OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective To investigate the efficacy and safety of ultrafiltration therapy in elderly patients with congestive heart failure(CHF)and frailty.Methods A total of 88 hospitalized elderly patients with CHF and frailty were randomly assigned to the ultrafiltration group(n=44)and the control group(n=44).The control group treated with standard drug therapy.The ultrafiltration group treated with ultrafiltration,however,diuretics were not used during ultrafiltration treatment.Efficacy assessment was compared between the two groups,including patient body weight,N-terminal pro-brain natriuretic peptide(NT-proBNP)levels at 48 hours after treatment,dyspnea severity scores at 48 hours and 1 week after treatment,hospitalization duration and readmission rate within 3 months.Safety assessment parameters included serum creatinine,urea nitrogen,Na+and K+concentration at 48 hours after treatment and creatinine level 1 week after treatment.Results Efficacy assessment indicated that at 48 hours after treatment,both groups showed a significant reduction in patient body weight and NT-proBNP levels compared to pre-treatment levels(P＜0.05).However,there were no significant difference in body weight and NT-proBNP levels before and after treatment between the two groups(P＞0.05).Dyspnea severity scores for both groups increased at 48 hours after treatment,then decreased at 1 week after treatment.The ultrafiltration group exhibited higher dyspnea severity scores than that of the control group at 48 hours after treatment(P＜0.05).The length of hospital stay and the rate of re-hospitalization within 3 months were lower in the ultrafiltration group compared to those of the control group(P＜0.05).Safety assessment revealed that there were no significant differences in serum urea nitrogen and Na+levels before and 48 hours after treatment between the two groups(P＞0.05).However,serum K+levels were higher after 48-hours treatment in the ultrafiltration group than those of the control group(P＜0.05).There were no significant changes in creatinine levels before and after treatment in the control group(P＞0.05),while creatinine levels were lower 1 week after treatment in the ultrafiltration group compared to those of pre-treatment and 48 hours after treatment,and were lower than those of the control group(P＜0.05).Conclusion Ultrafiltration is a safe and effective method for elderly patients with CHF and frailty.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

In 2020, the prevalence of abnormal spinal curvature among 54 079 students in Shandong Province was 1.54%. The multivariate logistic regression model analysis showed that, compared with those in primary school, economically underdeveloped areas, and non-residential schools, students in middle and high schools, economically average areas, and residential schools had a higher risk of abnormal spinal curvature, with OR (95%CI) values of 2.029 (1.662-2.476), 2.746 (2.208-3.416), 2.237 (1.740-2.875) and 2.057 (1.705-2.483), respectively. Compared with those in economically underdeveloped areas, who were underweight, who had seat adjustments≤1 time per academic year, and who had physical education classes≤1 per week, students in economically developed areas, who were normal weight, overweight, and obese, who had seat adjustments≥2 times per academic year, and who had physical education classes 2-3 or≥4 per week, had a lower risk of abnormal spinal curvature, with OR (95%CI) values of 0.690 (0.521-0.915), 0.722 (0.546-0.955), 0.535 (0.389-0.735), 0.383 (0.274-0.535), 0.835 (0.711-0.980), 0.561 (0.474-0.663) and 0.491 (0.315-0.766), respectively.
Humans ; Risk Factors ; Prevalence ; Spinal Curvatures ; Schools ; Students

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

In 2020, the prevalence of abnormal spinal curvature among 54 079 students in Shandong Province was 1.54%. The multivariate logistic regression model analysis showed that, compared with those in primary school, economically underdeveloped areas, and non-residential schools, students in middle and high schools, economically average areas, and residential schools had a higher risk of abnormal spinal curvature, with OR (95%CI) values of 2.029 (1.662-2.476), 2.746 (2.208-3.416), 2.237 (1.740-2.875) and 2.057 (1.705-2.483), respectively. Compared with those in economically underdeveloped areas, who were underweight, who had seat adjustments≤1 time per academic year, and who had physical education classes≤1 per week, students in economically developed areas, who were normal weight, overweight, and obese, who had seat adjustments≥2 times per academic year, and who had physical education classes 2-3 or≥4 per week, had a lower risk of abnormal spinal curvature, with OR (95%CI) values of 0.690 (0.521-0.915), 0.722 (0.546-0.955), 0.535 (0.389-0.735), 0.383 (0.274-0.535), 0.835 (0.711-0.980), 0.561 (0.474-0.663) and 0.491 (0.315-0.766), respectively.
Humans ; Risk Factors ; Prevalence ; Spinal Curvatures ; Schools ; Students

Objective:To summarize clinical manifestations and histopathological features of granular parakeratosis (GP) after exposure to benzalkonium chloride.Methods:A retrospective analysis was performed on 7 GP cases with a history of benzalkonium chloride exposure in the Department of Dermatology at Wuhan No.1 Hospital from April to August 2022. Data were collected on the general condition, skin lesion manifestations, pathological examination, treatment, and follow-up of the patients, and retrospectively analyzed.Results:The 7 adult patients with GP typically presented with erythema and brown scales in the intertriginous area, exhibiting an annular distribution pattern. All the 7 patients reported recent exposure to disinfectants containing benzalkonium chloride. A total of 10 skin biopsies were taken from the 7 patients. Histopathological examination showed characteristic hyperkeratosis and fine blue-gray parakeratotic granules in the stratum corneum. All skin lesions improved 1 month after cessation of exposure to benzalkonium chloride.Conclusion:GP has a distinct clinical pattern and histopathological manifestations, and a history of exposure to benzalkonium chloride can be helpful for the diagnosis of GP.