1.Visual Analysis of Literature Research on Compatibility of Bitter and Pungent Medicinals in Traditional Chinese Medicine
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):19-28
ObjectiveTo analyze the research situation, hotspots, and trend of the compatibility of bitter and pungent medicinals in traditional Chinese medicine by knowledge mapping and provide reference for the inheritance and clinical application of this theory. MethodsThe literature on the compatibility of bitter and pungent medicinals was retrieved from 6 databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SinoMed, Web of Science, and PubMed. The literature was searched with the keywords of bitter medicinals, pungent medicinals, compatibility, Banxia Xiexin decoction, Zhuyu pills, and Zuojin pills. The search time ranged from January 1, 1984 to August 10, 2024. NoteExpress 3.7 was used for literature screening, and CiteSpace 6.1.R2 was used to visualize the number of publications, authors, institutional cooperation network, and the co-occurrence, clustering, time line, and burst of keywords. ResultsA total of 628 Chinese articles and 151 English articles related to the compatibility of bitter and pungent medicinals were included, and the annual number of publications rose with fluctuations. WEI Wei was the core author of Chinses articles and SHEN Tao and ZHAO Yanling were the core authors of English articles. China Academy of Chinese Medical Sciences formed a close cooperative network with many research institutions at home and abroad. The high-frequency keywords included pungent dispersing and bitter descending, Coptidis Rhizoma, Euodiae Fructus, Banxia Xiexin decoction, Zuojin pills, compatibility, spleen and stomach diseases, and gut microbiota, which mainly involved common prescriptions, diseases responding specifically to traditional Chinese medicine, mechanism research and so on. The keyword bursts concentrated in famous doctors' experience, network Meta-analysis, inflammatory bowel disease, diabetes mellitus, intestinal microbiota, etc. The compatibility of bitter medicinals and pungent medicinals was widely used in clinical practice. Based on pungent dispersing and bitter descending, the middle energizer was regulated for treating spleen and stomach diseases and inflammatory bowel disease. Bitter and pungent medicinals descending the turbid were used to treat diabetes mellitus and hyperlipidemia by lowering blood glucose and lipid levels. The mild bitter and slightly pungent medicinals were used as supplements to treat depression and COVID-19 by regulating Qi movement. ConclusionIn the past 40 years, the number of publications on the compatibility of bitter and pungent medicinals has been increasing, and the research team has begun to take form. Clinically, the compatibility of bitter and pungent medicinals is the main treatment for spleen and stomach diseases and glycolipid metabolic diseases. At present, the modern scientific essence of the compatibility of bitter and pungent medicinals is mainly explained based on famous doctors' experience inheritance, network meta-analysis, and intestinal flora.
2.Zhuyuwan in Treatment of Hyperlipidemia Complicated with Carotid Atherosclerosis: A Randomized Controlled Trial
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):38-45
ObjectiveTo observe the efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis. MethodsA total of 120 patients with hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis were randomly allocated into a treatment group and a control group, with 60 patients in each group. The control group orally took rosuvastatin calcium tablets, 10 mg each time, once a day. The treatment group took Zhuyuwan granules, 1 dose a day in 3 times. Both groups received diet and exercise guidance and were treated for 24 consecutive weeks. The traditional Chinese medicine (TCM) symptom scores were recorded before and after treatment. The levels of blood lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], carotid color ultrasound [carotid intima-media thickness (IMT), plaque number, maximum plaque area, and maximum plaque thickness], vascular intimal repair-related factors [nitric oxide (NO), endothelin-1 (ET-1), soluble intercellular adhesion molecule 1 (sICAM-1), and thromboxane B2 (TXB2)], and oxidative stress-related indicators [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] were measured before and after treatment. The occurrence of adverse reactions was observed during treatment, and the clinical efficacy of the two groups was compared after treatment. ResultsThe trial was completed and 112 patients (57 in the treatment group and 55 in the control group) were included in the statistical analysis, and the general information of the two groups was comparable. The total response rate in the treatment group was 87.72% (50/57), which was higher than that (74.55%, 41/55) in the control group (χ2=4.823, P<0.05). After treatment, the scores of main TCM symptoms such as body obesity, chest tightness, and limb numbness, the scores of secondary symptoms such as palpitation, insomnia, tastelessness in the mouth, reduced appetite, tongue and pulse manifestation scores, and the total TCM symptom score decreased in both groups (P<0.05, P<0.01). Moreover, the treatment group had lower scores of main symptoms such as body obesity, head heaviness, chest tightness, nausea, salivation, and limb numbness, scores of secondary symptoms such as tastelessness in the mouth and reduced appetite, and total TCM symptom score than the control group (P<0.05, P<0.01). After treatment, both groups showed declines in TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.05, P<0.01) and elevations in levels of HDL-C, NO, and SOD (P<0.05, P<0.01). The treatment group had lower TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.01) and higher levels of HDL-C, NO, SOD, and GSH-Px (P<0.05, P<0.01) than the control group. During treatment, adverse reactions occurred in 3 cases (5.26%, 1 case of dizziness, 1 case of acid reflux, and 1 case of constipation) in the treatment group and 4 cases (7.27%, 2 cases of upper respiratory tract infection, 1 case of abdominal pain, and 1 case of low back pain) in the control group. ConclusionZhuyuwan can effectively reduce blood lipid levels, inhibit the formation of carotid atherosclerotic plaque, and alleviate the syndrome of phlegm turbidity and obstruction by promoting vascular intima repair and improving the antioxidant function.
