THE SCOPING REVIEW OF CHINESE AND WESTERN MEDICINE TREATMENT OF DIABETIC FOOT IN ASIA

Diabetic foot is a common and serious chronic complication of diabetes due to the simultaneous occurrence of diabetic peripheral neuropathy and vascular lesion. Among all complications, foot ulcers in diabetic ulcers account for the first place among the reasons for hospitalization and treatment of diabetic patients. 15% of diabetic patients may have foot diseases, and 85% of patients may have foot ulcers as the cause of amputation. Diabetic foot seriously affects the quality of life of patients. Although there are many methods to treat diabetic foot, the therapeutic effect of diabetic foot is not ideal in general. The main purpose of this scoping review was analyzing the existing loopholes of researches on diabetic foot in Asia. Used Pub Med, CNKI, Wangfang data, CQVIP to search and select 5 traditional Chinese medicine literatures and 5 western medicine literatures, through the comparison of various conditions between literatures to analyze the lack of research. Ten pieces of literature were retained through 183 records and included 9 drugs or decoction, they were adipose-derived stem cell–hydrogel complex, hyperbaric oxygen therapy, Xenogeneic (porcine) a cellular dermal matrix, alprostadil, salvia miltiorrhiza polyphenols for injection and collagen sponge, Taohong Siwu Decoction, Simiao Yong an Decoction, Jiawei Simiao Yong an Decoction, Huangqi Guizhi Wuwu Tang, and Wuwei Xiaodu Drink. The obvious problems found by this scoping review were the quantity and quality deficiency of the research in the diabetic foot in Asia. Scoping review is an effective method of evidence identification and synthesis, which can provide a basis for the further development of a certain field. In the further study of the diabetic foot, more attention should be paid to the verification of experimental data as well as the feasibility of the researches on oral drugs.


INTRODUCTION
Diabetic foot is a general term for a series of clinical manifestations of the foot caused by peripheral vascular disease, neuropathy, and infection in diabetic patients due to long-term and chronically elevated blood glucose, including foot ulcers, infection and deep tissue destruction. Once diabetic foot occurs, it is difficult to treat, with the high cost and poor prognosis. If the treatment is not timely or adequate, there is often a risk of amputation. Diabetic foot is one of the main complications of diabetes. According to the IDF diabetes map (9 th edition), about 463 million adults worldwide suffered from diabetes in 2019, and it is estimated that 700 million people could have diabetes by 2045 Figure 1 shows the global distribution of diabetes patients in 2019 1 . At the national level, the top three countries with diabetes in 2019 were China, India and the United States, with about 118 million, 78 million and 30 million diabetics (20-79 years old), respectively. And China and the United States also have a high expenditure with diabetics 1. Figure 2 shows the top 10 countries with the highest number of diabetes in 2019. Based on the above data, the number of diabetes patients in Asia is the first in the world. In global diabetes research, the study of American forces dominates. Diabetes research in China in the number of papers and patents statistics on has and Germany are close to, or more than these countries, but from the paper quality in new drug research and clinical research level, with Europe and the United States and other developed countries have a certain gap 2 . Because Asian countries the number of diabetes and the number of concurrent with diabetic foot ulcers are more, but at this stage of clinical research level is not high, the number of new drug research, research direction is fuzzy, therefore decided to Asian drug therapy for diabetic foot ulcers group scoping review, to provide reference for drug treatment for the future research direction. A scoped review is a design approach "to rapidly map the key concepts underpinning the research field as well as the key resources and types of available evidence" 3 . This scoping review is to summarize the current clinical research literature on Chinese medicine and western medicine for diabetic foot treatment in Asia, so as to provide new ideas for the future research direction of diabetic foot medicine in Asia and facilitate the further development of research.

Eligibility Criteria
Literature including nearly five years (2015-2019) in four databases of free text articles. Literature type limited to the clinical trial. Intervention limited to drugtreatment. Study design limited to randomized controlled trials. The population limit for Asians, any gender, most was over 35 years old, and the study population was limited to 30 or more (N > 30).

