The Chinese Journal of Burns Wounds and Surface Ulcers 1999, (4): 36-56

Transcription

1 Development of MEBT/MEBO in the Past 10 Years-on the Occasion of 10 th Anniversary of the Founding of The Chinese Journal Of Burns Wounds & Surface Ulcers Zhang Xiangqing 139 Hospital of Chinese People's Liberation Army (253002) The Chinese Journal of Burns Wounds & Surface Ulcers is a country-level medical learned periodical directed by Ministry of Public Health. This quarterly has been published on a continuing basis for 10 years since November 1989, when the initial issue was released. In the past ten years, under the organization and leadership of editor-in-chief Xu Rongxiang, The Chinese Journal of Burns Wounds & Surface Ulcers has kept on carrying out the aim of publication, propagandizing and reporting the information about MEBT (Moist Exposed Burn Therapy) and MEBO (Moist Exposed Burn Ointment) zealously, and treating different kinds of body surface burns, wounds and ulcers, and related diseases. Great deals of experience and significant curative effects have been acquired. As is well known, MEBT/MEBO is a new therapy for burns invented by Xu Rongxiang, a young burn scholar of our country, in accordance with the law of life, and based on the dialectical theory, methods, prescriptions and drugs of tradition Chinese medicine, so it is called "Chinese burns wounds and ulcers medicine. The academic key point of this technique is to expose the burn tissues tridimensionally in the physiologic moist environment, to regenerate and restore them according to the law of disease development (The Chinese Journal of Burns Wounds & Surface Ulcers, similarly hereinafter, 1989, 1: 4). Since it breaches the conventional routine therapy (dryness-scab-skin-grafting) in theory and practice, it is inevitable led to disputes in some scholars of conventional therapeutics when it came into the world. In the past 10 years, with the principle of "let a hundred of flowers blossom and a hundred schools of thought contend", we have given full play to the strong points of different kinds of medical sciences, study, approach, summarized, and exchanged the experience in treating burn wounds and ulcers from all sides, accelerated academic advancement, and promoted the development of "burn wounds and ulcers medicine", and ensured the successful realization of " popularization plan of a hundred of fruits in 10 years". Under the commitment of the editorial board of periodical office, I skimmed through all the articles published in this periodical, and read through the important treatises, so as to summarize the 10 years' academic development of MEBT/MEBO and the task in the next century. The purpose is to review the past, look forward to the future objectively, popularize and develop this new technique unshakeably. We hope that MEBT/MEBO can serve for the human health all round in the early years of the next century. A. Statistical Analysis of Articles (A) Article Types and Constitution - 1 -

2 There were 39 issues (not including article compilation) and 1083 articles published from the initial issue of The Chinese Journal of Burns Wounds & Surface Ulcers to the second issue of These articles were classified, and the types and constitution of them were summarized in Table 1 (see Table 1). Table 1. Types and Constituent Ratio of the 1083 Articles Burns Wounds Monograph Plastics Synthesis Scoop Care Others Philosophy and Ulcers Number of articles Constitution (%) Ranking Note: Wounds and ulcers: Including body surface wounds, knife trauma, ulcers and the related diseases. Synthesis: Including lecture, review, commentary etc. Others: including small renovation, small information, discussion etc. It can be seen from Table 1 that the occupancies (constituent ratio) of articles on burns, wounds and ulcers are 40.35% and 20.78% respectively (61.13% in total); the articles of monographic study on burns, wounds and ulcers are the third most (13.02%). That is to say, more than 2/3 of the 1083 articles (74.15%) are articles about burns, wounds and ulcers. It can be seen from this that The Chinese Journal of Burns Wounds & Surface Ulcers has given an outstanding contribution in summarizing and perfecting "Chinese burns wounds and ulcers medicine". However, it also can be seen that the philosophical articles analyzing and illuminating MEBT/MEBO are insufficient, which will be the direction of improving and perfecting the content of this journal for the future. (B) Therapies and Constitution According to the content of the articles, there were cases with definite therapies (there might be repeated use of cases in the articles written by authors from the same unit). Then 87.67% of the patients used MEBT/MEBO, 12.33% of the patients did not use MEBT/MEBO (Table 2). This shows that our publication attaches great importance to the unprecedented new technique, MEBT/MEBO beyond all else

3 Table 2. Therapies and Constituent Ratio of the Patients MEBT/MEBO Non-MEBT/MEBO Total Number of Cases Constitution (%) (C) Diseases Treated by MEBT/MEBO and Their Constitution The diseases of the patients receiving MEBT/MEBO therapy are summarized in Table 3 (See Table 3). Table 3. The Diseases of the Patients Receiving MEBT/MEBO Therapy and Their Constituent Ratio Burns Wounds Dermatological Gynecologic Diseases of Chilblain Others Total and Ulcers Diseases Diseases Ophthalmology, Otorhinolaryngology and stomatology Number of Cases Constitution (%) Ranking Table 3 shows: Most of the patients receiving MEBT/MEBO therapy are burn patients, and nearly 4/5 (78.58%) of the total cases are burn patients. Wounds and ulcers are the second most diseases (16.16%), followed by dermatological diseases, gynecologic diseases, diseases of ophthalmology, otorhinolaryngology and stomatology, chilblain, non-body-surface diseases, and the cases using MEBO series of drugs. This also shows: burns, body surface wounds and ulcers are the best indications for MEBT/MEBO, but in the 10 years' clinical practices, its indications have been expanded to the diseases of dermatology, gynecology, ophthalmology, otolaryngology, stomatology and chilblain etc. Because of its good curative effects, the use of MEBT/MEBO in treating diseases related to burns, wounds and ulcers is on the rise. The experience is abundant and valuable. (D) MEBT/MEBO and Treatment Level of Burns There were cases of burn patients receiving MEBT/MEBO therapy. Among them, patients were healed and the cure rate was 99.29%. There were patients with burn surface area less than 50% TBSA, among which patients were healed and the cure rate was 99.87%; there were 6572 patients with burn surface area greater than or equal to 50%TBSA, among which 6002 patients were healed, and the cure rate was 91.33% (see Table 4). According to the total cure rate and the cure - 3 -

