Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Clinical efficacy of acupoint catgut embedding in the treatment of allergic rhinitis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of acupoint catgut embedding in the treatment of allergic rhinitis by Meta-analysis. METHODS: Pubmed, Web of Science, Embase, Elsevier, CNKI, and VIP databases were searched for clinical randomized controlled trials (RCTS) on acupoint catgut embedding for allergic rhinitis from the establishment of the database to December 30, 2022. RevMan5.4 and Stata12 software were used for Meta-analysis. RESULTS: A total of 17 articles were included, involving 1231 patients. Meta-analysis showed that the total effective rate of acupoint catgut embedding for allergic rhinitis was higher than that of the control group [Pooled Odds Ratio = 5.19, 95%CI (3.14, 8.58), P < 0.00001]. Sensitivity analysis indicated that the total effective rate of acupoint catgut embedding in the treatment of allergic rhinitis was stable. The efficacy of the acupoint embedding group was better than that of the western medicine group [OR = 5.78, 95%CI (3.25, 10.27), P < 0.00001]. Acupoint embedding decreased serum IL-33 levels [MD = -70.79, 95%CI (-102.60, -38.98), P < 0.0001] and improved TNNSS score [MD = -0.25, 95%CI (-0.40, -0.11), P = 0.0005] was statistically different from the control group. CONCLUSION: Acupoint catgut embedding in the treatment of allergic rhinitis has a certain effect, but the accuracy of this conclusion still needs to be verified by higher-quality RCT in the later stage.

Efficacy and safety of Dachaihu Decoction for acute pancreatitis: Protocol for a systematic review and meta-analysis.

BACKGROUND: Dachaihu Decoction (DCD) is a traditional herbal formula widely used for treating acute pancreatitis (AP) in China. However, the efficacy and safety of DCD has never been validated, limiting its application. This study will assess the efficacy and safety of DCD for AP treatment. METHODS: Relevant randomized controlled trials of DCD in treating AP will be searched through Cochrane Library, PubMed, Embase, Web of Science, Scopus, CINAHL, China National Knowledge Infrastructure database, Wanfang Database, VIP Database, and Chinese Biological Medicine Literature Service System database. Only studies published between the inception of the databases and May 31, 2023 shall be considered. Searches will also be performed in the WHO International Clinical Trials Registry Platform, Chinese Clinical Trial Registry, and ClinicalTrials.gov. Preprint databases and grey literature sources such as OpenGrey, British Library Inside, ProQuest Dissertations & Theses Global, and BIOSIS preview will also be searched for relevant resources. The primary outcomes to be assessed will include mortality rate, rate of surgical intervention, proportion of patients with severe acute pancreatitis transferred to ICU, gastrointestinal symptoms, and the acute physiology and chronic health evaluation II score. Secondary outcomes will include systemic complications, local complications, the normalization period of C-reactive protein, length of stay in the hospital, TNF-α, IL-1, IL-6, IL-8, and IL-10 levels, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted independently by two reviewers using the Endnote X9 and Microsoft Office Excel 2016 software. The risk of bias of included studies will be assessed by the Cochrane "risk of bias" tool. Data analysis will be performed using the RevMan software (V.5.3). Subgroup and sensitivity analysis will be performed where necessary. RESULTS: This study will provide high-quality current evidence of DCD for treating AP. CONCLUSION: This systematic review will provide evidence of whether DCD is an effective and safe therapy for treating AP. TRIAL REGISTRATION: PROSPERO registration number CRD42021245735. The protocol for this study was registered at PROSPERO, and is available in the S1 Appendix. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021245735.

Auricular acupressure for adverse events following immunization after COVID-19 vaccine injection: A multicentre, blinded, randomized controlled trial.

