Short-term and long-term effectiveness of acupuncture and Tuina on knee osteoarthritis: study protocol for a randomized controlled trial.

Background: The effectiveness of acupuncture and tuina in treating knee osteoarthritis (KOA) is still controversial, which limits their clinical application in practice. This study aims to evaluate the short-term and long-term effectiveness of acupuncture and tuina on KOA. Methods/design: This parallel-group, multicenter randomized clinical trial (RCT) will be conducted at the outpatient clinic of five traditional Chinese medicine hospitals in China. Three hundred and thirty participants with KOA will be randomly assigned to acupuncture, tuina, or home-based exercise group with a ratio of 1:1:1. The primary outcome is the proportion of participants achieving a minimal clinically important improvement defined as a ≥ 12% reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain dimension on short term (week 8) and long term (week 26) compared with baseline. Secondary outcomes are knee joint conditions (pain, function, and stiffness), self-efficacy of arthritis, quality of life, and psychological conditions, which will be evaluated by the WOMAC score and the Patient Global Assessment (PGA), and in addition, the respondents index of OMERACT-OARSI, Short Form 12 Health Survey (SF-12), arthritis self-efficacy scale, and European five-dimensional health scale (EQ-5D). Adverse events will be collected by self-reported questionnaires predefined. Clinical trial registration: https://www.chictr.org.cn.

Hemispheric asymmetry of auditory oddball detection: An MEG study.

The capacity of the human brain to detect unattended deviant information from frequent information in our environment shows a hemispheric asymmetry, with stronger brain activation in the right temporal area. This lateralization is distinct from the functional left-ward asymmetry of auditory information processing.

Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis.

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 of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis.

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.

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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).

[Sham acupuncture and placebo acupuncture in clinical trials].

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.

[Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine].

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

[ASPIRE guidelines and their enlightenment on application of sham acupuncture in clinical researches].

Reasonable and standard application of sham acupuncture control is the key to determine the quality of acupuncture clinical trials, and is also a difficult problem faced by acupuncture clinical research. The UK National Institute for Health Research and the Medical Research Council jointly published the Applying Surgical Placebo in Randomised Evaluation (ASPIRE) guidelines on the application of placebo surgical operation in randomized evaluation, which includes 4 parts: rationale and ethics, design, conduct, and interpretation and translation, providing comprehensive guidance for the application of placebo controls in surgical trials. As an operational intervention, acupuncture is similar to surgery, so, ASPIRE guidelines can also provide certain guidance for the application of sham acupuncture. In the present paper, we introduce the ASPIRE guidelines, and put forward its enlightenment and reference to the application of sham acupuncture control in combination with retrospecting the current situations of sham acupuncture research. We hold that future studies should strengthen the consideration of the rationality and ethics of sham acupuncture, standardize the design of sham acupuncture control, and convey the information related to sham acupuncture to patients with appropriate descriptions.

[Improving acupuncture research: progress, guidance, and future directions].

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.

[Research on ontology construction of acupuncture effect based on ISO/TS 16843-6: 2022].

In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.

Discussion on Collection of Clinical Questions in International Clinical Practice Guidelines of Acupuncture-Moxibustion.

The clinical questions of acupuncture-moxibustion (Acup-Mox) guidelines are complicated, including not only the curative effect of Acup-Mox intervention measures, but also the operational elements of Acup-Mox. This paper aimed to put forward the idea and process of collecting clinical questions in developing international acupuncture clinical practice guidelines. The experience was collected and the idea of collecting clinical questions of Acup-Mox was formed through expert consultation and discussion in combination with expert opinions. Based on the characteristics of Acup-Mox discipline. This paper put forward the thinking of collecting elements of clinical questions following the intervention-population-outcome-control (I-P-O-C) inquiry process, according to the discipline of Acup-Mox. It was emphasized that in the process of collecting clinical questions, "treatable population" and "alleviable outcome indicators" for a specific Acup-Mox intervention with certain therapeutic effect should be focused on, so as to highlight the pertinence of clinical questions of Acup-Mox guidelines in terms of population and outcome elements.

Changes of DOM and its correlation with internal nutrient release during cyanobacterial growth and decline in Lake Chaohu, China.

The seasonal changes in dissolved organic matter (DOM), and its correlation with the release of internal nutrients during the annual cycle of cyanobacteria in the eutrophic Lake Chaohu, China, were investigated from four sampling periods between November 2020 and July 2021. The DOM fluorescence components were identified as protein-like C1, microbial humic-like C2, and terrestrial humic-like C3. The highest total fluorescence intensity (FT) of DOM in sediments during the incubation stage is due to the decomposition and degradation of cyanobacteria remains. The lowest humification of DOM and the highest proportion of C1 in waters during the initial cyanobacterial growth indicate that fresh algae are the main source. The highest molecular weight of DOM and FT of the C2 in sediments during cyanobacterial outbreaks indicate the concurrent deposition of undegraded cyanobacterial remains and microbial degradation. The components of DOM are affected mainly by the dissolved total phosphorus in waters, while the temperature drives the annual cycle of cyanobacteria. The decreasing C1 in sediments and increasing nutrients in waters from the cyanobacterial incubation to outbreak indicate that mineralization of algal organic matter contributes importantly to the release of internal nutrients, with the strongest release of phosphorus observed during the early growth of cyanobacteria. The humic-like C2 and C3 components could also affect the dynamics of internal phosphorus through the formation of organic colloids and organic-inorganic ligands. The results show that the degradation of DOM leads to nutrients release and thus supports the continuous growth of cyanobacteria in eutrophic Lake Chaohu.

