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N6, 2′ -O-dimethyladenosine (m
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Fibrosis is a repair response initiated by tissues and organs after injury, and is a self-protection mechanism of the body. It has been found that endothelium-to-interstitial transdifferentiation (EndMT) is involved in the physiological and pathological processes of various organ fibrosis, which has become a focus of the research on fibrotic diseases. In recent years, the study has found that EndMT plays an important role in many pathological processes in cardiovascular system, lungs, kidneys, liver, pancreas fibrosis, and so on. This article summarizes EndMT regulatory mechanism and its role in each organ fibrosis, as well as the related treatment progress of EndMT targets, so as to provide new targets for prevention and control of organ fibrosis.
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Aim To explore he preventive and therapeutic effects of Tongbu-fangchan prescription on aceylcholine-calcium chloride (Ach-CaCl
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Objective To investigate the value of intraoperative transesophageal echocardiography (TEE) in the diagnosis and treatment of renal cell carcinoma with inferior vena cava tumor thrombus. Methods Ten patients of renal cell carcinoma with inferior vena cava tumor thrombus treated in the Second Hospital of Hebei Medical University from January 2017 to January 2021 were selected.TEE was employed to locate the position of the tumor thrombus,determine the occlusion point of the inferior vena cava,count the intraoperative tumor thrombus shedding rate,examine the tumor thrombus resection integrity,and measure blood loss and other indicators,on the basis of which the application value of TEE in the operation of renal cell carcinoma with inferior vena cava tumor thrombus was evaluated. Results All the 10 patients had completed the operations successfully,including 8 patients of open operation and 2 patients of laparoscopic operation.TEE showed tumor thrombi clearly,and all the tumor thrombi were completely removed.There was no tumor thrombus shedding during the operation.The blood loss varied within the range of 300-800 ml,with the mean of (520.0±193.2) ml.The grade III tumor thrombi in 2 patients and the grade I tumor thrombus in 1 patient diagnosed before operation were reduced to grade Ⅱ and upgraded to grade Ⅱ,respectively,by TEE.One patient had no floating tumor thrombus at the end of tumor thrombus before operation,and the blocking position was adjusted in time with the assistance of TEE to avoid the shedding of the floating tumor thrombus. Conclusion TEE can accurately determine and dynamically monitor the location and shape of inferior vena cava tumor thrombus,which provides an important reference and has a significant clinical value in the operation of renal cell carcinoma with inferior vena cava tumor thrombus.
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Humans , Carcinoma, Renal Cell/surgery , Echocardiography, Transesophageal , Vena Cava, Inferior , Echocardiography , Kidney Neoplasms/surgeryABSTRACT
AIM: To observe the effects and mechanisms of ferroptosis on high glucose(HG)-induced retinal pigment epithelium(RPE)cells injury, and to provide new ideas for the treatment of diabetic retinopathy(DR).METHODS: The ARPE-19 cell lines cultured in vitro were divided into normal control group(NC group), high glucose group(HG group), and high glucose+Ferrostatin-1 group(Fer-1 group). The cell viability of each group was detected by CCK-8 assay. The expressions of interleukin 6(IL-6), IL-1β and monocyte chemotactic protein-1(MCP-1)were detected using ELISA kits. The levels of malondialdehyde(MDA), glutathione(GSH), glutathione peroxidase 4(GPX4)and iron content were detected using the corresponding assay kits. The mitochondrial changes in ARPE-19 cells were observed by transmission electron microscopy. The expressions of ferroptosis-related proteins including long-chain lipoyl CoA synthase 4(ACSL4)and GPX4, as well as vascular endothelial growth factor(VEGF)were detected by Western blotting and immunofluorescence staining.RESULTS: Compared with NC group, the cell viability of HG group decreased significantly, the expression levels of inflammatory factors in cell supernatant increased, the contents of MDA and iron significantly increased, GSH and GPX4 significantly decreased(all P<0.01), the mitochondria of ARPE-19 cells shrunk, the expression of proteins ACSL4 and VEGF increased, while the expression of GPX4 decreased(all P<0.01). Compared with HG group, the cell viability of Fer-1 group significantly increased, the expression levels of inflammatory factors in cell supernatant decreased, MDA and iron contents significantly decreased, GSH contents and GPX4 viability significantly increased(all P<0.05), the morphology of mitochondria in ARPE-19 cells improved, the expression of ACSL4 and VEGF decreased, while the expression of GPX4 increased(all P<0.05).CONCLUSION: Ferroptosis is involved in the injury of RPE induced by HG. Inhibiting ferroptosis can improve cell viability, reduce inflammation and oxidative stress, and alleviate HG-induced RPE cells injury.