4 rate of extensive burn lager than 50% TBSA, MEBT/MEBO is the top-ranking burn therapy in our country even in the world. Table 4. Therapeutic results of burn patients Number of Cases Number of Healed Cases Cure Rate <50% TBSA % TBSA Total (E) Statistics of the Patients Receiving Non-MEBT/MEBO Therapies In the past 10 years, The Chinese Journal of Burns Wounds & Surface Ulcers has not only propagandized and reported the technological development of MEBT/MEBO, but also published some articles unrelated to MEBT/MEBO, among which there cases. The therapies of these cases are summarized in Table 5 (see Table 5). Table 5. Therapies and Constituent Ratio of Non-MEBT/MEBO Cases Conventional Therapy Epidemiological Survey Plastics Others Total Number of Cases Constitution (%) Ranking Note: The cases receiving conventional therapy included the control cases of MEBT/MEBO, treatment lessons, complication reports. Others included fundamental research and those with no indication of therapies. The patients receiving non-mebt/mebo treatment were summarized in Table 5. Among them, there were the control cases of MEBT/MEBO (54.32%), general epidemiological survey cases (28.67%), plastic cases (14.14%), and other cases related in monographic study and other studies (2.87%). The cases receiving conventional therapy included the control cases of MEBT/MEBO, and the cases related to the treatment lessons and complications. Plastic cases included surgery plastic cases and the patients treated with MEBO ScarReducer. B. Evaluation on Large-amount Burn Clinical Data The articles containing more than 1000 cases are called large-amount clinical data, and there are 13 articles of large-amount clinical data in the 437 MEBT/MEBO burn - 4 -

5 articles published in the 39 periodicals. According to the order of time when the articles were published, they include "clinical investigation report of 2076 cases treated with burn moist exposed burn therapy" written by Zhang Linxiang, Yang Kefei (1989, initial issue: 22); "clinical analysis on 1567 burn patients treated with moist exposed burn therapy"(1991, 1: 25) written by Yang Kefei, Yangjun et al., "clinical analysis of 1003 burn patients treated with moist exposed burn therapy" written by Zhao Junxiang, Yang Guoming et al.; and the articles written by Qiao Haibing (1994, 3: 29), Wi Yuyun (1996, 1: 32), Wang Hezhen (1996, 1: 27), Zhao Junxiang (1998, 4: 24), Xiao Xinming (1998, 4: 26), Wang Hong( 1998, 4: 27), Hui Lei (1998, 2: 28), Xu Degao (1998, 4: 30), Sha Guangxin (1998, 4: 31), Zhou Baoguo (1998, 4: 35). The articles are considered to be with precise structure, true content and reliable materials based on the careful study on the above 13 articles. For example, the total cure rates were between 94.36% and 99.80% (not including the data of medium to small area burns). It is better in analgesia effects and the degree it eases the patients' pains than conventional therapy. It can be concluded that MEBT/MEBO has definite curative effects and good repeatability. It should be noted that the articles written by Zhang Linxiang and Yang Kefei were published in the initial issue, when MEBT/MEBO came into being in our country. The two old specialists, who had used conventional therapy for many years, used the new technique like sailing against the current, and had foreknowledge in the theory of Xu at that time, which indicated their vision in the development of science was still keen although they were old. What they did not only produced deep influence on the decision by Ministry of Public Health on September 1, 1991, who decided to popularize the moist exposed burn therapy and moist exposed burn ointment in all countries, but also were the true turn of the revolutionary academic advancement ("the great historic turn on burn therapeutics") in thought and actions. Undoubtedly, their foreknowledge and actions were a noiseless call to the young scholars, the subsequent scientists who transformed and carried out the MEBT/MEBO techniques. For this reason, we should praise them for the popularization of MEBT/MEBO techniques and their great devotions to the start-up of the "popularization plan of a hundred of fruits in 10 years" of Ministry of Public Health, at the time 10 years after The Chinese Journal of Burns Wounds & Surface Ulcers started publication. There were also other old specialists who struck out on this new path, such as professor Ma Enqing. He is the burn surgery professor of Hunan Medical University, who has great scientific attainments in burns, and made an example for us in understanding, popularizing MEBT/MEBO techniques and the related fundamental research. Professor Xu Rongxiang evaluated these old specialists as follows: the innovation in academic thought and medical treatment techniques is not a simple thing some people do not have such good idea, concept, academic sense and scholastic attainments as professors Zhang Linxiang, Yang Kefei, Ma Enqing, Zhang Xiangqing do (1997, 3: 33). The contributions by Professor Ma Enqing are to be - 5 -

