Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effec...Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedent...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.展开更多
Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to trea...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.展开更多
目的:采用Logistic回归分析和ROC曲线评估步态运动学特征联合MRI总负荷对脑小血管病(cerebral small vessel disease,CSVD)步态障碍患者跌倒风险的预测价值。方法:选取2019年3月1日—2020年3月30日就诊于甘肃省人民医院中法神经康复科...目的:采用Logistic回归分析和ROC曲线评估步态运动学特征联合MRI总负荷对脑小血管病(cerebral small vessel disease,CSVD)步态障碍患者跌倒风险的预测价值。方法:选取2019年3月1日—2020年3月30日就诊于甘肃省人民医院中法神经康复科诊断为CSVD且以步态障碍为主要症状的43例患者为研究对象,统计临床数据,根据TUG测试时间将所有患者分为高跌倒风险(high risk of falling,HRF;TUG时间≥15s)组和低跌倒风险(low risk of falling,LRF;TUG时间<15s)组,采用Logistic回归分析和ROC曲线评估步态运动学特征联合MRI总负荷对CSVD步态障碍患者跌倒风险的预测价值。结果:研究共纳入43例患者,平均年龄(71.07±8.17)岁。其中女性26例(60.4%),高血压患者30例(69.8%),Logistic回归分析显示,在校正年龄和TUG后,步长(OR 0.821,95%CI 0.702—0.959,P=0.013)为CSVD步态障碍患者跌倒风险的独立保护因素,MRI总负荷(OR 4.217,95%CI 1.444—12.317,P=0.009)为CSVD步态障碍患者跌倒风险的独立危险因素。ROC曲线分析显示步长和MRI总负荷联合对CSVD步态障碍患者的跌倒风险具有较高的预测价值(AUC=0.904),敏感性为82.6%,特异性为90%。结论:步长联合MRI总负荷对CSVD步态障碍患者的跌倒风险有较高的预测价值。展开更多
目的探讨不同剂量奥氮平治疗脑器质性和躯体疾病所致精神障碍患者的效果。方法以收治的108例脑器质性和躯体疾病致精神障碍患者为研究对象,用随机数字表法分为对照组和观察组,每组54例。对照组予以大剂量奥氮平片治疗,观察组予以小剂量...目的探讨不同剂量奥氮平治疗脑器质性和躯体疾病所致精神障碍患者的效果。方法以收治的108例脑器质性和躯体疾病致精神障碍患者为研究对象,用随机数字表法分为对照组和观察组,每组54例。对照组予以大剂量奥氮平片治疗,观察组予以小剂量奥氮平片治疗。2组均治疗8周。比较2组治疗后的效果,治疗前后阳性与阴性症状量表(positive and negative symptom scale,PANSS)评分、神经功能缺损评分量表(national institute of health strokescale,NIHSS)评分、日常生活能力量表(activity of daily living,ADL)评分、简明精神病评定量表(brief psychiatric rating scale,BPRS)评分和糖脂代谢指标。结果治疗后,观察组的临床总有效率高于对照组;2组阳性症状评分、阴性症状评分、一般精神病理评分、总评分、NIHSS评分及BPRS评分均降低,且观察组低于对照组(P<0.05),ADL评分升高,且观察组高于对照组(P<0.05);2组血清总胆固醇(total cholesterol,TC)、低密度脂蛋白-胆固醇(low-density lipoprotein cholesterol,LDL-C)、三酰甘油(triglycerides,TG)、空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、稳态胰岛素评价指数(homeostasis model assessment of insulin resistance,HOMA-IR)及餐后2 h血糖(2 hours postprandial blood glucose,2 h PBG)水平均升高,且观察组低于对照组,血清高密度脂蛋白-胆固醇(high-density lipoprotein cholesterol,HDL-C)水平均降低,且观察组高于对照组(P<0.05)。结论脑器质性和躯体疾病所致精神障碍患者应用小剂量奥氮平能够有效提高其临床治疗效果及日常生活能力,改善其精神状况、临床症状及神经功能,同时对患者糖脂代谢的影响较小。展开更多
The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m6A modifi...The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m6A modification. FTO catalyzes the demethylation of m6A to alter the processing, maturation and translation of the mRNAs of lipid-related genes. FTO overexpression in the liver promotes lipogenesis and lipid droplet (LD) enlargement and suppresses CPT-1–mediated fatty acid oxidation via the SREBP1c pathway, promoting excessive lipid storage and nonalcoholic fatty liver diseases (NAFLD). FTO enhances preadipocyte differentiation through the C/EBPβ pathway, and facilitates adipogenesis and fat deposition by altering the alternative splicing of RUNX1T1, the expression of PPARγ and ANGPTL4, and the phosphorylation of PLIN1, whereas it inhibits lipolysis by inhibiting IRX3 expression and the leptin pathway, causing the occurrence and development of obesity. Suppression of the PPARβ/δ and AMPK pathways by FTO-mediated m6A demethylation damages lipid utilization in skeletal muscles, leading to the occurrence of diabetic hyperlipidemia. m6A demethylation by FTO inhibits macrophage lipid influx by downregulating PPARγ protein expression and accelerates cholesterol efflux by phosphorylating AMPK, thereby impeding foam cell formation and atherosclerosis development. In summary, FTO-mediated m6A demethylation modulates the expression of lipid-related genes to regulate lipid metabolism and lipid disorder diseases.展开更多
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
基金Supported by the Chongqing Science and Health Joint Medical Research Project,No.2022MSXM133the First Batch of Key Disciplines on Public Health in Chongqing,Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.