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The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.
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Humans , Papillomaviridae , Biomedical Research , Papillomavirus VaccinesABSTRACT
Lysine succinylation is a novel post-translational modification, which plays an important role in regulating distinct cellular functions control, therefore it is necessary to accurately identify succinylation sites in proteins. As traditional experiments consume material and financial resources, prediction by calculation is an efficient method being proposed recently. In this study, we developed a new prediction method iSucc-PseAAC, which uses a variety of classification algorithms combined with different feature extraction methods. Moreover, it is found that under the feature extraction based on coupled sequence (PseAAC), the classification effect of support vector machine is the best, and it could be combined with ensemble learning to solve the problem of data imbalance. Compared with the existing methods, iSucc-PseAAC has more significance and practicality in predicting lysine succinylation sites.
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The decline of body function and senile diseases caused by aging seriously affect human health and life span， which is an important topic in the field of life science. Bazi Bushen capsules is a representative Chinese patent medicine for tonifying essence， invigorating Qi and anti-aging， guided by Qiluo doctrine， and essence， Qi and spirit theory. Previous pharmacological and clinical studies have confirmed that this preparation has the comprehensive advantages of anti-aging， and prevention and treatment of aging-related diseases. Among them， pharmacological studies showed that Bazi Bushen capsules had the effect of improving the appearance status of mice， improving the level of sex hormones， inhibiting the formation of atherosclerosis， improving cardiac function， improving learning and memory cognitive ability， improving neurological function， improving osteoporosis and muscle function， improving sperm count and quality. The mechanism was related to the up-regulation of the recombinant sirtuin （SIRT6） level， down-regulation of the levels of aging-related proteins p53 and p16， up-regulation of telomerase reverse transcriptase level， and alleviation of inflammation and oxidative response. Clinical studies have proved that it can improve the symptoms of patients with kidney essence deficiency， improve exercise ability， and improve the sexual function of impotence patients. Anti-aging research of Bazi Bushen capsules based on Qiluo doctrine fully embodies the new mode of academic innovation and transformation of traditional Chinese medicine （TCM） with the combination of "theory-new drug-experiment-clinic"， which has made a demonstration for the anti-aging research of TCM.
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Along with increasing degree of population aging globally， senility， good health and long life have become the focus of the world. Guided by Qiluo doctrine， an essence， Qi and spirit theory is proposed as below， essence is the origin of life， Qi is the impetus of life and spirit is the embodiment of life. Based on holistic view of kidney deficiency involving the five internal organs and injuries of the five internal organs definitely affecting the kidney， a mechanism of aging is proposed as below， deficiency of kidney essence is the foundation of aging， deficiency of promordial Qi is the key of aging and physical and spiritual loss is the manifestation of aging. It provides a theoretical guidance for anti-aging study of rejuvenating the elderly and making the strong person stronger. By virtue of the experiences in kidney-tonifying medication accumulated for more than two thousand years， Bazi Bushen capsules has been developed， which has anti-aging efficacy， including tonifying kidney， replenishing essence， coordinating Yin and Yang， supplementing primordial Qi and nourishing body and spirit. Experimental researches have demonstrated that Bazi Bushen capsules can improve overall aging and systemic aging， as well as prevent and treat aging related diseases. Preliminary clinical studies demonstrate that this capsules can enhance athletic ability and improve sexual function， and is expected to become a representative Chinese patent medicine of anti-aging. This paper addresses aging and anti-aging on the basis of Qiluo doctrine， in the hope of helping prevention and treatment of aging related diseases.