Search Strategy
The databases used are CNKI (China National Knowledge Infrastructure), PubMed and CQVIP (China Science and Technology Journal Database), Wanfang Data Knowledge Service Platform. In the process of visual search of three databases, the search of the literature will be stopped until the literature in the database does not conform to the content of the literature required by the re problem which is researched. The search strategy is based on the review of the clinical research progress of Chinese and western medicine in treating diabetic foot and the management of diabetic foot ulcers and extends to the differences in the treatment of diabetic foot with Chinese and western medicine 4,5 . The common terms used in different databases include diabetic foot (including diabetes foot); broad terms such as nonsurgical debridement agents; narrower terms such as hydrogels. The literature published after 2015 was searched until all the required literature was retrieved.

Study Selection
Three researchers examined the search records of the first layer cooperatively, at the first place screening by the published date, title and abstract, secondly, by full text. When a disagreement arises between the researchers, the controversial papers should first be retained and then screened according to drug type of the papers as well asa comparison of the literature describing the same classification of drugs.

Charting the Data
Before the data analysis, two articles were used to discuss the process of data analysis. After collecting the data, three researchers summarized, analyzed and compared, and agreed on the types of data items including drug therapy, study method, inclusion and exclusion criteria of participants (not included in the report) and treatment results.

RESULTS
The purpose of this scoping review is to summarize the existing studies on drug therapy (western medicine and Chinese medicine) for diabetic foot patients in Asia, so as to provide references for future research directions on drug therapy and the combination of Chinese and western medicine. Figure 3 shows the process of identifying, screening, including, and excluding literature.

Components of Drug Therapy
After screening, 10 articles and 9 drugs for treating diabetic foot ulcers were retained. Taohong Siwu Decoction has two pieces of literature, while other medicines only have one. Table 1 shows the nine drugs and their effects in treating diabetic foot.

