis. Studies have elucidated that ginsenosides demonstrate potential effects on inflammatory responses stemming from parenchymal cell damage, myofibroblast activation leading to extracellular matrix (ECM) production, and myofibroblast apoptosis or inactivation. Additionally, potential downstream targets and pathways associated with these pathological processes have been identified as being influenced by ginsenosides. This review presents a comprehensive overview of the efficacious treatments utilizing ginsenosides for various tissue fibrosis types and their potential anti-fibrotic mechanisms. Furthermore, it offers a reference for the development of novel candidate drugs for future organ fibrosis therapies.
Ginsenosides/pharmacology* ; Humans ; Fibrosis/drug therapy* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal/therapeutic use*

Objective To evaluate the preemptive analgesic effect of diclofenac sodium combined with tramadol in outpatient intrauterine device(IUD)removal surgery for postmenopausal women,and to explore its feasibility and effectiveness in clinical application.Methods The clinical data of postmenopausal women who underwent IUD removal surgery at the obstetrics and gynecology outpatient department of the Hunan Schistosomiasis Prevention and Control Institute from February 2022 to January 2023 were retrospectively collected.A propensity score matching(PSM)method for 1∶1 matching was applied.The combination group received diclofenac sodium suppositories combined with tramadol for analgesia,while the control group received diclofenac sodium suppositories combined with lidocaine.Surgical duration,analgesic effect,adverse reactions,cervical softening,and success rate of IUD removal were compared between the two groups.Results Data from 142 patients were collected.After PSM,there were 53 patients in each group.The surgery time in the combination group was significantly shorter than in the control group(2.58±0.51 vs.4.76±1.37 minutes,P＜0.001).The numeric rating scale(NRS)scores in the combination group was better than in the control group(1.43±0.75 vs.3.87±1.33,P＜0.001).The cervical softening rate in the combination group was 94.34％,significantly higher than the 71.70％in the control group(P＜0.05),while the success rate of IUD removal in the combination group was 96.23％,also significantly higher than 84.91％in the control group(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Diclofenac sodium combined with tramadol provides significant preemptive analgesic effects in IUD removal surgery for postmenopausal women.It helps to shorten surgical duration,alleviate intraoperative pain,promote cervical softening,and increase the success rate of IUD removal,demonstrating high clinical value.

Objective:To evaluate the preservation efficacy of 7 non-inactivating virus preservation solutions.Methods:Equal amounts of H1N1 virus were added to 7 commercially available non-inactivating virus preservation solutions, and the samples were stored at -20 ℃, 4 ℃, 25 ℃ and 37 ℃ for 1 hour, 6 hours, 1 day, 3 days, and 5 days. The viral nucleic acid in each simulated sample under different storage conditions was measured using real-time quantitative PCR. The hemagglutination (HA) titer was determined through viral isolation culture and hemagglutination assay, comparing the differences in viral growth activity across different storage solutions and conditions.Results:Except for solution E, the other solutions effectively protected viral nucleic acid at the 4 storage temperatures. In terms of viral activity, solutions A, B, C, and D effectively maintained viral viability. A and B showing the best performance, E and F showed poorer performance, and G performed the worst.Conclusions:Most non-inactivating virus preservation solutions effectively protect viral nucleic acid, but there are significant differences in their ability to maintain viral viability. To ensure optimal virus preservation, it is recommended that medical institutions evaluate the effectiveness of preservation solutions before use.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To observe the impact factors of vascular heat sink effect during in vitro microwave ablation(MWA)of porcine lung.Methods Simulation models were established using in vitro porcine lung tissue blocks based on isobaric inflation with an air pump and cyclic perfusion of duck blood with a glass tube and peristaltic pump,etc.MWA was performed under 8 different combining conditions(vessel diameter of 3 or 5 mm,blood perfusion of 30 or 50 cm/s,as well as distance between vessel and ablation antenna of 5 or 10 mm)each for 3 times.The highest temperature TV on vessel side and TC on control side during MWA,and ablation depth DV on vessel side and DC on control side after MWA were recorded.Multi-factor linear regression equations were constructed based on simulated vessel diameters,blood perfusion and distance between vessel and ablation antenna,and the impact factors of|TC-TV|and|DC-DV|were screened,respectively.Results Simulated vessel diameter showed linear positive correlation with both|TC-TV|and|DC-DV|(both P＜0.001).Simulated distance between vessel and ablation antenna showed linear negative correlation with both|TC-TV|and|DC-DV|(both P＜0.001),and the latter had more obvious impact on vascular heat sink effect than the former.Meanwhile,no significant linear relationship was found between simulated blood perfusion and|TC-TV|nor|DC-DV|(both P＞0.05).Conclusion Simulated vessel diameter and distance between vessel and ablation antenna were both impact factors of vascular heat sink effect during in vitro MWA of porcine lung,and the latter was more influential,whereas simulated blood perfusion showed no significant impact on it.