Exogenous Febrile Disease Research Articles

Fei-Yan-Qing-Hua decoction attenuates influenza virus infection by enhancing host antiviral response through microbiota-derived acetate.

Fei-Yan-Qing-Hua decoction (FYQHD) is derived from the well-known Ma Xing Shi Gan decoction, which was documented in Zhang Zhong Jing's "Treatise on Exogenous Febrile Disease" during the Han Dynasty. Although FYQHD has been used in the treatment of pneumonia and has demonstrated clinical efficacy for decades, the underlying mechanism by which FYQHD protects against influenza virus infection through modulation of gut flora remains unclear. Here, we examined the regulatory impacts of FYQHD on an influenza virus-infected mouse model and explored the mechanisms involved. An infectious mouse model was created by intranasal instillation of influenza A virus (IAV). The effectiveness of FYQHD was assessed through various measures, including weight loss, lung wet/dry ratio, oxidative stress levels, viral load in lung tissues, and intestinal injuries. Changes in gut microbiota and SCFA production were also examined. The results showed that FYQHD significantly reduced viral load, increased the production of type I interferon (IFN-I), and restored the integrity of the intestinal barrier following IAV challenge. Additionally, FYQHD significantly corrected the dysbiosis of gut microbiota induced by influenza virus infection, enhancing the abundance of SCFA-producing bacteria and acetate production. However, the depletion of gut microbiota significantly attenuated the protective effects of FYQHD against influenza virus infection. In vitro, the antiviral effect of acetate was demonstrated through the upregulation of concentrations of IFN-β. FYQHD attenuates influenza virus-induced lung and intestinal injuries by boosting the host antiviral response through increasing the abundance of Lachnospiraceae_NK4A136 and Roseburia, along with elevated acetate levels. The study advances our understanding of the therapeutic mechanisms of FYQHD and provides a theoretical basis for the application of FYQHD in the treatment of influenza.

Fei-Yan-Qing-Hua decoction decreases hyperinflammation by inhibiting HMGB1/RAGE signaling and promotes bacterial phagocytosis in the treatment of sepsis

Ethnopharmacological relevanceFei-Yan-Qing-Hua decoction (FYQHD), derived from the renowned formula Ma Xing Shi Gan tang documented in Zhang Zhong Jing's “Treatise on Exogenous Febrile Disease” during the Han Dynasty, has demonstrated notable efficacy in the clinical treatment of pneumonia resulting from bacterial infection. However, its molecular mechanisms underlying the therapeutic effects remains elusive. Aim of the studyThis study aimed to investigate the protective effects of FYQHD against lipopolysaccharide (LPS) and carbapenem-resistant Klebsiella pneumoniae (CRKP)-induced sepsis in mice and to elucidate its specific mechanism of action. Materials and methodsSepsis models were established in mice through intraperitoneal injection of LPS or CRKP. FYQHD was administered via gavage at low and high doses. Serum cytokines, bacterial load, and pathological damage were assessed using enzyme-linked immunosorbent assay (ELISA), minimal inhibitory concentration (MIC) detection, and hematoxylin and eosin staining (H&E), respectively. In vitro, the immunoregulatory effects of FYQHD on macrophages were investigated through ELISA, MIC, quantitative real-time PCR (Q-PCR), immunofluorescence, Western blot, and a network pharmacological approach. ResultsThe application of FYQHD in the treatment of LPS or CRKP-induced septic mouse models revealed significant outcomes. FYQHD increased the survival rate of mice exposed to a lethal dose of LPS to 33.3%, prevented hypothermia (with a rise of 3.58 °C), reduced pro-inflammatory variables (including TNF-α, IL-6, and MCP-1), and mitigated tissue damage in LPS or CRKP-induced septic mice. Additionally, FYQHD decreased bacterial load in CRKP-infected mice. In vitro, FYQHD suppressed the expression of inflammatory cytokines in macrophages activated by LPS or HK-CRKP. Mechanistically, FYQHD inhibited the PI3K/AKT/mTOR/4E-BP1 signaling pathway, thereby suppressing the translational level of inflammatory cytokines. Furthermore, it reduced the expression of HMGB1/RAGE, a positive feedback loop in the inflammatory response. Moreover, FYQHD was found to enhance the phagocytic activity of macrophages by upregulating the expression of phagocytic receptors such as CD169 and SR-A1. ConclusionFYQHD provides protection against bacterial sepsis by concurrently inhibiting the inflammatory response and augmenting the phagocytic ability of immune cells.

