Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, associated with abdominal pain, diarrhea, and bloody stools. In addition, joints, eyes, skin, or liver may also be infected.[1,2] UC occurs on the surface of the intestinal mucosa, starting the rectum and then spreading to the entire colon.[3,4] In recent years, it is becoming a global disease, publications showed that UC is not only occurring in Western countries,[5–7] but is also increasing in developing regions such as Asia and Africa, 1 study showed that there was a six-fold increase of incidence from 1986–1988 to 2004–2006 in Hong Kong. About the pathogenesis of UC, there is still no specific clinical conclusion, but most people think it is related to environment, genetics and immune.[4,9,10] In addition, recent studies focused on gastrointestinal barrier function and gut microbes which may play an important role in causing the disease.[11–13]
Now, medicine and surgery are the common therapies for UC.[4,14,15] However, recurring condition of UC and adverse effects are still problems to clinicians. [4,6,16] Some studies have showed that there is nausea, vomiting, headache, and anemia during oral medications.[14,15] Thus, safe and effective therapies are needed to be discovered. Acupuncture, a traditional Chinese treatment, demonstrates its superiority in UC. It increases beneficial flora in the body, such as Lactobacillus and Bifidobacterium, while inhibiting harmful flora, such as Bacteroidetes and Clostridium perfringens. In addition, animal and human experiments also had shown that stimulation of skin muscles can affect gastrointestinal function.[13,17,18] Acupoints catgut embedding evolved from acupuncture, it inherited the advantages of acupuncture which are definitive efficacy and few negative. Remarkably, it takes less time to heal but works for longer.[19,20] So we will organize, analyze, summarize studies that we could find on all databases about acupoints catgut embedding for UC to provide a clear and significant evidence for clinicians.
This protocol had been registered in International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), the registration number is INPLASY202040166, and the DOI number is 10.37766/inplasy2020.4.0166.
2.1 Inclusion criteria
2.1.1 Type of studies
We will only include randomized controlled trials (RCTs) of acupoints catgut embedding for UC, regardless of reviews, protocols, animal experiments, case studies, non-therapeutic clinical studies.
2.1.2 Types of participants
All participants were clinically diagnosed with UC, without restrictions on the TCM classification of UC, such as age, sex, disease duration, and race. But some special patients will not be included even if they meet the clinical criteria for UC, such as pregnant or nursing women, people with severe heart, liver or lung disease, those with the history of major trauma surgery, and local skin injuries at specific acupoints.
2.1.3 Type of intervention
188.8.131.52 Acupoints catgut embedding intervention
The observation group only include acupoints catgut embedding, and we will no restrictions on the equipment, frequency, course of the treatment, depth of needling, numbers of acupuncture points.
184.108.40.206 Comparison intervention
The control group chose to take Western medicine, enema, moxibustion, placebo, Chinese herbal medicine, or other treatments regularly.
2.2 Type of outcomes
2.2.1 Primary outcomes
The primary outcome is clinical effectiveness. It is based on the consensus opinion of diagnosis and therapy of UC proposed by the inflammatory bowel disease (IBD) group of the gastroenterology branch of Chinese medical association in 2018, and there is 3 levels: relief, effective, ineffective. The total effectiveness rate is a percentage, which is the ratio of the sum of the number of mitigators and effective people to the total number.
2.2.2 Secondary outcomes
The secondary outcomes include inflammatory cytokines, the Baron and Mayo scores of UC.[22,23] Inflammatory cytokines include IL-6, TNF-α, etc. The Baron score uses 0-4 to show the severity of the mucosa under colonoscopy. The Mayo score uses 0-3 to show a change of symptoms, including: stool frequency, rectum bleeding, findings of flexible proctosigmoidoscopy, and physicians global assessment. In addition, adverse reaction rate is an important indicator of safety.
