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

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Objective:To investigate the efficacy of Saussurea involucrata injection (SII) in alleviating rheumatoid arthritis (RA) and to explore the mechanism of action of SII in alleviating RA through the Toll-like receptor 4 (TLR4)/nuclear factor-kappaBp65 (NF-κBp65) pathway-mediated M1 macrophage polarization.Methods:In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model. After successful modeling, the CIA rats were randomly assigned into five groups ( n=10 per group): CIA control group, MTX group, low-dose SII (L-SII) group, medium-dose SII (M-SII) group, and high-dose SII (H-SII) group. The efficacy of SII in alleviating RA was evaluated using arthritis index scores, histopathology, and ELISA to measure serum levels of nitric oxide (NO), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Subsequently, Western blot analysis was used to detect the expression of inducible nitric oxide synthase (iNOS) and CD86 proteins in synovial tissue. In vitro experiments involved first isolating and inducing rat bone marrow-derived macrophages (BMDMs). Then, BMDMs were polarized toward the M1 phenotype using lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ). Concurrently, cells were treated with SII and the TLR4 inhibitor TAK242. Subsequently, ELISA was used to detect NO, IL-1β, TNF-α levels in the cell culture supernatant via ELISA. RT-qPCR was used to detect the expression of IL-1b, IL-6, and TNF-α genes in each group of cells. Western blot analysis was performed to detect the expression of iNOS, CD86, TLR4, myeloid differentiation primary response 88 (MyD88), and p-NF-κBp65/NF-κBp65 proteins in the cells. Data analysis between multiple groups was performed using one-way analysis of variance, and between pairs using LSD- t-tests. Results:In vivo experimental results showed that compared with the CIA group(7.90 ± 0.70), MTX and SII both improved the pathological symptoms of rats and reduced the ankle joint pathological score [MTX (4.40 ± 0.92), L-SII (7.00 ± 0.89), M-SII (5.10 ± 1.30), H-SII (4.90 ± 0.94), t=33.86, P<0.001; t=9.10, P<0.001; t=2.38, P=0.029; t=5.69, P<0.001; t=7.66, P<0.001], while downregulating serum levels of NO, IL-1β, IL-6, and TNF-α levels in serum, as well as iNOS [ t=30.01, P<0.001; t=6.17, P=0.003; t=10.86, P<0.001; t=28.95, P<0.001; t=19.03, P<0.001] and CD86 [ t=65.61, P<0.001; t=8.76, P<0.001; t=13.18, P<0.001; t=13.22, P<0.001; t=18.91, P<0.001] expression. In vitro experimental results showed that compared with BMDMs treated with LPS and IFN-γ, SII and TAK242 treatment reduced the levels of NO, IL-1β, IL-6, and TNF-α in the supernatant and decreased the expression of IL-1b, IL-6, and TNF-α genes. Additionally, SII and TAK242 treatment downregulated the expression of iNOS and CD86 proteins in cells, and simultaneously downregulated TLR4, MYD88, and p-NF-κBp65/NF-κBp65 expression ( t=35.84, P<0.001; t=15.69, P<0.001; t=21.99, P<0.001; t=23.64, P<0.001; t=22.50, P<0.001). Additionally, compared with the TAK242 group alone, TAK242 + H-SII showed no significant differences in the modulation of M1 macrophage polarization and TLR4/NF-κBp65 pathway-related indicators. Conclusion:SII exerts anti-inflammatory and anti-RA effects by inhibiting TLR4/NF-κBp65-mediated M1 macrophage polarization.

