Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis / 中西医结合学报

BACKGROUND@#The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.@*OBJECTIVE@#This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.@*SEARCH STRATEGY@#PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.@*INCLUSION CRITERIA@#Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.@*DATA EXTRACTION AND ANALYSIS@#Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.@*RESULTS@#Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.@*CONCLUSION@#Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.

Sham acupuncture and placebo acupuncture in clinical trials / 中国针灸

The commonly used terms "sham acupuncture" and "placebo acupuncture" in clinical acupuncture research is compared and analyzed in this article. In terms of their respective characteristics, sham acupuncture has a wider scope, including various types of acupoints, needle insertion at non-acupoint or non-insertion at acupoints, while placebo acupuncture mainly focuses on non-insertion at acupoints. Sham acupuncture mainly emphasizes the appearance similarity to real acupuncture, while placebo acupuncture emphasizes both similarity in appearance and the absence of therapeutic effects. Properly distinguishing and applying sham acupuncture and placebo acupuncture can help standardize their usage in terminology. Considering the difficulty in setting up qualified placebo acupuncture, it is suggested that researchers use the term "sham acupuncture" to describe the acupuncture control methods used in clinical research.

Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm / 中国中药杂志

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis / 中国结合医学杂志

BACKGROUND@#Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate.@*OBJECTIVE@#To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis.@*METHODS@#Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.@*RESULTS@#A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence.@*CONCLUSION@#Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.@*OBJECTIVE@#To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.@*METHODS@#Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.@*RESULTS@#A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.@*CONCLUSIONS@#Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).

Factors associated with positive results in English literature of acupuncture for chronic pain / 中国针灸

OBJECTIVE@#To analyze the main factors affecting the positive results of acupuncture for chronic pain in English literature of randomized controlled trial (RCT), in order to provide reference for the design of acupuncture clinical research.@*METHODS@#The RCTs of acupuncture for chronic pain published before March 26, 2020 were searched in PubMed, EMbase and Cochrane Library by computer. A total of 21 factors were analyzed by single-factor analysis, and the factors with statistically significant difference were selected for multivariate Logistic regression analysis.@*RESULTS@#A total of 69 RCTs were included, including 47 RCTs (68.12%) with positive results and 22 RCTs (31.88%) with non-positive results. The multivariate Logistic regression analysis was performed with the three screened factors (publication year, treatment frequency and intervention form) selected by single-factor analysis, and the results showed that the positive results were related to the frequency of acupuncture treatment. The positive rate of RCT with frequency≥2 times a week was 3.24 times of that with frequency<2 times a week (OR=3.24, 95%CI =[1.07,9.83], P<0.05).@*CONCLUSION@#Acupuncture frequency may be the main factor affecting the positive results of RCT in English literature of acupuncture for chronic pain. More researches are needed in the future to explore the influence of acupuncture frequency on the curative effect.

Review of clinical research in acupuncture and moxibustion from 2010 to 2020 and future prospects / 中国针灸

The progress of Chinese clinical research on acupuncture and moxibustion in recent 10 years was reviewed and analyzed, and corresponding suggestions were put forward for the current problems. In the past 10 years, Chinese clinical research on acupuncture and moxibustion has made considerable progress, mainly in the following areas: a series of internationally recognized clinical research evidences have been published, a preliminary acupuncture clinical evaluation system has formed, sham/placebo acupuncture control is widely used internationally, acupuncture clinical research norms and standards have been initially established. However, the following issues still need to be paid attention to in follow-up research: focus on the overall layout and refinement of clinical research, further improvement of clinical evaluation system, developing relevant norms for sham/placebo acupuncture setting and reporting, strengthening data sharing and platform integration, building a smooth basic and two-way transformation clinical pathway, etc.

Optimization and implementation of clinical trial of acupuncture: reflection on the successful case of acupuncture for postprandial distress syndrome / 中国针灸

Taking the clinical trial of acupuncture in treatment of postprandial distress syndrome as an example, this paper proposes that the acupuncture clinical trial protocol should be optimized in view of acupuncture prescription, acupuncture frequency and outcomes. Besides, the data quality of acupuncture clinical trial should be improved in consideration of data sharing and electronic data capture so as to provide a reference for the majority of researchers to optimize and implement acupuncture clinical trial.

Application and reflection on pilot study in acupuncture clinical research / 中国针灸

Pilot study is essential prerequisite for large-scale research. Acupuncture is a complex intervention measure. The factors of its clinical effect and effect mechanism are complicated. Hence, the resource waste is easily induced in research if the large-scale clinical research is rashly carried out before scientific verification. Currently, there is still a lack of high-quality evidence of clinical research, which affects the promotion and application of the curative effect of acupuncture. The pilot study of acupuncture can evaluate the feasibility and the process coordination of trial, optimize program and process and provide the basis of sample size calculation prior to launching a full-scale trial. Thereby, the methodological quality of acupuncture research and the reliability of trial results can be improved. In the paper, the arguments focus on the definition, design and report of pilot study so as to provide the approaches and references for the design and implementation of pilot study of clinical research of acupuncture.