BACKGROUND: Some adverse events following immunization (AEFI) were observed in potential corelation with COVID-19 vaccination but without prevention or ongoing trial for it. We aimed to investigate efficacy of auricular acupressure (AuriAc) therapy in preventing AEFI after first dosage of the vaccine. METHODS: We performed a multicentre randomized controlled trial with three arms, including AuriAc, SAuriAc (sham auricular acupressure), and TrAsU (treatment as usual) group, carried out in four medical institutions in Chengdu, China, from March 17th to April 23rd, 2021. We enrolled participants based on eligibility criteria and randomized them into three groups: AuriAc (AEFI-specific auricular points applied, n = 52), SAuriAc (n = 51) or TrAsU (n = 44) group. Primary outcomes were percentages of any AEFI and local pain, and secondary outcomes were percentages who reported other AEFI. They were followed at 1, 3, 5, 7, and 14 days, by phone or online, with severity evaluated. RESULTS: 147 participants (73.47% females) were included with median age as 31 years (25-45, IQR). One day after the injection, participants in AuriAc group reported significant reduction on percentages of any AEFI [intention-to-treat, difference of percentage (DP) = -20.13, 95%CI: - 0.39, - 0.02, p = 0.01; per-protocol, DP = -22.21, 95%CI: - 0.40, - 0.03, P = 0.02] and local pain (per-protocol, DP = -18.40, 95%CI: -0.36, -0.01, P = 0.04), compared with TrAsU group. The effects were slight at other follow-up days and for other outcomes, and with a low percentage of mild local allergic reactions. CONCLUSIONS: We firstly explored potential of AuriAc for preventing AEFI related to COVID-19 vaccine injection, which is beneficial for the vaccine recipients, but evidence is limited. TRIAL REGISTRATION: chictr.org.cn no. ChiCTR2100043210 (http://www.chictr.org.cn/showproj.aspx?proj=121519).

Prevalence and Risk Factors for Allergic Rhinitis in China: A Systematic Review and Meta-Analysis.

The prevalence of allergic rhinitis (AR) has increased tremendously in the recent year in China. Evidence-based medicine to objectively evaluate the prevalence and risk factors for AR in China is urgently required. Toward this, we systematically searched four English and four Chinese databases to identify the literature on the same, from the year of website establishment until November 2021. A total of 51 studies were evaluated, and data were obtained through Stata 16 analysis. Overall pooled risk factors for adult AR were smoking (odds ratio [OR] = 1.89, 95% confidence interval [CI]: 1.25, 2.87), asthma (OR = 3.30, 95% CI: 1.48, 7.39), a family history of AR (OR = 3.17, 95% CI: 2.31, 4.34), a family history of asthma (OR = 3.99, 95% CI: 2.58, 6.16), drug allergy (OR = 1.62, 95% CI: 1.38, 1.89), food allergy (OR = 2.29, 95% CI: 1.39, 3.78), pollen allergy history (OR = 2.41, 95% CI: 1.67, 3.46), antibiotic use (OR = 2.08, 95% CI: 1.28, 3.36), occupational dust exposure (OR = 2.05, 95% CI: 1.70, 2.47), home renovation (OR = 1.73, 95% CI: 0.99, 3.02), and middle school education (OR = 1.99, 95% CI: 1.29, 3.06). Overall pooled risk factors for AR in children were passive smoking (OR = 1.70, 95% CI: 1.02, 2.82), asthma (OR = 3.26, 95% CI: 2.42, 4.39), a family history of AR (OR = 2.59, 95% CI: 2.07, 3.24), a family history of allergy (OR = 4.84, 95% CI: 3.22, 7.26), a history of allergic diseases (OR = 2.11, 95% CI: 1.52, 2.94), eczema(OR = 2.29, 95% CI: 1.36, 3.85), owning pets (OR = 1.56, 95% CI: 1.37, 1.77), eating seafood (OR = 1.30, 95% CI: 1.10, 1.55), boys (OR = 1.58, 95% CI: 1.43, 1.74), and breastfeeding (OR = 0.82, 95% CI: 0.55, 1.22). The results of our meta-analysis showed that the prevalence of allergy rhinitis was 19% (95% CI 14-25) among adults and 22% (95% CI 17-27) among children, with boys showing a higher prevalence than girls. The development of AR in China is associated with several factors, including allergic diseases (eczema, asthma, pollen allergy, and food allergy), a family history of allergy (AR, asthma, and other allergies), and dwelling and working environment (smoking or passive smoking, occupational dust exposure, and owning pets); conversely, breastfeeding can reduce the risk.

Efficacy and safety of traditional Chinese medicine nasal irrigation on chronic rhinosinusitis recovery after endoscopic sinus surgery: A protocol for a systematic review and meta-analysis.

