Yao Liao , Bei Yin , Zhen Jin , Guang-Bing Bao , You-Sheng Li

1.Jinan University School of Chinese Medicine, Guangzhou 510632, China

2.Guangzhou University School of Chinese Medicine, Guangzhou 51000, China

3. Shenzhen people's hospital department of Chinese medicine, Shenzhen 519020, China

Keywords:Huashi Baidu formula Novel Coronavirus Pneumonia Severe COVID-19 Epidemic Virus Closure Syndrome Formula Pharmacology

ABSTRACT The main symptom elements of the severe novel coronavirus pneumonia epidemic virus closed lung syndrome are cold, damp, poisonous, heat, dryness, blood stasis, and deficiency, which mainly involve the lung and spleen, and are closely related to the heart, liver, kidney, and large intestine. Chinese medicine has accumulated rich academic theories and clinical experience in the prevention and treatment of infectious diseases. The treatment of lung syndrome recommends the use of Huashibaidu formula in the treatment of novel coronavirus pneumonia with integrated traditional Chinese and western medicine. The prescription for removing dampness and detoxification is composed of Maxingshigan formula in "Treatise on Febrile Diseases", "Tingli Dazao Xiefei formula" in "An Outline of Jinkui", Xuanbai Chengqi formula in "Diagnosis of Warm Diseases", "Medical Source Moisture" The combination of four prescriptions of Huopu Xialing formula in "On" is made according to the specific requirements. Through the composition of the prescription of Huashibaidu formula and the pharmacological research involving drugs, the mechanism of the novel coronavirus pneumonia severe epidemic closed lung syndrome may be combined with the blocking of cytokine inflammation storm, immune regulation, antispasmodic and asthma, and improvement Related to hemodynamics.

COVID-19 (hereinafter referred to as "COVID-19",COVID-19) by will be coronavirus (SARS-CoV-2), but interpersonal infection caused by acute respiratory infectious diseases, the disease has stronger infectivity, respiratory droplets and close contact is the main route of transmission, can be isolated in dung and urine will be coronavirus, exposure conditions may occur because of excrement and urine and the environmental pollution caused by aerosol contact transmission[1].Currently, COVID-19 is clinically classified as mild, normal, severe, or critical. Studies have shown[2] that once severe COVID-19 patients develop acute respiratory distress syndrome (ARDS), the case fatality rate is close to 50%, and if ARDS reaches moderate to severe, the case fatality rate reaches 70%. Traditional Chinese medicine has accumulated rich academic theories and clinical experience in the prevention and treatment of infectious diseases. It not only plays a role in the treatment of mild COVID-19 patients, but also plays an auxiliary role in the treatment of severe and even critically ill patients by combining western medicine.The main syndrome elements of severe COVID-19 are cold, dampness, toxicity, heat, dryness, stasis and deficiency, mainly involving the location of the disease in the lungs and spleen and closely related to the heart, liver, kidney and large intestine. It is characterized by mixed cold and heat, combined dryness and dampness, deficiency and fullness with symptoms[3]. Patients with severe COVID-19 often show significant shortness of breath, shortness of breath, little yellow and sticky phlegm, short and red urine, poor stool, fatigue and fatigue, etc., indicating that heat, cold and dampness, poison and blood stasis are obvious in the course of the disease, and fatigue and fatigue are also symptoms of poison and evil spirits.

1. TCM theory analysis of Huashi Baidu decoction

Traditional Chinese medicine has accumulated rich academic theory and clinical experience in the prevention and treatment of infectious diseases. State health commissioner for heavy epidemic poison closed treatment of lung card's recommended to use wet disease[4-5], the wet disease by Maxingshigan decoction in the treatise on febrile disease, the synopsis of Tingli Dazao Xiefei decoction, the article warm disease cause, Xuanbai Chengqi decoction, in medicine, the theory of moisture, Huopu Xialing decoction four prescriptions combination and cutting system, and the Fang Qing lung heat discharge opening and closing, dry wet spleen, qi and remove stasis, foster.

