Li Lin, Xiao-Ning Yan, Wen-Bin Li, Yi-Ding Zhao

1.The First Clinical Medical College of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, 712046 China

2.Department of Dermatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, 710004 China

Keywords:

ABSTRACT

1. Introduction

Herpes zoster is a viral skin disease, which is called "snake string sores", "loin-burning fiery pill" and "sandwich sores" by Chinese medicine. Western medicine believes that this disease is an acute inflammatory non-infectious skin disease caused by the resurgence of latent varicella-zoster virus. The lesions are mainly clustered small blisters, which are unilaterally distributed along the nerve direction, usually accompanied by obvious Nerve pain [1]. The disease is caused by dampness, heat and poison, invading the blood to form poison, heat and poison are confined to the skin, the meridian is blocked, and the blood and blood are constricted. Traditional Chinese medicine believes that the cause of this disease is emotional trauma, resulting in hepatobiliary fire, or spleen dampness and fire, damp heat content, and external poisoning induced [2]. The treatment of Western medicine often uses anti-viral, nutritional nerve and other methods, but the long-term effect is not obvious. In addition to the traditional Chinese medicine decoction, traditional Chinese medicine treatment also has unique external treatment methods such as fire acupuncture, electroacupuncture, cupping, acupoint injection, pricking bloodletting, moxibustion, etc. [3]. Among them, pricking bloodletting therapy is more common in clinical treatment of herpes zoster, and has the characteristics of definite curative effect and no toxic and side effects [4]. At present, many studies have shown that bloodletting with pricking blood has obvious clinical effects on treating herpes zoster, relieving pain, and improving the quality of life of patients, but there is no corresponding systematic review. In this paper, a meta-analysis of the clinical efficacy of pricking bloodletting therapy for herpes zoster is used to provide evidence-based support for pricking bloodletting therapy for herpes zoster.

2. Materials and methods

2.1 Literature search

The computer searches CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library databases, and the search time limit is set from the construction of the library to December 31, 2019. Using free words and keywords, Chinese search uses "herpes zoster", "snake string sores", "bleeding blood", "thorn", and "random" as keywords to conduct a combined search. The English search uses "Her pes zoster, HZ", "Spinal bloodletting", "Random" as keywords.

2.2 Inclusion criteria

(1) Type of literature study: a randomized controlled trial consisting of a treatment group and a control group, and a clear evaluation result has been obtained. Whether blind or not. (2) Intervention measures: the experimental group is treated with pricking bloodletting alone or pricking bloodletting as the main treatment, and the control group is given other conventional treatments. (3) Research objects: patients with a definite diagnosis of herpes zoster, regardless of age or gender. (4) Curative effect indexes: curative effect, VAS score, scab, scab, analgesic, bleb-stopping time, and incidence of sequelae neuralgia.

2.3 Exclusion criteria

(1) Unrelated literature; (2) Non-clinical studies (animal experiments, reviews, experience, etc.); (3) Non-randomized controlled studies; (3) Treatment group interventions that are not suitable for bloodletting or control are not suitable; (4 ) Duplicate literature.

2.4 Data extraction

Based on the inclusion and exclusion criteria, two researchers independently screened the literature, extracted the data, crosschecked, and evaluated the quality of the literature. When there were differences, a third party intervened in the discussion and made a decision. The extracted contents include: author name, publication time, total number of cases, type of paper, control method, intervention measures, treatment course, curative effect evaluation index, adverse events, etc.

2.5 Literature quality evaluation

The literature quality was evaluated according to the bias risk evaluation standard provided by Cochrane Handbook 5.1.0. Bias risk evaluation criteria include random sequence generation, allocation concealment, blind method, data incompleteness, selective reporting, and other biases. The results are expressed as low risk, unclear, and high risk according to the above indicators.

2.6 Statistical methods

Use RevMan5.3 software to statistically analyze the collected data and select a random effect model or a fixed effect model according to whether there is heterogeneity. When the heterogeneity is large, use Stata15 software for sensitivity analysis and use OR (95% CI) It is a binary variable statistic, and MD (95% CI) is a continuous variable statistic. And through the funnel chart analysis to determine whether the research is biased.

3. Results

3.1 Literature search results

A total of 416 articles were initially searched, 167 duplicate articles were screened using NoteExpress software, 49 irrelevant articles were read after reading the title and abstract, and 20 articles in the review category and non-RCT category were excluded. , 152 documents that do not meet the inclusion criteria, such as incomplete indicators, exclude 7 documents that are too complicated or of low quality. A total of 21 meta-analysis literatures can be included [4-13]. A total of 21 RCTs were included in the literature, including 1533 patients, including 778 in the treatment group and 755 in the experimental group. The specific document retrieval process is shown in Figure 1.