BACKGROUND: Continuous comprehensive treatment is still needed after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) to promote the recovery of sinus mucosal morphology and function. Traditional Chinese medicine (TCM) nasal irrigation is a promising external treatment of TCM, but at present, the application of TCM nasal irrigation after ESS for CRS has not been recommended by the guidelines. Therefore, this article aims to develop a systematic overview and meta-analysis protocol to assess the effectiveness and safety of Chinese herbal nasal rinse for CRS recovery after ESS. METHODS: Seven databases shall be retrieved from their inception until December 2021. Eligible randomized controlled trials will be covered in the study. The outcome indicators of the survey will consist of efficacy, visual analogue scale score, Lund-Kennedy score for nasal endoscopy, Lund-Mackay score for sinus computed tomography and other secondary outcome indicators. The selection of literature, extraction of data, and methodological quality evaluation of literature shall be conducted by two researchers separately. If there is any dispute, it can be discussed and solved by a third researcher. Review Manager 5.3 software will be applied to data analysis. RESULTS: The article will make a detailed research programme to explore the efficacy and safety of TCM nasal irrigation on CRS recovery after ESS. CONCLUSION: This protocol is suitable for evaluating the effectiveness and safety of TCM nasal rinse for CRS recovery after ESS, and can provide corresponding evidence-based medical evidence. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework Registration DOI: 10.17605/OSF.IO/ZV73Q.

Head Acupuncture Plus Schuell's Language Rehabilitation for Post-Stroke Aphasia: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION: HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).

Hedyotis diffusae Herba-Andrographis Herba inhibits the cellular proliferation of nasopharyngeal carcinoma and triggers DNA damage through activation of p53 and p21.

Dysregulation of the cell cycle and the resulting aberrant cellular proliferation has been highlighted as a hallmark of cancer. Certain traditional Chinese medicines can inhibit cancer growth by inducing cell cycle arrest. In this study we explore the effect of Hedyotis diffusae Herba-Andrographis Herba on the cell cycle of nasopharyngeal carcinoma (NPC). Hedyotis diffusae Herba-Andrographis Herba-containing serum was prepared and then added to the cell culture medium. BrdU, comet, and FUCCI assays, western blot analysis and flow cytometry analysis revealed that Hedyotis diffusae Herba-Andrographis Herba treatment significantly alters cell proliferation, DNA damage, and cell cycle distribution. Xenograft mouse model experiments were performed, confirming these in vitro findings in vivo. Treatment with Hedyotis diffusae Herba-Andrographis Herba inhibited cell proliferation, promoted DNA damage, and arrested NPC cells progression from G1 to S phase. Further examination of the underlying molecular mechanisms revealed that treatment with Hedyotis diffusae Herba-Andrographis Herba increased the expression of p53 and p21, while reducing that of CCND1, Phospho-Rb, E2F1, γH2AX, and Ki-67 both in vivo and in vitro. Conversely, the inhibition of p53 and p21 could abolish the promoting effect of Hedyotis diffusae Herba-Andrographis Herba on the NPC cell cycle arrest at the G1 phase, contributing to the proliferation of NPC cells. Hedyotis diffusae Herba-Andrographis Herba suppressed the tumor growth in vivo. Overall, these findings suggest that Hedyotis Diffusae Herba-Andrographis prevent the progression of NPC by inducing NPC cell cycle arrest at the G1 phase through a p53/p21-dependent mechanism, providing a novel potential therapeutic treatment against NPC.

Auricular acupressure for adverse events following immunization related to COVID-19 vaccine injection: study protocol for a multicenter, three-arm, blinded randomized controlled trial.

BACKGROUND: Some pain, fatigue, and gastrointestinal adverse events were observed in potential association with injection of COVID-19 vaccines, while there was no preventive intervention for it. We aim to investigate the efficacy of auricular acupressure (AA) therapy in preventing and relieving AEFI after injection of COVID-19 vaccine. METHODS: The study design is a randomized, multicentre, three-arm controlled, single-blind trial. Participants meeting the inclusion criteria will be advertised and enrolled and assigned in the medical institutions randomly for post-injection observation. No less than 360 participants will be randomized into one of three groups: auricular acupressure group, sham auricular acupressure group, and wait-list group. Interventions will be performed immediately and will happen 4 to 5 times per day for 5 days. The primary clinical outcomes will be quality and quantity evaluation among participants who reported any AEFI and who reported local pain at injection site. Secondary outcomes will concern headache, muscle and (or) joint pain, fatigue, nausea, vomiting, diarrhoea, and other potential events. All the outcomes will be assessed at baseline and 1, 3, 5, 7, and 14 days after the injection. Both intention-to-treat and per-protocol analyses will be performed, with significance level determined as 5%. DISCUSSION: Results of this trial will help to clarify the value of auricular acupressure therapy in preventing and relieving overall and certain adverse events following immunization after injection of COVID-19 vaccine. TRIAL REGISTRATION: China Clinical Trial Registry (ChiCTR) ( ChiCTR2100043210 ). Registered on 8 February, 2021.

