Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrat...Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.展开更多
The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used ...The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.展开更多
Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limi...Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limitations in efficacy for some patients and raises potential safety concerns.Ezetimibe,as a novel lipid-modulating agent,exhibits potential advantages in the treatment of hyperlipidemia.Based on this,the present study investigated the therapeutic efficacy of ezetimibe in CHD patients with hyperlipidemia,as well as its effects on lipid metabolism and the amelioration of atherosclerosis.Methods In this study,150 clinical cases with CHD and hyperlipidemia admitted in our hospital from July 2022 to July 2024 were collected for retrospective analysis.According to different treatment methods,they were randomly divided into the Atorvastatin group(control group,n=75)and the Atorvastatin+Ezetimibe group(experimental group,n=75).Control group received atorvastatin monotherapy,while experimental group were administered additional ezetimibe as an adjunct to the atorvastatin-based treatment regimen.The clinical efficacy of the two treatment groups was analyzed,including cardiac function-related parameters such as the cardiac index(CI),cardiac output(CO),left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDD)before and after treatment.The observed indicators encompassed coronary angiography findings,the Gensini score for assessing coronary stenosis severity,the inflammatory marker high-sensitivity C-reactive protein(hs-CRP),and lipid profile parameters including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,the occurrence of adverse reactions during treatment was monitored.Results After treatment,the total effective rate in experimental group was significantly higher than that in control group,with a statistically significant difference(P<0.05).In the comparison of the baseline data,both groups showed marked improvements in CI,CO,LVEF,and HDL-C.However,at the same time points,the experimental group demonstrated significantly better results in these parameters than control group(P<0.05).Additionally,LVEDD,LDL-C,hs-CRP and Gensini scores were significantly reduced after treatment in both groups compared to pretreatment levels.Moreover,at identical time points,the aforementioned parameters in the experimental group demonstrated significantly greater reductions compared to control group(P<0.05).Regarding safety assessment,comparative analysis of adverse drug reaction(ADR)incidence rates between the two treatment groups revealed no statistically significant difference(P>0.05).Conclusions In patients with CHD complicated by hyperlipidemia,ezetimibe demonstrates significant therapeutic advantages.It effectively enhances treatment efficacy,regulates lipid profiles,improves cardiac function,and mitigates the progression of atherosclerosis.This regimen exhibits a favorable safety profile and holds substantial clinical value for both therapeutic processes and rehabilitation outcomes in this patient population.展开更多
The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus...The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus pentosaceus PP04(PP04)could colonize in intestine to regulate gut microbiota and it’s metabolites directly,the rebalanced intestinal flora mediated by PP04 could facilitate the secretion of short chain fatty acids to control body weight gain,PP04 intervention also changed bile acid(BA)profiles and enhanced the ileal concentrations of antagonists including tauro-α/β-muricholic acid sodium salt and ursodeoxycholic acid to inhibit intestinal farnesoid X receptor/fibroblast growth factor 15(FXR/FGF15)signaling coupled with the activation of hepatic FXR/small heterodimer partners signaling,which accelerated the hepatic BA de novo synthesis and excretion with feces to eliminate HFD caused hyperlipemia effectively.This study provided important evidence regarding PP04 as dietary supplement to relieve hyperlipidemia by influencing BA enterohepatic circulation.展开更多
BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe...BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe hypercholesterolemia as a result of impaired cholesterol metabolism.This report describes a patient with Alagille syndrome in whom a JAG1 mutation was detected by whole-exome sequencing.CASE SUMMARY The patient presented with severe hypercholesterolemia,biliary and hepatic impairment,pruritus,and triangular facial features.Mutations in the JAG1 gene,which encodes the Notch signaling pathway,were detected by whole-exome sequencing,leading to a diagnosis of Alagille syndrome.The patient was treated using a combination of traditional Chinese and Western medicines.Her cholesterol levels,liver function,and pruritus subsequently improved.CONCLUSION The possibility of Alagille syndrome should be considered in children who present with abnormal liver function and severe hypercholesterolemia.Genetic testing is needed to screen for disease-causing mutations and the disease can be treated with Traditional Chinese medicine.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