Decoction Prescription Differentiation and Treatment of Palpitation in Treatise on Exogenous Febrile Disease

Heart palpitation is a common clinical disease, including various types of arrhythmias caused by organic or functional diseases in modern medicine. By analysing and sorting out the original texts and prescriptions concerned about heart palpitation in Treatise on Exogenous Febrile Disease through decoction prescription differentiation, seven types of decoction prescriptions for heart palpitation are summarized: Guizhi Gancao Decoction syndromes with deficiency of heart Yang, Fuling Gancao Decoction, Linggui Zhugan Decoction and Zhenwu Decoction syndromes with upward adverse flow of fluid-retention, Xiaojianzhong Decoction and Zhigancao Decoction syndromes with deficiency of Yin-blood, Chaihu Decoction syndromes with disharmony of Shaoyang, Sinisan syndromes with blockade of Yang Qi, Huanglian Ejiao Decoction syndromes with deficiency of Yin and hyperactivity of fire, Banxia Xiexin Decoction syndromes with comorbidities of heart and stomach, which totally include 14 prescriptions.

Qingdu decoction can reduce LPS induced ACLF endotoxemia by regulating microRNA-34c/MAZ/TJs and microRNA-122a/Zonulin/EGFR signal pathway

Ethnopharmacological relevanceQingdu Decoction (QDT) is a traditional Chinese medicine (TCM) that was derived from Xiaochengqi Decoction, a famous decoction documented in the book of Treatise on Exogenous Febrile Disease in the Eastern Han Dynasty. According to our years of clinical application, QDT showed satisfactory efficacy in the treatment of endotoxemia in acute-on-chronic liver failure (ACLF). However, the underlying molecular mechanisms remain largely unknown. Aim of studyIn this study, we aimed to systematically evaluate the intervention effect of QDT on endotoxemia in rats and further clarify its potential regulatory mechanism. Materials and methodsThe rat model of ACLF endotoxemia was induced by TAA and LPS + D-Gal. Then the rats were treated with clinical doses of QDT and lactulose. The rats were divided into four groups: CG, MG, QG and LG. The target microRNA was screened by high-throughput sequencing. The rat weight, liver index, hepatointestinal phenotype, serum biochemical indexes, mast cell activity, and hepatointestinal histopathology were used to evaluate the intervention effect. Western blot analysis was used to detect the expression levels of MAZ and its downstream genes ZO-1 and Occludin, and the expression levels of Zonulin and its downstream gene EGFR in colon. Finally, the expression of the miR-34c, MAZ, ZO-1, Occludin, miR-122a, Zonulin, and EGFR in colon was detected by qRT-PCR to further confirm the mechanism of the miR-34c/MAZ/TJs pathway and the miR-122a/Zonulin/EGFR pathway. ResultsThe rat weight, liver index, liver and colon phenotype, and serum biochemical indexes showed that QDT could significantly reduce liver and intestine injury and inhibit the progress of ACLF and endotoxemia. Toluidine blue staining and cytokine indexes showed that QDT could inhibit the activity of MCs and reduce the release of inflammatory factors. Mechanistically, QDT can inhibit the activity of MCs, activate miR-34c/MAZ/TJs pathway and miR-122a/Zonulin/EGFR pathway in colon, promote the recovery of intestinal barrier homeostasis, reduce and restore the damage of endotoxemia. ConclusionOur results suggested that QDT can significantly reduce rat ACLF endotoxemia by regulating the miR-34c/MAZ/TJs pathway and the miR-122a/Zonulin/EGFR pathway in colon.

Zhen Wu decoction represses renal fibrosis by invigorating tubular NRF2 and TFAM to fuel mitochondrial bioenergetics