1.1 Composition of Huashi Baidu decoction

Huashi Baidu decoction[1]composition:sheng Ma Huang 6 g, almond 9 g, raw plaster 15 g, licorice 3 g, Agarice 10 g (posterior lower), magnolia 10 g, Atractylodes 15 g, grass fruit 10 g, Pinellia terba 9 g, Poria cobolae 15 g, sheng Rhubarb 5 g (posterior lower), sheng Huangqi 10 g, nemorosa leiocarpa 10 g, 10 g. 1-2 doses daily, decocted in water for each time 100-200ml, 2-4 times a day, oral or nasal feeding. It is suitable for patients with severe disease closure of lung.

1.2 Solution of the decoction contained in the wet septic prescription

1.2.1 Maxingshigan decoction

Article 63 in Treatise on Febrity: "If you sweat and gasp for breath without great heat, you can have Maxingshigan decoction." As the pathogenic factors obstructed the lung, the lung was lost and subsided, and the pathogenic factors filled the inside and outside. Therefore, patients with severe COVID-19 had severe fever or moderate fever, cough and acute gas, or even nasal wing agitation, which treated the cooling of the lungs and relieved the asthma. Ephedra can stimulate the human body yangqi, sweating solution table, xuanfei asthma, dispersing cold tong Stagnation. "Ben Cao Zheng" cloud: "Ephedra to light Yang taste, and also the nature of xin Wen, so good to reach the surface of the muscle, walk the channels and collaterals, great ability table to disperse wind evil, dispel cold poison. A fever, malaria, miasma, mountain haze, any sufficient evidence of three Yang, must be used." Cold dampness accumulation of heat, with xingan Da Han gypsum qingxu lung heat, ephedra gypsum, xuanfei asthma without heat, gypsum get ephedra, qingxie lung heat but not cool stem, solution table and qingfei use. Almond tongli lung qi cough, and ephedra with xuanxia phase. Stir the liquorice to enrich the qi and moderate the cold and warm between. "Typhoid fever bead set" cloud: "to ephedra, almond xin and into the lung, lung qi, spread evil. The gan ping of licorice, the gan Xin of gypsum and cold, benefit lung gas, in addition to heat, and cassia twiggy can not more line. Cover the evil in the lung, non - ephedra, almond can not be sent, and cold depression of the heat, not gypsum can not be removed, licorice is not to save the lung gas trapped, to slow the fierce gypsum is also. Although maxing Shigan decoction has four flavors, it is well combined to relieve heat and cold, relieve asthma and stop dampness in patients with severe disease and closed lung syndrome.

1.2.2 Tingli Dazao Xiefei decoction

"Synopsis of Golden Chamber" nemorosa djujube dyspra-lung soup should be "Tingli Dazao Xiefei decoction". "Traditional Chinese medicine should be Tingli Dazao Xiefei decoction". Evil spirits of cold dampness depress lungs, evil spirits attack throat and diaphragm, turbidity gas goes up against, cough, wheeze, turbidity gas does not fall and goes against the chaos in the chest, then the diaphragm is full; Sputum dampness with heat, then spit yellow sputum, blood sputum; Licorice yellow greasy, pulse slippery number, are damp heat dryness closed lung signs. COVID-19 pathology of lung tissue in patients with severe inflammatory cell infiltration, focal hemorrhage, necrosis, the imaging findings of double lung infiltrates multiple ground glass shadow, shadow, serious can appear lung consolidation and based on this can be attributed to the traditional Chinese medicine "lung bi" category, the wet disease and party take sheen, bitter, severe cold rolling fierce of semen lepidii water to drink in lung and phlegm fire, specializing in gas under the reality of the lung and smooth wheezing, heavy patients urine short red, semen lepidii through the channel, the gas lines of water, make indicates accumulated in the lung of the hot and humid poison from the solution, and big jujube in case the disadvantages of wet heat generating behind closed doors to keep coach.