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Interventional or thrombolytic therapy for acute myocardial infarction （AMI） has the effect of opening occluded coronary arteries. However， due to no myocardial regurgitation， ischemia/reperfusion injury and microvascular structure and function destruction， leading to myocardial fibrosis following AMI， ventricular remodeling， and even cardiac failure may occur. Collaterals doctrine is used to guide the investigation into traditional Chinese medicine pathogenesis and clinical treatment of myocardial fibrosis following AMI. Consequently， it proposes the pathogenesis characteristic of "Qi deficiency and blood stasis， collaterals obstruction" and medication principle of "dispersing and dredging"， to develop the formula of Tongxinluo. Fundamental and clinical researches have demonstrated it can effectively protect the structure and function of myocardial microvascular endothelial cells， improve no reflow and reperfusion injury， and inhibit myocardial fibrosis after AMI， which further supports scientific value of the collaterals doctrine.
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Objective:Guided by nutrient-defense stages in the vessel-collateral theory， the modern medical cases of unstable angina pectoris（UAP） were systematically collated and analyzed to explore the rules of syndrome and treatment of UAP and the molecular mechanism of core Chinese herbal combination in the treatment of UAP based on network pharmacology. Method:All medical cases with UAP treated by Chinese medicinal compounds were retrieved from PubMed，China National Knowledge Infrastructure （CNKI），Wanfang Data， VIP， and SinoMed published between database inception and November 2020. The syndromes of medical cases were determined based on the nutrient-defense stages of the vessel-collateral theory. Rules of syndrome and treatment of UAP were investigated by data mining methods， such as frequency statistics， cluster analysis， and enhanced FP-Growth algorithm. The molecular mechanism of core Chinese herbal combination in the treatment of UAP was analyzed by network pharmacology. Result:The first four syndromes of UAP with high frequencies were deficiency and stagnation of collateral Qi， blood stasis obstructing collaterals， depression and stagnation of collateral Qi， and turbid phlegm obstructing collaterals. The Chinese herbal medicines with high frequencies included Salviae Miltiorrhizae Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， and Astragali Radix， which were effective in resolving stasis， dredging collaterals， replenishing Qi， consolidating defensive Qi， regulating Qi， relieving depression， and dispelling phlegm. The association analysis indicated that the core Chinese herbal combination in the treatment of UAP was Salviae Miltiorrhizae Radix Chuanxiong Rhizoma-Astragali Radix. Four Chinese herbal combinations were obtained by cluster analysis. As revealed by network pharmacology， the key components of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix in the treatment of UAP included quercetin， luteolin， and tanshinone Ⅱ<sub>A</sub>， and the key targets included serine/threonine-protein kinase 1 （Akt1）， mitogen-activated protein kinase 1 （MAPK1）， Jun， interleukin （IL）-6， and MAPK8. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis showed that phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might serve as the main pathway for its therapeutic efficacy. Conclusion:The basic pathogenesis of UAP is deficiency/depression and stagnation of collateral qi and turbid phlegm obstructing collaterals. The treatment should follow the principles of replenishing Qi， resolving stasis， and dredging collaterals， assisted with regulating Qi and resolving phlegm. The therapeutic efficacy of Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma-Astragali Radix was achieved via multi-component， multi-target， and multi-pathway. This study is expected to inspire future UAP-related studies at the molecular level based on vessel-collateral theory.
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Airway mucus is an important part of the defense barrier function of the airway. Abnormal secretion of airway mucus is closely related to recurrent attacks， delay or aggravation of respiratory infectious or infectious diseases such as chronic obstructive pulmonary disease （COPD）， community-acquired pneumonia， and coronavirus disease 2019 （COVID-19）. Lianhua Qingke tablets， an innovative traditional Chinese medicine （TCM） developed under the guidance of the theory of collateral disease of TCM， has the function of reducing phlegm and relieving cough， which can reduce the generation and viscosity of sputum and promote sputum excretion. Clinical studies have shown that it can significantly improve the symptoms of expectoration and cough in patients with acute bronchitis or COVID-19， confirming its scientific connotation and clinical value of reducing phlegm and relieving cough to improve ventilation and exchanging function.