BackgroundZhen Wu Decoction (ZWD) is a prescription from the classical text “Treatise on Exogenous Febrile Disease” and has been extensively used to control kidney diseases since the time of the Eastern Han Dynasty. HypothesisWe hypothesized that ZWD limits tubular fibrogenesis by reinvigorating tubular bio-energetic capacity. Study Design / MethodsA mouse model of chronic kidney disease (CKD) was established using unilateral ureteral obstruction (UUO). Three concentrations of ZWD, namely 25.2 g/kg (high dosage), 12.6 g/kg (middle dosage), and 6.3 g/kg (low dosage), were included to study the dose-effect relationship. Real-time qPCR was used to observe gene transcription in blood samples from patients with CKD. Different siRNAs were designed to study the role of mitochondrial transcription factor A (TFAM) and nuclear factor (erythroid-derived 2)-related factor 2 (NRF2) in transforming growth factor (TGF)-β1 induced fibrogenesis and mitochondrial damage. ResultsWe showed that ZWD efficiently attenuates renal function impairment and reduces renal interstitial fibrosis. TFAM and NRF2 were repressed, and the stimulator of interferon genes (STING) was activated in CKD patient blood sample. We further confirmed that ZWD activated TFAM depended on NRF2 as an important negative regulator of STING in mouse kidneys. Treatment with ZWD significantly reduced oxidative stress and inflammation by regulating the levels of oxidative phosphorylation (OXPHOS) and pro-inflammatory factors, such as interleukin-6, interleukin-1β, tumor necrosis factor receptor 1, and mitochondrial respiratory chain subunits. NRF2 inhibitors can weaken the ability of ZWD to increase TFAM expression and heal injured mitochondria, playing a similar role to that of STING inhibitors. Our study showed that ZWD elevates the expression of TFAM and mitochondrial respiratory chain subunits by promoting NRF2 activation, after suppressing mitochondrial membrane damage and cristae breakdown and restricting mitochondrial DNA (mtDNA) leakage into the cytoplasm to reduce STING activation. ConclusionZWD maintains mitochondrial integrity and improves OXPHOS which represents an innovative insight into “strengthening Yang-Qi” theory. ZWD limits tubular fibrogenesis by reinvigorating tubular bioenergetic capacity.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

BACKGROUNDRadiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM).AIMTo explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODSWe used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed.RESULTSWMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1β, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid).CONCLUSIONWMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

Network Analysis on Herbal Formulas from Wenrejingwei and Shang Han Lun.

ObjectivesThis study aims to describe the utilization of herbal formulas from Wenrejingwei by using network analysis and understand the treatment of acute exogenous febrile diseases.MethodsWe constructed a matrix of high-frequency herbal combinations (HCs) from Wenrejingwei and Shang Han Lun and cluster networks based on cohesive analysis. Network analysis was performed to compare the results.ResultsThe results of the high-frequency HC network in Wenrejingwei showed cohesive patterns in three categories corresponding to dampness-heat and warm-fever treatment. Compared to the Shang Han Lun network, the Wenrejingwei network indicated a careful approach in the use of pungent and warm herbs such as Guizhitang. Moreover, the combination of Scutellaria baicalensis and Coptis chinensis along with the use of herbs strengthening yin, such as Ginseng Radix and Liriopes Radix, provide evidence of a holistic approach in the treatment of exogenous febrile diseases by considering the balance of the human body damaged by heat.ConclusionThe results of this study could help select appropriate herbal formulas and treatment methods for treating Onbyeong and modern acute febrile infectious diseases.

Inhibitory Effects of Gyeji-Tang on MMP-9 Activity and the Expression of Adhesion Molecules in IL-4- and TNF-α-Stimulated BEAS-2B Cells.

Gyeji-tang (GJT), a traditional herbal formula composed of five herbal medicines, is commonly used to treat the common cold, exogenous febrile disease, fever and headaches in Korea, China and Japan. Although various pharmacological activities of GJT have been reported in several studies, the effect of GJT water extract (GJTWE) on airway inflammation has not yet been investigated. This study aimed to evaluate the effects of GJTWE on airway inflammation-related factors using human bronchial epithelial BEAS-2B cells, and to identify the phytochemicals in GJTWE by ultra-performance liquid chromatography-diode array detector-tandem mass spectrometry (UPLC-DAD-MS/MS) analysis. GJTWE significantly decreased the production of chemokines, including eotaxin-3, eotaxin-1, regulated on activation normal T-cell expressed and secreted (RANTES), and matrix metalloproteinase-9, and the expression of the adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, in interleukin-4 + tumor necrosis factor-α (IT)-stimulated BEAS-2B cells. In the UPLC-DAD-MS/MS analysis, 21 phytochemicals, including six flavonoids, two chalcones, five terpenoids, six phenolics, one phenylpropanoid and one coumarin, were identified in GJTWE. The findings suggested that GJTWE might exhibit anti-inflammatory effects on airway inflammation by regulating the expression of inflammatory response-related factors in IT-stimulated BEAS-2B cells; further studies are required to determine the bioactive compounds involved in the inhibition of airway inflammation.