目的系统评价托莱西单抗治疗高脂血症的有效性和安全性。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、中国知网、万方、维普等数据库,检索时限为建库至2025年2月,对符合纳入标准的托莱西单抗治疗高脂血症的随机...目的系统评价托莱西单抗治疗高脂血症的有效性和安全性。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、中国知网、万方、维普等数据库,检索时限为建库至2025年2月,对符合纳入标准的托莱西单抗治疗高脂血症的随机对照研究,采用Rev Man 5.4软件进行Meta分析。结果纳入文献3篇,共计1061例患者。有效性分析结果显示:每4周给予450 mg托莱西单抗治疗与安慰剂相比显著降低低密度脂蛋白胆固醇(LDL-C)水平(MD=-63.76%,95%置性区间(CI)为-67.17%~-60.53%,P<0.00001),以及同时能够显著性地改善其他相关指标,差异具有统计学意义。安全性结果显示:托莱西单抗治疗高脂血症的安全性相关主要终点和次要终点与安慰剂组均无显著性差异(P>0.05)。结论托莱西单抗对中国成人高脂血症患者具有良好的有效性和安全性。展开更多
As a culinary and medicinal herb, rosemary is widely used. The present work aimed to investigate the effects of rosemary extracts on metabolic diseases and the underlying mechanisms of action. Liver cells stably expre...As a culinary and medicinal herb, rosemary is widely used. The present work aimed to investigate the effects of rosemary extracts on metabolic diseases and the underlying mechanisms of action. Liver cells stably expressing SREBP reporter were used to evaluate the inhibitory effects of different fractions of rosemary extracts on SREBP activity. The obese mice induced by Western-type diet were orally administered with rosemary extracts or vehicle for 7 weeks, the plasma and tissue lipids were analyzed. SREBPs and their target genes were measured by quantitative RT-PCR. We demonstrated that the petroleum ether sub-fraction of rosemary extracts(PER) exhibited the best activity in regulating lipid metabolism by inhibiting SREBPs, while water and n-Bu OH sub-fraction showed the SREBPs agonist-effect. After PER treatment, there was a significant reduction of total SREBPs in liver cells. PER not only decreased SREBPs nuclear abundance, but also inhibited their activity, resulting in decreased expression of SREBP-1c and SREBP-2 target genes in vitro and in vivo. Inhibiting SREBPs by PER decreased the total triglycerides and cholesterol contents of the liver cells. In the mice fed with Western-type diet, PER treatment decreased TG, TC, ALT, glucose, and insulin in blood, and improved glucose tolerance and insulin sensitivity. Furthermore, PER treatment also decreased lipid contents in liver, brown adipose tissue, and white adipose tissue. Our results from the present study suggested that petroleum ether fraction of rosemary extracts exhibited the best potential of improving lipid metabolism by inhibiting SREBPs activity.展开更多
Objective: To investigate the effects of Xuezhikang capsule (XZK,血脂康胶囊) on blood lipids level, platelet activation and coagulation-fibrinolysis activity in patients with hyerlipidemia. Methods: Seventy-six patien...Objective: To investigate the effects of Xuezhikang capsule (XZK,血脂康胶囊) on blood lipids level, platelet activation and coagulation-fibrinolysis activity in patients with hyerlipidemia. Methods: Seventy-six patients of hyperlipidemia were randomly divided into two groups, the XZK group (n=38) treated with XZK 600mg, taken two times per day and the Simvastatin (SIM) group (n = 38) treated with SIM 20mg per day, with the treatment lasting 8 weeks for both groups. Levels of fasting serum lipids, including total cholesterol (TC), triglyceride (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C), plasma GMP-140, fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-) and prothrombin time (PT) were all measured before and 8 weeks after treatment. Data were compared before and after treatment and also compared with those measured in 20 healthy subjects of control. Results: Before treantment the levels of TC, TG and LDL-C were obviously higher and HDL-C level was significantly lower in hyperlipidemia patients than those in healthy subjects (P<0.05 or P<0.01). After 4-8 weeks of XZK treatment, the levels of TC, TG, LDL-C and FIB and activities of GMP-140 and PAI-1 were obviously lowered (P<0. 05 or P<0. 01). But in the SIM group there was no obvious change in FIB (P>0.05), instead it showed obvious increase of HDL-C and decrease of TC and LDL-C after treatment (P<0.05 or P<0.01). Conclusion: XZK could inhibit platelet activity and improve coagulation-fibrinolysis function, besides its lipids lowering effect.展开更多
To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM pat...To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. Results. The serum levels of total cholesterol （TO）, triglycerides （TG） and low density lipoprotein-cholesterol （LDL-C） were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol （HDL-C） was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment （all P〈0.05）, but they did not differ statistically between the two groups （P〉0.05）. There was no significant changes in hemoglobin A1 c （HbA1c）. Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. Conclusion： In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.展开更多
基金funded by the National Natural Science Foundation of China(31901624)the Key-Area Research and Development Program of Guangdong Province(2018B020206001)+2 种基金Guangdong Province Zhujiang Talent Program(2019ZT08H476)Shenzhen Science and Technology Program(KQTD20180412181334790)the Innovation Team Project of Universities in Guangdong Province(2020KCXTD023)。
文摘Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.
