1.Effects of Jishe Qushi Capsule (脊蛇祛湿胶囊) on Serum NETs Levels and Macrophage Polarization in Collagen-Induced Arthritis Model Rats
Nina REN ; Wukai MA ; Yi LING ; Xueming YAO ; Ying HUANG ; Daomin LU ; Changming CHEN ; Weichen HUANG
Journal of Traditional Chinese Medicine 2026;67(1):60-68
ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule (脊蛇祛湿胶囊, JQC) in treating rheumatoid arthritis (RA) from the perspective of macrophage polarization mediated by neutrophil extracellular traps (NETs). MethodsTwenty-four female SD rats were randomly divided into four groups, blank control group, model group, JQC group, and peptidylarginine deiminase 4 (PAD4) inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis (CIA). After successful model establishment, rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily; rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank, model, and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7, 14, 21, 28, and 35 after model establishment, and arthritis index (AI) scores were recorded. At 24 h after the final administration, histopathology of knee joints, including HE staining, safranin O-fast green staining, and TRAP staining, was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP, NETs, TNF-α, IL-1β, and iNOS. Western Blotting and qRT-PCR were used to measure MPO, NE, RANKL, OPG, and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group, the model group showed increased AI scores (P<0.05), marked synovial inflammatory infiltration, angiogenesis, and bone-cartilage destruction, increased TRAP-positive osteoclasts, increased M1 macrophages and decreased M2 macrophages, elevated serum TRACP, NETs, TNF-α, IL-1β, and iNOS (P<0.05), elevated MPO, NE, RANKL, and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue (P<0.05). Compared with the model group, the JQC group exhibited improved synovial inflammation, angiogenesis, and bone-cartilage damage, reduced AI scores on day 21, 28, and 35, decreased osteoclast counts, decreased M1 macrophages and increased M2 macrophages, reduced serum TRACP, NETs, TNF-α, IL-1β, and iNOS (P<0.05), decreased MPO, NE, RANKL, and p65 protein/mRNA expression and increased OPG expression (P<0.05). Compared with the PAD4 inhibitor group, the JQC group showed significantly lower AI scores, reduced M1 macrophages, increased M2 macrophages (P<0.05), reduced serum TRACP, TNF-α, IL-1β, and iNOS, decreased MPO, RANKL, and p65 expression, and increased OPG levels (P<0.05). ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation, downregulation of the RANKL/NF-κB signaling pathway, and regulation of macrophage M1/M2 polarization imbalance, thereby suppressing osteoclastogenesis and inflammatory bone destruction.
2.Current status of research on the mechanism of action of emodin in the prevention and treatment of chronic liver diseases
Yajie CHEN ; Xin WANG ; Yunjuan WU ; Ying SU ; Yuhan WANG ; Jinxue ZHANG ; Ning YAO ; Ying QIN ; Xiaoning ZUO
Journal of Clinical Hepatology 2026;42(1):228-234
Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time, resulting in irreversible pathological changes that last longer than 6 months. Emodin (EMO) is a natural anthraquinone derivative derived from Rheum officinale, and its pharmacological effect has been extensively studied, exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases, and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy, EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism, in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.
3.Mechanism of Huangqin decoction in improving ulcerative colitis based on the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor axis
Ying CHEN ; Rong XU ; Yao HE ; Ying LI ; Zhiyu ZHANG ; Zhijiu WU
China Pharmacy 2026;37(9):1173-1179
OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis (UC) through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor (AhR) axis. METHODS Mice were randomly divided into normal group (normal saline), model group (normal saline), microbiota depletion-model group (normal saline), microbiota depletion-Huangqin decoction group (9.1 g/kg, by crude drug, similarly hereinafter), Huangqin decoction group and mesalazine group (positive control group, 0.4 g/kg), with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling, each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration, body weight change ratio, disease activity index (DAI) score, and colon length were evaluated; colon pathological changes were observed; serum levels of interleukin-6 (IL-6), IL-10, IL-22, and tumor necrosis factor-α (TNF-α) were measured; the expressions of Occludin, zonula occluden-1 (ZO-1), and AhR in colon tissue were detected; fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group, Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio, colon length, serum content of IL-10, the expressions of Occludin, ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid (IPA), N -acetylserotonin (NAS) and indole-3-acetic acid (IAA) were all significantly increased ( P <0.05); DAI score, serum levels of IL-6, TNF-α, and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased ( P <0.05); gut microbiota structure was improved, with increased relative abundances of beneficial bacteria such as Lactobacillus , and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However, after antibiotic-induced microbiota depletion, although Huangqin decoction significantly increased the content of NAS in the feces of mice, the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA, thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.
