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.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

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.

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.

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.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

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.

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.

BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

Green prescription is a written prescription aimed at improving health by promoting physical activity and improving diet， with advantages such as high cost-effectiveness， strong feasibility， and minimal harm to patients. The theory of traditional Chinese medicine （TCM） green prescription integrates the health philosophy of "following rule of yin and yang， and adjusting ways to cultivating health"， the exercise philosophy of balancing yin-yang and the five elements， and the dietary philosophy of moderation and balance， which embody core TCM concepts such as treating disease before its onset and harmony between humans and nature. It has also developed traditional exercise practices like Tai Chi， Baduanjin， Wuqinxi， Yi-Gin-Ching， and Qigong， as well as dietary adjustments like medicated diet and herbal wines. However， it is believed that the TCM green prescription currently suffers from insufficient evidence-based research， low patient awareness and acceptance， and weak basic research. Based on this， it is proposed that large-sample clinical trials should be conducted in the future to improve the quality of evidence-based medicine， basic research can be carried out with the help of artificial intelligence and other methods in research design， the hospital information system （HIS） can be used for control at the implementation level， and publicity and patient education can be strengthened through the new media， so as to promote the development and application of the TCM green prescriptions in the field of global health treatment.