基金supported by 2024 Liaoning Province Graduate Education Teaching Reform Research Project(LNYJG2024251).
文摘The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.
文摘Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limitations in efficacy for some patients and raises potential safety concerns.Ezetimibe,as a novel lipid-modulating agent,exhibits potential advantages in the treatment of hyperlipidemia.Based on this,the present study investigated the therapeutic efficacy of ezetimibe in CHD patients with hyperlipidemia,as well as its effects on lipid metabolism and the amelioration of atherosclerosis.Methods In this study,150 clinical cases with CHD and hyperlipidemia admitted in our hospital from July 2022 to July 2024 were collected for retrospective analysis.According to different treatment methods,they were randomly divided into the Atorvastatin group(control group,n=75)and the Atorvastatin+Ezetimibe group(experimental group,n=75).Control group received atorvastatin monotherapy,while experimental group were administered additional ezetimibe as an adjunct to the atorvastatin-based treatment regimen.The clinical efficacy of the two treatment groups was analyzed,including cardiac function-related parameters such as the cardiac index(CI),cardiac output(CO),left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDD)before and after treatment.The observed indicators encompassed coronary angiography findings,the Gensini score for assessing coronary stenosis severity,the inflammatory marker high-sensitivity C-reactive protein(hs-CRP),and lipid profile parameters including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,the occurrence of adverse reactions during treatment was monitored.Results After treatment,the total effective rate in experimental group was significantly higher than that in control group,with a statistically significant difference(P<0.05).In the comparison of the baseline data,both groups showed marked improvements in CI,CO,LVEF,and HDL-C.However,at the same time points,the experimental group demonstrated significantly better results in these parameters than control group(P<0.05).Additionally,LVEDD,LDL-C,hs-CRP and Gensini scores were significantly reduced after treatment in both groups compared to pretreatment levels.Moreover,at identical time points,the aforementioned parameters in the experimental group demonstrated significantly greater reductions compared to control group(P<0.05).Regarding safety assessment,comparative analysis of adverse drug reaction(ADR)incidence rates between the two treatment groups revealed no statistically significant difference(P>0.05).Conclusions In patients with CHD complicated by hyperlipidemia,ezetimibe demonstrates significant therapeutic advantages.It effectively enhances treatment efficacy,regulates lipid profiles,improves cardiac function,and mitigates the progression of atherosclerosis.This regimen exhibits a favorable safety profile and holds substantial clinical value for both therapeutic processes and rehabilitation outcomes in this patient population.
基金supported by the Jilin Province Science and Technology Plan Project(20230402032GH)the Jilin Province Science and Technology Development Project(20220508115RC).
文摘The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus pentosaceus PP04(PP04)could colonize in intestine to regulate gut microbiota and it’s metabolites directly,the rebalanced intestinal flora mediated by PP04 could facilitate the secretion of short chain fatty acids to control body weight gain,PP04 intervention also changed bile acid(BA)profiles and enhanced the ileal concentrations of antagonists including tauro-α/β-muricholic acid sodium salt and ursodeoxycholic acid to inhibit intestinal farnesoid X receptor/fibroblast growth factor 15(FXR/FGF15)signaling coupled with the activation of hepatic FXR/small heterodimer partners signaling,which accelerated the hepatic BA de novo synthesis and excretion with feces to eliminate HFD caused hyperlipemia effectively.This study provided important evidence regarding PP04 as dietary supplement to relieve hyperlipidemia by influencing BA enterohepatic circulation.
基金Natural Science Foundation of Hebei Province,China,No.H2020209160Scientific Research Projects in Chinese Medicine of Hebei Province,China,No.2019168.