1.2.3 Xuanbai Chengqi decoction

Article 17 in The book "Wen Bing Tian Bian" cloud: "Asthmatism, phlegm obstructing, right inch is too big, lung qi does not fall, Xuanbai Chengqi decoction main. The lung and large intestine are interconnected in the channels and channels, and the lung's qi can be cleansed and lowered, so as to promote the conduction of large intestine and facilitate the dross to descend. In patients with severe COVID-19, the heat and toxin will permeate the lungs with phlegm and dampness. In this case, the lung gas will not drop, the large intestine will not conduct properly, and constipation of the chest and wheezing will occur. Xuanbai Chengqi decoction to clear lung and determine asthma, purging heat and defecation, to almond taste bitter down, descending and Xuanhair lung gas; Gypsum qingrehua phlegm, qi wide chest, rhubarb purged gastrointestinal stagnation, melting white tiger, bearing gas at one side, purged viscera, viscera combined treatment. As Wu Ju said: "Almonds, gypsum to promote lung qi bi, rhubarb to the knot of the stomach, the zangfu treatment is also." The rhubarb in the middle of the recipe USES the decocting method to enhance its effect of relieving turbidization and detoxifying. Covid-19 belongs to "cold and dampness epidemic" because of trichosanthes Kirilowii in the original prescription. In order to avoid dampness and cold, it should be removed from this prescription. All drugs are used together to play the function of xuanfei qi and Chang Fu Qi.

1.2.4 Huopu Xialing decoction is derived from Yiyuan

Humidity Theory written by Shi Shou Tang, a physician in the Qing Dynasty, which has no name in the original book. It is now quoted as "Epimedium Puxia-Ling Soup" in Jianyi Certificate Summary by Yan Hongzhi. It is also replaced by light fermented black beans, propagated by this prescription with ventilator, dryness and profitability-water, and it indicates that the pathogenic factors of dampness and heat are concentrated in the gas and stressed in the humidity. In severe COVID-19 patients, the pathogenic factors of cold and dampness transmit qi from wei, and qi becomes hot and abundant, followed by phlegm, heat, turbidity, toxin obstructing the lungs and viscera, and heat and toxin are abundant. The pathogenic factors of cold and dampness are obstructed by qi, which can be seen in the course of the disease, such as fatigue and tiredness, chest distress, nausea and lack of food, pulse erosion, thick and greasy skin and other obvious symptoms of dampness obstruction. Epimedium Puxia Ling soup set aromatic humidification, bitter temperature dryness and dampness, light permeability and wet treatment of three methods for a side, external publicity internalization, tongli urination. The method of pinellia ternata is used to break up the impurities, and stop the vomiting, magnolia officinalis and pinellia ternata to dry and transport the spleen, so that the spleen can transport the water and wet, without being affected by the dampness. Almond opens and expels the lung gas on the upper part, so that the lung gas can be dispelled, then the waterway is self-regulating, poria invigorates the spleen and helps the water to permeate, which makes the waterway clear and wet. Since most severe COVID-19 patients clinically show signs of dehydration due to body fluid loss, the original prescription contains too much cardamom seed, coix seed, porcine coils, alisma alisma, and transvernia, which may aggravate body fluid loss. Therefore, they were all removed.