[Purpose]To analyze the incidence and mortality of liver cancer in Fusui County of Guangxi Zhuang Autonomous Region in 2019 and the trend of change from 201 1 to 2019.[Meth-ods]Based on the incidence and mortality data of liver cancer in Fusui County from 2011 to 2019,the crude incidence rate,crude mortality rate,age-standardized rate by Chinese standard population(ASIRC/ASMRC),age-standardized rate by world standard population(ASMRW/ASM-RW),disability-adjusted life years(DALY),years of life lost(YLL),years of lived with disability(YLD)were calculated.The Joinpoint linear regression model was used to calculate the average annual percentage change(AAPC)of the ASIRC/ASMRC and DALY rate of liver cancer in Fusui County from 2011 to 2019.[Results]In 2019,there were 345 new cases and 298 deaths of liver cancer in Fusui County,accounting for 28.49％and 35.86％of all new cases and death cases of malignant tumors in Fusui County,respectively.The crude incidence rate,ASIRC and ASIRW were 74.71/105,67.55/105 and 65.63/105,respectively;the crude mortality rate,ASMRC and ASMRW were 64.53/105,58.78/105 and 56.88/105,respectively.In 2019,ASIRC/ASMRC of men were higher than those of women(105.32/105 and 95.67/105 for men;27.26/105 and 19.11/105 for women).The peak incidence and mortality rates were in the 65～69 and 80～84 age groups,re-spectively.The incidence rate of liver cancer in Fusui County declined from 82.50/105 in 2011 to 67.55/105 in 2019,with an AAPC of-3.01％(P=0.024),but the mortality rate did not have sig-nificant changes(AAPC=-1.44％,P=0.224).The rate of DALY decreased from 14.51/105 to 10.36/105,with an AAPC of-2.82％(P=0.050).[Conclusion]The incidence rate and DALY rate of liv-er cancer in Fusui County showed an overall decreasing trend from 2011 to 2019,but still re-mained at a high level.It is necessary to further strengthen the prevention,screening and early treatment of liver cancer in this region,especially for men and the elderly.

[Purpose]To analyze the incidence and mortality of liver cancer in Fusui County of Guangxi Zhuang Autonomous Region in 2019 and the trend of change from 201 1 to 2019.[Meth-ods]Based on the incidence and mortality data of liver cancer in Fusui County from 2011 to 2019,the crude incidence rate,crude mortality rate,age-standardized rate by Chinese standard population(ASIRC/ASMRC),age-standardized rate by world standard population(ASMRW/ASM-RW),disability-adjusted life years(DALY),years of life lost(YLL),years of lived with disability(YLD)were calculated.The Joinpoint linear regression model was used to calculate the average annual percentage change(AAPC)of the ASIRC/ASMRC and DALY rate of liver cancer in Fusui County from 2011 to 2019.[Results]In 2019,there were 345 new cases and 298 deaths of liver cancer in Fusui County,accounting for 28.49％and 35.86％of all new cases and death cases of malignant tumors in Fusui County,respectively.The crude incidence rate,ASIRC and ASIRW were 74.71/105,67.55/105 and 65.63/105,respectively;the crude mortality rate,ASMRC and ASMRW were 64.53/105,58.78/105 and 56.88/105,respectively.In 2019,ASIRC/ASMRC of men were higher than those of women(105.32/105 and 95.67/105 for men;27.26/105 and 19.11/105 for women).The peak incidence and mortality rates were in the 65～69 and 80～84 age groups,re-spectively.The incidence rate of liver cancer in Fusui County declined from 82.50/105 in 2011 to 67.55/105 in 2019,with an AAPC of-3.01％(P=0.024),but the mortality rate did not have sig-nificant changes(AAPC=-1.44％,P=0.224).The rate of DALY decreased from 14.51/105 to 10.36/105,with an AAPC of-2.82％(P=0.050).[Conclusion]The incidence rate and DALY rate of liv-er cancer in Fusui County showed an overall decreasing trend from 2011 to 2019,but still re-mained at a high level.It is necessary to further strengthen the prevention,screening and early treatment of liver cancer in this region,especially for men and the elderly.

