To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases ri...To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.展开更多
The B-cell lymphoma 2(Bcl2)family of proteins participates in cell death or survival through a mitochondrial pathway.The pro-apoptotic members of the Bcl2 family such as Bim,Bid,Bax and Bak trigger cell death by contr...The B-cell lymphoma 2(Bcl2)family of proteins participates in cell death or survival through a mitochondrial pathway.The pro-apoptotic members of the Bcl2 family such as Bim,Bid,Bax and Bak trigger cell death by contributing to the enhancement of mitochondrial outer membrane permeability to pro-apoptotic factors such as cytochrome c,with展开更多
Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or hu...Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or human immunodeficiency virus(HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease(CVD) and type 2 diabetes(T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2 D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2 D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2 D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.展开更多
Objective To investigate the effects of microvesicles(MVs) derived from hypoxia/reoxygenation(H/R)-treated human umbilical vein endothelial cells(HUVECs) on endothelium-dependent relaxation of rat thoracic aortic ring...Objective To investigate the effects of microvesicles(MVs) derived from hypoxia/reoxygenation(H/R)-treated human umbilical vein endothelial cells(HUVECs) on endothelium-dependent relaxation of rat thoracic aortic rings.Methods H/R injury model was established to induce HUVECs to release H/R-EMVs.H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium.H/R-EMVs were characterized using 1 urn latex beads and anti-PE-CD144 by flow cytometry.Thoracic aortic rings of rats were incubated with 2.5,5,10,20 μg/ml H/R-EMVs derived from H/R-treated HUVECs for 4 hours,and their endothelium-dependent relaxation in response to acetylcholine(ACh) or endothelium-independent relaxation in response to sodium nitroprusside(SNP) was recorded in vitro.The nitric oxide(NO) production of ACh-treated thoracic aortic rings of rats was measured using Griess reagent.The expression of endothelial NO synthase(eNOS) and phosphorylated eNOS(p-eNOS,Ser-1177) in the thoracic aortic rings of rats was detected by Western blotting.Furthermore,the levels of SOD and MDA in H/R-EMVs-treated thoracic aortic rings of rats were measured using SOD and MDA kit.Results H/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation.The membrane vesicles(< 1 urn) induced by H/R were CD144 positive.ACh-induced relaxation and NO production of rat thoracic aortic rings were impaired by H/R-EMVs treatment in a concentration-dependent manner(P<0.05,P<0.01).The expression of total eNOS(t-eNOS)was not affected by H/R-EMVs.However,the expression of p-eNOS decreased after treated with H/R-EMVs.The activity of SOD decreased and the level of MDA increased in H/R-EMVs treated rat thoracic aortic rings(P<0.01).Conclusion ACh induced endothelium-dependent relaxation of thoracic aortic rings of rats was impaired by H/R-EMVs in a concentration-dependent manner.The mechanisms included a decrease in NO production,p-eNOS expression and an increase in oxidative stress.展开更多
Hypoglycemia unawareness(HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms.It is a major limitation to achieving tight diabetes and reduced quality of life.HU occurs in...Hypoglycemia unawareness(HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms.It is a major limitation to achieving tight diabetes and reduced quality of life.HU occurs in approximately 40% of people with type 1 diabetesmellitus(T1DM) and with less frequency in T2 DM.Though the aetiology of HU is multifactorial,possible mechanisms include chronic exposure to low blood glucose,antecedent hypoglycaemia,recurrent severe hypoglycaemia and the failure of counter-regulatory hormones.Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms,but the mechanisms and mediators remain largely unknown.Prevention and management of HU is complex,and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team.Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes.Several medications are thought to worsen or promote HU,whereas others may have an attenuating effect on the problem.This article reviews recent advances in how the brain senses and responds to hypoglycaemia,novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses.The consequences that HU has on the person with diabetes and their family are also described.Finally,it examines the evidence for prevention and treatment of HU,and summarizes the effects of medications that may influence it.展开更多
