Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis.

Background: Chronic fatigue syndrome (CFS) is a global public health concern. We performed this systematic review of randomised controlled trials (RCTs) to evaluate the effects and safety of traditional Chinese mind-body exercises (TCME) for patients with CFS. Methods: We comprehensively searched MEDLINE, Embase, Web of Science, PsycINFO, Cochrane Library, CNKI, VIP databases, and Wanfang Data from inception to October 2022 for eligible RCTs of TCME for CFS management. We used Cochran's Q statistic and I2 to assess heterogeneity and conducted subgroup analyses based on different types of TCME, background therapy, and types of fatigue. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results: We included 13 studies (n = 1187) with a maximal follow-up of 12 weeks. TCME included Qigong and Tai Chi. At the end of the treatment, compared with passive control, TCME probably reduces the severity of fatigue (standardised mean differences (SMD) = 0.85; 95% confidence interval (CI) = 0.64, 1.07, moderate certainty), depression (SMD = 0.53; 95% CI = 0.34, 0.72, moderate certainty), anxiety (SMD = 0.29; 95% CI = 0.11, 0.48, moderate certainty), sleep quality (SMD = 0.34; 95% CI = 0.10, 0.57, low certainty) and mental functioning (SMD = 0.90; 95% CI = 0.50, 1.29, low certainty). Compared with other active control therapies, TCME results in little to no difference in the severity of fatigue (SMD = 0.08; 95% CI = -0.18, 0.34, low certainty). For long-term outcomes, TCME may improve anxiety (SMD = 1.74; 95% CI = 0.44, 3.03, low certainty) compared to passive control. We did not identify TCME-related serious adverse events. Conclusions: In patients with CFS, TCME probably reduces post-intervention fatigue, depression, and anxiety and may improve sleep quality and mental function compared with passive control, but has limited long-term effects. These findings will help health professionals and patients with better clinical decision-making. Registration: PROSPERO: CRD42022329157.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Performance-enhanced regenerated cellulose film by adding grape seed extract.

Eco-friendly packaging material with intelligent colorimetric performance has been a requirement for food safety and quality. This work focused on a food packaging material from regenerated cellulose films that added the grape seed extract (GSE) and polyethylene glycol 200 (PEG). FTIR and SEM techniques were employed to prove the compatibility of GSE with cellulose matrix. The composite film showed an enhanced elongation at break (16.61 %) and tensile strength (33.09 MPa). The addition of PEG and GSE also improved the water contact angle of regenerated-cellulose film from 53.8° to 83.8°. Moreover, the composite films exhibited UV-blocking properties while maintaining adequate transparency. The GSE induced the regenerated films with a macroscopic change in color under different pH conditions. Furthermore, the loading of GSE slowed down the decomposition of strawberries and delayed the self-biodegradation compared with the control for more than 3 days and 18 days. The present study showed a regenerated cellulose film with acceptable mechanical and hydrophilia properties, pH-responsiveness, anti-decomposition, and delayed biodegradation performances, indicating a potential color sensor in food packaging.

[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.

Ginsenoside Rb1 Suppresses AOM/DSS-induced Colon Carcinogenesis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Current treatments, including surgery, radiotherapy, and chemotherapy, are limited by severe side effects and the development of resistance. OBJECTIVE: Therefore, it is important to find additional therapies to combat the problem. Ginsenoside Rb1 is the main active ingredient of ginseng, which is a well-known herb in traditional Chinese medicine. Ginsenoside is reported to play an important role in the prevention and treatment of cancer. METHODS: We established Azoxymethane (AOM)/Dextran sodium sulfate (DSS) colon cancer model based on inflammation, observed the beneficial effect of ginsenoside Rb1, and detected the changes in gut microbiota. RESULTS: Our experimental results showed that ginsenoside Rb1 significantly reduced the levels of TNF-α, IL-6, IL- 17A, IL-33, IL-1ß, and IL-22, increased the level of IL-10, and also changed the gut microbiota composition. These results suggested that ginsenoside Rb1 can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC by relieving chronic inflammation and restoring the gut microenvironment in the AOM/DSS-induced model of colitis-associated colorectal cancer in mice. CONCLUSION: Ginsenoside Rb1 significantly attenuated AOM/DSS-induced colon carcinogenesis.