6 described in "infection of burn" and related sections. "Clinical analysis of 1003 patients treated with moist exposed burn therapy" was written by the two middle-aged and young scholars, Zhao Junxiang and Yang Guoming in the early nineties (1992, 1: 36). They summarized the clinical experience in treating 1003 burn patients with MEBT/MEBO in the burn center, Nanshi hospital, Henan, in nearly 3 years between December, 1987 to October, Among them, there were 386 cases of severe and very severe burns (38.5%), 118 cases of children with severe burns or burns with burn surface area exceeding 50%TBSA (11.8%). There were 977 cases in this group, and the total cure rate was 97.41%. According to the data provided by the article, the half lethal burn area (LA50) was 82.11%TBSA. The curative effects of Nanshi Hospital in the late 1980s and early 1990s were as followed: the probability of dying was 50% when the burn area was 82.11%TBSA. It has been reported domestically that the half lethal burn area is 75.93%TBSA. The author also indicated: LA50 had reached 75-80%TBSA or above in our country (Li Ao et al., Burn Therapeutics, the peoples medical publishing house, 1995; 2). The reason Nanshi Hospital acquired such good curative effects may include both the supervision and direction by Professor Xu Rongxiang, and the use of new MEBT/MEBO techniques by the middle-aged and young scholars without blind worship for conventional therapy. C. Study on Improving Stagnant Zone There were 3 pathological zones in the deep burn wound from superficies to interior: the surface layer (or core zone) is the inconvertible necrotic zone, the bottom layer (or peripheral zone) is the hyperemia zone and inflammatory reaction zone; the layer between the above two zones is the stagnant zone. According to the above pathological changes, the key points of burn wound treatment include not only to prevent the stagnant zone from developing into hyperemia zone, but also to treat it with effective therapies to reduce and recover it, which is the fundamentality of the technical design of MEBT/MEBO. The microcirculation change law of conventional dry exposed therapy had been proved by Professor Xu Rongxiang through the experimental study on the microcirculation of burnt rabbit ear (1994, 4: 42): after injury, the blood capillaries of stagnant zone and hyperemia zone were constricted, and the blood stream in the blood capillaries increased; 30 minutes after injury, the blood vessels were blurred, and the tissue edema was apparent; 3 days after burn injury, the wounds turn dry, most of the terminal capillary blood vessels were stagnant, the blood stream decreased, and the number of blood vessels was reduced; 10 days after injury, the injury area was almost completely necrotic, and only 1 case recovered (1/7). MEBT/MEBO treatment group: The changes within 10 minutes after injury was similar to that of the conventional treatment group, but the tissue edema and the blood vessel blur change occurred later than those of the conventional treatment group did; 3 days after burn injury, the wound was moist, most of the terminal blood vessels were in flow condition, the flowing true capillaries increased, - 6 -

7 the blood capillary blood stream in the core zone was normal, there was no formation of blood capillary network in the stagnant zone, but there still existed true capillaries and blood stream; 10 days after injury, most of the wounds were healed (6/7). It is believed at present that the progressive damage process of the stagnant zone includes several change events, such as dermis ischemia, blood clotting and blood vessel obstruction. It has many kinds of causes, and it is related to vasospasm, abnormal hemorrheology, oxygen free radical and neutrophilic granulocyte conglutination etc. It was brought forward by Xu Rongxiang many years ago that the enlargement of burn wound stagnant zone occurred not only in the local part, but also in the whole body. There forms progressive thrombosis in the microcirculation of whole body due to the blood coagulation mechanism, blood vessel structure and pelohemia changes in the local area. The changes in the local area and in the whole body interact as both cause and effect. The above viewpoint of Xu was confirmed by Wang Guangshun et al. in "study on the hemorrheology in the burnt rabbits treated with MEBO". The apparent viscosity of blood and the plasma viscosity of the 10% TBSA Ⅱ degree burns in the back of rabbit treated with dry exposed therapy alone were significantly higher than those in the MEBO treatment group. The above indices only increased 24 hours after injury in the MEBO treatment group, and there were no statistical difference between the normal animals and the burnt animals 2, 3, 6 days after injury. As a result, in MEBO treatment, the drugs act on the local area, but they can improve the microcirculation indices of the whole body (hemorrheology), thereby promote the restoration of the local burnt areas. It has been proved by the animal experiments by Yan Ze et al.(first Military Medical University) recently (1998, 4: 21) that there was a sharp decline of blood in the microcirculation in the stagnant zone in the burn wounds of both the MEBO treatment group and conventional dry exposed therapy group in the early stage of Ⅲ degree burns in the rabbit back, which decreased to the minimal values after 2 hours. However, the blood flow decreases in different time phases (5min-72h) in the conventional therapy group were significantly greater than those in the MEBO treatment group (p<0.01). The content of MDA (malondialdehyde), the oxygen free radical product in the stagnant zone of both groups increased 4 hours after injury. However, the content in the MEBO group began to decrease before long and reached the values before injury at 24 hours after injury, while that in the conventional therapy group kept persistently high. The moisture content of stagnant zone 4 and 48 hours after injury was higher than that before injury, but the increase in the MEBO group was not as significant as that in the conventional therapy group. It can be seen from this that there was difference in the capillary permeability and tissue edema degree in the two groups. The necrotic area of the conventional therapy group (20.96±3.1 mm 2 ) was significantly higher than that of the MEBO treatment group( 8.38±1.78 mm 2 ) 14 days after injury. The author considered MEBT/MEBO could improve the microcirculation of wound stagnant zone, alleviate the local progressive damage in the early stage of burns