Current progress in epigenetic research supports the view that diet and dietary components are important in cancer etiology by enhancing or inhibiting carcinogenesis.Since diet and dietary factors may significantly co...Current progress in epigenetic research supports the view that diet and dietary components are important in cancer etiology by enhancing or inhibiting carcinogenesis.Since diet and dietary factors may significantly contribute to the causation and progression of many cancers,it is important to find the molecular mechanisms of action of such dietary factors for cancer prevention and treatment.Recently,the role of epigenetic mechanisms in the cancer development and progression has attracted more attention as additional evidence along with traditional DNA sequence based mechanisms such as mutations and structural re-arrangements.Such an increasing interest in cancer epigenetics has also accelerated the development and application of molecular assays and tools for DNA methylation detection and histone modification enrichment analysis.In this paper,key assays and methods for epigenetic research are reviewed and discussed in terms of their utility and usability.In addition,more advanced methods for genome-wide analysis are introduced as part of upcoming research trends and directions.展开更多
Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to i...Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion(I/R) injury in rats. Methods: Myocardial IPC was elicited by three cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending(LAD) coronary artery. Platelet-free plasma(PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFP. PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 μm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure(MAP), heart rate(HR) and ST-segment of electrocardiogram(ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin(HE) staining. The activity of plasma lactate dehydrogenase(LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining. Results: Total IPC-MVs and different phenotypes, including platelet-derived MVs(PMVs), endothelial cell-derived MVs(EMVs), leucocyte-derived MVs(LMVs) and erythrocyte-derived MVs(RMVs) were all isolated which were identified membrane vesicles(<1 μm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats(P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR(P<0.01), decreased ST-segment and LDH activity(P<0.05, P<0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment(P<0.01). Conclusion: The method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.展开更多
In clinical practice obesity is primarily diagnosed through the body mass index. In order to characterize patients affected by obesity the use of traditional anthropometric measures appears misleading. Beyond the body...In clinical practice obesity is primarily diagnosed through the body mass index. In order to characterize patients affected by obesity the use of traditional anthropometric measures appears misleading. Beyond the body mass index, there are overwhelming evidences towards the relevance of a more detailed description of the individual phenotype by characterizing the main body componentsas free-fat mass, muscle mass, and fat mass. Among the numerous techniques actually available, bioelectrical impedance analysis seems to be the most suitable in a clinical setting because it is simple, inexpensive, noninvasive, and highly reproducible. To date, there is no consensus concerning the use of one preferred equation for the resting energy expenditure in overweight and/or obese population. Energy restriction alone is an effective strategy to achieve an early and significant weight loss, however it results in a reduction of both fat and lean mass therefore promoting or aggravating an unfavourable body composition(as sarcobesity) in terms of mortality and comorbidities. Therefore the implementation of daily levels of physical activity should be simultaneously promoted. The major role of muscle mass in the energy balance has been recently established by the rising prevalence of the combination of two condition as sarcopenia and obesity. Physical exercise stimulates energy expenditure, thereby directly improving energy balance, and also promotes adaptations such as fiber type, mitochondrial biogenesis, improvement of insulin resistance, and release of myokines, which may influence different tissues, including muscle.展开更多
Objective To investigate the effects of endothelial microvesicles(EMVs) induced by calcium ionophore A23187 on H9c2 cardiomyocytes. Methods Human umbilical vein endothelial cells(HUVECs) were treated with 10 μmol/L A...Objective To investigate the effects of endothelial microvesicles(EMVs) induced by calcium ionophore A23187 on H9c2 cardiomyocytes. Methods Human umbilical vein endothelial cells(HUVECs) were treated with 10 μmol/L A23187 for 30 min. EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. EMVs were characterized using 1 and 2 μm latex beads and antiPE-CD144 antibody by flow cytometry. For functional research, EMVs at different concentrations were cocultured with H9c2 cardiomyocytes for 6 h. Cell viability of H9c2 cells and the activity of LDH leaked from