Ear Acupressure for Allergic Rhinitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The treatment effects and safety of ear acupressure (EAP) for patients with allergic rhinitis (AR) have yet to be clarified. OBJECTIVE: To evaluate the effects and safety of EAP in AR patients. DESIGN: Systematic review of published studies. METHODS: A total of 24 English and Chinese databases (PubMed, EMBASE (Excerpta Medical Database), Cochrane Central Register of Controlled Trials, CINAHL, Informit, ScienceDirect, LILACS (Latin American and Caribbean Health Sciences), ProQuest, AMED, Blackwell Synergy, PsycINFO, Panteleimon, AcuBriefs, KoreaMed, IndMed, Ingenta, mRCT, ISI Web of Knowledge, ERIC, VIP Information (http://www.cqvip.com), China National Knowledge Infrastructure (http://www.cnki.net), Cochrane Library, Chinese Cochrane Centre Controlled Trials Register Platform, and Wanfang Chinese Digital Periodical and Conference Database) were searched from their respective inceptions to August 2020 to collect randomized controlled trials of ear acupressure for allergic rhinitis. We performed literature inclusion, data extraction, and trial quality evaluations. Methodological quality was assessed according to the Cochrane Handbook. Revman5.3 was used for all analyses. RESULTS: A total of 203 trials were identified and eleven studies involved 1094 participants aged 3-70 years. EAP was better than control group interventions in terms of effectiveness (risk ratio (RR): 0.51; 95% confidence interval (CI): 0.36-0.70; P < 0.0001). EAP was superior to sham EAP in terms of improvement of the total nasal symptom score (RR: -0.50; 95% CI: -0.96-0.05; P = 0.03), sneezing score (RR: -0.36; 95% CI: -0.59-0.12; P = 0.003), global QoL score (RR: 0.42; 95% CI: 0.04-0.08; P = 0.03), and eye symptom score (RR: -0.36; 95% CI: -0.67-0.05; P = 0.02). CONCLUSIONS: Despite the positive results, it is premature to confirm the efficacy of EAP for treating AR. More high-quality studies are needed to confirm safety and efficacy.

Yu ping feng san for pediatric allergic rhinitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The potential treatment effects and safety of Yu ping feng san (YPFS) for pediatric allergic rhinitis (PAR) patients have yet to be studied systematically. OBJECTIVES: To assess the effects and safety of YPFS for treat pediatric patients, allergic rhinitis. METHODS: We systematically searched PubMed, EMBASE (Excerpta Medical Database), Cochrane library, Chinese Cochrane Centre's Controlled Trials Register platform, Wanfang Chinese Digital Periodical and Conference Database, China National Knowledge Infrastructure Database, and VIP Chinese Science, from inception dates to November 1, 2019. Randomized controlled trials (RCTs) were included. The risk of bias in the trials was assessed in accordance with the Cochrane Handbook, version 5.1.0. RevMan 5.3 software was used to perform a meta-analysis. Grading of Recommendations Assessment, Development and Evaluation methodology was applied to evaluate the evidence quality for each outcome. The quality of evidence for each outcome measurement was low for 4 outcomes and very low for 5 outcomes. RESULTS: A total of 10 RCTs involving 1069 participants (3-15 years old) fulfilled the inclusion criteria. After exclusion, 8 RCTs were pooled for efficacy assessment. The overall efficacy evaluation result did not show benefit for the experimental group (relative risk 0.32, CI 95% 0.24-0.45; P = .98;) Investigation of variation of serum IgA, immunoglobulin E, IgG in three studies in 2 groups returned no statistical significance. YPFS gave relatively better safety (relative risk 0.29, CI 95% 0.14-0.58; P = .0005; Fig. S8, http://links.lww.com/MD/F751) and lower recurrence rates than did Western medical therapy. CONCLUSIONS: Current evidence cannot support the routine use of YPFS for treatment of PAR. This may be due to poor-quality study-design limitations of the included YPFS studies. Our data showed that the use of YPFS for PAR is relatively safe compared to Western medical therapy, but a conclusion could not be drawn because only 5 studies were analyzed. Every study suffered from some methodological limitation. Therefore, further large, rigorously-designed studies are necessary to determine conclusively the utility of YPFS in PAR.

