Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

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

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

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 association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Objective:To establish a method for determining the sialylation levels of N-glycan profiles based on ion-exchange chromatography in glycoprotein drugs.Methods:The separation was performed in a column picking with anion-exchange resin(4.6 mm × 250 mm,5 μm,or equivalent).Mobile phase A was 20％ acetonitrile solution,while mobile phase B was a 20％acetonitrile solution containing 0.1 mol·L-1 ammonium formate(pH 4.5).The flow rate was 0.60 mL·min-1.Detection was performed using a fluorescence detector with excita-tion and emission wavelengths of 330 and 420 nm,respectively.The injection volume was 5 μL.Results:Within the target loading sample range of 40％ to 160％,the peak area showed a good linear relationship with protein concentration(r＞0.99).The average recovery rates at three concentration levels were 106.25％,100.00％,and 106.67％,respectively.The limit of quantification was 0.03％.Conclusion:This method is suitable for detecting the sialylation levels of N-glycan profiles in various glycoprotein drugs.

Objective To explore the effectiveness of"near peer learning"(NPL)in the electromyo-graphy(EMG)teaching module for neurology residents.Methods The Department of Neurology,Peking Union Medical College Hospital implemented an NPL instructional design for a course on EMG for residents from November 2020 to March 2024.This teaching session was held annually,in which senior residents in-structed juniors who were 1 or 2 years earlier in their training.The residents participated in the pre-course/post-course tests and completed a feedback survey at the end of the session.This evaluation method was used to un-derstand the effectiveness of the NPL intervention in EMG teaching.Results Over four years,a total of 83 residents participated.Among them,there were 24 postdoctoral students,52 postgraduates and 7 junior resi-dents.The results showed that the post-course test scores were significantly improved compared with pre-course test scores(74.33±2.43 vs.70.11±2.49,P=0.005),with the most remarkable improvements seen for"tu-tees"(73.84±20.53 vs.70.29±21.46,P=0.020),postgraduates(74.04±22.51 vs.68.97±21.40,P=0.009),first-year residents(70.19±4.02 vs.63.59±3.59,P=0.040)and first-time participating resi-dents(65.23±3.24 vs.60.97±3.21,P=0.030).The post-program feedback showed that both tutors and tu-tees thought highly of NPL,believing that it enabled them to gain knowledge and helped them to improve teaching skills.Conclusions The NPL intervention is suitable for the teaching of EMG,because of its contri-bution to knowledge acquisition and basic clinical skills improvement.The NPL is worth replicating in other teaching and learning programs.

AIM To establish the HPLC characteristic chromatograms for Yixin Fumai Granules,and to determine the contents of sodium danshensu,protocatechualdehyde,chlorogenic acid,calycosin-7-O-β-D-glucoside,ferulic acid,rosalinic acid,salvianolic acid A,salvianolic acid B,schisandrol A.METHODS The analysis was performed on a 35 ℃ thermostatic Acutfex PA-C18 column(4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 210,250,280,320 nm.Subsequently,cluster analysis and principal component analysis were performed.RESULTS There were 11 characteristic peaks in the characteristic chromatograms for 15 batches of samples with the similarities of more than 0.980.Nine constituents showed good linear relationships within their own ranges(r≥0.999 6),whose average recoveries were 97.60％-107.02％with the RSDs of 0.78％-1.87％.Various batches of samples were clustered into 4 categories,2 principal components demonstrated the accumulative variance contribution rate of 89.454％.CONCLUSION This sensitive and reproducible method can provide a reference for the quality evaluation and control of Yixin Fumai Granules.

Objective:To investigate the correlation between the ratio of apolipoprotein B to apolipoprotein A-I (ApoB/ApoA-I) and unstable carotid plaque in a neurologically healthy population receiving health check-ups.Methods:This cross-sectional study consecutively enrolled 1 149 neurologically healthy individuals who underwent physical examinations at the Health Management Centre of Beijing Tiantan Hospital, Capital Medical University, from October 2021 to September 2022. All eligible participants completed standardized questionnaires, physical examinations and laboratory tests. Laboratory tests of lipid metabolism-related biomarkers included total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), ApoA-I, and ApoB; non-high-density lipoprotein cholesterol and the ApoB/ApoA-I ratio were subsequently calculated. The carotid plaque stability was evaluated using superb microvascular imaging technology. The participants were classified into unstable plaque group (341 cases) and stable plaque group (808 cases) according to the presence or absence of intraplaque neovascularization. The univariate and multivariate logistic regression analyses were used to explore the correlation between the ApoB/ApoA-I ratio and unstable carotid plaques.Results:The study enrolled 1 149 participants totally, with a median age of 57 (49-63) years, including 771 males (67.10%) and 378 females (32.90%), and 341 cases (29.68%) were found with unstable carotid plaques. The unstable plaque group had a higher proportion of males, smoking history, diabetes history, along with higher waist-to-hip ratio and ApoB/ApoA-I ratio compared to the stable plaque group [76.54% vs 63.12%, 33.43% vs 22.77%, 19.06% vs 13.37%, 0.91 (0.85, 0.94) vs 0.89 (0.84, 0.93), 0.64 (0.51, 0.76) vs 0.59 (0.48, 0.72)], while HDL-C and ApoA-I levels were lower [1.39 (1.19, 1.63) vs 1.44 (1.24, 1.66) mmol/L, 1.43 (1.29, 1.60) vs 1.51 (1.36, 1.68) g/L] (all P<0.05). An elevated ApoB/ApoA-I ratio was positively associated with the risk of unstable carotid plaque ( OR=1.61, 95% CI: 1.13-2.29, P=0.008; P for trend<0.001). After adjusting for age, gender, waist-to-hip ratio, history of hypertension, history of diabetes, dyslipidemia, cardiovascular disease, history of smoking and estimated glomerular filtration rate, the positive association between elevated ApoB/ApoA-I ratio and the risk of unstable carotid plaque remained significant ( OR=1.48, 95% CI: 1.01-2.16, P=0.044; P for trend=0.004). Conclusion:In a neurologically healthy population receiving health check-ups, an elevated ApoB/ApoA-I ratio may increase the risk of unstable carotid plaque.