3.2 Including research features

A total of 21 articles were included to extract the general conditions required for this analysis: the first author of the literature and the year of publication, the sample size of the experimental group and the control group, the two groups of interventions, treatment course, and outcome indicators. The maximum sample size included in the study was 150, and the minimum sample size was 32; the interventions in the treatment group were mostly pricking bloodletting or pricking bloodletting-based treatment. 4 articles in the control group were treated with acupuncture and 1 document was treated with traditional Chinese medicine The remaining 16 articles are all treated with Western medicines, and the commonly used drugs are acyclovir, valacyclovir, mecobalamin, etc., 2 of which are combined with Western hormone therapy. The duration of treatment for all studies was 5-15 days, 19 of the outcome indicators reported the efficacy, 6 articles reported the time of scab, 2 articles reported the time of scab, 7 articles reported the time of pain relief, 7 One article reported the time to stop the blister, 9 articles reported the VAS score, 5 articles mentioned the follow-up results, and 2 articles monitored the adverse reactions. The specific research characteristics included in the literature are shown in Table 1.

3.3 Quality evaluation of included research methods

Eleven of the 21 articles mentioned specific random methods, of which 8 were allocated according to the random number table method, 1 was drawn by lot, 1 was ordered by treatment, and 1 was grouped by random sampling. The remaining 10 articles all mention random but no specific method. None of the 21 articles mentioned blinding and allocation concealment. One article mentioned shedding but did not affect the analysis. The results of the selective reports were unclear. The treatment period of one article was 5 days, considering the risk of bias and other biases The source is unclear. The specific risk of bias is summarized in Figure 2.

Figure 2 Bias risk map Figure 2 Bias risk map

3.4 Meta analysis

3.4.1 Total efficiency analysis

A total of 19 articles in 21 articles report the efficacy of the experimental group and the control group, and draw a forest map based on the data (see Figure 3). The results p = 0.99, I2 = 0 indicates that the literature is homogenous, using a fixed effect model Combined effect size analysis, OR = 5.11, 95% CI: (3.48, 7.50), Z= 8.33, P <0.00001 shows that pricking bloodletting treatment for herpes zoster has obvious advantages over conventional treatment, and the conclusion is statistically significant.

Table 1 Features of included studies

Figure 3 Total effective forest map

Considering the different interventions included in the study, a subgroup analysis was conducted on the included studies of different interventions, and the included studies were divided into subgroup 1 (puncture bleeding and acupuncture therapy) and subgroup 2 (puncture bleeding and VS) Traditional Chinese Medicine), subgroup 3 (puncture bloodletting VS Western medicine routine), and draw a forest map (see Figure 4). Subgroup 1 results: OR = 5.17, 95% CI: 3.32, 8.04, P = 0.98, I2 = 0%, subgroup 2 results OR = 2.25, 95% CI: 0.51,9.99, subgroup 3 results OR = 6.42, 95% CI: 2.54, 16.20, P = 0.86, I2 = 0%. This indicates that bloodletting and bloodletting therapy has obvious advantages over conventional Western medicine and acupuncture, and the results are statistically significant (p <0.0001). Since the subgroup 2 bloodletting and traditional Chinese medicine comparison of curative effect is less included in the literature, it is not statistically significant. Drawing an inverted funnel plot based on the results suggests that the results are basically symmetrical, indicating that the results are not significantly biased.

Figure 4 Subgroup analysis forest map

Figure 5 Inverted funnel plot for subgroup analysis

3.4.2 VAS score

A total of 9 articles in 21 articles report on the VAS score, and its effect indicators include weighted mean difference (WMD) and standardized mean difference (SMD), which can be analyzed as continuous variable data. The forest chart shows 3 studies The intersection with the invalid line indicates that it is not statistically significant, and the remaining 6 articles have statistical significance on the left side of the invalid line. The 95% CI is (-2.46, -1.99), the test of the combined effect size, Z = 18.73, P <0.000 01, I2 = 98%, indicating that the included articles are more heterogeneous, and the random effect model is used to combine the effect size , And conducted a meta-regression analysis, and found that the year of publication, case control ratio and other factors were not statistically significant. The results of sensitivity analysis using Stata15 software showed that the heterogeneity came from the research published by Pan Dong, and after removing this document, the heterogeneity Sexuality is significantly reduced. This indicates that the improvement of the VAS pain score in the bloodletting and bleeding group is significantly better than that of the conventional treatment group, and the difference is statistically significant, as shown in Figure 3-5.