Epidemic Diseases and Chinese Medicine: Example of Severe Acute Respiratory Syndrome and COVID-19.

Epidemic diseases, known and studied in China since antiquity, are one of the main chapters of the School of Exogenous Febrile Diseases (). Along with the legends about epidemic demons, China has developed over the centuries a medical approach based on the teachings of Huang Di Nei Jing (Internal Classic), Nan Jing (Classic of Difficulties), and Shang Han Lun (Treatise of Harmful Cold). However, it was in the 17th century, after the great break of the Song, Jin, and Yuan eras that an innovative spirit Wu Youxing () first foresaw the existence of microorganisms as we know them now. His Wen Yi Lun (Treatise on Pestilences) foreshadows an original approach to epidemic diseases, particularly emerging infectious diseases of the 21st century: severe acute respiratory syndrome 2003-2004 and the COVID-19 pandemic are perfect examples. In this first article, which will be followed by two others, we will examine the classical and modern Chinese definitions of these dreadful plagues.

Research on Herb Pairs of Classical Formulae of ZHANG Zhong-Jing Using Big Data Technology

ObjectiveTo analyze various herbal combinations in Treatise on Exogenous Febrile Diseases (Shang Han Lun,《伤寒论》) and Synopsis of Prescriptions of the Golden Chamber (Jin Gui Yao Lve, 《金匮要略》), seeking to identify fundamental rules dictating the selection of herbal combinations through probability models and big data technology. MethodsA total of 252 formulae were collected from Treatise on Exogenous Febrile Diseases (Shang Han Lun, 《伤寒论》) and Synopsis of Prescriptions of the Golden Chamber (Jin Gui Yao Lve, 《金匮要略》) by ZHANG Zhong-Jing. Formulae were then preprocessed with all herb names standardized. The concepts of candidate herb pair and candidate herb pair probability were proposed to analyze the rules of combinations in classical formulae based on probability statistics. MapReduce parallel computing framework of distributed big data technology was adopted to analyze large data samples combined with inverted index algorithm. ResultsThe results showed that the core herbs were Glycyrrhizae Radix Rhizoma (Gan Cao, 甘 草 ), Cinnamomi Ramulus (Gui Zhi, 桂 枝 ), Zingiberis Rhizoma Recens (Sheng Jiang, 生姜), Jujubae Fructus (Da Zao, 大枣), Paeoniae Radix Alba (Bai Shao, 白 芍 ), etc. 43 high-frequency pairs co-occurring 10 times or above were extracted, and 35 of these combinations were recognized as traditional herb pairs, such as Cinnamomi Ramulus (Gui Zhi, 桂枝) - Glycyrrhizae Radix Rhizoma (Gan Cao, 甘草), Zingiberis Rhizoma Recens (Sheng Jiang, 生姜) - Jujubae Fructus (Da Zao, 大枣), and Cinnamomi Ramulus (Gui Zhi, 桂枝) - Ginseng Radix Et Rhizoma (Ren Shen, 人参). The other 8 pairs of combinations, such as Paeoniae Radix Alba (Bai Shao, 白芍) - Zingiberis Rhizoma Recens (Sheng Jiang, 生姜), Paeoniae Radix Alba (Bai Shao, 白 芍 ) - Jujubae Fructus (Da Zao, 大 枣 ), and Zingiberis Rhizoma Recens (Sheng Jiang, 生姜) - Ginseng Radix Et Rhizoma (Ren Shen, 人参), were not defined traditionally, but in connection with commonly used herbs. Classical formulae took the core herbs as principles, focusing on tonifying deficiency, strengthening the spleen and the stomach, strengthening the healthy Qi, and eliminating pathogenic factors. The compatibility pattern of properties involved was mainly acrid and sweet, which reflected the compatibility laws of benefiting Qi and tonifying Yang, replenishing Qi and nourishing blood, etc. ConclusionsThe research of classical formulae provides common understanding of some basic rules that have been adopted to tackle common illnesses/diseases using herbal medicine. The results help to reinforce theoretical understanding and development of traditional Chinese medicine (TCM), and revealing the hidden rules of combination in TCM data. Analyzing wider data samples of various herbal combinations through computation and big data technology can further optimize the use of TCM.