Objective:To investigate the efficacy of Saussurea involucrata injection (SII) in alleviating rheumatoid arthritis (RA) and to explore the mechanism of action of SII in alleviating RA through the Toll-like receptor 4 (TLR4)/nuclear factor-kappaBp65 (NF-κBp65) pathway-mediated M1 macrophage polarization.Methods:In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model. After successful modeling, the CIA rats were randomly assigned into five groups ( n=10 per group): CIA control group, MTX group, low-dose SII (L-SII) group, medium-dose SII (M-SII) group, and high-dose SII (H-SII) group. The efficacy of SII in alleviating RA was evaluated using arthritis index scores, histopathology, and ELISA to measure serum levels of nitric oxide (NO), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Subsequently, Western blot analysis was used to detect the expression of inducible nitric oxide synthase (iNOS) and CD86 proteins in synovial tissue. In vitro experiments involved first isolating and inducing rat bone marrow-derived macrophages (BMDMs). Then, BMDMs were polarized toward the M1 phenotype using lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ). Concurrently, cells were treated with SII and the TLR4 inhibitor TAK242. Subsequently, ELISA was used to detect NO, IL-1β, TNF-α levels in the cell culture supernatant via ELISA. RT-qPCR was used to detect the expression of IL-1b, IL-6, and TNF-α genes in each group of cells. Western blot analysis was performed to detect the expression of iNOS, CD86, TLR4, myeloid differentiation primary response 88 (MyD88), and p-NF-κBp65/NF-κBp65 proteins in the cells. Data analysis between multiple groups was performed using one-way analysis of variance, and between pairs using LSD- t-tests. Results:In vivo experimental results showed that compared with the CIA group(7.90 ± 0.70), MTX and SII both improved the pathological symptoms of rats and reduced the ankle joint pathological score [MTX (4.40 ± 0.92), L-SII (7.00 ± 0.89), M-SII (5.10 ± 1.30), H-SII (4.90 ± 0.94), t=33.86, P<0.001; t=9.10, P<0.001; t=2.38, P=0.029; t=5.69, P<0.001; t=7.66, P<0.001], while downregulating serum levels of NO, IL-1β, IL-6, and TNF-α levels in serum, as well as iNOS [ t=30.01, P<0.001; t=6.17, P=0.003; t=10.86, P<0.001; t=28.95, P<0.001; t=19.03, P<0.001] and CD86 [ t=65.61, P<0.001; t=8.76, P<0.001; t=13.18, P<0.001; t=13.22, P<0.001; t=18.91, P<0.001] expression. In vitro experimental results showed that compared with BMDMs treated with LPS and IFN-γ, SII and TAK242 treatment reduced the levels of NO, IL-1β, IL-6, and TNF-α in the supernatant and decreased the expression of IL-1b, IL-6, and TNF-α genes. Additionally, SII and TAK242 treatment downregulated the expression of iNOS and CD86 proteins in cells, and simultaneously downregulated TLR4, MYD88, and p-NF-κBp65/NF-κBp65 expression ( t=35.84, P<0.001; t=15.69, P<0.001; t=21.99, P<0.001; t=23.64, P<0.001; t=22.50, P<0.001). Additionally, compared with the TAK242 group alone, TAK242 + H-SII showed no significant differences in the modulation of M1 macrophage polarization and TLR4/NF-κBp65 pathway-related indicators. Conclusion:SII exerts anti-inflammatory and anti-RA effects by inhibiting TLR4/NF-κBp65-mediated M1 macrophage polarization.

Histone deacetylases(HDACs)can deacetylate histones,leading to tighter DNA binding,and thereby playing a role in inhibiting gene transcription.On the contrary,histone deacetylase inhibitors(HDACis)can promote chromatin relaxation,enabling various transcription factors to bind specifically to DNA and activate transcription genes.Dental stem cells(DSCs)are human adult stem cells.These cells have the characteristics of less damage and low immune rejection during sampling,and are especially important seed cells in the process of osteogenesis,odontogenesis and other differentiation.A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation,signal transduction,regulation of cellular inflammation and other life processes.This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs,aiming to provide insights into the study of the interaction between HDACs and HDACis,and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.

Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.