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

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective To investigate the dynamic expression with the time change of N6-methyladenosine(m6A)methylation-related factors in the repair process of skeletal muscle injury and its mechanism in the inflammatory response of macrophage in the injure process.Methods In vivo mice models of BaCl2 injury in the gastrocnemius were established.Four mice per group in the control group and injury group.Gastrocnemius tissues were harvested at day 1,3,5,7,and 9 after injury for experiments.Primary gastrocnemius muscle tissue cells,muscle satellite cells,muscle cells,and cell line C2C12 cells were treated with dexamethasone(DEX,50 μmol/L)to mimic injury.Lipopolysaccharide(LPS,100 μg/L)induced RAW264.7 cell lines to mimic the inflammatory response after skeletal muscle injury,and STM2457(30 μmol/L)was added to inhibit the effect of methyltransferase 3(Mettl3)before LPS treatment.The expression of m6A methylation-related factors(Writers,Erasers,Readers)and inflammation factors were detected by Real-time PCR and Western blotting.Results The muscle fibers were dissolved and then gradually repaired with the extension of injury time,the number of monocytes/macrophages increased first and then decreased,and the Pax7 mRNA level increased first and then decreased with the change of injury time.Compared with the control group,the mRNA and protein levels of m6A methylation-related factors in gastrocnemius did not change significantly on the injury-1 day.However,they were significantly increased on the injury-3 days compared with the control group(P＜0.05),and then obviously decreased on the injury-5 days group compared with the injury-3 days group(P＜0.05).Compared with the control group,they were no significant differences on the injury-7 days group and-9 days group.In vitro DEX decreased the mRNA levels of m6A methyltransferase factors in primary muscle satellite cells and C2C12 cells and increased the mRNA expression level of methylation-recognition enzyme factors(P＜0.05).The mRNA levels of m6A methylation-related factors increased significantly in skeletal muscle tissue cells and myocytes after DEX treatment(P＜0.05).After LPS treatment,the mRNA and protein expression levels of m6A methylation-related factors and the mRNA expression levels of inflammatory factors interleukin(IL)-6 and IL-1β in macrophages increased significantly(P＜0.05),while the levels of IL-6 and IL-1β mRNA in macrophages decreased significantly when the Mettl3 was inhibited(P＜0.05).Conclusion m6A methylation-related factors primarily is activated in the damaged muscle cells and inflammation response of macrophages.Inhibition of m6A methyltransferase can reduce the inflammatory response of macrophages.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To compare the application value of three image post-processing techniques volume rendering(VR),multiplanar reformation(MPR)and curved planar reformation(CPR)in the identifi-cation of rib fracture malunion.Methods The types and numbers of rib fracture malunion in 75 pa-tients were recorded,and the sensitivity,specificity,accuracy and Youden index of VR,MPR and CPR in the diagnosis of rib fracture malunion were compared.Receiver operator characteristic(ROC)curve was drawn and area under the curve(AUC)was calculated,and the detection rates of three image post-processing techniques for different types of rib fracture malunion were compared.Results A total of 243 rib fractures were malunion in 75 patients.The diagnostic sensitivity of VR,MPR and CPR for rib fracture malunion was 52.67%,79.84%and 91.36%,the specificity was 99.58%,97.89%and 99.15%,the accuracy was 83.66%,91.76%and 96.51%,the Youden index was 0.52,0.78 and 0.91,the AUC was 0.761,0.889 and 0.953,respectively.Compared with VR,there were statistically signifi-cant differences in the number of broken rib end misalignment over 1/3,broken rib end overlap,bro-ken rib end angulation and intercostal bridge detected in MPR(P<0.05).Compared with VR,there was a statistically significant difference in the number of different types of rib fracture malunion de-tected by CPR(P<0.05).Compared with MPR,there were statistically significant differences in the number of broken rib end misalignment over 1/3,broken rib end separation and intercostal bridge de-tected in CPR(P<0.05).Conclusion The three image post-processing techniques are of great signifi-cance for the identification of rib fracture malunion.Especially CPR is highly effective in the diagno-sis of rib fracture malunion,and can be used as the main post-processing technique for forensic clini-cal identification of rib fracture malunion.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Heme oxygenase-1(HO-1)is an inducible heme oxygenase and a catalytic enzyme for heme decomposition reactions,which can catalyze the heme decomposition into CO,biliverdin and Fe2+.HO-1 and its metabolites have anti-inflammatory,antioxidant and anti-apoptotic effects in human body,and play an important role in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease.This article will review the production,distribution,and gene structure of HO-1,the biological characteristics of its metabolites,and the role and mechanism of HO-1 in neurodegenerative diseases,in order to provide a theoretical basis for the clinical application of HO-1.