Exploration of Chaige Jieji Decoction formula syndromes based on severe cases of critical care and its application for acute exogenous fever and nosocomial infection

Chaige Jieji Decoction recorded in Six Books of Exogenous Febrile Disease could be used to treat exterior syndrome due to wind-cold and heat caused by stagnation. The indications of Chaige Jieji Decoction include acute exogenous febrile diseases,such as influenza,upper respiratory tract infection,nosocomial infection; symptoms and signs,such as headache,eye pain,orbital pain,dizziness; fever,cold and hot exchanges; dry mouth,thirst,cold drinks,bitter mouth,dry throat; dry nose,stuffy nose,runny nose; poor appetite,silent appetite; strong neck,stiff back; insomnia,difficulty in sleeping; cough and sputum; abdominal pain,limb twitching;slightly torrent pulse. Disease involving all three Yang channels is very common in acute exogenous febrile diseases; the pathogenesis of exogenous diseases is quite different between cases in South China and North China. Most of the exogenous diseases in North China involves all three Yang channels. Disease involving all three Yang channels is the core of the pathogenesis of Chaige Jieji Decoction syndrome,in which headache is the key indications. Chaige Jieji Decoction can not only treat exogenous diseases,but also treat nosocomial infections in critically ill patients during hospitalization. Although Chaige Jieji Decoction,Xiaochaihu-Maxing Shigan Decoction,and Xiaochaihu-Daqinglong Decoction could be used to treat disease involving all three Yang channels,there are differences in indicators among them.

Exploration on connotation of Zhigancao Decoction formula syndrome from the perspective of modern pathophysiology and severe cases of critical care and its clinical efficacy on cardioversion,maintenance of sinus rhythm,hemostasis,increasing platelets count,and tonifying deficiency

Zhigancao decoction recorded in Treatise on Febrile Disease by Zhang Zhongjing in the Han dynasty have been widely used in treating palpitation and irregular pulse by traditional Chinese medicine physicians for thousands of years. It is all known that Zhigancao Decoction is used to treat consumptive disease. However,why it has been used to treat exogenous febrile disease? According to studies,Fumai Decoctions in Treatise on Differentiation and Treatment of Epidemic Febrile Disease,that was modified based on Zhigancao Decoction,have their names without reality. Serious defects,including unclear diagnosis,curative effect,and prognosis,have been found in ancient and modern medical records about Zhigancao Decoction. The indications of Zhigancao Decoction include atrial premature beats,ventricular premature beats,and viral myocarditis; tachyarrhythmia( supraventricular tachycardia,atrial fibrillation)with long interval or conduction block,during or after severe infection or high fever; chronic consumptive disease due to tumor after radiotherapy and chemotherapy,malignant fluid state of tumor,hematopathy,terminal stage of heart failure after major operation,and acute hemorrhage after control of severe infection and other major diseases; cough,phlegm and asthma due to chronic obstructive pulmonary disease,pulmonary interstitial fibrosis,lung cancer,after lung cancer surgery; increased heart rate and decreased blood pressure due to insufficient capacity after acute blood loss; the symptoms included palpitation,chest tightness,sweating,lassitude,lacking in strength,shortness of breath,syncope,sudden death,cough,expectoration,excessive phlegm,clear and dilute sputum,emaciation,dry and haggard skin,constipation,haemorrhagic,uterine bleeding,enjoy sweet taste,red tongue without moss,knotted pulse,intermittent pulse,thready rapid pulse,and weak pulse. Besides,Zhigancao Decoction has effect on cardioversion and maintenance of sinus rhythm without thrombosis in persistent atrial fibrillation and permanent atrial fibrillation. Zhigancao Decoction could stop bleeding soon for acute upper gastrointestinal bleeding,and achieve positivity of occult blood test; Zhigancao Decoction could promote thrombocytopenia for idiopathic thrombocytopenic purpura,with the number of platelets 1×109/L. Zhigancao Decoction could promote the rise of granulocytic,erythroid and megakaryocytic hematopoietic lines in unexplained severe anemia,thrombocytopenia,and leukocyte reduction. Zhigancao Decoction could treat cough,asthma,and chest tightness in lung cancer and after lung cancer surgery; chronic consumptive disease due to lung cancer after lung cancer surgery,hematopathy and acute blood loss,which all belonged to the scope of consumptive disease. Zhigancao Decoction could ascend platelets,which was considered as " oriental interleukins" for the ancients. Zhigancao Decoction possesses dual-directional regulation on anticoagulant and hemostasis,which was considered as " oriental low molecular heparin" and " oriental proton pump inhibitors". Large dose of Rehmannia glutinosa is the key of the efficacy of Zhigancao Decoction. This study is expected to enrich the guidelines for modern medical diagnosis and treatment. However,the clinical evidence,relevant genes and targeting network need to be deepened in future studies. In conclusion,it may be a shortcut to restore and explain Zhigancao Decoction formula syndromes based on modern pathophysiology and severe cases of critical care.