Reporting quality of economic evaluations of the negotiated Traditional Chinese Medicines in national reimbursement drug list of China: A systematic review.

Background: Traditional Medicine (TM) has a wide uptake in most countries. In China, Traditional Chinese Medicine (TCM) is a common kind of primary health because of its beneficial effects. This review aimed to appraise the publication reporting quality of economic evaluations for selective TCM in the National Reimbursement Drug List (NRDL), Version 2020, based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Methods: Electronic databases were searched for economic evaluation that supported the TCM negotiations in NRDL (2020 version) published from 2001 to 2021, including PubMed, Web of Science, Embase, CNKI, WanFang, and SinoMed. The CHEERS statement was used to appraise the reporting quality of included TCM economic evaluations. Results: A total of 360 articles were retrieved, but only 38 economic evaluations met the inclusion criteria. None of the articles reported all items in the CHEERS checklist. The mean score of included articles is low at 10.93±2.62, with an average scoring rate of 51.31±10.53%. The least reported items included: "Characterizing heterogeneity," "Conflicts of interest", "Discount rate," and "Study perspective," with a reporting rate of 0.00%, 5.26%, 7.89%, and 15.79%, respectively. Conclusion: An upward trend occurred in the quantity and quality of the economic evaluation publications of TCM in China. TCM economic evaluations are still at an early stage, with an urgent need for improving reporting quality. It may result from research experiences or different ideas between TCM and Western Medicine. Adhering to reporting guidelines like CHEERS and educating economic evaluation investigators can improve TCM economic evaluations' reporting quality.

Co-existence effect of copper oxide nanoparticles and ciprofloxacin on simultaneous nitrification, endogenous denitrification, and phosphorus removal by aerobic granular sludge.

Nanoparticles and antibiotics are toxic to humans and ecosystems, and they inevitably coexist in the wastewater treatment plants. Hence, the co-existence effects and stress mechanism of copper (II) oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) on simultaneous nitrification, endogenous denitrification and phosphorus removal (SNEDPR) by aerobic granular sludge (AGS) were investigated here. The co-existence stress of 5 mg/L CuO NPs and 5 mg/L CIP resulted in the synergistic inhibitory effect on nutrient removal. Transformation inhibition mechanisms of carbon (C), nitrogen (N) and phosphorus (P) with CuO NPs and CIP addition were time-dependent. Furthermore, the long-term stress mainly inhibited PO43--P removal by inhibiting phosphorus release process, while short-term stress mainly inhibited phosphorus uptake process. The synergistic inhibitory effect of CuO NPs and CIP may be due to the changes of physicochemical characteristics under the co-existence of CuO NPs and CIP. This further altered the sludge characteristics, microbial community structure and functional metabolic pathways under the long-term stress. Resistance genes analysis exhibited that the co-existence stress of CuO NPs and CIP induced the amplification of qnrA (2.38 folds), qnrB (4.70 folds) and intI1 (3.41 folds) compared with the control group.

[Selection and application of explanatory and pragmatic randomized controlled trials in clinical research of acupuncture].

In the view of the controversy that there is no efficacy difference between true and sham acupuncture in acupuncture randomized controlled trials (RCTs), it is analyzed that one of the reasons is that many clinical studies do not properly understand the design of RCT research and interpret the research results. Starting from the concept and coverage of explanatory RCT and pragmatic RCT, this study lists the application examples of two types of RCTs in the field of acupuncture from five aspects: research purpose and trial environment, subject selection, intervention measures, control measures and outcome evaluation, so as to provide some ideas for their application in clinical trials.

Factors Associated with the Magnitude Of acUpuncture treatment effectS (FAMOUS): a meta-epidemiological study of acupuncture randomised controlled trials.

OBJECTIVE: To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas. DATA SOURCE: Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019. STUDY SELECTION: The inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons. DATA ANALYSIS: The potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model. RESULTS: 1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (>0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2-0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (<0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25). CONCLUSION: Patients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects.