Pattern Classification of Enterovirus 71-Associated Hand, Foot, and Mouth Disease in Chinese Medicine: A Retrospective Study in 433 Cases / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine whether patterns of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) were classified based on symptoms and signs, and explore whether individual characteristics were correlated with membership in particular pattern.</p><p><b>METHODS</b>Symptom-based latent class analysis (LCA) was used to determine whether patterns of EV71-HFMD existed in a sample of 433 cases from a clinical data warehouse system. Logistic regression was then performed to explore whether demographic, and laboratory data were associated with pattern membership.</p><p><b>RESULTS</b>LCA demonstrated a two-subgroup solution with an optimal fit, deduced according to the Bayesian Information Criterion minima. Hot pattern (59.1% of all patients) was characterized by a very high fever and high endorsement rates for classical HFMD symptoms (i.e., rash on the extremities, blisters, and oral mucosa lesions). Non-hot pattern (40.9% of all patients) was characterized by classical HFMD symptoms. The multiple logistic regression results suggest that white blood cell counts and aspartate transaminase were positively correlated with the hot pattern (adjust odds ratio=1.07, 95% confidence interval: 1.006-1.115; adjust odds ratio=1.051, 95% confidence interval: 1.019-1.084; respectively).</p><p><b>CONCLUSIONS</b>LCA on reported symptoms and signs in a retrospective study allowed different subgroups with meaningful clinical correlates to be defined. These findings provide evidence for targeted prevention and treatment interventions.</p>

On-site quality control of acupuncture randomized controlled trial: design of content and checklist of quality control based on PICOST / 中国针灸

To effectively guarantee quality of randomized controlld trial (RCT) of acupuncture and develop reasonable content and checklist of on-site quality control, influencing factors on quality of acupuncture RCT are analyzed and scientificity of quality control content and feasibility of on-site manipulation are put into overall consideration. Based on content and checklist of on-site quality control in National 11th Five-Year Plan Project Optimization of Comprehensive Treatment Plan for TCM in Prevention and Treatment of Serious Disease and Clinical Assessment on Generic Technology and Quality Control Research, it is proposed that on-site quality control of acupuncture RCT should be conducted with PICOST (patient, intervention, comparison, out come, site and time) as core, especially on quality control of interveners' skills and outcome assessment of blinding, and checklist of on-site quality control is developed to provide references for undertaking groups of the project.

Individual patient data meta-analysis is needed in Chinese medical research / 中国结合医学杂志

Publication biases and collection limitations are the main disadvantages of a traditional meta-analysis based on aggregate patient data (APD) from published articles. Individual patient data (IPD) meta-analysis, as the gold standard of systematic review, is a possible alternative in this context. However, the publications relative to IPD meta-analyses are still rare compared with the traditional ones, especially in the research oriented to Chinese medicine (CM). In this article, the strengths and detailed functioning of IPD meta-analysis are described. Furthermore, the need for IPD meta-analysis to assess the treatments based on CM was also discussed. Compared with the traditional APD meta-analysis, the IPD meta-analysis might give a more accurate and unbiased assessment and is worth to be recommended to CM researchers.

Serum low-density lipoprotein and heart rate related to the effectiveness in the treatment of angina pectoris with two similar Chinese medicine herbal formulae / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule () and Kangxin Capsule () targeting on qi deficiency and blood stasis pattern in Chinese medicine (CM) in the treatment of angina pectoris.</p><p><b>METHODS</b>The data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1:1 ratio to Tongxinluo Capsule group (119 cases) and Kangxin Capsule group (120 cases). Angina effectiveness and electrocardiogram (ECG) improvement were selected as the therapeutic outcomes.</p><p><b>RESULTS</b>After a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively (P <0.05). Serum low-density lipoprotein (LDL) level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate [Symbol: see text]80 beats/min.</p><p><b>CONCLUSION</b>LDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.</p>

RNAi-mediated silencing of the Bmi-1 gene causes growth inhibition and enhances doxorubicin-induced apoptosis in MCF-7 cells

The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G1/S phase transition. The number of target cells was found to increase in phase G0/G1 and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer.