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.

Research on ontology construction of acupuncture effect based on ISO/TS 16843-6: 2022 / 中国针灸

In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.

Improving acupuncture research: progress, guidance, and future directions / 中国针灸

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.

Discussion on Collection of Clinical Questions in International Clinical Practice Guidelines of Acupuncture-Moxibustion / 中国结合医学杂志

The clinical questions of acupuncture-moxibustion (Acup-Mox) guidelines are complicated, including not only the curative effect of Acup-Mox intervention measures, but also the operational elements of Acup-Mox. This paper aimed to put forward the idea and process of collecting clinical questions in developing international acupuncture clinical practice guidelines. The experience was collected and the idea of collecting clinical questions of Acup-Mox was formed through expert consultation and discussion in combination with expert opinions. Based on the characteristics of Acup-Mox discipline. This paper put forward the thinking of collecting elements of clinical questions following the intervention-population-outcome-control (I-P-O-C) inquiry process, according to the discipline of Acup-Mox. It was emphasized that in the process of collecting clinical questions, "treatable population" and "alleviable outcome indicators" for a specific Acup-Mox intervention with certain therapeutic effect should be focused on, so as to highlight the pertinence of clinical questions of Acup-Mox guidelines in terms of population and outcome elements.

[Comparative analysis of the reporting guidelines on simulated acupuncture in randomized controlled trials of acupuncture].

The standardized reports of simulated acupuncture control are conductive to understanding and replicating the control method for researchers and readers. At present, the reporting quality of the simulated control in the clinical research of acupuncture is low and there is not a guideline, specification or standard specifically for the report of simulated acupuncture control. In this article, we compared in-depth the checklists between STRICTA (standards for reporting interventions in clinical trials of acupuncture) and TIDieR-Placebo (a guide and checklist for reporting placebo and sham controls), and assessed their applicability in acupuncture clinical research. The checklist of STRICTA is a particular standard for reporting acupuncture intervention measures, including the items of acupuncture control, especially the reporting of the details in acupuncture control; while, the checklist of TIDieR-Placebo is for the comprehensive reporting of placebo or sham control, covering a wider range of content. It specifies the overall reporting of the placebo control setting, intervention delivery and blindness assessment. Although both of the checklists provide a certain reference for reporting simulated acupuncture, they are not applicable for adequately reporting the simulated acupuncture control. Therefore, it is urgent to develop a specific guideline for reporting simulated acupuncture control so as to improve the reporting quality.

[Enlightenments of DITTO framework and its application for setting up mock acupuncture in clinical research].

How to set up a placebo control scientifically and effectively is a problem in clinical research on acupuncture therapy. In 2020, the UK National Institute of Health Research established a standardized methodological framework DITTO, that is, "Deconstruct""Identify""Take out""Think" and "Optimize" to standardize the setting of invasive console-control intervention. Acupuncture therapy theoretically belongs to the category of invasive therapeutic intervention, and the percutaneous puncture therapy was also considered when the DITTO framework was developed. Therefore, this framework can be applied to clinical research of acupuncture, and may provide a reference for the appropriate setting of simulated acupuncture. In this article, we introduce the formulation process and main contents of the DITTO framework, and analyze the adjustments needed to be made and possible problems encountered in the application of each part of the framework in acupuncture clinical research through medical cases. The DITTO framework can guide and standardize the design of mock acupuncture control in acupuncture clinical research to a certain extent, which is conducive to finding a more suitable implementation method of mock acupuncture, thus promoting the improvement of the quality of acupuncture clinical research. However, because there is no precedent in the field of acupuncture in traditional Chinese medicine, further research is needed in the future practical application so that it can be better combined with the characteristics of acupuncture and the purpose of clinical research.

[Minimal clinically important difference of the frequency of bowel movement for patients with chronic severe functional constipation treated with acupuncture].

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. METHODS: In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. RESULTS: The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. CONCLUSION: The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.

Mitochondrion, lysosome, and endoplasmic reticulum: Which is the best target for phototherapy?

Photodynamic therapy (PDT) is a robust cancer treatment modality, and the precise spatiotemporal control of its subcellular action site is crucial for its effectiveness. However, accurate comparison of the efficacy of different organelle-targeted PDT approaches is challenging since it is difficult to find a single system that can achieve separate targeting of different organelles with separable time windows and similar binding amounts. Herein, we conjugated chlorin e6 (Ce6) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (ammonium salt) (DSPE-PEG5000-NH2) to afford DSPE-PEG-Ce6, which could migrate from mitochondrion to lysosome and ultimately to endoplasmic reticulum (ER) after cellular internalization. Benefiting from the dynamic subcellular distribution of DSPE-PEG-Ce6 with tunable organelle-binding amounts, we accurately determined the PDT efficacy order of the molecule, i.e., mitochondrion > ER > lysosome. This work proposes an ideal model system for accurately evaluating the specific organelle-targeted PDT efficacy and may promote the future development of effective PDT strategies.