Treatise on Febrile Diseases and critical care medicine: exploring connotation of original, dosage, and essence of six meridians from perspective of critical care medicine and integrative medicine

Treatise on Febrile Diseases is one of the greatest classics in traditional Chinese medicine. Currently, so many key scientific problems including unclear connotation of the original, dosage of Chinese herbal medicine, and the essence of the six meridians were identified. On the basis of years of clinical experience in critical care medicine, it was advocated that the connotation of Treatise on Febrile Diseases should be explored from the perspective of critical care medicine and integrative medicine. It was identified that, the traditional study from the perspective of pathogenesis and textual research couldn't meet the current clinical needs due to its repeated deduction and circular argument in conceptual terms and unclear diagnosis and prognosis of modern diseases. The concept of exogenous febrile disease is the narrow sense, the essence of which may be acute febrile infectious diseases. Treatise on Febrile Diseases is a monographs for critical care medicine. The clinical manifestation of so many critical care medicine can be identified in Treatise on Febrile Diseases. The distinction standard of Treatise on Febrile Diseases and Synopsis of Golden Chamber is not external injury but contagious disease. The dosage problem in Treatise on Febrile Diseases mainly refers to large dose. The essence of six meridians in Treatise on Febrile Diseases is severe infection. Six meridians are different stages of severe infection, including the inflammation-based three Yang stages and deficiency-based three Yin stages. Additionally, the six meridians could be recognized by look, while not speculation. The struggle between cold and warm schools could be unified based on our research. The most direct and fundamental methods in studying Treatise on Febrile Diseases lies in critical care medicine and integrative medicine. The modern research of Treatise on Febrile Diseases is intensely calling for new treatment principle based on pathogenesis combined with pathology and property combined with pharmacology. Therefore, cultivation of ability in critical care medicine and integrative medicine should be emphasized in future studies.

Ding Ganren and the Shanghai Professional College of Chinese Medicine

Ding Ganren (1866-1926), a distinguished representative of the Menghe Medical School, created a new school of unifying the Cold pathogenic disease with Warm febrile disease by adopting a new therapeutic method of integrating the Six-channel and Defense-qi-nutrient-blood syndrome differentiation, and simultaneously applying the classical formula with seasonal formula for treating against the exogenous febrile disease, which was quite an innovative approach. Ding Ganren paid high attention to the advancement of the education of Chinese medicine and founded the first official medical school in 1916 called the "Shanghai Professional College of Chinese Medicine" . He was self-appointed the Director of the School, and responsible for its daily administration. Till the founding of new China, the School had trained 30 classes of students, totaling 869 graduates, most of them became well-known doctors and later the backbone of medical education and clinical science in the New China era.

The Seongho () School's Study of the Ancient Learning () and Its Influence on the Debate about Materia Medica in the Late Joseon Dynasty

This study will determine the ways in which the ancient learning (gu xue, ) scholarship of the Seongho School, and its interest in the materia medica (ben cao xue, ) were related during the late Joseon period. The Seongho School centered its studies mainly on classical Chinese texts of the Han (206 BC－AD 220) and pre-Han (?－221 BC) (xian-qin lianghan, ) periods rather than those of the Tang and Song dynasties (618-1279). gu xue scholarship emerged during the Ming dynasty era (1368 －1644) as an alternative to the scholarly trends of the Song dynasty, which were dependent on Zhu Xi's (, 1130－1200) Neo-Confucianism and its interpretation of Han and pre-Han classical Chinese texts. This scholarly trend influenced Korean and Japanese literature, philosophy, and even medicine from the seventeenth through the nineteenth centuries. Focusing on Korean scholarship, we find a great deal of research regarding the influence of gu xue on Korean classical Chinese literature and Confucian philosophy in the late Joseon period; however, no study has examined how this style of scholarship influenced the field of medicine during the same period. This study will investigate how the intellectuals of the Seongho School, who did the most to develop gu xue among Joseon intellectuals, were influenced by this style of scholarship in their study of the materia medica. Jeong Yak-yong (1762－1836), the representative intellectual of the Seongho School, did not focus on complicated metaphysical medical theories, such as the Yin-Yang and Five Elements theory (yin yang wu xing shui, ) or the Five Movements and Six Atmospheres theory (wu yun liu qi shui, ). Instead, his interests lay in the exact diagnoses of diseases and meticulous herbal prescriptions which formed an essential part of the Treatise on Exogenous Febrile Disease (Shang han lun, ) written by Zhang Zhungjing (, 150－219) in the Han dynasty. The Treatise was compatible with the scholarly purpose of gu xue in that they both eschewed metaphysical explanations. The Seongho School's interest in the materia medica stemmed from a desire to improve the delivery and quality of medical practices in rural communities, where metaphysical theories of medicine did not prevail and the cost of medicine was prohibitive.