4.Expression characteristics of galectin-3 in silicosis and its mechanism in promoting pulmonary fibrosis via TGF-β1/Smads pathway
Ying CAO ; Xuxi CHEN ; Shuyu GONG ; Ling ZHANG ; Yuqin YAO ; Wen DU
Journal of Environmental and Occupational Medicine 2026;43(5):643-650
Background Silicosis, caused by inhalation of silica (SiO2) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO2 suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO2 suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO2-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO2 for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO2-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.
5.Expression characteristics of galectin-3 in silicosis and its mechanism in promoting pulmonary fibrosis via TGF-β1/Smads pathway
Ying CAO ; Xuxi CHEN ; Shuyu GONG ; Ling ZHANG ; Yuqin YAO ; Wen DU
Journal of Environmental and Occupational Medicine 2026;43(5):643-650
Background Silicosis, caused by inhalation of silica (SiO2) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO2 suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO2 suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO2-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO2 for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO2-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.
6.Discussion on processing time for Polygonatum kingianum based on analysis of correlation between sugar components and color changes
GUO Hong ; YAO Rui ; LI Zhe ; FAN Jing ; WANG Ying ; GUO Xiaohan ; CHEN Jia ; DUAN Baozhong ; YANG Jianbo ; JING Wenguang ; CHENG Xianlong ; WEI Feng
Drug Standards of China 2026;27(1):0083-0091
Objective: To investigate the correlation between color parameters (L*, a*, b*, Eab*) and the contents of reducing sugars, total polysaccharides, total oligosaccharides, as well as four saccharides (fructose, glucose, sucrose, and kestose) during the nine cycles of steaming and sun-drying processing of Polygonatum kingianum, and to preliminarily explore the optimal processing duration.
Methods: The color changes were objectively evaluated using a colorimeter. The anthrone-sulfuric acid method was employed to determine total polysaccharides and oligosaccharides. The 3,5-dinitrosalicylic acid (DNS) colorimetric method was used to measure total reducing sugar content. High-performance liquid chromatography coupled with charged aerosol detection (HPLC-CAD) was applied for quantitative analysis of fructose, glucose, sucrose, and kestose. Multivariate statistical analysis was conducted to assess samples from different processing stages.
Results: Significant variations in color and component contents were observed across processing stages. The herbal pieces progressively darkened with increased processing cycles: brightness (L*) and total color difference (Eab*) initially decreased then stabilized, while a* (red-green) and b* (yellow-blue) values first increased then declined. Total polysaccharides and oligosaccharides showed overall decreasing trends, whereas reducing sugars initially increased before stabilizing. Fructose and glucose levels rose continuously, while sucrose and kestose decreased progressively, becoming undetectable after five cycles.
Conclusion: The chromatic alteration and saccharide composition of P. kingianum showed significant correlation with processing duration. Both total color difference (Eab*) and reducing sugar content stabilized after four processing cycles (12 hours), suggesting that four cycles of steaming and sun-drying may represent the optimal processing duration.