文摘目的:采用Logistic回归分析和ROC曲线评估步态运动学特征联合MRI总负荷对脑小血管病(cerebral small vessel disease,CSVD)步态障碍患者跌倒风险的预测价值。方法:选取2019年3月1日—2020年3月30日就诊于甘肃省人民医院中法神经康复科诊断为CSVD且以步态障碍为主要症状的43例患者为研究对象,统计临床数据,根据TUG测试时间将所有患者分为高跌倒风险(high risk of falling,HRF;TUG时间≥15s)组和低跌倒风险(low risk of falling,LRF;TUG时间<15s)组,采用Logistic回归分析和ROC曲线评估步态运动学特征联合MRI总负荷对CSVD步态障碍患者跌倒风险的预测价值。结果:研究共纳入43例患者,平均年龄(71.07±8.17)岁。其中女性26例(60.4%),高血压患者30例(69.8%),Logistic回归分析显示,在校正年龄和TUG后,步长(OR 0.821,95%CI 0.702—0.959,P=0.013)为CSVD步态障碍患者跌倒风险的独立保护因素,MRI总负荷(OR 4.217,95%CI 1.444—12.317,P=0.009)为CSVD步态障碍患者跌倒风险的独立危险因素。ROC曲线分析显示步长和MRI总负荷联合对CSVD步态障碍患者的跌倒风险具有较高的预测价值(AUC=0.904),敏感性为82.6%,特异性为90%。结论:步长联合MRI总负荷对CSVD步态障碍患者的跌倒风险有较高的预测价值。
文摘目的探讨不同剂量奥氮平治疗脑器质性和躯体疾病所致精神障碍患者的效果。方法以收治的108例脑器质性和躯体疾病致精神障碍患者为研究对象,用随机数字表法分为对照组和观察组,每组54例。对照组予以大剂量奥氮平片治疗,观察组予以小剂量奥氮平片治疗。2组均治疗8周。比较2组治疗后的效果,治疗前后阳性与阴性症状量表(positive and negative symptom scale,PANSS)评分、神经功能缺损评分量表(national institute of health strokescale,NIHSS)评分、日常生活能力量表(activity of daily living,ADL)评分、简明精神病评定量表(brief psychiatric rating scale,BPRS)评分和糖脂代谢指标。结果治疗后,观察组的临床总有效率高于对照组;2组阳性症状评分、阴性症状评分、一般精神病理评分、总评分、NIHSS评分及BPRS评分均降低,且观察组低于对照组(P<0.05),ADL评分升高,且观察组高于对照组(P<0.05);2组血清总胆固醇(total cholesterol,TC)、低密度脂蛋白-胆固醇(low-density lipoprotein cholesterol,LDL-C)、三酰甘油(triglycerides,TG)、空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、稳态胰岛素评价指数(homeostasis model assessment of insulin resistance,HOMA-IR)及餐后2 h血糖(2 hours postprandial blood glucose,2 h PBG)水平均升高,且观察组低于对照组,血清高密度脂蛋白-胆固醇(high-density lipoprotein cholesterol,HDL-C)水平均降低,且观察组高于对照组(P<0.05)。结论脑器质性和躯体疾病所致精神障碍患者应用小剂量奥氮平能够有效提高其临床治疗效果及日常生活能力,改善其精神状况、临床症状及神经功能,同时对患者糖脂代谢的影响较小。
基金The authors gratefully acknowledge the financial supports from the National Natural Science Foundation of China (No. 81770460)the Natural Science Foundation of Guangxi Zhuang Autonomous Region, China (No. 2019JJA140728)+3 种基金the Natural Science Foundation of Hunan Province, China (No. 2020JJ4532)Scientific Research Foundation for the Excellent Youth of the Education Department of Hunan province, China (No. 18B264)Aid Program (No. 2017KJ268)Key Lab for Clinical Anatomy & Reproductive Medicine, China (No. 2017KJ182) from the Science and Technology Bureau of Hengyang City, China.
文摘The goal this review is to clarify the effects of the fat mass and obesity-associated protein (FTO) in lipid metabolism regulation and related underlying mechanisms through the FTO-mediated demethylation of m6A modification. FTO catalyzes the demethylation of m6A to alter the processing, maturation and translation of the mRNAs of lipid-related genes. FTO overexpression in the liver promotes lipogenesis and lipid droplet (LD) enlargement and suppresses CPT-1–mediated fatty acid oxidation via the SREBP1c pathway, promoting excessive lipid storage and nonalcoholic fatty liver diseases (NAFLD). FTO enhances preadipocyte differentiation through the C/EBPβ pathway, and facilitates adipogenesis and fat deposition by altering the alternative splicing of RUNX1T1, the expression of PPARγ and ANGPTL4, and the phosphorylation of PLIN1, whereas it inhibits lipolysis by inhibiting IRX3 expression and the leptin pathway, causing the occurrence and development of obesity. Suppression of the PPARβ/δ and AMPK pathways by FTO-mediated m6A demethylation damages lipid utilization in skeletal muscles, leading to the occurrence of diabetic hyperlipidemia. m6A demethylation by FTO inhibits macrophage lipid influx by downregulating PPARγ protein expression and accelerates cholesterol efflux by phosphorylating AMPK, thereby impeding foam cell formation and atherosclerosis development. In summary, FTO-mediated m6A demethylation modulates the expression of lipid-related genes to regulate lipid metabolism and lipid disorder diseases.