2.3 Search Strategy
The computer will index RCTs trials on acupoints catgut embedding for UC published from build to December 31, 2019 and restrict the language to English and Chinese. We will search 7 databases, including 4 Chinese databases: VIP, Wanfang, CNKI, and the Chinese Biomedical Literature Database (CBM), and 3 English databases: the Web of Science, Pubmed, and Embase databases. Depending on the inclusion criteria, the following search words will be used: acupoint catgut embedding, acupoint therapy, ulcerative colitis, clinical trial, randomized controlled trial, and so on. (Table 1 shows the search strategy in Pubmed). Other databases will be searched in the same way as this one, or slightly modified to fit different databases.
2.4 Studies selection and data extraction
Firstly, all studies should be imported into Endnote in order to remove duplicates, and then 2 researchers will meticulously skim the title and abstract to include studies that meet the inclusion criteria. After this, 2 investigators will carefully read the full text of the included studies and then use a uniform data extraction table to extract important information. The table includes time, authors, interventions, outcomes, adverse effects, etc. At all steps, the 2 have to work independently and if there a disagreement between 2 people, it will be decided by a group. This selection process will follow the PRISMA guidelines as shown in Figure 1.
2.5 Assessment of risk of bias
Two researchers will evaluate the quality of RCTs by using the risk assessment tool recommended in Cochrane Handbook 5.3. This evaluation includes 6 factors: generation of random sequences, blinding of investigators and participants, blinding of study results, completeness of outcome data, selectivity in reporting of results, and other biases. If there are missing or unclear data, we will attempt to contact the original authors by email. If no reply is received or the authors have not saved the original data, we will analyze only the data that are useful in the literature or analyze the missing data in the discussion.
2.6 Data analysis
Revman 5.3 software will be used to combine and analyze the results of all the studies. This study involves bicategorical and continuous variables. The relative risk (RR) is used as an effect measure in the bicategorical variables and the mean differences (MD) in the continuous variables, and the software is able to obtain the point estimates and the 95% confidence interval (CI) for the 2. I2 is an important index for making the heterogeneity judgment. If I2 < 50%, a fixed effects model is used; if I2 ≧ 50%, a random effects model is used. For each combined analysis, the test of heterogeneity is measured using the cardinality statistic. If I2 ≧ 50%, substantial heterogeneity is considered to be present. If heterogeneity is present, we will analyze the cause through subgroup analysis and sensitivity analysis.
2.7 Grading the quality of evidence
We will evaluate the risk based on 4 areas: bias, inconsistency, indirectness, inaccuracy, and publication bias, and then grade the evaluate of results: high, moderate, low, and very low.
This is a systematic review and will not involve patients personal data, so ethical consent is not required.
In recent years, more and more researches have been devoted to UC, but there still is not a golden standard for treatment. Ulcerative colitis (UC) which characterize by recurring inflammation of the bowel not only brings financial strain, but also affects patients quality of life (QoL).[1,5,24] The theory of acupoints embedding is from Chinese medicine, which can balance the bodys yin and yang by continuously stimulating acupuncture points. It is getting more and more attention as a form of therapy. And acupoints embedding plays a role in osteoporosis, insomnia, obesity.[19,25,26] Acupoints embedding has been a routine treatment in Chinese, but there is still no clear evidence of its effectiveness and safety in UC. Therefore, it is significant to study these of acupoints embedding for UC. We will refine this protocol to get useful results and provide Chinese solutions to medical professionals around the world.
Conceptualization: Jinhua Lu, Lu Wang, Jun Zhou.
Data curation: Jinhua Lu.
Funding acquisition: Chun Zhong.
Investigation: Lu Wang, Bo Jia.
Methodology: Xu Chen, Jun Zhou.
Project administration: Jinhua Lu, Xu Chen.
Software: Jun Zhou.
Supervision: Chun Zhong.
Validation: Lu Wang.
Writing – original draft: Jinhua Lu, Lu Wang.
Writing – review & editing: Jun Zhou, Bo Jia.
. Yu YR, Rodriguez JR. Clinical presentation of Crohn's, ulcerative colitis, and indeterminate colitis: symptoms, extraintestinal manifestations, and disease phenotypes. Semin Pediatr Surg 2017;6:349–55.
