A protocol for systematic review and meta-analysis

h Abstract Background: Dental caries is a common disease under the action of many factors. Dental caries may occur in all age groups, among which children and adolescents are at high risk of dental caries. Early identification of the risk factors of dental caries is very important for clinical staff to prevent and intervene as soon as possible and reduce the incidence of dental caries. Although Chinese scholars have studied and summarized the risk factors of dental caries in children and adolescents, the conclusions are different. Therefore, in this study, meta-analysis was used to summarize the risk factors of dental caries in Chinese children and adolescents, and to explore the characteristics of high-risk groups of dental caries, so as to provide reference for early detection and prevention of dental caries. Methods: Medical specialty databases like PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, andWanfang Database were consistently and exhaustively searched. According to the method of evidence-based medicine, the inclusion and exclusion criteria were established, and the meta-analysis of all eligible research results was carried out by using Review Manager 5.3 software. Results: We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals. Conclusions: Our study was carried out to estimate the pooled prevalence of dental caries and its associated factors among Chinese children and adolescents. OSF Registration Number: DOI 10.17605/OSF.IO/RA9D6.


Introduction
Hepatocellular carcinoma (HCC) is the fifth largest malignant tumor in the world, and its incidence is increasing every year. [1] It is estimated that there will be more than 1 million new cases of HCC every year by the year of 2025, bringing a huge health burden to people all over the world. [2] China is a large country for HCC, [3] with 55% of the world's HCC patients in China. HCC has become the second leading cause of cancer death among Chinese residents. [4] Currently, a variety of approaches and disciplines coexist in the treatment of HCC using liver transplantation, surgical resection, minimally invasive interventions, and drug combination therapy. [5] As most of the patients are complicated with liver cirrhosis, or the symptoms are in the middle and late stage, the chance of surgical resection is only 20% to 30%. [6] Transarterial chemoembolization (TACE) has received increasing attention because of its minimally invasive, effective, and reproducible features. [7] Most of the patients treated with TACE are in the middle and advanced stage of HCC, of which immune function is low, coupled with the damage to local tissue caused by invasive operation and the inhibition of immune function caused by chemotherapeutic drugs, leading to postoperative infection of TACE and seriously affect the prognosis of patients with HCC. [8] Therefore, to explore the influencing factors of postoperative infection of HCC after TACE has become one of the problems that must be solved in the treatment of HCC patients with TACE.
Identifying the risk factors of infection after TACE is helpful to accurate infection prevention and controlling and solving the problem. Domestic and foreign reports on the prevention and treatment of infection after TACE are inconsistent, and so are the mentioned risk factors of infection. [9][10][11][12][13][14] In this study, to screen out the risk factors of infection and provide a reference basis for clinical prevention and reduction of post-TACE infection in patients with HCC, meta-analysis was conducted on the published literature on the risk factors of post-TACE infection in patients with HCC.

Study registration
This protocol has been registered on Open Science Framework grant number (OSF Registration number: DOI 10.17605/OSF. IO/26P5X). This report is based on the preferred reporting items for systematic review and meta-analysis protocols. [

Study selection
Two researchers independently screened and extracted data according to the inclusion and exclusion criteria of the literature. In case of disagreement, the 2 parties have discussed and resolved the matter or sought the opinions of a third party. The process of the selection is exhibited in Figure 1.

Data extraction
Data extraction includes: publication time, first author, type of study, sex, age, sample size, related risk factors, and so on.

Assessment of the risk of bias
Two researchers independently used the Newcastle-Ottawa scale [16] to evaluate the included study. The full score of 9 stars and ≥7 stars indicates that the quality of the literature is high. [17] After the evaluation, the 2 researchers discussed it. In case of disagreement, they have discussed and decided with the third researcher.

Data analysis
Meta-analysis was performed using RevMan 5.3 software. All the variables included in the study were binary variables, expressed by relative risk and 95% confidence interval. If there are no findings of statistical heterogeneity, the Mantel-Haenszel fixed effect model would be adopted for data synthesis. [18] If there is significant statistical heterogeneity, we would apply the DerSimonian-Laird random effect model. [19]

Assessment of heterogeneity
The magnitude of heterogeneity in the results was determined by x2 test and I 2 quantitative analysis. When P < .1, and (or) I 2 > 50%, the random effect model would be adopted for the combined analysis. Otherwise, the fixed effect model would be adopted.

Subgroup analysis
Subgroup analysis was conducted according to race, literature quality, and sample size.

Sensitivity analysis
The stability of the results was tested by removing the maximum weight from the study and looking at the change in the amount of effect.

Assessment of reporting biases
If no less than 10 articles are included, we would use funnel chart to analyze the publication bias. [20] 2.12. Management of missing data The object of the study is the defects of the original data. We contacted the author by email and asked for the original data. If the original data was not available, we analyze the existing data. The content of this article do not involve moral approval or ethical review and will be presented in print or at relevant conferences.

Discussion
TACE therapy has become a recognized nonoperative therapy at home and abroad. [21,22] The injection of chemotherapy drugs and embolic drugs into the hepatic artery of HCC patients through a catheter is conducive to increasing the local concentration of drugs, effectively blocking the blood supply, and killing cancer cells, thereby improving the survival quality of patients with advanced HCC who have missed the chance of surgery. [23][24][25][26] Puncture, intubation, and drug injection should be performed during TACE, which is easy to cause certain trauma to the respiratory tract, digestive tract, skin, and soft tissue of the patients. In addition, chemotherapeutic drugs can lead to side effects such as nausea, vomiting, and myelosuppression, which can reduce the body resistance and cause infection. According to the Shawker study, the incidence of transient fine bacterial infection associated with TACE was 4%, while that of liver abscess was 1.4%. [27] The death rate of liver abscess after TACE was 13.4% to 50.0% without proper treatment. [9,[28][29][30] In clinic, the ratio of application of prophylactic antibiotics in TACE intervention is confused, and the types and time of application are different. Therefore, it is important to explore the risk factors of infectious complications after TACE for HCC and to find ways to reduce or avoid infectious complications after TACE. In this study, meta-analysis was used to analyze the risk factors of post-TACE infection in patients with HCC, which provided a basis for the prevention and treatment of post-TACE infection.

Author contributions
Data collection: Zhipeng Shi.