Figure 6 VAS score forest map

Figure 7 VAS score sensitivity analysis

3.4.3 Remission of symptoms and signs

A total of 7 articles reported the effect on scab time [MD-2.23, 95% CI (-2.53, -1.60), p <0.00001]; a total of 2 articles reported the effect of two groups on the scab time [MD- 2.06, 95% CI (-2.69, -1.43), p <0.00001]; a total of 7 literatures reported the effect on pain relief time [MD-2.67, 95% CI (-2.89, -2.45), p <0.00001]; total 7 articles reported the effect on the time of blister arrest [MD-1.21, 95% CI (-1.98, -0.44), p = 0.002], the results showed that the blood-letting and bleeding group was better than other conventional treatment groups in the time of scab removal The difference was statistically significant and the heterogeneity between studies was low (p = 0.26, I2 = 20%). Puncture bloodletting therapy has advantages in symptom scores such as crusting time, blistering time, and pain relief time, and the difference is statistically significant. However, the results show that the heterogeneity between the studies is high. After excluding the literature one by one and combining and analyzing with the random effect model, no clear source has been found. It may be that the studies included in this article are all TCM literature, and the quality level is not related. Research with higher quality literature.

3.4.4 The incidence and time of post-neural neuralgia

A total of 5 literatures mentioned follow-up of patients and reported follow-up results, the follow-up time was 1-3 months. The analysis of the extracted data showed that p = 0.72, I2 = 0%, indicating that the homogeneity between the studies is high. After using the fixed effect model to combine the effect size, OR = 0.21, 95% CI: (0.09, 0.51), Z = 3.48, P = 0.0005 see Figure 3-5. The results showed that the incidence of sequelae neuralgia in the pricking bloodletting group was significantly lower than that in the western medicine group, and the difference was statistically significant. The funnel chart shows that the literature is basically symmetrical and there is no obvious publication bias.

Figure 8 Forest map of sequelae neuralgia

Figure 9 PHN neuralgia bias

4. Discussion

Shingles is a cluster of red papules on the skin, which quickly turns into piles of millet to mung bean large herpes, which travels along the nerves. It occurs more frequently on one side, does not exceed the median line, and can occur before or during the rash. There is pain, and some of the rashes can still be left behind after the rash is healed. Chinese medicine believes that the disease is caused by damp heat and poison, invading the blood and forming poison, heat and poison in the skin, meridian block, qi and blood stasis. Western medicine believes that the disease is caused by a viral infection [26]. Pricking Bloodletting Therapy refers to piercing acupuncture points or superficial blood collaterals of the human body with a needle such as a triangular prism, and releasing appropriate amounts of blood to relieve heat and detoxify, reconcile qi and blood, promote blood circulation and remove blood stasis, pass through the collaterals, clear the heat, and adjust. The internal organs of the human body make the internal organs harmonious, cure diseases and cure diseases [27]. And the toxic and side effects are small, and the effect is fast. It is a common treatment method for Chinese herpes zoster.

In this paper, through observation of multiple indexes of bloodletting and bloodletting to treat herpes zoster, it is found that bloodletting and bloodletting is more effective in treating herpes zoster than other conventional therapies. There are also obvious advantages in terms of remission and the incidence of sequelae neuralgia. In the two studies on monitoring and reporting of adverse reactions, the results of Zhao Bohua and others showed that there were no obvious adverse reactions in the experimental group, and the control group was treated with conventional Western medicine. After 5-7 days, a total of 10 patients experienced insomnia and other adverse reactions were relieved by taking estazolam. In the study of Li Yangfan and others, 3 patients in each of the treatment combination control group developed dizziness and drowsiness and other adverse reactions were relieved without treatment. This indicates that there are fewer adverse events in the bloodletting and bloodletting treatment for herpes zoster. The purpose of this article is to compare all the indicators in the treatment of herpes zoster with traditional bloodletting and pricking blood therapy to Western medicine or other conventional therapies, and to systematically evaluate the treatment of herpes zoster with bloodletting and pricking blood. For reference. However, there are shortcomings in this article that all the included documents are Chinese documents, and the quality is uneven, which needs to be further proved by the study of higher quality large samples.