H9c2 cells were tested by colorimetry. Moreover, apoptosis of H9c2 cells was observed through Hoechst 33258 staining and tested by FITC-Annexin V/PI double staining. Results EMVs were induced by A23187 on HUVECs, and isolated by ultracentrifugation. We identified the membrane vesicles(< 1 μm) induced by A23187 were CD144 positive. In addition, the EMVs could significantly reduce the viability of H9c2 cells, and increase LDH leakage from H9c2 cells in a dose dependent manner(P<0.05). Condensed nuclei could be observed with the increasing concentrations of EMVs through Hoechst 33258 staining. Furthermore, increased apoptosis rates of H9c2 cells could be assessed through FITC-Annexin V/PI double staining by flow cytometry. Conclusion Microvesicles could be released from HUVECs after induced by A23187 through calcium influx, and these EMVs exerted a pro-apoptotic effect on H9c2 cells by induction of apoptosis.展开更多
AIM To establish the ability of magnetic resonance(MR) and computer tomography(CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors(Pan NET) in a caseload of a tertiary referral center.METHODS Pati...AIM To establish the ability of magnetic resonance(MR) and computer tomography(CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors(Pan NET) in a caseload of a tertiary referral center.METHODS Patients submitted to surgery for Pan NET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination(MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman(BA) and Mountain-Plot(MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok(PB) regression analysis was used to check the agreement between MR and CT.RESULTS Our study population consisted of 292 patients. Seventy-nine(27.1%) were functioning Pan NET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning-Pan NET, respectively. Limits of agreement(LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-Pan NET, no statistical significance was found in the size estimation rate of MR and CT(P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology.CONCLUSION MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of Pan NET.展开更多
BACKGROUND Primary biliary cholangitis(PBC)is a serious disease that causes significant morbidity.PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis.The performance of a...BACKGROUND Primary biliary cholangitis(PBC)is a serious disease that causes significant morbidity.PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis.The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations.AIM To assess the diagnostic performance of several autoantibodies for the diagnosis of PBC in Latin American individuals.METHODS We studied 85 female adult Colombians,43 cases with biopsy-confirmed PBC and 42 controls in whom a liver biopsy ruled out PBC.Plasma anti-mitochondrial antibodies(AMAs),anti-smooth muscle antibodies(ASMAs)and anti-nuclear antibodies(ANAs),as well as total immunoglobulin(Ig)M and IgG were determined using immunofluorescence or enzyme-linked immunosorbent assay in all study participants within 1 year of the biopsy.For all variables,values analyzed were those closest to the date of the biopsy.Patients with viral or alcoholic hepatitis were excluded.RESULTS Mean age at diagnosis was 58.7 years for cases and 56.9 years for controls,and the body mass index was lower among cases.Most cases received ursodeoxycholic acid,while most controls received vitamin E.Sjögren syndrome and Hashimoto’s thyroiditis were the most frequent autoimmune comorbidities of PBC.The prevalence of AMA positivity among PBC cases was unexpectedly low.The sensitivity and specificity values were respectively 44.2%and 76.2%for AMA,74.4%and 38.1%for ANA,14.0%and 73.8%for ASMA,26.7%and 80.0%for IgG,and 57.1%and 85.7%for IgM.The combination of positive AMA plus positive IgM had 91%positive predictive value for PBC.Among AMA-negative cases,the most prevalent antibodies were ANA(87.5%).In all,62%of AMA-positive and 84.6%of IgM-positive individuals had fibrosis in their biopsy.CONCLUSION AMA positivity was very low among female Latin American patients with PBC.The performance of all antibodies was quite limited.These results highlight the urgent need for better PBC biomarkers.展开更多
目的总结在我院就诊的女性患者性功能障碍的患病率和患病类型,探讨其影响因素。方法选取420例就诊于北京妇产医院内分泌科的围绝经期女性及女性家属,采用女性性功能指数量表(female sexual function in-dex,FSFI)和自制量表进行问卷调查...目的总结在我院就诊的女性患者性功能障碍的患病率和患病类型,探讨其影响因素。方法选取420例就诊于北京妇产医院内分泌科的围绝经期女性及女性家属,采用女性性功能指数量表(female sexual function in-dex,FSFI)和自制量表进行问卷调查,并进行统计学分析。结果本组女性患者性功能障碍总体发病率为84.1%,性欲障碍、性唤起障碍、阴道润滑、性高潮、性交痛和性满意度发生率分别为95.5%,69.4%,57.9%,66.9%,68.5%和69.1%。不同年龄、月经情况、收入及是否有合并症/激素补充治疗女性性功能FSD发生率差异均有统计学意义(P<0.05)。结论影响女性性功能的主要因素有年龄、绝经、激素补充、经济水平和身体健康状况。展开更多
Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considera...Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.展开更多
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty...Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.展开更多
文摘To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.