8 It can be concluded from the above research results that MEBT/MEBO can improve the stagnant zone of burns. These studies provided sufficient theoretical bases for the clinical curative effects of MEBT/MEBO and the action principles of MEBO. D. Ⅲ Degree Burns and "Combination of Drugs and Knife" and "Ploughing Therapy (A) Treatment on Ⅲ Degree Burn Wounds The therapy for Ⅲ degree burn wounds was definitely described by Xu Rongxiang in the "burn moist exposed burn therapy" courses and teaching materials in the middle and late 1980s (1989, 1: 9): The Ⅲ degree burn wound was different from the deep II degree burns due to the necrosis of all layers of skin. In the conventional therapy, the necrotic tissues were excised by surgery, then skin-grafting treatment was used, and there were no other effective methods. This may be the reason why nobody performed further study on this for a number of years. It has been found by Xu through clinical practice that the superficial Ⅲ degree burn wounds diagnosed according to common clinical diagnosis standard are completely healed by MEBT/MEBO treatment. Therefore, he performed further intensive study. It was proved by histological examination that 20% of the eccrine glands existed in the subcutaneous tissues; the sweat gland epithelia could grow on the wounds and cover the wounds so that skin-grafting could be avoided. It was also considered small area of deep Ⅲ degree burn wounds could be treated with this technique, and also could be healed through the propagation of epithelia at the edge of wound. However, large area of deep Ⅲ degree burn wounds should be also treated with skin grafting. Therefore, the viewpoint of some persons that the therapy of Xu does not require skin-grafting is a misconception or bias on MEBT/MEBO. As a matter of fact, a great number of superficial Ⅲ degree wounds considered to be in need of excision of eschar and skin-grafting have been healed by MEBT/MEBO. All these cases had systemic clinical data or image proof, such as the cased reported by Xiao Mo in "treatment experience of MEBT/MEBO promoting the regeneration and restoration of deep burn wounds" (1999, 1: 18). The deep Ⅲ degree burns in which the muscle layer has been damaged are difficult to treat. Xu Rongxiang held that MEBT/MEBO was used to liquidize and remove the necrotic layer, the subcutaneous tissues should be kept as much as possible, and then skin grafting was performed to cover the wounds. It should be noted that excision of eschar was replace by drug liquefaction with the view of avoiding injury to the subcutaneous tissues in negligence (1997, 3: 8). It has been proved by clinical practice that the local area treated with this therapy was plump, and this therapy was better than conventional excision and skin-grafting therapy. There was another key problem in the treatment of superficial Ⅲ degree and deep Ⅲ degree wounds, namely the release of pressure on deep tissues by necrotic skin, so as to protect the whole layer of the necrotic skin. After the whole layer of skin is damaged, the flexibility of skin disappears due to the damage to the fiber structure in the dermis; the hypodermic fluid pressure will increase because of the progressive increase of the exudation in the subcutaneous tissues. It has been proved by the fundamental research by Zhang Xiangqing (1995, 1: 13) that the fluid pressure in the subcutaneous tissues around the annular eschars could be as high as more than 35cm H 2 O, which might lead to the obstruction of the blood circulation in the distal ends of - 8 -

9 limbs (fingers) or limit the expansion ratio of neck and chest. Xu Rongxiang advocated the pressure on the deep tissues by the necrotic skin should be released in the early stage, ploughing therapy should be used to accelerate the transformation of information tissues in the subcutaneous tissues, so as to make the fresh skin island tissues grow (1997, 3: 9). (B)"Combination of Drugs and Knife" and "Ploughing Therapy" With regard to the treatment on large-area degree wounds with MEBT/MEBO techniques, Xu Rongxiang has analyzed the local basic changes of Ⅲ degree burns in the initial issue (1989, 1: 9) and indicated large-area Ⅲ degree burns should be also treated with skin grafting, and reported the bold attempt of Nanyang Burn Center on the treatment of Ⅲ degree wound necrotic tissues. Many incisions were made on the necrotic tissues with scalpels in order to enhance the liquefaction effects of drugs and improve curative effects. In the beginning of 1990, Zhao Junxiang et al. put forward the method of "many times of excision of necrotic tissues in turn with knife" in the article "experience in the treatment of 4 cases of large-area burns with moist exposed burn therapy" (1990, 1: 18). In the ensuing year, Yang Kefei brought forward the new conception of treating Ⅲ degree wounds with combination of drugs and knife based on a great lot of clinical practice (1991, 1: 25). Yang thought the treatment effects on Ⅲ degree wounds with MEBO alone were not as good as those with combination of drugs and knife. "Combination of drugs and knife" means that drugs promote the effects of knife, while knife enhances the potency of drugs, drugs and knife are combined to remove the Ⅲ degree necrotic tissues in a short time. Since this method was really effective for the treatment on Ⅲ degree wounds, which could protect the vital tissues free of damage, accelerate the liquefaction of necrotic tissues, his article about "combination of drugs and knife" was used for reference by other doctors before long. In 1992, Zhao Junxiang, Yang Guoming et al. put forward the special term "ploughing therapy" in the article " Clinical Reports of 103 Patients Treated with Moist Exposed Burn Therapy and Ploughing Therapy". The initial method was using scalpel to make a "well" form scratch, and then a suitable "ploughing knife" was developed. The objective of using this method was to give play to the action of drugs on the wounds, so as to create a good liquefaction environment for the Ⅲ degree wounds, and save the dead-alive tissues as much as possible. Owing to the reasonable design of this method, it is also used by other doctors for reference, and plays a major role in treating Ⅲ degree wounds. On June 23, 1997, Xu Rongxiang confirmed the above method in the "Advanced Academic Course for Leaders in Burn Field". He said it was difficult to get ideal liquefaction effects when using the methods applied on deep II degree burns to treat deep Ⅲ degree burns, that is, the hydration reaction, enzymolysis reaction, rancidity reaction and saponification were difficult to be started. Therefore, ploughing therapies and other therapies should be used to assist it. For the Ⅲ degree wounds with muscular layer damaged, most of the necrotic tissue layers can be excised, MEBT/MEBO should be applied on the wounds to culture granulation tissues, grow dermal cells, and cover the wounds (1997, 3: 44-45). E. Clinical and Experimental Study on The Effects of Anti-inflammation and Preventing and Treating Infections - 9 -