Aesculetin exhibited anti-inflammatory activities through inhibiting NF-кB and MAPKs pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Aesculetin (6,7-dihydroxy-2H-1-benzopyran-2-one) has been reported to exhibit potent anti-inflammatory property both in vitro and in vivo. AIMS OF THIS STUDY: In this study, we evaluated the anti-inflammatory effect and investigated underlying molecular mechanisms of aesculetin in LPS-induced RAW264.7 macrophages and DSS-induced colitis. MATERIALS AND METHODS: In this study, the production of NO, TNF-α, and IL-6 were measured to identify the aesculetin with potent anti-inflammatory effect. Then, the underlying anti-inflammatory mechanisms were explored by western blotting in LPS-induced cells. Next, we verify the anti-inflammatory potential of aesculetin in DSS-induced colitis in vivo. The clinical symptoms of colitis, including weight loss, DAI, colon length and MPO activity, and the secretion of TNF-α and IL-6 were evaluated. Finally, Western blot analysis was applied to further investigate underlying mechanism in DSS-induced colitis model. RESULTS: Our studies showed that aesculetin exhibited anti-inflammatory potential by inhibiting NO, TNF-α, and IL-6 production and reducing iNOS and NLRP3 expression in LPS-induced RAW264.7 cells. Mechanically, we found that aesculetin significantly inhibited LPS-induced activation of NF-κB and MAPKs signaling pathways. In DSS-induced mouse model, the colitis-related symptoms were relieved by treatment with aesculetin. Besides, aesculetin also inhibited the secretion of TNF-α and IL-6, and the activation of NF-κB and MAPKs signaling pathways in DSS-induced colitis. CONCLUSIONS: The anti-inflammatory effect of aesculetin was connected with its inhibition on the activation of NF-κB and MAPKs signaling pathways both in vitro and in vivo. Therefore, aesculetin was expected to be developed as an anti-inflammatory drug.

Enhancing the In Vitro Biological Activity of Degraded Silk Sericin and Its Analog Metabolites.

Two sericins of high and low molecular weight (HS and LS) were prepared from commercial silkworm cocoon silk with a boiling water and Ca(OH)2 solution with ultrasonic treatments, respectively. This study first investigated the release concentration of the two abovementioned sericins in simulated saliva, gastric juice, and intestinal juice (pH 6.8, 2.0, and 7.4, respectively) within 10 h. The results showed that the order of sericin release rate and its amount in the simulated environment was gastric juice > saliva > intestinal juice. Second, the molecular weights of both sericin metabolites formed by in vitro enzymatic degradation were lower than 15 kDa. The α-glucosidase inhibitory activities of both sericins and their analog metabolites were positively correlated with their concentrations. The IC50 values of the HS- and LS-derived metabolites were 1.02 ± 0.12 mg/mL and 0.91 ± 0.15 mg/mL, respectively, which were five to seven times lower than those of both original sericins. The total antioxidant capacities and hydroxyl radical scavenging capacities of both metabolites were enhanced by one- to three-fold compared with HS and LS. These results indicate that both sericins, regardless of molecular size, have significantly enhanced antioxidant, superoxide free radical scavenging, and glycosidase inhibitory activities after simulated metabolism, and that LS is better than HS regardless of simulated digestion. These results confirm that sericin is important in the sustainable development and utilization of silk resources, especially the reduction in environmental pollution, and provides new ideas for the development of adjuvant treatments for diabetes and the development of foods with anti-hyperglycemic functions.

Characteristics and quality of clinical practice guidelines addressing acupuncture interventions: a systematic survey of 133 guidelines and 433 acupuncture recommendations.