文摘The B-cell lymphoma 2(Bcl2)family of proteins participates in cell death or survival through a mitochondrial pathway.The pro-apoptotic members of the Bcl2 family such as Bim,Bid,Bax and Bak trigger cell death by contributing to the enhancement of mitochondrial outer membrane permeability to pro-apoptotic factors such as cytochrome c,with
文摘Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or human immunodeficiency virus(HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease(CVD) and type 2 diabetes(T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2 D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2 D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2 D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(20101202110005)the Natural Science Foundation of Tianjin(11JCZDJC18300)+1 种基金the Research Foundation of Tianjin Municipal Education Commission(20110106)the National Key Basic Research Program of China(973 Program, 2011CB933100)
文摘Objective To investigate the effects of microvesicles(MVs) derived from hypoxia/reoxygenation(H/R)-treated human umbilical vein endothelial cells(HUVECs) on endothelium-dependent relaxation of rat thoracic aortic rings.Methods H/R injury model was established to induce HUVECs to release H/R-EMVs.H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium.H/R-EMVs were characterized using 1 urn latex beads and anti-PE-CD144 by flow cytometry.Thoracic aortic rings of rats were incubated with 2.5,5,10,20 μg/ml H/R-EMVs derived from H/R-treated HUVECs for 4 hours,and their endothelium-dependent relaxation in response to acetylcholine(ACh) or endothelium-independent relaxation in response to sodium nitroprusside(SNP) was recorded in vitro.The nitric oxide(NO) production of ACh-treated thoracic aortic rings of rats was measured using Griess reagent.The expression of endothelial NO synthase(eNOS) and phosphorylated eNOS(p-eNOS,Ser-1177) in the thoracic aortic rings of rats was detected by Western blotting.Furthermore,the levels of SOD and MDA in H/R-EMVs-treated thoracic aortic rings of rats were measured using SOD and MDA kit.Results H/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation.The membrane vesicles(< 1 urn) induced by H/R were CD144 positive.ACh-induced relaxation and NO production of rat thoracic aortic rings were impaired by H/R-EMVs treatment in a concentration-dependent manner(P<0.05,P<0.01).The expression of total eNOS(t-eNOS)was not affected by H/R-EMVs.However,the expression of p-eNOS decreased after treated with H/R-EMVs.The activity of SOD decreased and the level of MDA increased in H/R-EMVs treated rat thoracic aortic rings(P<0.01).Conclusion ACh induced endothelium-dependent relaxation of thoracic aortic rings of rats was impaired by H/R-EMVs in a concentration-dependent manner.The mechanisms included a decrease in NO production,p-eNOS expression and an increase in oxidative stress.
文摘Hypoglycemia unawareness(HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms.It is a major limitation to achieving tight diabetes and reduced quality of life.HU occurs in approximately 40% of people with type 1 diabetesmellitus(T1DM) and with less frequency in T2 DM.Though the aetiology of HU is multifactorial,possible mechanisms include chronic exposure to low blood glucose,antecedent hypoglycaemia,recurrent severe hypoglycaemia and the failure of counter-regulatory hormones.Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms,but the mechanisms and mediators remain largely unknown.Prevention and management of HU is complex,and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team.Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes.Several medications are thought to worsen or promote HU,whereas others may have an attenuating effect on the problem.This article reviews recent advances in how the brain senses and responds to hypoglycaemia,novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses.The consequences that HU has on the person with diabetes and their family are also described.Finally,it examines the evidence for prevention and treatment of HU,and summarizes the effects of medications that may influence it.