3.Exploration of Zhuyuwan in Treatment of Atherosclerosis from Perspective of Lipid Transport Disorder
Wei SONG ; Zhongyi ZHANG ; Hairong QIU ; Mei ZHAO ; Zubing ZHOU ; Tao SHEN ; Yong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):54-61
This article discusses the key pathogenesis of atherosclerosis (AS) based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS, aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances, lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement, the accumulation of dampness and turbidity, and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors: deficiency of healthy Qi, phlegm-turbidity, and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids, their impaired dispersion may lead to phlegm-turbidity and blood stasis, the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore, AS is rooted in spleen-stomach disorder, manifests as plaques formed by pathological product accumulation in vessels, with lipid transport disorder as its core pathogenesis. Specifically speaking, the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage, and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan, first recorded in Taiping Holy Prescriptions for Universal Relief, contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma, bitter and cold, exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus, pungent-bitter and hot, disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang, assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism, Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance, improving gut microbiota composition and metabolism, and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS, this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder, giving novel insights into the prevention and treatment of AS.
4.Visual Analysis of Literature Research on Compatibility of Bitter and Pungent Medicinals in Traditional Chinese Medicine
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):19-28
ObjectiveTo analyze the research situation, hotspots, and trend of the compatibility of bitter and pungent medicinals in traditional Chinese medicine by knowledge mapping and provide reference for the inheritance and clinical application of this theory. MethodsThe literature on the compatibility of bitter and pungent medicinals was retrieved from 6 databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SinoMed, Web of Science, and PubMed. The literature was searched with the keywords of bitter medicinals, pungent medicinals, compatibility, Banxia Xiexin decoction, Zhuyu pills, and Zuojin pills. The search time ranged from January 1, 1984 to August 10, 2024. NoteExpress 3.7 was used for literature screening, and CiteSpace 6.1.R2 was used to visualize the number of publications, authors, institutional cooperation network, and the co-occurrence, clustering, time line, and burst of keywords. ResultsA total of 628 Chinese articles and 151 English articles related to the compatibility of bitter and pungent medicinals were included, and the annual number of publications rose with fluctuations. WEI Wei was the core author of Chinses articles and SHEN Tao and ZHAO Yanling were the core authors of English articles. China Academy of Chinese Medical Sciences formed a close cooperative network with many research institutions at home and abroad. The high-frequency keywords included pungent dispersing and bitter descending, Coptidis Rhizoma, Euodiae Fructus, Banxia Xiexin decoction, Zuojin pills, compatibility, spleen and stomach diseases, and gut microbiota, which mainly involved common prescriptions, diseases responding specifically to traditional Chinese medicine, mechanism research and so on. The keyword bursts concentrated in famous doctors' experience, network Meta-analysis, inflammatory bowel disease, diabetes mellitus, intestinal microbiota, etc. The compatibility of bitter medicinals and pungent medicinals was widely used in clinical practice. Based on pungent dispersing and bitter descending, the middle energizer was regulated for treating spleen and stomach diseases and inflammatory bowel disease. Bitter and pungent medicinals descending the turbid were used to treat diabetes mellitus and hyperlipidemia by lowering blood glucose and lipid levels. The mild bitter and slightly pungent medicinals were used as supplements to treat depression and COVID-19 by regulating Qi movement. ConclusionIn the past 40 years, the number of publications on the compatibility of bitter and pungent medicinals has been increasing, and the research team has begun to take form. Clinically, the compatibility of bitter and pungent medicinals is the main treatment for spleen and stomach diseases and glycolipid metabolic diseases. At present, the modern scientific essence of the compatibility of bitter and pungent medicinals is mainly explained based on famous doctors' experience inheritance, network meta-analysis, and intestinal flora.