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Objective:To seed for stable time window of the integrated disease-syndrome animal model based on the counterevidence from Chinese medicinal prescriptions， and to verify syndrome stability and reliability. Method:A model of depression was established by exposing rats to chronic unpredictable mild stress （CUMS）， followed by body weight measurement， sugar water test， behavioral test， and brain 5-hydroxytryptamine（5-HT） detection. The identification of liver depression and spleen deficiency syndrome was conducted after the equivalent transformation of human clinical symptoms into macroscopic representations of rats. Based on the dynamically collected macroscopic representation scale， Xiaoyaosan was used to reversely verify the stability and reliability of the integrated disease-syndrome animal model of depression due to liver depression and spleen deficiency. Result:The sugar water consumption and the number of crossings and the total movement distance in the open field test of 16-week-old rats in the CUMS （eight weeks of CUMS） group were significantly lower than those in the normal group （<italic>P</italic><0.05）. According to the immunohistochemical results， the 5-HT content in hippocampal area CA2 of rats in the CUMS group was also significantly lowered as compared with that in the normal group（<italic>P</italic><0.05），which indicated that depression was successfully modeled. The liver depression and spleen deficiency syndrome was present in 14-week-old rats （six weeks after CUMS）of the CUMS group， and the number of rats experiencing the liver depression and spleen deficiency syndrome reached the peak in the 16th week （eight weeks after CUMS），accounting for 70% of the total number. Thereafter， the number decreased gradually. The syndrome scores of the 14-， 16-， 18-， 20-， and 22-week-old rats in the Xiaoyaosan group were reduced by 66.6%， 70.7%， 54.8%， 50.4%， and 44.8%， which were graded as effective， marked effective， effective， effective， and effective， respectively. Conclusion:The age of 14-16 weeks（six to eight weeks after CUMS） is considered the stable and reliable time window for depression due to liver depression and spleen deficiency.
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The global incidence of breast cancer has increased year by year. Breast cancer has the highest mortality rate in female patients with malignant tumors. Traditional Chinese medicine（TCM） has made great contribution to health of human being， improving the overall curative effect， reducing the patients' pain， improving the quality of life and alleviating adverse reactions in patients. TCM and its active compounds can inhibit the proliferation of breast cancer cells by inducing cell cycle arrest， invasion， metastasis and reversing multidrug resistance. The effect of the compounds in TCM is obvious on inducing the arrest of the breast cancer cells cycle. It′s a novel method to fight against breast cancer by influencing the progress of the breast cancer cell cycle and inducing the cell cycle arrest in breast cancer cells. Lots of studies have shown that the G2/M phase checkpoint which transition from gap-phase （G2 phase） to mitotic phase （M phase） in the cell cycle is the key point for cell survival or death. Many antitumor drugs can inhibit the proliferation of tumor cells through the cell cycle arrest. We summarized the domestic and foreign literatures in recent years， and comprehensively explained the research progress on the related regulatory molecules in G2/M arrest. In addition， we summarized and sorted out the researches on the methods and ways of alkaloids， polysaccharides， terpenes， flavonoids， saponins and other active compounds of TCM in inducing the G2/M arrest of human breast cancer cells. By summarizing the active compounds of various Chinese medicines in inducing G2/M arrest of breast cancer cells， and reviewing the research progress on mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells， we will， in this paper， investigate the mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells through inducing G2/M arrest of human breast cancer cells， so as to provide a scientific basis for in-depth research on the anti-breast cancer mechanism of the active compounds in TCM.
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Based on the syndrome and treatment system of collateral disease， and inheriting the development of the bloodline theory of traditional Chinese medicine （TCM）， academician WU Yi-ling systematically constructed the vessel-collateral theory of TCM and proposed that its core theory was the theory of Yingwei， that is， "Ying in the vein， and Wei outside the vein" （Huangdi Neijing·Lingshu·Yingwei Shenghui）， "obstructing of Yingwei， congelation of blood" （Treatise on Febrile Diseases· Pulse Differentiation Method）， "pathogen transferring through blood vessels， obstructed by blocking" （Jinkui Yaolue·Zangfu Jingluo Xianhou Bingmaizheng First）， and "damage of the heart， adjust its Yingwei". Based on the consistency of vessel-collateral as the channel of blood circulation in TCM with the blood vessels in western medicine， and guided by the Yingwei theory of vessel-collateral theory， the diagnostic criteria of syndrome differentiation of disease of vessel-collateral and vascular system represented by coronary heart disease， arrhythmia， heart failure and others was established to guide the prevention and treatment of vascular diseases. Based on the above analysis， guided by the Yingwei theory of vessel-collateral theory， and on the basis of related researches of vessel-collateral and vascular system， this paper discussed the etiology and pathogenesis of chronic coronary syndrome （CCS） in TCM. Taking useful collateral with unblocking as the treatment principle， the representative Tongluo prescription （Tongxinluo） was constructed， the research progress of Tongxinluo from various aspects such as animal experiment research， pharmacological research and clinical evidence-based research was summarized， a comprehensive system from etiology， pathogenesis， syndrome differentiation to treatment was formed， in order to provide new ideas for the clinical treatment of CCS.