Experimental design
The experimental designs were based on the route of drug use, different experimental sites, and the degree of disease. Comparing different experimental designs needed to be done from different aspects, thus the following Table 2 and Table 3 discussed the ten literature from the number of participants, age of participants, experimental location, country, degree of the lesion in patients and specific experimental operation. Of the 44 participants, 25 were assigned to the experimental group and 19 were assigned to the matched group. 3 participants in the experimental group and 2 participants in the matched group were excluded because they did not reach high blood glucose levels (>450). Patients of both groups were treated with 3% hydrogen peroxide and a saline solution to remove dirt and other debris from their ulcers, and both groups were covered with polyurethane foam. The difference between the two groups' patients was that the experimental group used allograft ASC sheets as the primary dressing and the matched group used mesh polyurethane films with silicone adhesives as the primary wound dressing. In both groups, drugs were changed once a week. Hyperbaric Oxygen Therapy 7 Blood tests were performed on all patients to detect HbAlc levels, white blood cell counts and serum creatinine levels before debridement, and they were divided into two groups. Among them, the experimental group conducted ten courses of HBOT (One session of HBOT uses oxygen at 2.4 ATA for 90 minutes per day at several hyperbaric chambers) and the matched group adopted the standard treatment. Five courses of treatment per week, it took two weeks altogether. Xenogeneic(po rcine) acellular dermal matrix 8 All participants were given anti-infection, nutritional support treatment, diabetes specialist guidance diabetic diet, insulin treatment, monitoring and regulating blood sugar，wound secretion culture-sensitive antibiotics guide treatment as well as other comprehensive systemic treatment. The wound surface was washed with 1.5% hydrogen peroxide solution, iodinevolt solution and 0.9% sodium chloride solution in turn, and the wound surface was wrapped and fixed with gauze, and the dressing was changed once a day. Experimental group: One week later, under subarachnoid anesthesia and spinal anesthesia, the Sonoca180 low-frequency ultrasonic debridement device (produced by Germany surin-cieser company) was applied to debridement of the diabetic foot, and the wound surface was expanded and created stealthily. Matched group: The matched group was treated with sulfadiazine silver cream (1% sulfadiazine silver, 60 g, Guangdong Hengjian pharmaceutical co., LTD.). Alprostadil 9 Of the 100 participants, 50 were assigned to the experimental group and 50 to the matched group. Patients in both groups received conventional treatment and were treated with hypoglycemic drugs. The wounds were washed with normal saline and hydrogen peroxide, and the wound was wrapped with iodoform gauze. Patients were treated for 2 weeks and the results were reviewed. Salvia miltiorrhiza polyphenols for injection and collagen sponge 10 Of the 115 participants, 60 were assigned to the matched group and 55 to the experimental group. Patients in both groups were treated with conventional type 2 diabetic foot therapy, wound cleaning, and spraying 0.9% sodium chloride solution on the wound with the same type of antibiotic. The difference between the two groups was that the patients in the experimental group were treated with collagen dressing, dissolved 200 mg Danshen polyphenols in 5% glucose injection, and given intravenous infusion once a day. For four weeks of one course of treatment, patients' ulcer recovery before and after treatment and during treatment were observed after two courses of treatment. TaohongSiwu Decoction 11 All participants received basic treatment for diabetes, including diet control, insulin control of blood glucose, and decompression therapy. Foot superficial ulcer was disinfected with iodophor, local antibiotics were given wet compress, and on this basis, the experimental group was given Tao Hong Siwu Decoction(Tao Ren 30g, Hong Hua 30g, Dang Gui 30g, Chuanxiong 20g, Shu Di Huang 20g, Shen Jin Cao 30g, Hai Feng Teng 30g, Ai Ye 30g), which was fried and soaked in feet once a day for 15 minutes each time. Simiao Yong＇an Decoction 13 All patients were given diabetes education and a diabetic diet, and the experimental group was given Simiao Yong＇an Decoction (Dang Gui 30g, Xuan Shen 15g, Huang Qi 15g, Jin Yin Hua 15g, Ji Xue Teng 15g, Gan Cao 6g) which was fried in water, one dose per day and separated one dose for two times. In the meantime, the matched group was not given any medication.

Jiawei Simiao Yong＇an Decoction 12
Of the 86 participants, 43 were assigned to the experimental group and 43 to the matched group. Patients in the two groups were first given conventional treatment to control their blood glucose, and the same antibiotics were selected to control infection. Physical methods and drugs were used to improve the blood circulation in the lower extremities of the patients. The ulcer of the patients was changed once a day and the patients were given cilostazol tablets twice a day, 100mg each time.

HuangqiGuiZhi Wuwu Tang 14
Of the 128 participants, 64 were assigned to the experimental group and 64 to the matched group. Two groups of patients simultaneously received non-drug treatment, control of blood glucose, blood pressure, blood lipid, and other drug treatment. Patients were given probucol tablets at breakfast and dinner with 0.5g each time. Oral aspirin enteric-coated tablets were taken 100mg per day for 3 months. Intravenous infusion of alprostadil injection, 10 mg a day, plus 10ml normal saline, continuous injection for 15 days, 15 days rest for a course of treatment, a total of 3 courses of treatment. Patients with hot chest, palm and foot were added to Xuan Shen 15g and Mu Dan Pi 15g. Soak the medicine in water for 30min and cook it twice a day.

Wuwei Xiaodu Drink 15
Of the 150 participants, 75 were assigned to the experimental group and 75 to the control group. Patients in the two groups were given insulin injection at the same time, 20 units a day, and subcutaneously injected at 3 times in the morning, the middle and the evening 30 minutes before the meal, and the patients were given tissue engineering full-layer skin treatment. The difference between the two groups was that the experimental group was treated with Wuwei Xiaodu drink