5.Zhuyuwan in Treatment of Hyperlipidemia Complicated with Carotid Atherosclerosis: A Randomized Controlled Trial
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):38-45
ObjectiveTo observe the efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis. MethodsA total of 120 patients with hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis were randomly allocated into a treatment group and a control group, with 60 patients in each group. The control group orally took rosuvastatin calcium tablets, 10 mg each time, once a day. The treatment group took Zhuyuwan granules, 1 dose a day in 3 times. Both groups received diet and exercise guidance and were treated for 24 consecutive weeks. The traditional Chinese medicine (TCM) symptom scores were recorded before and after treatment. The levels of blood lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], carotid color ultrasound [carotid intima-media thickness (IMT), plaque number, maximum plaque area, and maximum plaque thickness], vascular intimal repair-related factors [nitric oxide (NO), endothelin-1 (ET-1), soluble intercellular adhesion molecule 1 (sICAM-1), and thromboxane B2 (TXB2)], and oxidative stress-related indicators [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] were measured before and after treatment. The occurrence of adverse reactions was observed during treatment, and the clinical efficacy of the two groups was compared after treatment. ResultsThe trial was completed and 112 patients (57 in the treatment group and 55 in the control group) were included in the statistical analysis, and the general information of the two groups was comparable. The total response rate in the treatment group was 87.72% (50/57), which was higher than that (74.55%, 41/55) in the control group (χ2=4.823, P<0.05). After treatment, the scores of main TCM symptoms such as body obesity, chest tightness, and limb numbness, the scores of secondary symptoms such as palpitation, insomnia, tastelessness in the mouth, reduced appetite, tongue and pulse manifestation scores, and the total TCM symptom score decreased in both groups (P<0.05, P<0.01). Moreover, the treatment group had lower scores of main symptoms such as body obesity, head heaviness, chest tightness, nausea, salivation, and limb numbness, scores of secondary symptoms such as tastelessness in the mouth and reduced appetite, and total TCM symptom score than the control group (P<0.05, P<0.01). After treatment, both groups showed declines in TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.05, P<0.01) and elevations in levels of HDL-C, NO, and SOD (P<0.05, P<0.01). The treatment group had lower TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.01) and higher levels of HDL-C, NO, SOD, and GSH-Px (P<0.05, P<0.01) than the control group. During treatment, adverse reactions occurred in 3 cases (5.26%, 1 case of dizziness, 1 case of acid reflux, and 1 case of constipation) in the treatment group and 4 cases (7.27%, 2 cases of upper respiratory tract infection, 1 case of abdominal pain, and 1 case of low back pain) in the control group. ConclusionZhuyuwan can effectively reduce blood lipid levels, inhibit the formation of carotid atherosclerotic plaque, and alleviate the syndrome of phlegm turbidity and obstruction by promoting vascular intima repair and improving the antioxidant function.
6.Exploration of Zhuyuwan in Treatment of Atherosclerosis from Perspective of Lipid Transport Disorder
Wei SONG ; Zhongyi ZHANG ; Hairong QIU ; Mei ZHAO ; Zubing ZHOU ; Tao SHEN ; Yong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):54-61
This article discusses the key pathogenesis of atherosclerosis (AS) based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS, aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances, lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement, the accumulation of dampness and turbidity, and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors: deficiency of healthy Qi, phlegm-turbidity, and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids, their impaired dispersion may lead to phlegm-turbidity and blood stasis, the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore, AS is rooted in spleen-stomach disorder, manifests as plaques formed by pathological product accumulation in vessels, with lipid transport disorder as its core pathogenesis. Specifically speaking, the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage, and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan, first recorded in Taiping Holy Prescriptions for Universal Relief, contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma, bitter and cold, exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus, pungent-bitter and hot, disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang, assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism, Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance, improving gut microbiota composition and metabolism, and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS, this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder, giving novel insights into the prevention and treatment of AS.