10 (A) Anti-inflammatory Action The inflammatory reactions and bacterial infections of burnt tissues are two different concepts, but they are often mistaken for each other by some persons. It was believed by Xu Rongxiang in the article "Anti-inflammatory Action and Principle of MEBT/MEBO" (The Chinese Burns Wounds and Ulcers, Page 11) that one of the changes of burns was inflammation, but for a number of years people were only absorbed in the study of bacteria impairment, and inflammatory reactions were lost sight of, therefore there was still no methods and drugs to treat burn inflammatory reactions. The burn wound itself is an infected wound based on inflammation, but this does not mean the wound has been infected. This viewpoint of Xu is similar to the present knowledge of burn pyaemia. It has been confirmed that the essence of pyaemia is the reaction of the human body to the inflammatory materials, such as tumor necrosis factor, interleukin, platelet activating factor, leukotrienes and oxygen free radical etc. If these materials are not cleaned up in time, they will lead to extensive endotheliitis, disturbance of blood coagulation, abnormal angiotasis and cardiac muscle inhibition etc. Bacteria are the principal materials starting up the above factors and leading to the chain reaction, but except for bacteria, different kinds of damages, such as wound, heat injury, shock etc., can directly start up the chain reaction of inflammatory factors. After the inflammatory reaction is started up, it can continue not dependent on the presence of infective agents, and result in multi-aspect impairment to the human body. Its presentation is the same with results of bacteria start-up. MEBO contains natural β-sitosterol, the local application of which can generate favorable anti-inflammatory actions. Its mechanism of action is similar to that of glucocorticoid, which can lower capillary permeability, reduce hyperemia and exudation, so as to inhibit inflammatory reactions. According to molecular pharmacology, β-sitosterol can be combined with inflammatory factors and form intermediate factor, thereby eliminate the actions of inflammatory factors, and inhibit the growth and reproduction of bacteria (1997, 3: 40). Furthermore, another antiphlogistic component in MEBO is baicalin, the anti-inflammatory actions of which are realized by counteracting the actions of epinephrine, noradrenalin and catecholamine. It can block β 1 and β 2 receptors, eliminate superoxides, alleviate stress and inflammatory reactions. The study on the oxygen free radical removing functions of MEBO has been confirmed by the animal experiment by Yan Ze (1998, 4: 21). The content of malondialdehyde (MDA) in the tissues of wound having treated with MEBO is significantly lower than that in the dry exposed treatment group. (B) Actions of Preventing and Curing Infection It was indicated by Xu Rongxiang in the academic report "Great Historic Turn in Burn Therapeutics" that burn environmental pollution mainly referred to the aggression of the bacteria in the air, therefore there was no denying that a great lot of

11 bacteria in the environment might adhere to the outer layer of the drug. However, since there was no water or oxygen contained in the drug layer, the aerobic bacteria in need of water could not reproduce. If anaerobic bacteria fell onto the wounds, the cere would insulate them in the air for a while, thus they would be oxidized, and their growth would be inhibited (1989, 1: 9). The following has been confirmed by the study of Xu: The wounds of the same depth could be divided into two parts, and were inoculated with Pseudomonas aeruginosa. One part was bound up with the wound moist, and moist exposed burn therapy was applied on the other. It was found on the second day that there was green fluid exudation on the binding-up top dressing and there appeared infection signs in the wounds. This indicated that the drugs in the area of binding-up would be absorbed by the top dressings, the inoculated bacteria were in direct touch with the necrotic tissues of wounds, and began to grow and reproduce. In the area treated with moist exposed burn therapy, the inoculated bacteria also adhered to the drug layer, but the drugs inhibited the growth and reproduction of them. The mechanism concerned with this finding is required to be further explored. The first scholar conducting prevention and cure study against bacterial infection was Professor Ma Enqing, Hunan Medical University, who performed many times of clinical and experimental studies on the bacteriostatic action of this therapy in succession (1990, 1: 25). It has been shown in clinical research that MEBO has bacteriostasic activity on Pseudomonas aeruginosa (the positive incidence of wound germiculture is only 17.7%), but it has weak actions on Staphylococcus aureus and Escherichia coli. However, there was no sepsis in the patients with positive wound germiculture results. He thought: MEBO was lipophilic oil soluble concentrate with good actions of inducing flow, and made against the growth and reproduction of these bacteria. Subsequently, Professor Ma directed his graduate student, Chen Xiaowu to conduct a comparative study on the control actions of MEBO, SD-Ag cream and warming exposed therapy on Pseudomonas aeruginosa infection (1990, 3: 29). They came to a conclusion that MEBO had similar inhibiting action on Pseudomonas aeruginosa with that of the present acknowledged effective inhibitor SD-Ag, and had the same control action on the invasive infection of Pseudomonas aeruginosa to the burn wounds. In the meantime, the study on the inhibiting action of MEBO on Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli by Lin Zhengya et al. (1990, 1: 55) indicated: the wound infection rate of the above 3 dominant bacteria at admission were 80.76%, 84.61% and 92.30% respectively. Germiculture results at 4, 7, 10 days after MEBO treatment: The infection rates of Pseudomonas aeruginosa were 53.84%, 19.23% and 0% respectively; the infection rates of Staphylococcus aureus were 61.53%, 26.92% and 15.38% respectively; and the infection rates of Escherichia coli were 65.38%, 34.61% and 26.92% respectively. It was proved by the above study that MEBO had significant bacteriostasic activity on Pseudomonas aeruginosa, and had a control action to a certainty on other dominant bacteria, such as Staphylococcus aureus, Escherichia coli etc. The bacteria count study on the wounds treated with MEBO by Zhang Xiangqing also proved (1991, 4: 5) that MEBO could inhibit the growth of Pseudomonas aeruginosa, and its action was stronger than that of SD - Ag and SD - Zn. Luo Chengqun et al. summarized the bacteria detection results of 155 specimens in 63 patients treated with MEBO (1998, 2: 10). The positive incidence of wound bacterial culture was 84.5% (131/155), but the positive incidence of blood bacterial culture was only 5% (2/40), and the 2 positive specimens were from