文摘BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe hypercholesterolemia as a result of impaired cholesterol metabolism.This report describes a patient with Alagille syndrome in whom a JAG1 mutation was detected by whole-exome sequencing.CASE SUMMARY The patient presented with severe hypercholesterolemia,biliary and hepatic impairment,pruritus,and triangular facial features.Mutations in the JAG1 gene,which encodes the Notch signaling pathway,were detected by whole-exome sequencing,leading to a diagnosis of Alagille syndrome.The patient was treated using a combination of traditional Chinese and Western medicines.Her cholesterol levels,liver function,and pruritus subsequently improved.CONCLUSION The possibility of Alagille syndrome should be considered in children who present with abnormal liver function and severe hypercholesterolemia.Genetic testing is needed to screen for disease-causing mutations and the disease can be treated with Traditional Chinese medicine.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
文摘目的系统评价托莱西单抗治疗高脂血症的有效性和安全性。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、中国知网、万方、维普等数据库,检索时限为建库至2025年2月,对符合纳入标准的托莱西单抗治疗高脂血症的随机对照研究,采用Rev Man 5.4软件进行Meta分析。结果纳入文献3篇,共计1061例患者。有效性分析结果显示:每4周给予450 mg托莱西单抗治疗与安慰剂相比显著降低低密度脂蛋白胆固醇(LDL-C)水平(MD=-63.76%,95%置性区间(CI)为-67.17%~-60.53%,P<0.00001),以及同时能够显著性地改善其他相关指标,差异具有统计学意义。安全性结果显示:托莱西单抗治疗高脂血症的安全性相关主要终点和次要终点与安慰剂组均无显著性差异(P>0.05)。结论托莱西单抗对中国成人高脂血症患者具有良好的有效性和安全性。
基金supported by the Funds for Creative Research Groups of ChinaNational Natural Science Foundation of China(No.81421005)National Natural Science Foundation of China(No.81274159)
文摘As a culinary and medicinal herb, rosemary is widely used. The present work aimed to investigate the effects of rosemary extracts on metabolic diseases and the underlying mechanisms of action. Liver cells stably expressing SREBP reporter were used to evaluate the inhibitory effects of different fractions of rosemary extracts on SREBP activity. The obese mice induced by Western-type diet were orally administered with rosemary extracts or vehicle for 7 weeks, the plasma and tissue lipids were analyzed. SREBPs and their target genes were measured by quantitative RT-PCR. We demonstrated that the petroleum ether sub-fraction of rosemary extracts(PER) exhibited the best activity in regulating lipid metabolism by inhibiting SREBPs, while water and n-Bu OH sub-fraction showed the SREBPs agonist-effect. After PER treatment, there was a significant reduction of total SREBPs in liver cells. PER not only decreased SREBPs nuclear abundance, but also inhibited their activity, resulting in decreased expression of SREBP-1c and SREBP-2 target genes in vitro and in vivo. Inhibiting SREBPs by PER decreased the total triglycerides and cholesterol contents of the liver cells. In the mice fed with Western-type diet, PER treatment decreased TG, TC, ALT, glucose, and insulin in blood, and improved glucose tolerance and insulin sensitivity. Furthermore, PER treatment also decreased lipid contents in liver, brown adipose tissue, and white adipose tissue. Our results from the present study suggested that petroleum ether fraction of rosemary extracts exhibited the best potential of improving lipid metabolism by inhibiting SREBPs activity.
文摘Objective: To investigate the effects of Xuezhikang capsule (XZK,血脂康胶囊) on blood lipids level, platelet activation and coagulation-fibrinolysis activity in patients with hyerlipidemia. Methods: Seventy-six patients of hyperlipidemia were randomly divided into two groups, the XZK group (n=38) treated with XZK 600mg, taken two times per day and the Simvastatin (SIM) group (n = 38) treated with SIM 20mg per day, with the treatment lasting 8 weeks for both groups. Levels of fasting serum lipids, including total cholesterol (TC), triglyceride (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C), plasma GMP-140, fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-) and prothrombin time (PT) were all measured before and 8 weeks after treatment. Data were compared before and after treatment and also compared with those measured in 20 healthy subjects of control. Results: Before treantment the levels of TC, TG and LDL-C were obviously higher and HDL-C level was significantly lower in hyperlipidemia patients than those in healthy subjects (P<0.05 or P<0.01). After 4-8 weeks of XZK treatment, the levels of TC, TG, LDL-C and FIB and activities of GMP-140 and PAI-1 were obviously lowered (P<0. 05 or P<0. 01). But in the SIM group there was no obvious change in FIB (P>0.05), instead it showed obvious increase of HDL-C and decrease of TC and LDL-C after treatment (P<0.05 or P<0.01). Conclusion: XZK could inhibit platelet activity and improve coagulation-fibrinolysis function, besides its lipids lowering effect.
文摘To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. Results. The serum levels of total cholesterol （TO）, triglycerides （TG） and low density lipoprotein-cholesterol （LDL-C） were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol （HDL-C） was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment （all P〈0.05）, but they did not differ statistically between the two groups （P〉0.05）. There was no significant changes in hemoglobin A1 c （HbA1c）. Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. Conclusion： In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.