文摘Current progress in epigenetic research supports the view that diet and dietary components are important in cancer etiology by enhancing or inhibiting carcinogenesis.Since diet and dietary factors may significantly contribute to the causation and progression of many cancers,it is important to find the molecular mechanisms of action of such dietary factors for cancer prevention and treatment.Recently,the role of epigenetic mechanisms in the cancer development and progression has attracted more attention as additional evidence along with traditional DNA sequence based mechanisms such as mutations and structural re-arrangements.Such an increasing interest in cancer epigenetics has also accelerated the development and application of molecular assays and tools for DNA methylation detection and histone modification enrichment analysis.In this paper,key assays and methods for epigenetic research are reviewed and discussed in terms of their utility and usability.In addition,more advanced methods for genome-wide analysis are introduced as part of upcoming research trends and directions.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(20101202110005)the Natural Science Foundation of Tianjin(11JCZDJC18300)the Research Foundation of Tianjin Municipal Education Commission(20110106)
文摘Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion(I/R) injury in rats. Methods: Myocardial IPC was elicited by three cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending(LAD) coronary artery. Platelet-free plasma(PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFP. PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 μm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure(MAP), heart rate(HR) and ST-segment of electrocardiogram(ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin(HE) staining. The activity of plasma lactate dehydrogenase(LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining. Results: Total IPC-MVs and different phenotypes, including platelet-derived MVs(PMVs), endothelial cell-derived MVs(EMVs), leucocyte-derived MVs(LMVs) and erythrocyte-derived MVs(RMVs) were all isolated which were identified membrane vesicles(<1 μm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats(P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR(P<0.01), decreased ST-segment and LDH activity(P<0.05, P<0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment(P<0.01). Conclusion: The method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.
文摘In clinical practice obesity is primarily diagnosed through the body mass index. In order to characterize patients affected by obesity the use of traditional anthropometric measures appears misleading. Beyond the body mass index, there are overwhelming evidences towards the relevance of a more detailed description of the individual phenotype by characterizing the main body componentsas free-fat mass, muscle mass, and fat mass. Among the numerous techniques actually available, bioelectrical impedance analysis seems to be the most suitable in a clinical setting because it is simple, inexpensive, noninvasive, and highly reproducible. To date, there is no consensus concerning the use of one preferred equation for the resting energy expenditure in overweight and/or obese population. Energy restriction alone is an effective strategy to achieve an early and significant weight loss, however it results in a reduction of both fat and lean mass therefore promoting or aggravating an unfavourable body composition(as sarcobesity) in terms of mortality and comorbidities. Therefore the implementation of daily levels of physical activity should be simultaneously promoted. The major role of muscle mass in the energy balance has been recently established by the rising prevalence of the combination of two condition as sarcopenia and obesity. Physical exercise stimulates energy expenditure, thereby directly improving energy balance, and also promotes adaptations such as fiber type, mitochondrial biogenesis, improvement of insulin resistance, and release of myokines, which may influence different tissues, including muscle.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(20101202110005)the Natural Science Foundation of Tianjin(11JCZDJC18300)+1 种基金the Research Foundation of Tianjin Municipal Education Commission(20110106)the National Key Basic Research Program of China(973 Program,2011CB933100)
文摘Objective To investigate the effects of endothelial microvesicles(EMVs) induced by calcium ionophore A23187 on H9c2 cardiomyocytes. Methods Human umbilical vein endothelial cells(HUVECs) were treated with 10 μmol/L A23187 for 30 min. EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. EMVs were characterized using 1 and 2 μm latex beads and antiPE-CD144 antibody by flow cytometry. For functional research, EMVs at different concentrations were cocultured with H9c2 cardiomyocytes for 6 h. Cell viability of H9c2 cells and the activity of LDH leaked from H9c2 cells were tested by colorimetry. Moreover, apoptosis of H9c2 cells was observed through Hoechst 33258 staining and tested by FITC-Annexin V/PI double staining. Results EMVs were induced by A23187 on HUVECs, and isolated by ultracentrifugation. We identified the membrane vesicles(< 1 μm) induced by A23187 were CD144 positive. In addition, the EMVs could significantly reduce the viability of H9c2 cells, and increase LDH leakage from H9c2 cells in a dose dependent manner(P<0.05). Condensed nuclei could be observed with the increasing concentrations of EMVs through Hoechst 33258 staining. Furthermore, increased apoptosis rates of H9c2 cells could be assessed through FITC-Annexin V/PI double staining by flow cytometry. Conclusion Microvesicles could be released from HUVECs after induced by A23187 through calcium influx, and these EMVs exerted a pro-apoptotic effect on H9c2 cells by induction of apoptosis.