12 the same patient. It was also confirmed that Staphylococcus aureus was the most, while Pseudomonas aeruginosa decreased to the 8th most. This indicated MEBO had powerful inhibiting effects on Pseudomonas aeruginosa. It also indicated although there were bacteria growing on the wounds, there was little chance of hematogenous spread. However, the hematogenous spread rate of dry therapy was as high as 49.1% according to the "Correlation Studies on the Wound Bacteria Positive Incidence and Hematogenous Spread in Dry Therapy" conducted by Wang Yongwu (1993,3:2). It was proved by the experimental study of Wang Guangshun (1992, 3: 7) that MEBO could prevent and control the bacterial infection of wounds. Zhou Zhongquan found (1994, 3: 34) the Pseudomonas aeruginosa infection occurring during SD - Ag treatment could be treated with MEBO. Professor Qu Yunying et al. (Binzhou Medical College) disclosed the reason why MEBO could inhibit the growth of bacteria and what the action mechanism was. She first studied the continuous passage culture of proteus, Escherichia coli and Staphylococcus aureus in the culture medium containing MEBO (1996, 1; 19). It was found there was variation in the biological characteristics of bacteria, there was synergistic action between MEBO and antibiotics, MEBO could increase the periphery white blood cells, PMN percentage and the phagocytic function of abdominal cavity phagocytes in the experimental animal. It was indicated by the author that MEBO could lead to the variation in the biological characteristics of common pathogens in burn wounds, slow down the growth and reproduction speed of bacteria, lower the pathogenicity of pathogenicity, enhance the nonspecific immunity of human body, so as to resist bacterial infection. It was confirmed by the study of Qu Yunying et al. (1998, 4: 15) that MEBO could result in the variation in the biological nature of anaerobic bacteria with spore (Clostridium tetani), anaerobic bacteria without spore( bacteroides fragilis, Propionibacterium) and fungi (Candida albicans), and MEBO could influence the reproduction speed and invasiveness of bacteria. Therefore, it was believed MEBO was a drug that could accelerate the healing of wounds with two-way regulating effects and strong broad-spectrum antibacterial actions. F. Clinical Observation and Experimental Study on Antalgic Effects There was a large proportion of articles reporting the antalgic effects of MEBO in the 39 issues. The author reviewed the articles with detailed record data, conducted a statistical analysis and added analysis and discussion. (A) Clinical Observation on Analgesic Effects Qie Zhengping et al. conducted a comparative study on the analgesic effects of MEBO and that of SD-Ag (1997, 1997, 4: 26). 325 patients were included (166 patients in MEBO group and 159 patients in SD- Ag group). The age, burn area and depth of the two groups were similar. The degree of pain in the original article was expressed with + and -. In order to conduct statistical analysis and make clear the problem, five levels (very good, good, fair, bad, very bad) were used in this article. The five levels were as follows:

13 Very good (++++): There were no pains, and the functions were normal. Good (+++): There were no pains, but there were pains that could be tolerated during movement. Fair (++): There were rest pains that could be tolerated and were aggravated during movement. Bad (+): There were rest pains and intramuscular injection of analgesic was in need. Very bad (-): There was sharp pain, and hibernation agent even anaesthetic was in need. The analgesic effects and the degree of pains of the two groups of patients were summarized in Table 6 according to the above standard of criterion (see Table 6). Table 6. Comparison on Analgesia Effects Group (Number of Cases) Very good Good Fair Bad Very bad MEBO (166) SD-Ag (159) Note: The rates of very good and good results in the two groups were compared. P<0.01. It was proved by Table 6 that there was no pain during dressing change in the MEBO group. The analgesic effects of MEBO were better than those of conventional therapy. In the conventional therapy group, only 56.60% (90/159) of patients could endure pains, and other patients should be treated according to the symptoms. Zhou Guojian reported 135 adult burn patients with burn area larger than 30%TBSA (1998, 2: 43). The sensitive rate to pains was used as the principal observational index. It was found that the sensitive rate to pains in the MEBO group (72 patients) was 3% and that in the SD-Ag group (65 patients) was 90%. Su Yongtao observed analgesic effects on a group of burn patients most of which were of deep Ⅱ degree (1998, 2: 32). Whether analgesic treatment was required and the pains were aggravated during dressing change were used as the indices of judgment for pain response. The results were as followed: The incidence rate of pain in MEBO group was 23.33%, and the incidence rate of pain in SD-Ag group was 83.33% (X2=10.848, p<0.01). The observed results of Heng Yang et al. (1997, 4: 24) were as followed: The incidence rate of pain in MEBO group (100 cases) was 3%, and the incidence rate of pain in SD-Ag group (100 cases) was 86%, and there was significant difference between the two groups. Zhao Junxiang (1998, 4: 25) reported that the analgesic effects lasted for 3-6 minutes after 6218 patients took MEBO for external use, but the effects in some patients were not satisfactory, in whom (5 case in this group) the pains began to be alleviated 5 days after injury (5 days after applying this medicine). He believed the leading cause of the above phenomenon was related to the applying method of medicine, overdose and underdose (the wounds would be easy to be dry) might result in pains, and there should be no dryness or maceration. It can be seen from above that MEBO treatment resulted in different analgesic effects indicating standard use of MEBO counted for