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Purpose@#Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. @*Materials and Methods@#Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. @*Results@#We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. @*Conclusion@#This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.
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Purpose@#Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. @*Materials and Methods@#Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. @*Results@#We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. @*Conclusion@#This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.
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Protein S-sulfonylation is a reversible protein post-translational modification (PTM) that plays a vital role in biological growth. It is also related to some diseases. Therefore from the perspective of basic research or drug development, we are faced with a challenging question: where are the S-sulfonylation sites on proteins? In order to solve this problem, we developed a method for site prediction. The working principle of the system is (1) Combine these proteins into isometric amino acids.(2) Use down sampling to balance the training data set;(3) Build a comprehensive prediction system through ensemble support vector machines. In the end, the accuracy rate on the independent tester reached 90. 77%. Compared with the existing methods, all other indicators have been improved, and the improvement effect is obvious. Thus we provided help for the development of bioinformatics. We have established a friendly web server prediction website: http://www.jci-bioinfo.cn/iSulf_Wide-PseAAC, through which the website can make the prediction online, without complicated calculation formulas. At the same time, the mathematical methods used in this article can solve many problems in similar related fields.
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This paper aims to systematically analyze the peptides and proteins from Asini Corii Colla(ACC) through shotgun proteomics. After high-pH reversed-phase fractionation, the proteins and peptides in the hydrolysate of ACC were further separated by nano LC-Q-Exactive-MS/MS under the following conditions: Thermo Scientific EASY column(100 μm×2 cm, 5 μm, C_(18)) as precolumn, Thermo Scientific EASY column(75 μm×100 mm, 3 μm, C_(18)) for solid phase extraction, gradient elution with 0.1% formic acid in water(mobile phase A) and 84% acetonitrile in water containing 0.1% formic acid(mobile phase B), and MS in positive ion mode. Based on Uniprot_Equus caballus, MS data, and literature, 2 291 peptides were identified from ACC by MaxQuant, with 255 Maillard reactions(AML, CML, CEL)-modified peptides identified for the first time. Through alignment, the peptides were found to belong to 678 equine proteins. In conclusion, the combination of nano LC-Q-Exactive-MS/MS and shotgun proteomics achieved rapid and accurate identification of the proteins and peptides in ACC, which provides the key information and new insights for further investigation of chemicals and effective substances in ACC.
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Animals , Chromatography, Liquid , Horses , Peptides , Proteins , Proteomics , Tandem Mass SpectrometryABSTRACT
Related records about discipline of diagnosis and treatment of exogenous febrile diseases by traditional Chinese medicine (TCM) were reviewed to summarize TCM knowledge about etiology, pathogenesis, progress and treatment of infectious epidemic diseases among exogenous febrile diseases. In consideration of onset time and major clinical manifestations of novel coronavirus pneumonia (NCP), this disease is considered as within the scope of pestilence in TCM, it is located in the lung, with etiology being poison of winter-warm syndrome, the viruses enter body via mouth and nose, and invade pulmonary collaterals. Based on the syndrome characteristics proposed in diagnosis and treatment schemes of various regions as well as the researches on medication rules, the present study points out the core pathogenesis of NCP is epidemic toxin invading the lung, pathogenic heat obstructing the lung and toxic heat blocking the lung. It also analyzes theoretical formula features of TCM Lianhua Qingwen and related clinical and experimental research results, in order to prove the clinical value of this drug in the outbreak of NCP.