This research scheme has been registered and reviewed on the international prospective register of systematic reviews (PROSPERO). We will prepare this scheme according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement . A detailed explanation document will be used as an assist guidance . We will further proceed with the work according to the worklist of PRISMA .
In this study, we will extract the information from the original studies, including PICO, study design, grouping, and time frame. We will record the year, language, publication status and type of the study.
All the clinical randomized controlled trials(RCT) involving the effect of acupuncture therapy on serum cytokines will be considered according to the inclusion and exclusion criteria in the review.
To obtain the results of a large-scale sample, this study will involve all adults(over 18 years old) regardless of race, age, gender or comorbidity in the original studies. Besides, this work will not limit the disease or condition types (whether acute or chronic diseases or surgery).
Any observation and comparison of serum inflammatory factors before and after acupuncture treatment(including normal acupuncture and electroacupuncture) will be included in this study. It is worth noting that acupuncture intervention must serve as treatment, so studies involving acupuncture for anesthesia or cosmetic purposes will not be included.
Primary Outcomes. Major serum cytokines: chemokines, interferons, interleukins, lymphokines, monokines, tumor necrosis factors.
Secondary Outcomes. Pain score, quality of life score, serum C-reactive protein level, improvement of primary diseases and side effects.
We will include articles reported in the English and Chinese. Possibly relevant studies in other languages will be displayed in an list.
Information sources and search strategy
We will search three English databases (PubMed, EMBASE and Cochrane Library) and four Chinese databases (Chinese biomedical literature database, VIP database for Chinese technical periods, China National Knowledge Infrastructure, and Wanfang). An example of the search protocol in PubMed is attached in the supporting materials(supplemental table 1). We will also review the references of the retrieved literature to further screen the studies that meet the inclusion criteria. We will manage to include more grey literature by contacting the authors according to their information on the trials’ registration websites(clinicaltrials and Chinese clinical trial registry). Duplicate data and studies will be strictly excluded.
In order to obtain eligible literature, we will import the titles and abstracts of all literature obtained according to the retrieval strategy into Endnote software (Version X9). After eliminating duplicate literature, two researchers will independently screen the literature based on the title, abstract and full text according to the inclusion criteria and exclusion criteria. After the screening work is completed, all controversies will be resolved by another researcher.
Data extraction and synthesis
Two researchers will independently extract data from the included literature by using the specific software Review Manager Version 5.4 (The Cochrane Collaboration, 2020) according to the requirements of PRISMA to reduce possible bias. The controversies will be finally resolved by a third researcher. Considering that we do not limit the time span, we will not contact the original author to further confirm the small amount of missing or unclear data. The extracted data are supposed to include the following information:
General information: title, first author, correspondence information, funding, publishing year, publisher.
Participants: age, nationality, race, gender, treatment purpose (disease or surgery), duration of suffering.
Intervention: treatment type, treatment period, treatment frequency, combined drugs, other details.
Outcomes: Primary outcomes (primary cytokines in peripheral circulating blood: Chemokines, Interferons, Interleukins, Lymphokines, Monokines, Tumor Necrosis Factors). Secondary outcomes. Pain scores, quality of life score, serum C-reactive protein, improvement of primary diseases and side effects. (if exist).
After data extraction, we will synthesize the data by quantitative or qualitative comparison. Based on our primary investigation, a quantitative analysis is going to be executed.
Assessment of heterogeneity and publication bias
Since this analysis is expected to include multiple studies, different evaluation methods may be used. We will evaluate the heterogeneity of these studies by using the I2 test. An I2 test value higher than 50% is considered to indicate heterogeneity. Otherwise, it is considered that there is no heterogeneity between these studies. If the literature is heterogeneous, we will re-examine the original data in the literature, and conduct subgroup analysis, regression analysis, and sensitivity analysis to identify the source of heterogeneity.
If the source of heterogeneity cannot be determined, we will change to descriptive statistics.
Based on the nature and quantity of data, we will show the publication bias of the included literature in the form of forest charts and funnel charts.
Assessment of certainty of evidence
To evaluate the quality of these studies, we will follow the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by using GRADE profiler software Version 3.6 (McMaster University, ON, Canada). Finally, a summary-of-finding list will be generated by the software to rank the candidate studies based on the indirectness, inconsistency, imprecision, and risk of publication bias of the review results.