1.2.5 TCM application on COVID-19

Full party, amomum, rhizoma atractylodis, radix paeoniae rubra, radix astragali analysis for cold dampness disease evil with aromatization wet muddy, thin film former embodied cure this disease, and is for reference in the whole party to drink using magnolia bark, amomum fierce with spicy dry film former, polyester turbidity of open and close, amomum tangy male gas, Fang Xiang monarch indecent, good at divide phlegmy wet, dry "compendium of justice, the:" dysentery by haze fog dew damp the evil, the most hurt QingYang gas, so the monarch pernicious multipurpose temperature dry fragrance, with sheng Yin huo wet muddy aggregates are special." Atractylodes dispels wind, dissipates cold, strengthens the spleen, dryness and dampness, relives depression, and cuts down filth. "Yulan Mandala medicine" said: "Dry soil benefits water, discharge and eliminate phlegm, blood stasis, open yu, drain, change tinea, eliminate disease, swallow acid and remove rot, open mountains and rivers and miasmas, return to the weak and soft, clear up the muddy waters of clear urination. As a result, qi stagnates and blood stasis occurs. The bitter and mild cold red peony root cools down blood circulation and spreads blood stasis, and attacks the accumulation of toxin and heat. According to the book "Herbal Truth", "Red peony can activate and stagnation in blood. Therefore, any lump of abdominal pain, blood herniation, eye occlusion, resulting from heat baths, could cool the blood and remove blood stasis." Heavy COVID-19 patients with wet sex sign is still obvious, its pathogenic factors, lingering long feet weary, sun be the spirit by consumed Yin jing, many clinical languid, dry mouth and similar gas Yin deficiency of performance, if use general tonic medicine could warm zi rich help to wet the disadvantages of the hot, wet with astragalus root into the party cure disease, in the treatment of the yellow sweat from synopsis, existing stilbene Que laurel wine soup attending deficiency of wet wind-cold v card, green origin, to drum evil out healthy qi, the preferred astragalus is imitation scattered ginseng disease and supporting the use of the poison out. The medicine has the effect of relieving lung asthma, relieving heat, opening and closing, dryness and dampness and invigorating the spleen, promoting blood circulation and removing blood stasis, supporting the health and removing pathogenic factors, and effectively improving the symptoms of patients with fever, cough and asthma, shortness of breath, adverse urination, poor stool and fatigue.

2. Discussion on the modern pharmacology mechanism of Huashi Baidu decoction

Pathological anatomy of severe COVID-19 can reveal pulmonary alveolar phrenic vascular congestion and edema, focal pulmonary necrosis, and pulmonary fibrosis. The spleen was significantly reduced and the number of bone marrow cells was decreased. Cardiomyocyte degeneration and necrosis, liver volume increase, hepatocyte degeneration and focal necrosis, high filling of gallbladder, degeneration and detachment of renal tubular epithelial cells[1]. The possible mechanism of multi-target intervention for severe COVID-19 injury to human organs is as follows.

2.1 Storm inflammatory cytokines in the COVID-19 deterioration

Blocking inflammatory cytokine storm inflammatory cytokines in the COVID-19 has played a very important role in the deterioration, high blood cytokines lead to inflammatory substances of aggregation and leakage, and the destruction of tissues and organs, causing multiple organ failure and acute respiratory distress, could be COVID-19 heavy, the important cause of death in critically ill patients with[6]. Modern pharmacological studies have shown that hemp apricot calaminae decoction can significantly inhibit the influenza virus cells induced the expression of cytokines and chemokines, including interleukin 6 (IL 6) and interferon induced protein 10 (IP - 10), tumor necrosis factor alpha (TNF alpha), interleukin 8 (IL 8) and chemokines 5 (CCL5), including the IP-10, IL-6 cut effect more pronounced[7]. Li Ling et al.[8] showed that Maxing Shigan decoction can up-regulate the expression of interleukin-2 (IL-2), interleukin-4 (IL-4) and down-regulate the protein expression of TNF-, regulate the secretion of cytokines, improve the immune function of the body, and thus play a role in the treatment of viral pneumonia. Sue ZhongHao[9]and so on by watching Xuanbai Chengqi decoction on acute lung injury rats lung tissue CD14 and nf-kappa B mRNA expression, found that the influence of gas with Xuanbai Chengqi decoction can make ALI induced by LPS significantly reduce edema, hemorrhage, lung tissue damage degree, CD14 and nf-kappa B mRNA expression level, suggests Xuanbai Chengqi decoction on endotoxin induced acute lung injury has a protective effect in rats. The above studies suggest that the mechanism of chemosepsis prescription in the intervention of severe and critical patients with COVID-19 may be related to the elimination of pathogens, inhibition of inflammatory response, blocking inflammatory storm and improvement of lung tissue damage.