Traditional Chinese medicine auricular point acupressure for the relief of pain, fatigue, and gastrointestinal adverse reactions after the injection of novel coronavirus-19 vaccines: a structured summary of a study protocol for a multicentre, three-arm, single-blind, prospective randomized controlled trial.

OBJECTIVES: To investigate if traditional Chinese medicine (TCM) auricular point acupressure (APA) can alleviate and (or) reduce the pain (including injection site pain, headache, other muscle and joint pain), fatigue, and gastrointestinal adverse reactions (including nausea, vomiting, diarrhea), after the injection of novel coronavirus-19 vaccines (NCVs). TRIAL DESIGN: The study is designed as a multicentre, parallel-group, three-arm, single-blind, prospective, randomized (1:1:1 ratio) study. PARTICIPANTS: More than 360 participants will be recruited from healthy people who vaccinate NCVs in 5 community healthcare centres in the Sichuan province of China and 1 university hospital (Hospital of Chengdu University of Traditional Chinese Medicine). INCLUSION CRITERIA: ①Vaccinators meets the conditions of NCVs injection and have no contraindications to it. The details shall be subject to the instructions of the NCVs used and the statement of medical institutions. The first dose of NCVs injection shall be completed within 24 hours from the time of injection to the time of enrolment; ②No redness, swelling, injury or infection of the skin or soft tissue of both ears, which is not suitable for APA; ③No history of alcohol and adhesive tape contact allergy; ④18-59 years old, regardless of gender; ⑤Those who were able to complete the questionnaire independently at the time of the first and second dose of NCVs and on the 3rd, 7th and 15th day after the first and second dose of NCVs respectively; ⑥Those who agree to participate in the trial and sign the informed consent, and can seriously abide by the precautions after the injection of NCVs and the requirements of traditional Chinese medicine auricular point plasters sticking and acupressure. EXCLUSION CRITERIA: ①Those who are not suitable to be vaccinated because they belong to the contraindication or cautious population; ②Those who have participated in other clinical trials within 4 weeks before the start of this study; ③No chronic/habitual/persistent headache, Muscle or joint pain, fatigue, diarrhea, nausea, retching or vomiting before the injection of NCVs, and no related diseases present (details of this item is listed in full protocol); ④Those who are in use or have received TCMAPA within 2 weeks before the trial; ⑤Pregnant or lactating women; ⑥Participants with other serious primary diseases and psychosis. INTERVENTION AND COMPARATOR: ①Auricular point acupressure group: participants receive bilateral, symptom-specific TCMAPA in 5 auricular points (per side, 10 points bilateral) for 5 days, 3-4 times (about 1 min each time) of self-acupressure per day, after each NCVs injection (10 days in total). ②Sham auricular point acupressure group: participants receive bilateral, none symptom-specific, sham APA in 5 auricular points (per side, 10 points bilateral) for 5 days, 3-4 times (about 1 min each time) of self-acupressure per day, after each NCVs injection (10 days in total). ③Blank control group: Non-intervention blank control. The Hebei medical device Co. Ltd, Hebei, China manufactured the auricular point sticking plasters. MAIN OUTCOMES: Primary outcomes are all scores of visual analogue scale (VAS) based on subjective judgment of the participants included, including VAS score of pain at injection site, headache, muscle and joint pain, fatigue, nausea, retching, vomiting and diarrhea. Time points for outcomes above are the same: ①Immediately after first and second injection of the vaccine (Baseline assessment); ②Three days after first and second injection of the vaccine; ③Seven days after first and second injection of the vaccine; ④Fifteen days after first and second injection of the vaccine. RANDOMISATION: Participants will be randomized in 1:1:1 ratio to each group by computerized random number generator, and independently in each sub-centre. BLINDING (MASKING): Participants, information collectors and statistical evaluators will be blinded between APA group and sham APA group. No blinding in the control group. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): No less than 360 participants will be randomized in 1:1:1 ratio to each group. TRIAL STATUS: Protocol version 2.0 of February 3rd, 2021. Recruitment is expected to start on February 18th, 2021, and to finish on March 12th, 2021. TRIAL REGISTRATION: This trial was registered in the China Clinical Trial Registry (ChiCTR) ( ChiCTR2100043210 ) on 8th February, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Efficacy and Safety of Guizhi Decoction AssociatedFormulas for Allergic Rhinitis: A Systematic Review.