The disease and treatment of the frontline soldiers in Han dynasty

This paper purports to identify and analyze the medical information of the frontline soldiers in the Northwest borderland provinces of Han Dynasty, especially Juyan and Dunhuang region, through an heuristic reading of the Juyan Bamboo Slips and the Dunhuang Bamboo Slips of the Han Dynasty. My findings are as follows. The most frequent disease found in the bamboo slips was the external injury. The injury of the frontline soldiers mainly occurred from the quarrels among armed soldiers using weapons. The bamboo slips also demonstrate that the quarrels usually arose due to the fierce tension caused by the frontier line service such as heavy guard activity and labour duty. Undernourishment and chronic stress the soldiers suffered might be another reasons. The second most common disease harassing the soldiers was exogenous febrile disease. In most cases reviewed in this paper, the exogenous febrile disease was usually concurrent with complex symptoms such as chills, fever, headache, etc. The bamboo slips show that the exogenous febrile disease was related to the harsh climate of the Northwest provinces, featuring extremely dry weather and the large magnitude of diurnal temperature fluctuations. In addition, the annual temperature range in the Northwest province was huge, fluctuating between very cold and dry winter and very hot and dry summer. The third most common disease this study identified was the disorder of the digestive system and respiratory system. However, these two types of disease were virtually indistinguishable in the bamboo slips, because the ancient Chinese chroniclers did not distinguish them, usually dubbing both diseases simply 'abdominal pain.' It should be mentioned that a few slips mention contagious disease such as dysentery and dermatolosis, and sudden death, as well. Overall, the bamboo slips demonstrate extremely poor status of the soldiers' heath condition and poor medical environment surrounding the soldiers stationing in the Northwest borderland military camps. The records also show that acupuncture, applying a plaster, drugs were the most common medical treatment. Drugs among them was the most frequently used. Whereas Acupuncture, applying a plaster were very rarely used. Medication has been used in three ways: powdered medicine, medicinal decoction and pill. Medicinal decoction was the most commonly used way.

Textual research on "Chigu Decoction" in Wooden Slips from the Site of the Ancient People's Dike in Zhangjiajie

In 1987, wooden slips named Zhi Chigu Fang (Chigu Decoction) were discovered on the site of the Ancient People's Dike in Zhangjiajie, Hunan Province. 15 drugs with dosage were listed on the front of the wooden slip and processing on the reverse side. Though there are two academic opinions about Chigu Decoction neither of them is convincing. Zhi means treatment and Chigu is the name of an ancient exogenous febrile disease with the symptoms of aversion to cold, fever, headache and neck pain, ankylosis, cough and asthma or cold pain in the gastric area and diarrhea. Chi is a descriptive word describing the appearance of exogenous febrile fever.

Discussion of time and space differentiation of three-yin and three-yang in Shanghan Lun

The concept of "three-yin and three-yang" in Shanghan Lun (Treatise on Cold Pathogenic Diseases), a classic written by Zhang Zhongjing in Han Dynasty, has been always the focus of dispute in successive dynasties. The essence of "three-yin and three-yang" has not been fully revealed up till now. Through studying the six divisions of day and night, the six diseases, the combination of syndromes, the complicated diseases, the complete recovery time and the space division of "three-yin and three-yang", the authors draw a conclusion that the "three-yin and three-yang" in Shanghan Lun is a concept of time-sequence, which is associated with the location of disease in space. So it is suggested that the "six diseases" in Shanghan Lun is a categorization for exogenous febrile diseases, and this categorization reveals a sort of inner relationship between the emergence, development, transformation of the febrile diseases and the time.