2.2 Immunomodulator Lymphocyte Ratio (NLR)

NLR has been reported in Beijing Ditan Hospital as an independent risk factor for the development of severe COVID-19 patients[10]. Xie iridium son[11], to analyze through the network pharmacology grandiflorum PiaoXia lingya herb decoction to the molecular mechanism of COVID-19 found PiaoXia three Chinese native medicine ingredient soup contains regulate the immune cells in patients with possible factor, by participating in IL - 6 - JAK2 - STAT3 signaling pathway, to adjust the IL6, TNF, affect B lymphocytes, T cells and other immune cells secrete. Mr Zhang[12] Maxingshigan decoction research for treatment of heavy COVID-19 such as the mechanism of action of 19, found that the main active ingredients can add and subtract Maxingshigan decoction by lowering MAKP activity of signaling pathways to suppress TNF, IL - 6, IL - 10, beta, etc. The expression level of IL - 1, the activation and adjust the immune cells, mediated T, B lymphocyte activation, proliferation, and immunomodulatory effect. The imbalance of lymphocyte subsets may be an indicator of abnormal immune response in patients with severe COVID-19. These basic studies provide an important theoretical basis for the treatment of abnormal immune response in patients with severe COVID-19 with Chemosepsis, which needs further verification.

2.3 Relieving spasm and relieving asthma

Jing Xinai ET al.[13] found that Maxingshigan decoction can reduce airway inflammation and airway epithelial reconstruction and reduce airway hyperresponsiveness by down-regulating the synthesis and release of nitric oxide (NO) and endotherin-1 (ET-1) in plasma and lung tissues. Zhang Haiou[14] observed the clinical efficacy of Xuanbai Chengqi decoction in the treatment of severe pneumonia with phlegm-heat obstructing the lung, and found that Xuanbai Chengqi decoction could reduce arterial oxygenate content and mechanical ventilation time, reduce the degree of pulmonary infection, and improve clinical symptoms as soon as possible. Modern pharmacology research shows that[15], glucosinolates are the effective ingredients for nemorosa nemorosa cough, and glucosinolates content is significantly increased after aba nemorosa Fried. The improvement of blood oxygen saturation and respiratory distress symptoms in severe patients may be related to the above mechanism, which needs further study.

2.4 Improve hemodynamics

Patients with severe COVID-19 may experience microcirculatory disturbances, sudden increases in heart rate by 20% or drops in blood pressure by more than 20%, accompanied by septic shock manifestations such as poor skin perfusion and decreased urine output. Studies have suggested[16] that the use of Xuanbai Chengqi decoction in the treatment of severe pneumonia caused by phlegm and hot organs can effectively reduce the leakage of plasma proteins from pulmonary vessels, reduce capillary permeability, regulate pulmonary vascular shunt, adjust the oxygenation state of patients, stabilize heart rate, keep blood pressure normal, and finally improve hemodynamics. Xuanbai Chengqi decoction can reduce inflammation and improve perfusion indexes, and has a significant effect on patients with sepsis caused by pneumonia. In the treatment of severe pneumonia in Chinese and western medicine, on the basis of full fluid resuscitation, in addition to the use of vasoactive drugs, taking chemosepsis prescription to improve patients' microcirculation and improve the hemodynamic mechanism may be related to the above studies.

3. Summary

In patients with severe COVID-19, there are multiple etiology and pathogenesis. The anti-sepsis decoction with multiple targets can prevent severe COVID-19 from damaging all organs of the body. Multiple prescription combinations can be selected to play the effects of clearing the lungs, relieving asthma, relieving heat, opening and closing, dryness and dampness, strengthening the spleen, promoting blood circulation and removing blood stasis, and supporting the health and removing pathogenic factors. Traditional Chinese medicine is a treasure of the Chinese nation. For thousands of years, the development of traditional Chinese medicine has its unique rules. Therefore, the research on traditional Chinese medicine decoctiontions should always adhere to the guidance of the theory of traditional Chinese medicine. In this paper, traditional Chinese and western medicine analysis was conducted on the compatibility of chemowet-septic prescription, so as to provide theoretical reference for clinical treatment of severe COVID-19. Colleagues in the traditional Chinese and western medicine sectors should follow the development rules of Chinese medicine, inherit the essence, keep innovation, promote the complementary advantages of traditional Chinese medicine and Western medicine, and give full play to the unique advantages and role of traditional Chinese medicine in the treatment of severe COVID-19.