7.Construction of nomogram for predicting indeterminate HER2 status by IHC in breast cancer based on ultrasonic SWE parameters and pathological characteristics
Shuangxiu TAN ; Xinyan QIN ; Yidan ZHANG ; Ying WANG ; Pengli YU ; Wentao KONG ; Jing YAO ; Qiaoliang CHEN
Cancer Research and Clinic 2025;37(9):654-660
Objective:To explore the predictive value of ultrasonic shear wave elastography (SWE) parameters and pathological characteristics on the status of human epidermal growth factor receptor 2 (HER2), which is difficult to be determined by immunohistochemistry (IHC) in breast cancer, and to construct a nomogram model.Methods:A retrospective case-control study was conducted. One hundred and fifteen cases of breast cancer diagnosed and treated in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from September 2018 to April 2022 were selected, and their HER2 was evaluated as IHC 2+; the HER2 expression status was determined by fluorescence in situ hybridization (FISH) detection, including 23 HER2 positive cases and 92 HER2 negative cases. The ultrasound SWE parameters [including maximum shear wave velocity (V max), mean shear wave velocity (V mean), median shear wave velocity (V median), minimum shear wave velocity (V min)] and clinicopathological characteristics between HER2 positive and negative groups were compared. The variables with statistically significant differences ( P < 0.05) between groups were included in a multivariate logistic regression model, the independent risk factors for HER2 positivity were screened, and a nomogram model was constructed based on these independent risk factors. With the FISH test results as the gold standard, the efficacy of nomogram in judging HER2 positivity in breast cancer which was difficult to be identified by IHC was evaluated with the receiver operating characteristic (ROC) curve; the accuracy and clinical net benefit of the nomogram model were evaluated using calibration curve and decision curve analysis (DCA), respectively. Results:The patients were all female, aged (56±13) years, ranging from 30 to 88 years old. V max [ M ( Q1, Q3)] [8.54 (7.38, 9.47) m/s vs. 6.46 (5.07, 8.42) m/s], V mean [(5.41±0.78) m/s vs. (4.53±1.22) m/s], V median [5.06 (4.48, 5.52) m/s vs. 4.35 (3.42, 4.96) m/s], V min [3.35 (2.68, 3.88) m/s vs. 2.59 (2.11, 3.34) m/s], the proportion of patients with axillary lymph node metastasis [56.5% (13/23) vs. 22.8% (21/92)], and the Ki-67 positivity index [35% (30%, 55%) vs. 25% (15%, 35%)] in the HER2 positive group were higher than those in the HER2 negative group, and the differences were statistically significant (all P < 0.05); There was no statistically significant difference in age, lesion location, pathological type, vascular invasion, nerve invasion and long diameter, short diameter, echo, regular shape, clear boundary, posterior echo, calcification, blood flow grading, Breast Imaging Report and Data System (BI-RADS) classification detected by ultrasound between the two groups (all P > 0.05). Multivariate logistic regression analysis showed that increased ultrasound V max ( OR = 1.786, 95% CI: 1.283-2.485, P = 0.001) and axillary lymph node metastasis ( OR = 4.185, 95% CI: 1.327-13.197, P = 0.015) and elevated Ki-67 positivity index ( OR = 1.042, 95% CI: 1.014-1.071, P = 0.003) were independent risk factors for HER2 positivity. ROC curve analysis showed that the area under the curve (AUC) of HER2 positive breast cancer which was difficult to be determined by IHC was 0.816 (95% CI: 0.732-0.883), that was higher than 0.712 (95% CI: 0.620-0.794) of V max, 0.601 (95% CI: 0.504-0.692) of axillary lymph node metastasis and 0.706 (95% CI: 0.613-0.788) of Ki-67 positivity index based on the nomogram constructed by the above independent risk factors, with statistically significant differences (all P < 0.05). The calibration curve showed that the predicted probability of the nomogram model was close to the actual probability, and DCA indicated that the clinical net benefit of the model was good. Conclusions:The nomogram constructed based on ultrasonic SWE parameter V max, axillary lymph node metastasis and Ki-67 positivity index has a good predictive effect on HER2 status of breast cancer which is difficult to be determined by IHC.