14 much. Wang Hezhen et al. analyzed the analgesic effects on 4373 patients (1996, 4: 27). The degree of reaction to pains of the patients was concerned with the applying time. Applying the ointment immediately after injury had better effects than postponed application did. In the patients using the ointment within 4 hours after injury (507 cases), the pains were alleviated after 3-15 minutes. The longer the time between the injury and applying the drug was, the later the analgesic effects occurred. The author speculated that the tissues generated less media when the drug was applied earlier, thus the secondary impairment to the injured nerve endings induced by environmental factors could be alleviated. Furthermore, it was concerned with the causes of burns and the tolerance of the patients to pains. (B) Fundamental Research in Analgesic Effects Although the analgesic time and effects of MEBO reported were different, the analgesic effects and the degree of pains eased were affirmative. MEBO had better analgesic effects than SD-Ag therapy did. In order to illuminate the mechanism of the analgesia of MEBO, Hang Guoying et al. observed the influence of MEBO on the threshold of pain of rabbit skin (1998, 2: 1). 19 animals were divided into 3 groups: saturated potassium chloride stimulation group, wound pain group and control group, and behavior pain-measuring methods were used for measurement. The pain threshold changes before and after application of MEBO: The results were as followed: The basic threshold of pain (mean±sd) in saturated potassium chloride electrode stimulation group was 2.079±0.214mA, the threshold of pain increased 3-30 minutes after MEBO was applied (significantly increased 6-9 minutes after application), the average values reached 2.986±0.283mA, and there was significant difference between the basic value and the increased value (p<0.001). The results of wound pain group were similar to those of the above group as followed: The basic threshold of pain was 1.968±0.054mA, the threshold of pain increased 3-30 minutes after MEBO was applied (significantly increased 9-18 minutes after application), the average values reached 2.986±0.283mA (mean±se), and there was significant difference between the basic value and the increased value (p<0.001). The average values of basic threshold of pain in the control group was 2.087±0.282mA, and there was no significant difference between the basic value and the value after vaseline cream was used (p>0.05). It was believed by the author that MEBO participated in the analgesic effects on skin. The action mechanisms may include the following aspects: (1) MEBO infiltrated into skin, protected the algesiroreceptors from damage, and lowered the sensibility of algesiroreceptors to algogenic substances. (2) MEBO made the K + penetrate into skin and the algogenic substances released from the damaged tissues diluted by the tissue fluid around and carried away by blood circulation so as to alleviate the pains through its actions of activating blood circulation to dissipate blood stasis, expanding blood vessels and ameliorating microcirculation. It is believed by Xu Rongxiang that the development of burn pains is mainly due to the stimulation to the damaged or unhurt pain sense nerve endings directly or indirectly by burn tissues and wounds. The conventional methods (including analgesia with Chinese traditional medicine and anaesthesia have no satisfactory analgesic effects; moreover, they may result in tissue damage. Therefore, the analgesic treatment on burns is a tall problem. One of the guiding ideology of the development of MEBO by Xu Rongxiang is to change the surface charge in peripheral nerves in the area with or without burns, and to turn it into normal state. The primary functions

15 include protecting the wound surface, insulating the air, avoiding the stimulation of dryness, relaxing the arrectores pilorum, making the discharge unobstructed, and removing the metabolic products including algogenic substances in time. Du Huaien believed (1998, 2: 3) there was relation between burn pains and the stimulation by inflammatory substances; MEBO had favorable anti-inflammatory actions and could help to relieve pains. Sha Guangxin analyzed the functions MEBO with traditional Chinese medicine theories (1998, 4: 31), and he believed there were many ingredients that could activate blood circulation to dissipate blood stasis, and improve microcirculation, so as to change the pains due to obstruction into indolence due to unobsturction. G. Healing Modes of Wounds and the Dermal Quality after Healing (A) Comparison of the Healing Modes of Wounds There are two modes of wounds healing: natural healing and surgery healing. In the conventional therapy, the burn wounds not more severe than deep Ⅱ degree are treated with excision of eschar and skin grafting except that superficial Ⅱ degree wounds are treated with natural healing. The epithelia are fragile in the natural healing of deep II degree wounds. There will appear blisters, even rupture and apparent scar after movement, pulling and abrasion. The functions are severely affected. The survival dermis is damaged due to dryness, infection, and necrosis. As a result, the burn wounds turn from deep Ⅱ degree into Ⅲ degree, so this kind of wound is usually treated with skin-grafting. In the Ⅲ degree wounds, the dermis and appendage are damaged, therefore skin-grafting is in need except for very small-area wounds in which self-healing may occur (Li Ao et al. Burn Therapeutics, 1995, Page 200). However, the author believes MEBT/MEBO is in favor of the natural healing of different kinds of burn wounds based on the summary and study of the wound treatment experience reported in The Chinese Journal of Burns Wounds & Surface Ulcers in the past 10 years. The quality of skin after healing is not the same with that in the conventional therapy. The so-called quality of skin should include the physical, biochemical, immunological and detoxification functions. But for burns, the principal evaluating indices include whether there is scar proliferation and its degree, whether the scar affects function, whether the skin color is normal, the elasticity, the protective and defense function, respiratory function and thermoregulation actions. Heng Yang et al. reported the treatment of deep Ⅱ degree and Ⅱ- Ⅲ mixing degree wounds (1997, 4: 24). The 200 patients were treated with MEBO and SD-Ag randomly (100 cases in each group). Since the deep Ⅱ degree or Ⅱ- Ⅲ mixing degree wounds are similar, the healing modes and development are summarized in the following table for analysis (Table 7). Table 7. The Healing Modes and Development of Deep Ⅱ and Deep Ⅱ- Ⅲ Mixing Degree Wounds Group Number of Cases Self-healing Rate (%) Skin-grafting Rate (%) Incidence Rate of Scar (%) MEBO Conventional Therapy