In this study, we aim to evaluate the efficacy and safety of Guizhi Decoction associated formulas for the treatment of allergic rhinitis. A total of seven online databases were searched to collect studies published up to Feb 23rd, 2020. Study quality of each included article was evaluated by the Cochrane Collaboration risk of bias tool. Systematic reviews were conducted based on the Cochrane systematic review method by using RevMan 5.3 Software. Among the included trials, Guizhi Decoction associated formulas alone (or plus Western medicine, or acupoint-based therapy) were main therapies in experimental groups. Interventions in control groups include Western medicine, Guizhi Decoction associated formulas alone, Chinese patent medicine, and placebo control. Primary outcomes in this study include recovery rate, accumulative marked effective rate, accumulative effective rate, and recurrence rate. Finally, 23 trials involving 2281 participants were included. Results of systematic reviews show that Guizhi Decoction and associated formulas alone, plus Western medicine or plus acupoint-based therapies, were significantly better compared with using Western medicine alone in terms of efficacy. In addition, the formulas plus nasal TCM fumigation therapy could improve effective rate for AR treatment compared to using the formulas alone. More types and cases of adverse events were reported in the control groups (Western medicine alone), but events of included trials were all mild and did not need specific medical intervention. More RCTs of high quality, and large sample size, with appropriate blinding methods or nonblinded pragmatic trials of Guizhi Decoction and associated formulas for AR are needed.

Effectiveness and safety of acupuncture for treatment of tinnitus: A protocol for systematic review and meta-analysis.

BACKGROUND: Tinnitus is a common disease in otolaryngology. In China, acupuncture has been used as a promising treatment for tinnitus. Yet, the specific effect and safety of acupuncture are still disputable. The ultimate goal of this paper is to formulate a protocol for systematic review and meta-analysis, which can be employed in assessing the benefits and safety of acupuncture on tinnitus. METHODS: Seven databases should be retrieved from their establishment until June 2020, including PubMed, Cochrane Central Register of Controlled Trials, Excerpt Medical Database, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure and Wan Fang Database. Randomized controlled trials of acupuncture treatment of tinnitus will be included. The experimental group is acupuncture or combined with additional treatment measures, and the control group is a placebo, sham acupuncture, Cognitive Behavioral Therapy, sound therapy, conventional medication, or same additional treatment. The clinical efficacy rate, Tinnitus Handicap Inventory, Tinnitus Questionnaire, visual analogue scale or other indicators are all concerned in the systematic evaluation of the program. Data collection, selection and extraction should be made separately by different researchers. The quality of the literature will be evaluated by the bias analysis table in the Cochrane Handbook, and Review Manager 5.3 software shall be applied to data analysis. RESULTS: This protocol has made a concrete plan to evaluate whether acupuncture is effective and safe in curing tinnitus. CONCLUSION: This protocol is suitable for evaluating the effectiveness and safety of acupuncture in curing tinnitus, and is helpful for subsequent evaluation.Open Science Framework Registration DOI: 10.17605/OSF.IO/85FCS.

Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer.

Abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in triple-negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti-cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF-κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss-128167, an inhibitor of SIRT6, dramatically attenuated anti-migration and anti-invasion effects of icariin. Transcriptomic analysis verified that impairment of NF-κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MDA-MB-231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF-κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.

The efficacy and safety of acupoint application combined with western medicine for allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupoint application combined with western medicine has been used for treating allergic rhinitis widely. However, the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis are unclear. This study aims to evaluate the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis. METHODS: Randomized controlled trials of acupoint application combined with western medicine for allergic rhinitis will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of acupoint application combined with western medicine for the treatment of allergic rhinitis. CONCLUSIONS: The findings of the study will provide helpful evidence for the efficacy and safety of acupoint application combined with western medicine in the treatment of allergic rhinitis, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/NSGJH.