文摘AIM To establish the ability of magnetic resonance(MR) and computer tomography(CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors(Pan NET) in a caseload of a tertiary referral center.METHODS Patients submitted to surgery for Pan NET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination(MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman(BA) and Mountain-Plot(MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok(PB) regression analysis was used to check the agreement between MR and CT.RESULTS Our study population consisted of 292 patients. Seventy-nine(27.1%) were functioning Pan NET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning-Pan NET, respectively. Limits of agreement(LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-Pan NET, no statistical significance was found in the size estimation rate of MR and CT(P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology.CONCLUSION MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of Pan NET.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a serious disease that causes significant morbidity.PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis.The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations.AIM To assess the diagnostic performance of several autoantibodies for the diagnosis of PBC in Latin American individuals.METHODS We studied 85 female adult Colombians,43 cases with biopsy-confirmed PBC and 42 controls in whom a liver biopsy ruled out PBC.Plasma anti-mitochondrial antibodies(AMAs),anti-smooth muscle antibodies(ASMAs)and anti-nuclear antibodies(ANAs),as well as total immunoglobulin(Ig)M and IgG were determined using immunofluorescence or enzyme-linked immunosorbent assay in all study participants within 1 year of the biopsy.For all variables,values analyzed were those closest to the date of the biopsy.Patients with viral or alcoholic hepatitis were excluded.RESULTS Mean age at diagnosis was 58.7 years for cases and 56.9 years for controls,and the body mass index was lower among cases.Most cases received ursodeoxycholic acid,while most controls received vitamin E.Sjögren syndrome and Hashimoto’s thyroiditis were the most frequent autoimmune comorbidities of PBC.The prevalence of AMA positivity among PBC cases was unexpectedly low.The sensitivity and specificity values were respectively 44.2%and 76.2%for AMA,74.4%and 38.1%for ANA,14.0%and 73.8%for ASMA,26.7%and 80.0%for IgG,and 57.1%and 85.7%for IgM.The combination of positive AMA plus positive IgM had 91%positive predictive value for PBC.Among AMA-negative cases,the most prevalent antibodies were ANA(87.5%).In all,62%of AMA-positive and 84.6%of IgM-positive individuals had fibrosis in their biopsy.CONCLUSION AMA positivity was very low among female Latin American patients with PBC.The performance of all antibodies was quite limited.These results highlight the urgent need for better PBC biomarkers.
文摘目的总结在我院就诊的女性患者性功能障碍的患病率和患病类型,探讨其影响因素。方法选取420例就诊于北京妇产医院内分泌科的围绝经期女性及女性家属,采用女性性功能指数量表(female sexual function in-dex,FSFI)和自制量表进行问卷调查,并进行统计学分析。结果本组女性患者性功能障碍总体发病率为84.1%,性欲障碍、性唤起障碍、阴道润滑、性高潮、性交痛和性满意度发生率分别为95.5%,69.4%,57.9%,66.9%,68.5%和69.1%。不同年龄、月经情况、收入及是否有合并症/激素补充治疗女性性功能FSD发生率差异均有统计学意义(P<0.05)。结论影响女性性功能的主要因素有年龄、绝经、激素补充、经济水平和身体健康状况。
文摘Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.
文摘Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.