8.Correlation of neutrophil/lymphocyte ratio,monocyte/high density lipoprotein cholesterol ratio and mild cognitive impairment in patients with type 2 diabetes mellitus
Jingjing CHEN ; Yao FANG ; Ruirui FU ; Xiaoyan ZHOU ; Changjiang YING
Chinese Journal of Diabetes 2025;33(9):641-645
Objective To explore the correlation of neutrophil/lymphocyte ratio(NLR),monocyte/high density lipoprotein cholesterol ratio(MHR)and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods 159 T2DM patients hospitalized in the Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University from February 2023 to April 2023 were selected.The subjects were divided into normal cognitive function(Con,n=72)group and MCI group(n=87)based on score of Montreal cognitive assessment scale(MoCA).NLR and MHR were calculated and compared between the two groups.Spearman correlation analysis was used to analyze the correlation between NLR,MHR and MoCA score.Logistic regression analysis of the factors influencing the association between T2DM with MCI.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of NLR and MHR for DM complicated with MCI.Results Compared with Con group,MCI group showed a significant increase in hemoglobin A1c(HbA1c),fasting plasma glucose,NLR,MHR,neutrophil count,monocyte count,serum creatinine,cystatin C,while high density lipoprotein cholesterol lymphocytes,visual space and executive function,naming,attention,language ability,abstract thinking,delayed memory,orientation and MoCA score decreased(P<0.05).Spearman correlation analysis showed that there was a negative correlation between MHR,NLR and MoCA score,visuospatial and executive function,delayed recall and attention.Logistic regression analysis showed that NLR,MHR,HbA1c were all risk factors for MCI in T2DM.ROC curve analysis showed that the area under the curve of NLR combined with MHR for diagnosing T2DM with MCI was 0.872,with corresponding sensitivity of 81.6%and specificity of 87.5%.Conclusions NLR and MHR are closely related to MCI in T2DM patients.The combination of NLR and MHR have certain efficacy in prediction T2DM with MCI.
9.Effects of acupuncture needle modification on acupuncture analgesia.
Ming-Zhu SUN ; Xin WANG ; Ying-Chen LI ; Yu-Hang LIU ; Yi YU ; Liu-Jie REN ; Wei GU ; Wei YAO
Journal of Integrative Medicine 2025;23(1):66-78
OBJECTIVE:
The analgesic effect of acupuncture has been widely accepted. Nevertheless, the mechanism behind its analgesic effect remains elusive, thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture. This paper investigated the role of acupuncture needle surface textures on acupuncture's analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.
METHODS:
Four types of acupuncture needles with different surface textures (the lined needle, circle needle, sandpaper needle, and threaded needle) were designed. Additionally, the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation. To perform acupuncture analgesia experiments, four experimental acupuncture needles and a normal needle were inserted into the Zusanli (ST36) acupoint of rats with inflammatory pain. By comparing the force and torque and the analgesic efficacy of the different acupuncture needles, these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.
RESULTS:
The analgesic effects of different acupuncture needle body textures varied. Specifically, the force required to penetrate the skin with the lined needle was not greater than that for the normal needle; however, the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion. Additionally, the torque of the lined needle reached 2 × 10-4 N·m under twisting manipulation, which was four times greater the torque of a normal needle (5 × 10-5 N·m). Furthermore, the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.
CONCLUSION
Optimizing the texture of acupuncture needles can enhance acupuncture analgesia. The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle; it was also linked to variable analgesic effects. This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy. Please cite this article as: Sun MZ, Wang X, Li YC, Liu YH, Yu Y, Ren LJ, Gu W, Yao W. Effects of acupuncture needle modification on acupuncture analgesia. J Integr Med. 2025; 23(1): 66-78.
Needles
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Acupuncture Analgesia/methods*
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Animals
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Rats
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Male
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Acupuncture Points
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Rats, Sprague-Dawley
10.Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey.
Xiao-Chao LUO ; Jia-Li LIU ; Ming-Hong YAO ; Ye-Meng CHEN ; Arthur Yin FAN ; Fan-Rong LIANG ; Ji-Ping ZHAO ; Ling ZHAO ; Xu ZHOU ; Xiao-Ying ZHONG ; Jia-Hui YANG ; Bo LI ; Ying ZHANG ; Xin SUN ; Ling LI
Journal of Integrative Medicine 2025;23(6):630-640
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*
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Humans
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Randomized Controlled Trials as Topic
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Placebo Effect
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Placebos
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Treatment Outcome

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