16 Note: 1 Comparison of the self-healing rate in the two groups: X 2 =20.994,p< Comparison of the incidence rate of scar in the two groups: X 2 >100, p<0.01. It was shown in Table 7 that, MEBO treatment could lead to natural healing in deep Ⅱ degree and Ⅱ- Ⅲ mixing degree wounds, skin grafting treatment was not in need, and the incidence rate of scar in MEBO group was significantly lower than that in conventional therapy group. The clinical observation results by Fang Tiyi et al. in 1994 (1994, 1: 17) were very similar to those of Heng Yang. The author reported the treatment results of 238 cases of different kinds of wounds, in which there were 123 cases of deep Ⅱ degree and superficial Ⅲ degree patients. Among them, 71 patients were treated with MEBO, and 52 patients were treated with SD-Ag. In MEBO group, the self-healing rate was 100.0%, and the incidence rate of scar was 4.0%; In SD - Ag group, the self-healing was 38.46% (that is, 61.54% of the patients were treated with skin grafting), and the incidence rate of scar was 100%. There was significant difference in both self-healing rate and incidence rate of scar between the two groups( p<0.01, X2>50). (B) Self-healing Time of Wounds and the Quality of Skin Wang Chengchuan et al. conducted a clinical observation on the natural healing time of different depths of wounds (1996, 1: 24). The results were as followed: the self-healing days of superficial II degree wounds were 7.90±1.17 days, the color and elasticity of skin were normal after 3 months treatment; the self-healing time of deep II degree wounds was 21.25±2.94 days, and there was no obvious scars; the self-healing time of superficial Ⅲ degree wounds was 39.45±6.91 days, and there was superficial scar and skewbald change; the deep Ⅲ degree wounds lasting for more than 4 weeks which were estimated to be incapable of self-healing were treated with auto-skin-grafting, the skin-grafting area was comparatively plump, and the elasticity and function were normal. Wang Shiyou performed a clinical observation on 15 cases of extensive burns with different depths treated with MEBO (1998, 1: 26), and the results were the same with those reported by Wang Chengchuan. The self-healing time of deep Ⅱ degree wounds was 25.23±2.74 days; The self-healing time of superficial Ⅲ degree wounds was 34.54±6.91 days; the self-healing time of deep Ⅲ degree wound with a diameter no more than 20cm was 51.45±9.63 days. In the 10 months' follow-up, there were no obvious scars in the deep Ⅱ degree wounds; the Ⅲ degree wounds were treated with MEBO SCAReducer after healing, and there were only a few scars. It was found in the comparative study of Xiao Mo (1999, 1: 18) that the treatment course of MEBO was significantly shorter than that of SD-Ag. The superficial Ⅱ degree wounds treated with MEBO could be healed in 5-7 days, while those treated with SD-Ag were healed in 8-10 days. MEBO could make deep Ⅱ degree superficial type, deep Ⅱ degree deep type and superficial Ⅲ degree wounds healed 7 days, 10 days and 20 days earlier respectively. It was believed by Li Chuangji (1999, 2: 23) that ploughing therapy used in the early stage of deep Ⅱ degree and Ⅲ degree wounds could accelerate the liquefaction and healing of wounds. In the 51 cases of extensive burns he reported (one patient died from alimentary tract massive haemorrhage), the healing time of deep Ⅱ degree superficial type wounds was 20.0±1.5 days, the healing time of deep Ⅱ degree deep

17 type was 26.5±2.6 days, and the healing time of superficial Ⅲ degree was 31.0±4.5 days. In the 11 cases of deep Ⅲ degree wounds, there were 3 patients with a burn area larger than 80%TBSA, the Ⅲ degree wounds reached the deep fascia, and they were treated with operative treatment after 1 month. The average healing time of deep Ⅲ degree wounds was 56.0±5.6 days. It was brought forward by the author that ploughing therapy in the early stage of deep burns could prompt the healing of wounds. The treatment results of small-area deep wounds reported by Hu Jianwu et al. (1997, 4: 44) could be compared with those reported by Li Chuanji. The self-healing time of MEBO group and SD-Ag group was summarized in Table 8 (See Table 8). Table 8. Self-healing Time of Small Area Wounds (day) DeepⅡ Ⅱ Ⅲ Ⅲ Ⅱ MEBO (Day) 12.67± ± ± ± Number of Cases SD-Ag (Day) 15.28± ± ± ± Number of Cases Note:1. The above wounds were all small-area burn wounds in the hands. 2.There was no significant difference in deep Ⅲ degree wounds, while there was significant difference in the other groups ( p<0.01). 3. Deep Ⅲ degree burn wounds should be also treated with skin grafting. Two conclusions could be acquired based on the analysis on the results in Table 8 and the comparison with the results from Li Chuanji as followed:( 1) MEBO therapy was better than SD- Ag therapy for deep Ⅱ degree and deep Ⅲ degree wounds. It could not only shorten the healing time, but also reduce the scar after healing; (2) In the wounds of same depth, the healing time could be affected by many factors, among which the burn area was a dominating influencing factor; the larger the burn area was, the longer the healing time was. What Li Chuanji reported was extensive burn (>50%TBSA). Ploughing therapy was used in the early stage, which could accelerate the healing of wounds, and shorten the healing time to that of small-area wounds. Furthermore, there was no scar formation like that in the SD-Ag group. Based on the analysis of the above cases, the difference in the self-healing time of the burn wounds of the same depth was a normal phenomenon, because there were many factors affecting the healing of wounds, such as the burn wound area, whether there was infection, whether there were complicated injury and complications, age, sex etc. Therefore, the healing time was not the most important thing; the quality of skin should be looked upon as the primary standard for curative effect judgment. (C) Excision of Eschar and Quality of Skin Excision of eschar in deep burns is a new burn treatment therapy with the technological development of surgery. This method was adopted by most of scholars in a long time in the past; many extensive burn patients were healed, so it became the