目的:探讨生活满意度、日常生活活动能力和社交活动在慢性病共病(multiple chronic conditions,MCCs)与抑郁关联中的多重平行中介作用。方法:数据来源于2020年中国健康与养老追踪调查(China Health and Retirement Longitudinal Study,C...目的:探讨生活满意度、日常生活活动能力和社交活动在慢性病共病(multiple chronic conditions,MCCs)与抑郁关联中的多重平行中介作用。方法:数据来源于2020年中国健康与养老追踪调查(China Health and Retirement Longitudinal Study,CHARLS)数据库,选取45~99岁调查对象进行横断面研究。结果:共纳入17318例研究对象,中老年人MCCs患病率为58.10%,抑郁患病率为37.56%,88.88%的中老年人对生活满意,日常生活活动能力(activities of daily living,ADL)评分为(6.53±1.50)分,社交活动评分的中位数为0(0,2.00)分。多重平行中介效应分析显示,在全部研究对象和各亚组中MCCs与抑郁症状关联的直接效应均有统计学意义(P<0.05),生活满意度和ADL评分在该关联中的中介效应也均有统计学意义(P<0.05),而社交活动的中介效应仅在老年人中有统计学意义(P<0.05)。结论:MCCs在直接影响抑郁症状的同时,还可通过生活满意度和ADL间接影响抑郁症状。因此,应关注中老年慢性病群体,预防与延缓慢性病进展的同时要增强日常生活自理能力,提高生活满意度,鼓励和帮助慢性病较多的老年人积极参与社交活动,以减少抑郁症状的发生。展开更多
Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-...Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.展开更多
BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extend...BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.展开更多
Objective:To assess the efficacy and safety profile of Auranti Fructus Immaturus flavonoid(AFIF)tablets in the treatment of patients with functional dyspepsia(FD).Methods:In this phase Ⅲ,randomized,control ed clinica...Objective:To assess the efficacy and safety profile of Auranti Fructus Immaturus flavonoid(AFIF)tablets in the treatment of patients with functional dyspepsia(FD).Methods:In this phase Ⅲ,randomized,control ed clinical trial,participants diagnosed with FD from 7 medical centers across China were assigned by stratified block randomization to either AFIF treatment group(3 AFIF tablets,0.29 g per tablet)or placebo group on the same schedule in a 3:1 ratio.The primary endpoint was the complete disappearance of 4 core FD symptoms,including postprandial ful ness,early satiety,upper abdominal pain,and upper abdominal burning,fol owing a 4-week treatment regimen(3 times daily).Secondary endpoints included the individual symptom disappearance rates and gastric emptying function after 4 weeks,as wel as the disappearance rates for al 4 individual symptoms of FD at 4 weeks after treatment.Subgroup analyses included 3 clinical symptoms and 4 Chinese medicine patterns.Safety assessments included monitoring treatment-emergent adverse events(AEs),serious adverse events(SAEs),intervention-related AEs,and any AEs leading to discontinuation.Results:Of the enrol ed patients,299 in the AFIF group and 99 in the control group were induded in the ful analysis set(FAS)and safety set(SS).After 4 weeks of treatment,the complete disappearance of al 4 core FD symptoms was achieved in 31.44%(94 cases)of patients in the AFIF group compared to 6.06%(6 cases)in the placebo group(P<0.01).At 4 weeks after end of treatment,the rates of symptom disappearance were 23.43%(67 cases)in the AFIF group and 2.22%(2 cases)in the placebo group(P<0.01).Individual symptom disappearance rates were significantly higher in the AFIF group at both week 4 and 4 weeks after treatment(al P<0.01).Additional y,the patients in the AFIF group exhibited a significantly greater improvement in gastric emptying at 2 h post-meal[66.55%(50.03,84.55)]compared to the placebo group[51.10%(44.75,68.93),P=0.027].At weeks 4 and 4 weeks after treatment,in the FAS,the disappearance rates of al 4 core FD symptoms remained higher in the AFIF group compared to the placebo group(al P<0.05).The per protocol set results similarly aligned with those observed in the FAS.Intervention-related AEs were reported in 6.02%(18 cases)of the AFIF group and 8.08%(8 cases)in the placebo group,with no SAEs recorded in either group.The patients in the AFIF group showed significantly higher complete symptom resolution rates of al 4 core FD symptoms at 4 weeks and 4 weeks after treatment across most subgroups,compared to the placebo group(al P<0.05).Al AEs related to AFIF Tablets were mild.Conclusion:AFIF tablets demonstrated robust efficacy in al eviating the symptoms of FD,with a favorable safety profile.(Registration No.CTR20132482)展开更多