Objective To construct models of viral transfection and hypoxia/reoxygenation induced cellular injury in adult mouse cardiomyocytes(AMCMs)isolated using a non-Langendorff method.Methods AMCMs were isolated,extracted,sedimented,and plated using a non-Langendorff method.The morphology and survival rate of the isolated cells were evaluated 2,24,48 and 72 h after plating,and their integrity was observed by immunofluorescence staining for α-actinin.The isolated AMCMs were infected with adenoviruses carrying an RFP-expressing vector and fluorescence images were obtained at 36 and 48 h post-infection and used to calculate transfection efficiency.The cells were cultured under hypoxic conditions for 45 min,reoxygenated for 24 h,and then stained with propidium iodide(PI)to verify establishment of the hypoxia/reoxygenation injury model.Results The survival rates of AMCMs at 2,24 and 48 h after plating were comparable,but survival was significantly reduced at 72 h.The integrity of the AMCMs was good and＞80%of the cells were transfected with adenovirus at 48 h.After hypoxia/reoxygenation treatment,42%of cells were stained by PI,suggesting successful establishment of the AMCM injury model.Conclusions In this study,we developed a non-Langendorff method for the fast and easy isolation of AMCMs with high cell viability.The isolated cells can be efficiently infected with adenovirus and respond to hypoxia/reoxygenation injury.These findings provide a systematic method for isolating AMCMs and for applying gene modification and hypoxia/reoxygenation injury in these cells.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility, bringing serious harm to women's physical and mental health. Acupuncture may be an effective treatment for PCOS. However, systematic reviews (SRs) on the efficacy and safety of acupuncture for PCOS have reported inconsistent results, and the quality of these studies has not been adequately assessed. OBJECTIVE: To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS, as well as to assess the quality and risks of bias of the available SRs. SEARCH STRATEGY: Nine electronic databases (Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Chinese Science and Technology Periodical Database, and China Biology Medicine disc) were searched from their establishment to July 27, 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "acupuncture," "polycystic ovary syndrome," and "systematic review." INCLUSION CRITERIA: SRs of randomized controlled trials that explored the efficacy and (or) safety of acupuncture for treating patients with PCOS were included. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted study data according to a predesigned form. Tools for evaluating the methodological quality, risk of bias, reporting quality, and confidence in study outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), were used to score the included SRs. RESULTS: A total of 885 studies were retrieved, and 11 eligible SRs were finally included in this review. The methodological quality of 2 SRs (18.18%) was low, while the other 9 SRs (81.82%) were scored as extremely low. Four SRs (36.36%) were considered to be of low risk of bias. As for reporting quality, the reporting completeness of 9 SRs (81.82%) was more than 70%. Concerning the confidence in study results, 2 study results were considered to have a high quality of evidence (3.13%), 14 (21.88%) a "moderate" quality, 28 (43.75%) a "low" quality, and 20 (31.24%) considered a "very low" quality. Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate (CPR) and ovulation rate, and reduce luteinizing hormone/follicle-stimulating hormone ratio, homeostasis model assessment of insulin resistance, and body mass index (BMI). When compared with medicine alone, acupuncture alone also can improve CPR. Further, when compared with no intervention, acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI. Acupuncture was reported to cause no adverse events or some adverse events without serious harm. CONCLUSION The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence. More high-quality studies are needed to support the use of acupuncture in PCOS.
Pregnancy ; Humans ; Female ; Polycystic Ovary Syndrome/etiology* ; Acupuncture Therapy/adverse effects* ; Infertility, Female/etiology* ; China