OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment， diet， and lifestyle， which is closely related to many diseases in modern medicine， such as hyperlipidemia， obesity， fatty liver， atherosclerosis， metabolic syndrome， and cardiovascular and cerebrovascular diseases， with a wide range of influence and far-reaching harm. According to the Huangdi Neijing， lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids， which has the function of nourishing， and it is the initial state and source of important substances in the human body such as brain， marrow， essence， and blood. Once the grease of the human body is abnormal， it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach， which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments， leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity， which accumulates in the body's meridians， blood vessels， skin pores， and organs， forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays， it was divided into four common pathogenesis types： ''inability to distinguish between the clear and turbid， turbid stagnation in the Ying blood''， ''spleen not rising clear， turbid accumulation in the vessels''， ''spleen dysfunction， lipid retention in the pores''， ''spleen failure to transportation and transformation， and grease accumulation in the liver''. According to the pathogenesis， it could be divided into four common syndromes， namely， turbid stagnation in the Ying blood， turbid accumulation in the vessels， lipid retention in the pores， and grease accumulation in the liver， and the corresponding prescriptions were given for syndrome differentiation and treatment， so as to guide clinical differentiation and treatment of the lipid turbidity disease.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

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.