. Ren PW, Yang WJ, Wang DD, et al. Kangfuxinye Enema combined with mesalamine for ulcerative colitis: a systematic review and GRADE approach. Evid Based Complement Alternat Med 2017;6019530.
. da Silva BC, Lyra AC, Rocha R, et al. Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis. World J Gastroenterol 2014;28:9458–67.
. Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet 2012;9853:1606–19.
. Wehkamp J, Stange EF. Recent advances and emerging therapies in the non-surgical management of ulcerative colitis. F1000Res 2018;1207–18.
. 2013;Adams SM, Bornemann PH. Ulcerative colitis American family physician. 87:699–705.
. Magro F, Gionchetti P, Eliakim R, et al. Third European Evidence-based consensus on diagnosis and management of ulcerative colitis. part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis 2017;6:649–70.
. Cheng-Xin Luo Z-HW, Zhen Yu, Wang Zhu-Jun, et al. Chinese research into severe ulcerative colitis has increased in quantity and complexity. World J Clin Cases 2018;35–43.
. Xu L, Lochhead P, Ko Y, et al. Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 2017;9:780–9.
. Vadstrup K, Alulis S, Borsi A, et al. Cost burden of Crohn's disease and ulcerative colitis in the 10-year period before diagnosis-a Danish register-based study from 2003-2015. Inflamm Bowel Dis 2019.
. Pastorelli L, De Salvo C, Mercado JR, et al. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol 2013;280:
. Nishida A, Inoue R, Inatomi O, et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol 2018;1:1–0.
. Song G, Fiocchi C, Achkar JP. Acupuncture in inflammatory bowel disease. Inflamm Bowel Dis 2019;7:1129–39.
. Katsanos KH, Papamichael K, Feuerstein JD, et al. Biological therapies in inflammatory bowel disease: beyond anti-TNF therapies. Clin Immunol 2019;9–14.
. Ford AC, Achkar JP, Khan KJ, et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol 2011;4:601–16.
. Yuan H, Zhang T, Huang S, et al. Six Gentlemen Decoction adding Aucklandia and Amomum (Xiangsha Liujunzi Tang) for the treatment of ulcerative colitis: a systematic review and meta-analysis of randomized clinical trials. Eur J Integr Med 2020.
. Xu Z, Li R, Zhu C, et al. Effect of acupuncture treatment for weight loss on gut flora in patients with simple obesity. Acupunct Med 2013;1:116–7.
. Stein DJ. Massage acupuncture, moxibustion, and other forms of complementary and alternative medicine in inflammatory bowel disease. Gastroenterol Clin North Am 2017;4:875–80.
. Huang F, Xie Y, Zhao S, et al. The effectiveness and safety of acupoint catgut embedding for the treatment of postmenopausal osteoporosis: a systematic review and meta-analysis. Evid Based Complement Alternat Med 2019;2673763.
. Huo J, Zhao J, Yuan Y, et al. Research status of the effect mechanism on catgut-point embedding therapy. Zhongguo Zhen Jiu 2017;11:1251–4.
. C. S. o. G. Inflammatory Bowel Disease Group. Chinese Medical Association, Chinese consensus on diagnosis and treatment of inflammatory bowel disease. Chin J Pract Intern Med 2018;796–813.
. Qiu Xinyun, Ma Jingjing, Jiao Chunhua, et al. Alterations in the mucosa-associated fungal microbiota in patients with ulcerative colitis 2017;107577–88.
. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol 2019;3:384–413.
. Roth LS, Chande N, Ponich T, et al. Predictors of disease severity in ulcerative colitis patients from Southwestern Ontario. World J Gastroenterol 2010;2:232–6.
. Xu F, Xuan LH, Zhou HJ, et al. Acupoint catgut embedding alleviates insomnia in different Chinese medicine syndrome types: a randomized controlled trial. Chin J Integr Med 2019;7:543–9.
. Chen IJ, Yeh YH, Hsu CH. Therapeutic effect of acupoint catgut embedding in abdominally obese women: a randomized, double-blind, placebo-controlled study. J Womens Health (Larchmt) 2018;6:782–90.