DISCUSSION
Nine different Chinese medicines and western medicines were used to treat diabetic foot. In the above paragraphs, different Chinese medicines and western medicines were compared one by one. Next, this section will analyze 10 articles used to determine the research direction of treating diabetic foot in the future. In "The Potential of Allogeneic Adipose-Derived Stem cells -Hydrogel Complex for Treating Diabetic Foot Ulcers" 6 , the author said research is likely to be the first report to prove Allogeneic Adipose-Derived Stem Cell for the effectiveness of the treatment of diabetic foot ulcers. So, the study has limitations, the action mechanism of allogeneic adipose-derived stem cells still need to be further confirmed. In the study of shortduration hyperbaric oxygen therapy 7 , the author found that the glucose metabolism and the mechanism of improving human renal function were still unclear, and further studies were needed to determine the effect of short-duration hyperbaric oxygen therapy on diabetic foot ulcer patients. When using the xenogeneic (porcine) acellular dermal matrix to repair diabetic foot ulcers 8 , it can not only shorten the wound healing time, reduce the number of dressing changes, but also reduce the psychological and economic burden of patients and reduce the infection rate. At the same time, it has wide sources, simple operation, and low price, and is worthy of clinical promotion. In the study of alprostadil 9 , it has been determined that alprostadil has a better clinical effect and higher safety. Research shows that alprostadil is worthy of extensive application in clinical practice. In the process of studying salvia miltiorrhiza polyphenols for injection and collagen sponge 10 , the direct therapeutic effect of salvianolic on diabetic foot still needs further study, but it can improve microcirculation, prevent microthrombosis, regulate vascular endothelial dysfunction and other effects have been able to play a positive role in the treatment of diabetic foot. The combination of salvianolic and collagen sponge played an active role in the treatment and healing of diabetic foot. In the process of studying of the Taohong Siwu Decoction 11 , it has proved flavoured Taohong Siwu Decoction combined thioctic acid injection on diabetic foot has good effect, but the author use samples is limited, did not add the diabetic foot higher severity of patients, so in further research, more data are needed to determine the curative effect of Taohong Siwu Decoction. In the two articles of Simiao Yong＇an Decoction, Jia Wei Simiao Yong an Decoction can improve the microvascular lesions of diabetic foot by repairing the damaged intima of arteries 12 , inhibiting inflammation 13 , and so on, so that diabetic foot can be relieved. However, the literature on Simiao Yong 'an Decoction is still very limited, and the molecular mechanism of Simiao Yong 'an Decoction remains to be further studied. In the study of Huangqi Guizhi Wuwu Tang  GuizhiWuwu drink could improve the vascular function and hemodynamics of the lower extremities, reduce the injury of vascular endothelial cells, and thus play a role in alleviating the progression of diabetic lower extremity vascular diseases. It is worthy of clinical promotion and application of such drugs. In the process of studying Wuwei Xiaodu drink combined with tissue engineering full-thickness skin 15 , it has been determined that it can improve the efficacy, improve the patient's condition and play an anti-inflammatory role without obvious adverse reactions. Therefore, it is a drug worthy of clinical promotion.

CONCLUSION
The purpose of the scoping review is to review the general situation of a certain research field, based on this paper; the principal contradiction discussed in this paper is comparing the researches of partial traditional Chinese medicine and western medicine treatment of the diabetic foot. Through studied and thought of these ten pieces of literature, some problems emerged obviously. The first problem was that the literature of diabetic foot in China was deficient. On the one hand, the quantity of literature in China may be considerable; on the other hand, the quality was dissatisfactory. These were two pieces of literature that had some statistical errors; both of these two pieces of literature were written by Chinese researchers. Proportionately, this kind of error maybe not only existed in the 10 literature but had a big amount in the published literature in China. The second problem was that the research of diabetic foot in Asia was not enough. According to the approach of PUBMED searches, a total of 60 articles were excluded from 33 because of geographical conditions. The third problem was that most of the literature that meets the requirements of this theme was cited fewer times, even some literature hasn't been cited before. That confirmed the lack of research on diabetic foot in Asia from another perspective and the low quality of that literature. To sum up, this scoping review proves that there was still a big loophole in the quality of research on diabetic foot in Asia.