7.Effects of Zhuyu Pill (茱萸丸) and its Ingredient on Aortic Plaque and the NLRP3/Asc/Caspase-1 Signaling Pathway in Aortic Tissue of Mice in Atherosclerosis Model
Wei SONG ; Zhongyi ZHANG ; Kai WANG ; Tao SHEN
Journal of Traditional Chinese Medicine 2024;65(6):618-626
ObjectiveTo investigate the possible mechanism of action and combination of medicinals of Zhuyu Pill (茱萸丸) in the treatment of atherosclerosis. MethodsThirteen normal C57BL/6J mice were used as blank group, and 40 ApoE
8.Treating Chronic Urticaria with the Method of Dredging Sanjiao (三焦)
Wei SONG ; Zhongyi ZHANG ; Bo JIA ; Tao SHEN ; Rudi AI ; Mingling CHEN ; Min XIAO
Journal of Traditional Chinese Medicine 2024;65(4):414-418
The membranous tube of sanjiao (三焦) is not only the path of the transport of fluid and qi, but the way of the invasion of pathogenic factors, therefore, it cooperates with the skin mucous membrane physically and influence on each other pathologically. It is believed that the core pathogenesis of chronic urticaria is pathogens intruding sanjiao, membrane collaterals acute spasm, and fluid and qi disturbance, of which defense qi insufficiency and pathogens intruding sanjiao initiates the disease, while struggle between healthy and pathogenic qi and membrane collaterals acute spasm is the intermediate stage, and disturbed fluid, qi and blood movement is the terminal stage. Following the core treatment principle of dredging sanjiao, the internal treatment is to open striae and interstices and dispel pathogens out using self-made Guben Shufeng Decoction(固本疏风汤)modifications, and the external treatment is to dredge and regulate membrane collaterals, move qi and fluid, and treat sanjiao simultaneously, commonly using cutting therapy on Danzhong (RN 17) to move qi and fluid, seal umbilical therapy on Shenque (RN 8) to supplement and nourish ying-wei (营卫), and natural moxibustion on Xuehai (SP 10) to move blood and unblock collaterals.
9.Historical Evolution and Herbal Textual Research of Jupi Zhurutang
Zhongyi ZHANG ; Xin HE ; Wei SONG ; Chunqiu ZHOU ; Qianrong GAN ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):161-173
Jupi Zhurutang originated from Synopsis of the Golden Chamber (《金匮要略》), which consists of Pericarpium Citri Reticulatae, Caulis Bambusae in Taenia, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, Jujubae Fructus, and Glycyrrhizae Radix et Rhizoma and is used to treat retching. It has been put on the list of Catalogue of Ancient Classical Prescription (First Batch) released by National Administration of Traditional Chinese Medicine. With the bibliometric method, we searched the medical classics containing Jupi Zhurutang and systematically examined the information on the origin of the prescription, the indications, compatibility rule, medicinals in the prescription, dosage and usage, processing method, and decocting method. It was found that there are many versions of Jupi Zhurutang, and there are common grounds of main symptoms, pathogenesis, composition and dosage between the same prescription with different names and different prescriptions with the same name. The prescription which is closest to the original version in Synopsis of the Golden Chamber is mainly used for the treatment of stomach deficiency and qi counterflow without obvious cold or heat. According to the weights and measures, ratio of Pericarpium Citri Reticulatae, Caulis Bambusae in Taenia, Radix Ginseng, Rhizoma Zingiberis Recens, and Radix Ginseng in Synopsis of the Golden Chamber is approximately 6∶2∶8∶5∶1. The Jupi Zhurutang derived from other ancient classics such as Yanshi Jisheng Fang(《严氏济生方》) is a different prescription for hiccups caused by the stomach heat, and the ratio of Pericarpium Citri Reticulatae to Caulis Bambusae in Taenia in this prescription is about 1∶1. It is also found that cold herbs such as Red Poria, Eriobotryae Folium and Ophiopogon Japonicus are added to the formula in later generations. Therefore, the Jupi Zhurutang used in modern times is mostly modified and different from that in Synopsis of the Golden Chamber. This study summarizes the historical evolution of Jupi Zhurutang and identifies the key information, with a view to providing a reference for the rational modification of this prescription in clinical settings and further research.
10.Severe Cutaneous Adverse Reactions: A Single-Center Retrospective Study of 173 Patients in China
Zhongyi XU ; Jie SHEN ; Yiwen YANG ; Ruoyue YUAN ; Leihong Flora XIANG ; Chengfeng ZHANG
Annals of Dermatology 2019;31(5):545-554
BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.
Acute Generalized Exanthematous Pustulosis
;
Adrenal Cortex Hormones
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Allopurinol
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Anti-Bacterial Agents
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Carbamazepine
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China
;
Cicatrix
;
Drug Hypersensitivity Syndrome
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Eosinophilia
;
Humans
;
Lymphatic Diseases
;
Mortality
;
Prognosis
;
Public Health
;
Retrospective Studies
;
Skin
;
Stevens-Johnson Syndrome
;
Tertiary Healthcare

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