OBJECTIVE: To systematically summarise acupuncture-related Clinical Practice Guidelines (CPGs)'s clinical and methodological characteristics and critically appraise their methodology quality. DESIGN: We summarised the characteristics of the guidelines and recommendations and evaluated their methodological quality using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument. DATA SOURCES: Nine databases were searched from 1 January 2010 to 20 September 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included the latest version of acupuncture CPGs, which must have used at least one systematic review addressing the benefits and harms of alternative care options to inform acupuncture recommendations. DATA EXTRACTION AND SYNTHESIS: Reviewers, working in pairs, independently screened and extracted data. When there are statistical differences among types of CPGs, we reported the data by type in the text, but when not, we reported the overall data. RESULTS: Of the 133 eligible guidelines, musculoskeletal and connective tissue diseases proved the most commonly addressed therapeutic areas. According to the AGREE II instrument, the CPG was moderate quality in the domain of clarity of scope and purpose, clarity of presentation, the rigour of development, stakeholder involvement and low quality in editorial independence, and applicability. The study identified 433 acupuncture-related recommendations; 380 recommended the use of acupuncture, 28 recommended against the use of acupuncture and 25 considered acupuncture but did not make recommendations. Of the 303 recommendations that used Grading of Recommendations Assessment, Development and Evaluation to determine the strength of recommendations, 152 were weak recommendations, 131 were strong recommendations, of which 104 were supported by low or very low certainty evidence (discordant recommendations). CONCLUSION: In the past 10 years, a large number of CPGs addressing acupuncture interventions exist. Although these guidelines may be as or more rigorous than many others, considerable room for improvement remains.

The renal protection of flavonoid-rich ethanolic extract from silkworm green cocoon involves in inhibiting TNF-α-p38 MAP kinase signalling pathway in type 2 diabetic mice.

BACKGROUND: Diabetic nephropathy (DN) is one of the major complications of diabetes. Sericin and flavonoids are two bioactive substances which have been demonstrated to have some therapeutical effect on diabetic nephropathy. The aim of this paper is to investigate the effect of ethanolic extract (EE) rich in quercetin and kaempferol and their glucosides from the green cocoon of silkworm Bombyx mori on DN in type 2 diabetic (T2D) mice induced by high-fat and streptozotocin (STZ). METHODS: Ethanolic extract from the green cocoon shell of silkworm Bombyx mori was used as material. Diabetic mice were orally treated with three doses (150, 250 and 350 mg/kg) of the extract for 7 weeks, then the levels of oxidases and related inflammatory factors were measured in kidneys. RESULTS: Compared with the negative control, EE administration resulted in an evident reduction in blood glucose levels and an improvement of the body weight in diabetic mice. Oral EE could inhibit the expressions of renal tumour necrosis factor TNF-α, monocyte chemoattractant protein-1 (MCP-1), fibronectin (FN) and P38 mitogen-activated protein kinase (p38 MAPK) in T2D mice. Moreover, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were significantly elevated in T2D mice treated with EE. CONCLUSIONS: The activities of anti-fibrosis and anti-inflammation contributed to the renal protective effects by reducing oxidative stress, which might be mediated by the inhibition of the TNF-α-p38 MAP kinase signalling pathway. It is suggested that the ethanolic extract from silkworm green cocoon might be potential as an herbal medicine for DN.

Mulberry Bark Alleviates Effect of STZ Inducing Diabetic Mice through Negatively Regulating FoxO1.

Dysfunction of insulin secretion and hyperglycaemia were commonly found due to damaged ß cells of pancreas. In our previous research, it was found that mulberry branch bark powder (MBBP) was effective in treating diabetes in mice which were induced by STZ and high fat diet. The present study was designed to evaluate the protective effect of MBBP on STZ-induced ß cells injury and investigate underlying mechanisms. By preventive administration of branch bark powder, the damage caused by STZ injection was found to be alleviated. In MBBP feed groups, pathological weight loss was inhibited, fasting blood glucose was controlled, the incidence of diabetes decreased, and blood lipid level and antioxidant capacities were restored. The PI3K/AKT/FoxO1 signal pathway was found to be activated by key proteins expression and gene testing. In liver, the increased PI3K and phosphorylated AKT, the phosphorylated, and inactivated FoxO1, which regulates the expression of gluconeogenic gene and explains the effect of relieving insulin resistance of MBBP. Therefore, the MBBP improves the tolerance of pancreas to the toxicity of STZ involving the PI3K/AKT/FoxO1 signalling pathway.