Activation and clinicopathologic significance of AKT/mTOR signaling pathway in diffuse large B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>(1) To investigate the activation of AKT/mTOR signaling transduction pathway in DLBCL and its association with the expression of bcl-6 and some other clinical pathologic factors. (2) To estimation of the signaling pathway function in diverse subtypes of DLBCL and its potential value in the targeted treatment of DLBCL.</p><p><b>METHODS</b>Immunohistochemical (IHC) EnVision staining was used to detect the expressions of pAKT and pmTOR in 100 DLBCL and 10 reactive hyperplasia fresh lymph node samples; TaqMan real-time reverse transcription polymerase chain reaction (real-time RT-PCR) technique was used to explore the expression of bcl-6 mRNA in the DLBCL samples. IHC staining was used to detect the expressions of bcl-6, CD10 and MUM1 in 75 of the 100 corresponding paraffin-embedded samples and these 75 DLBCL samples were subdivided into GCB and non-GCB subgroups.</p><p><b>RESULTS</b>(1) The expression of pAKT and pmTOR was 76% (76/100) and 75% (75/100), respectively, and the expression of the two proteins correlated with each other. (2) The expression of bcl-6 protein and mRNA significantly correlated with each other. The expression of bcl-6 protein and mRNA in pAKT and pmTOR high-expression group was significantly lower than that in low-expression group (both P < 0.01). (3) The expression of pAKT and pmTOR in non-GCB group was 82.5% (47/57) and 84.2% (48/57), respectively, which were significantly higher than that in GCB group, which showed an expression rate of 44.4% (8/18) and 44.4% (8/18), respectively (both P < 0.01). (4) The expression of pAKT and pmTOR in male was higher than that in female, and the percentage of patients with abnormal LDH in pAKT and pmTOR positive groups was higher than that in negative groups, although there were no statistical significance (both P > 0.05). There was no relationship between the expression of pAKT and pmTOR and age, sex, stage, KPS and B symptoms (P > 0.05).</p><p><b>CONCLUSIONS</b>Activation of AKT/mTOR signaling pathway plays an important role in the development of DLBCL, and it is closely related to the low or non-expression of bcl-6 and non-GCB subgroup. Molecules in this pathway might serve as the new targets in the treatment of certain group of DLBCL.</p>

Study on the germline mutation of MSH6 gene in Chinese hereditary nonpolyposis colorectal cancer pedigrees using PCR based sequencing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the germline mutation of mismatch repair gene (MSH6) in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds fulfilling different clinical criteria.</p><p><b>METHODS</b>The germline mutations of MSH6 gene were detected by PCR based DNA sequencing in 39 unrelated HNPCC probands fulfilling different clinical criteria in which MSH2 and MLH1 mutations were excluded. The exons with missense mutations were analyzed using PCR sequencing in the germline genomic DNA of 137 healthy persons. The expression of MSH6 protein was detected by Envision immunohistochemistry staining in the tumor tissues of the mutational probands.</p><p><b>RESULTS</b>Six germline mutations of MSH6 gene were detected in 39 probands of Chinese HNPCC kindreds, and the mutations distributed in the exon 4, 6, 9 and 10. Four out of six mutations were missense mutation, one was nonsense mutation and the remaining one was insertion mutation in splice site. The results of sequecing for the exons with above four missense mutations in 137 healthy persons' genomic DNA showed that 5 of 137 persons had the missense mutation of c.3488 A to T at codon 1163 of the 6th exon. The mutational rate was approximately 3.65% (5/137), so the mutation could be a single nucleotide polymorphism (SNP). The remaining missense mutations were not found in any germline genomic DNA of 137 healthy persons. Positive expression of MSH6 protein had been identified in the tumor of the SNP proband while the tumors had negative MSH6 protein expression in the rest probands of germline mutation MSH6 gene. The types of mutations and their potential significance were determined by comparing the following databases: http://www.ncbi.nlm.nih.gov/, http://www.ensembl.org/homo-sapies, and http://www.insight-group.org. Five out of the six mutations had not been reported previously and they were new pathological mutations, the rest one was a new SNP.</p><p><b>CONCLUSION</b>Germline mutations of MSH6 gene may play an important role in Chinese HNPCC kindreds fulfilling different clinical criteria. It is necessary to analyze the germline mutations of MSH6 gene using sequencing to identify HNPCC families in the probands in which MSH2 and MLH1 mutation were excluded.</p>

Analysis of clinicopathological featurs in patients with Chinese hereditary nonpolyposis colorectal kindreds / 中华消化杂志

Objective To explore clinical features and prognosis of patients with hereditary nonpolypnsis colorectal cancer(HNPCC).Methods Twenty-four kindreds of Chinese HNPCC according to Amsterdam standard were enrolled and their pedigree trees were drawn.Clinicopathological and follow- up data were collected,clinical features and prognosis of 24 kindreds of Chinese HNPCC were analyzed as well.Results Among 24 H NPCCkindreds,there were 116 cases of cancer including 16 cases of multiple cancers in probands and 9 cases of multiple cancers in the members of kindreds.The age of patients ranged from 19 to 74.Of all the patients,there were 120 loci of colorectal cancers and 32 foci of HNPCC related extracolonic cancers.Among probands of 24 HNPCC kindreds,the average incidence age of onset- ring first colorectal cancer was 42.5,the male and right-side colon cancer patiens were more than female and left-side colon cancer patiens,respectively.The most pathologic type was tubular adenocarcinomas with moderately differentiation,which accounted for 45.8%(11/24).Up to the deadline of follow-up, 14 cases had survived for more than 5 years accounting for 58.3%(14/24) Of them,9 cases survived for more than 10 years and 1 case survived for 27 years.Conclusions Chinese patients with HNPCC have special characteristics such as moderately differentiated tubular adenocarcinomas,early onset of coloreetal cancer,right-side colon involvement.