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 develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]

Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]

Objective·To explore the roles of hyaluronic acid methacryloyl(HAMA)hydrogel in skin wound healing and to characterize the microenvironmental landscape at wound sites.Methods·A full-thickness skin excision model was established in mice,which were randomly divided into a control group(n=3)and a HAMA group(n=3).The wound in the HAMA and control groups were covered with 100 μL of HAMA hydrogel and 100 μL of phenyl-2,4,6-trimethylbenzoylphosphonic acid lithium(LAP),respectively.Both groups were then irradiated with a UV lamp for 20 s.The residual wound areas was measured on days 0,3,7,10,and 14.Wound healing effects of HAMA hydrogel were analyzed by measuring the residual wound area and through H-E staining.Single-cell RNA sequencing technology was utilized to analyze the cellular profile of local wound skin tissues at day 14 post-injury.Immunofluorescence assay was used to detect the levels of type I collagen,type Ⅲ collagen,F4/80,CD206,and CD86 in the wound sites.The mRNA expression levels of Arg1,Nos2,Itgam,and Itgb2 in the mouse macrophage cell line Raw264.7 co-cultured with HAMA hydrogel for 24 h were detected by RT-qPCR.The fibroblasts and macrophages in the local skin of the mouse wound on day 14 were analyzed using the Seurat package,and the communication between fibroblasts and macrophages was analyzed using the CellChat package.Results·Mice treated with HAMA hydrogel exhibited a significantly faster rate of wound healing process compared to the control group.At day 14,wounds in the HAMA-treated mice had already healed,while those in the control group remained unhealed.Single-cell RNA sequencing analysis revealed a remarkable increase in the proportion of fibroblasts in the skin tissues of HAMA-treated wounds.The proportion of the Col3a1-high-expressing fibroblast subset increased(90.2%)compared to the control group(79.8%),while the proportion of the Col1a1-high-expressing fibroblast subset decreased(5.7%vs 15.9%).Immunofluorescence analysis confirmed that the level of type Ⅲ collagen in the wound tissues of the HAMA group was significantly higher than that in the control group(P=0.035),while the level of type Ⅰ collagen was significantly lower(P=0.044).Although there was no significant difference in the proportions of macrophages in the wound tissues between the HAMA-treated and control groups,scRNA sequencing data and in vitro experiments using Raw264.7 cells showed that HAMA hydrogel could induce the expression of Arg1 and decrease the expression of Nos2 in the macrophages(P<0.001).Additionally,macrophages in the HAMA-treated wounds expressed higher levels of CD206 and lower levels of CD86(P=0.042,P=0.011).The results of the CellChat analysis showed that,compared to the control group,increased communication intensity was observed between macrophages and fibroblasts subsets at the wound sites in the mice of HAMA group.Conclusion·The microenvironment after HAMA hydrogel treatment is conducive to skin wound healing,characterized by a local aggregation of anti-inflammatory macrophages and fibroblasts that secrete type Ⅲ collagen.

Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P＜0.01),office systolic/diastolic BP(P＜0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P＜0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP＞1,P＜0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.

Objective·To explore the roles of hyaluronic acid methacryloyl(HAMA)hydrogel in skin wound healing and to characterize the microenvironmental landscape at wound sites.Methods·A full-thickness skin excision model was established in mice,which were randomly divided into a control group(n=3)and a HAMA group(n=3).The wound in the HAMA and control groups were covered with 100 μL of HAMA hydrogel and 100 μL of phenyl-2,4,6-trimethylbenzoylphosphonic acid lithium(LAP),respectively.Both groups were then irradiated with a UV lamp for 20 s.The residual wound areas was measured on days 0,3,7,10,and 14.Wound healing effects of HAMA hydrogel were analyzed by measuring the residual wound area and through H-E staining.Single-cell RNA sequencing technology was utilized to analyze the cellular profile of local wound skin tissues at day 14 post-injury.Immunofluorescence assay was used to detect the levels of type I collagen,type Ⅲ collagen,F4/80,CD206,and CD86 in the wound sites.The mRNA expression levels of Arg1,Nos2,Itgam,and Itgb2 in the mouse macrophage cell line Raw264.7 co-cultured with HAMA hydrogel for 24 h were detected by RT-qPCR.The fibroblasts and macrophages in the local skin of the mouse wound on day 14 were analyzed using the Seurat package,and the communication between fibroblasts and macrophages was analyzed using the CellChat package.Results·Mice treated with HAMA hydrogel exhibited a significantly faster rate of wound healing process compared to the control group.At day 14,wounds in the HAMA-treated mice had already healed,while those in the control group remained unhealed.Single-cell RNA sequencing analysis revealed a remarkable increase in the proportion of fibroblasts in the skin tissues of HAMA-treated wounds.The proportion of the Col3a1-high-expressing fibroblast subset increased(90.2%)compared to the control group(79.8%),while the proportion of the Col1a1-high-expressing fibroblast subset decreased(5.7%vs 15.9%).Immunofluorescence analysis confirmed that the level of type Ⅲ collagen in the wound tissues of the HAMA group was significantly higher than that in the control group(P=0.035),while the level of type Ⅰ collagen was significantly lower(P=0.044).Although there was no significant difference in the proportions of macrophages in the wound tissues between the HAMA-treated and control groups,scRNA sequencing data and in vitro experiments using Raw264.7 cells showed that HAMA hydrogel could induce the expression of Arg1 and decrease the expression of Nos2 in the macrophages(P<0.001).Additionally,macrophages in the HAMA-treated wounds expressed higher levels of CD206 and lower levels of CD86(P=0.042,P=0.011).The results of the CellChat analysis showed that,compared to the control group,increased communication intensity was observed between macrophages and fibroblasts subsets at the wound sites in the mice of HAMA group.Conclusion·The microenvironment after HAMA hydrogel treatment is conducive to skin wound healing,characterized by a local aggregation of anti-inflammatory macrophages and fibroblasts that secrete type Ⅲ collagen.

Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P＜0.01),office systolic/diastolic BP(P＜0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P＜0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP＞1,P＜0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Objective To develop a low-oxygen mixed gas generator to make up for the deficiencies of low-pressure chambers and load-resistant hypoxia trainers during pilot hypoxia tolerance testing.Methods The device prepared the low-oxygen gas with the principle of gas separation,which was composed of a Sunsource OLF1100D-220AF air compressor,a SMC IDG75SAM4-03 filter,a buffer tank,an AIR Products PA3010 integrated assembly,a control box,sensors and regulators.The sensors included the pressure sensor,flow sensor,concentration sensor and dew point temperature sensor,and the control box consisted of a main control board,a power supply module,a transmission module,a communication module,a display and a housing.The embedded control software of the device was developed with KEIL 5 and C++.Results The device developed prepared the low-oxygen gas with the volume fraction being 4％to 18％and the maximum error of volume fraction being 0.05％,and the main components of the prepared gas met the technical requirements of medical oxygen as stipulated in GB 8982-2009 Oxygen supplies for medicine and aircraft breathing.Conclusion The low-oxygen gas prepared by the device has its volume fraction precisely controlled and can be used for hypoxia tolerance testing and acclimation training for pilots.[Chinese Medical Equipment Journal,2024,45(7):24-28]

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.