文摘目的:探讨生活满意度、日常生活活动能力和社交活动在慢性病共病(multiple chronic conditions,MCCs)与抑郁关联中的多重平行中介作用。方法:数据来源于2020年中国健康与养老追踪调查(China Health and Retirement Longitudinal Study,CHARLS)数据库,选取45~99岁调查对象进行横断面研究。结果:共纳入17318例研究对象,中老年人MCCs患病率为58.10%,抑郁患病率为37.56%,88.88%的中老年人对生活满意,日常生活活动能力(activities of daily living,ADL)评分为(6.53±1.50)分,社交活动评分的中位数为0(0,2.00)分。多重平行中介效应分析显示,在全部研究对象和各亚组中MCCs与抑郁症状关联的直接效应均有统计学意义(P<0.05),生活满意度和ADL评分在该关联中的中介效应也均有统计学意义(P<0.05),而社交活动的中介效应仅在老年人中有统计学意义(P<0.05)。结论:MCCs在直接影响抑郁症状的同时,还可通过生活满意度和ADL间接影响抑郁症状。因此,应关注中老年慢性病群体,预防与延缓慢性病进展的同时要增强日常生活自理能力,提高生活满意度,鼓励和帮助慢性病较多的老年人积极参与社交活动,以减少抑郁症状的发生。
基金funded by the Natural Science Foundation of Guangdong Province(grant number 2022A1515012315)Guangdong Medical Science and Technology Research Fund Project(grant number A2023185)+2 种基金the Discipline Construction Project of Guangdong Medical University(grant number 4SG22005G)the 2023 Provincial Basic and Applied Basic Research Fund Enterprise Joint Fund Project(grant number 2023A1515220149)Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project(SRSP2023016).
文摘Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.
基金Supported by the Projects of Design and Statistics of Clinical Trials in Traditional Chinese Medicine,No.A YXC2022-01-0110Exploring the Mechanism by which Pingyang Yuyin Granules Improve Hypertensive Kidney Injury Based on the'Balance'Theory of PPARγ/HGF and TGF-β1/Smads Signaling Pathways,No.Y2022ZR09.
文摘BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.
文摘Objective:To assess the efficacy and safety profile of Auranti Fructus Immaturus flavonoid(AFIF)tablets in the treatment of patients with functional dyspepsia(FD).Methods:In this phase Ⅲ,randomized,control ed clinical trial,participants diagnosed with FD from 7 medical centers across China were assigned by stratified block randomization to either AFIF treatment group(3 AFIF tablets,0.29 g per tablet)or placebo group on the same schedule in a 3:1 ratio.The primary endpoint was the complete disappearance of 4 core FD symptoms,including postprandial ful ness,early satiety,upper abdominal pain,and upper abdominal burning,fol owing a 4-week treatment regimen(3 times daily).Secondary endpoints included the individual symptom disappearance rates and gastric emptying function after 4 weeks,as wel as the disappearance rates for al 4 individual symptoms of FD at 4 weeks after treatment.Subgroup analyses included 3 clinical symptoms and 4 Chinese medicine patterns.Safety assessments included monitoring treatment-emergent adverse events(AEs),serious adverse events(SAEs),intervention-related AEs,and any AEs leading to discontinuation.Results:Of the enrol ed patients,299 in the AFIF group and 99 in the control group were induded in the ful analysis set(FAS)and safety set(SS).After 4 weeks of treatment,the complete disappearance of al 4 core FD symptoms was achieved in 31.44%(94 cases)of patients in the AFIF group compared to 6.06%(6 cases)in the placebo group(P<0.01).At 4 weeks after end of treatment,the rates of symptom disappearance were 23.43%(67 cases)in the AFIF group and 2.22%(2 cases)in the placebo group(P<0.01).Individual symptom disappearance rates were significantly higher in the AFIF group at both week 4 and 4 weeks after treatment(al P<0.01).Additional y,the patients in the AFIF group exhibited a significantly greater improvement in gastric emptying at 2 h post-meal[66.55%(50.03,84.55)]compared to the placebo group[51.10%(44.75,68.93),P=0.027].At weeks 4 and 4 weeks after treatment,in the FAS,the disappearance rates of al 4 core FD symptoms remained higher in the AFIF group compared to the placebo group(al P<0.05).The per protocol set results similarly aligned with those observed in the FAS.Intervention-related AEs were reported in 6.02%(18 cases)of the AFIF group and 8.08%(8 cases)in the placebo group,with no SAEs recorded in either group.The patients in the AFIF group showed significantly higher complete symptom resolution rates of al 4 core FD symptoms at 4 weeks and 4 weeks after treatment across most subgroups,compared to the placebo group(al P<0.05).Al AEs related to AFIF Tablets were mild.Conclusion:AFIF tablets demonstrated robust efficacy in al eviating the symptoms of FD,with a favorable safety profile.(Registration No.CTR20132482)