The efficacy and safety of Chinese herbal compound in pediatric patients with allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: We design this study to assess the efficacy and safety of Chinese herbal compound for allergic rhinitis in children. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) will be searched from the establishment of each database to July 2020. Randomized controlled trials of Chinese herbal compound for the treatment of allergic rhinitis in children will be included. Two researchers will screen the literature, extract data, and assess the risk of bias independently. Statistical analysis will be performed in RevMan 5.3. RESULTS: This study will summarize high quality evidence of randomized controlled trials on exploring the efficacy and safety of Chinese herbal compound for allergic rhinitis in children. CONCLUSIONS: The findings of study will provide scientific evidence of the efficacy and safety of Chinese herbal compound for allergic rhinitis in children for clinician and further studies. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/Q5TRZ.

Clinical effects and safety of electroacupuncture for the treatment of allergic rhinitis: A protocol for systematic review.

BACKGROUND: As the therapy of acupuncture continues to expand, electroacupuncture is increasing used in allergic rhinitis prevention and therapy, and many studies have published that it is effective in the treatment of allergic rhinitis. However, it is unclear if electroacupuncture provides an evidence-based clinical benefit in the allergic rhinitis population. METHODS/DESIGN: We will conduct a systematic review of electroacupuncture and health-related outcomes in allergic rhinitis patients according to the Preferred Reporting Items for Systematic Reviews. The primary objective is to assess the impact of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on clinical outcomes relevant to allergic rhinitis patients, such as effective rate, life-quality evaluation, and adverse events. The Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies according to the Cochrane handbook. RESULTS: We will perform a meta-analysis using standard techniques for the outcomes. CONCLUSION: The results of this systematic review may highlight the gaps in our knowledge of the relevance of electroacupuncture after treatment or after follow-ups.PROSPERO registration number: PROSPERO CRD42018104080. (https://www.crd.york.ac.uk/PROSPERO/#recordDetails).

Traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy: A systematic review and meta-analysis of 31 RCTs.

In this study, we aim to evaluate the efficiency and safety of traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy. A total of eight online databases were searched to collect studies published up to February 2019. Study quality of each included article was evaluated by the Cochrane Collaboration risk of bias tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using the RevMan 5.3 software. Traditional Chinese medicine foot bath combined with acupoint massage was the main therapy in experimental group. Interventions in control groups include western medicine, oral traditional Chinese medicine, other symptomatic treatment of western medicine, and blank control. Primary outcomes in this study include sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), total effective rate, and neuropathic syndrome score. Finally, 31 trials involving 3284 participants were included. The results of systematic reviews and meta-analyses showed that traditional Chinese medicine foot bath combined with acupoint massage was significantly better compared with the control groups in terms of the total effective rate, SNCV, MNCV, and neuropathic syndrome score. No case of adverse effect was reported. These findings show that traditional Chinese medicine foot bath combined with acupoint massage may be safer and more effective for the treatment of DPN. However, due to the low methodological quality, further research with randomized controlled trials (RCTs) of higher quality is required to prove its efficacy and better evidence for clinical treatment.

The effectiveness of catgut implantation at acupoints for allergic rhinitis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Catgut implantation at acupoint (CIAA) is increasing used in allergic rhinitis therapy, and many studies have published that it is effective in the treatment of allergic rhinitis. However, it is controversy if CIAA can provide an evidence-based clinical benefit in the allergic rhinitis population. METHODS: We will go through 8 databases, and conduct a systematic review of CIAA and health-related outcomes in allergic rhinitis patients according to the Preferred Reporting Items for Systematic Reviews. The primary objective is to assess the impact of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on clinical outcomes relevant to allergic rhinitis patients, such as effective rate, life-quality evaluation, and adverse events. Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies according to the Cochrane handbook. RESULTS: The results of this systematic review will provide a synthesis of current evidence of CIAA and we have a specific opportunity to determine the efficacy and safety of it. CONCLUSION: This study will explore whether or not CIAA can be used as one of the nondrug therapies to prevent or treat allergic rhinitis.PROSPERO registration number: CRD42018095074 (https://www.crd.york.ac.uk/PROSPERO/#recordDetails).