Objective To investigate the changes in cortical excitability and inhibitory circuits of patients with Alzheimer’s disease(AD)or behavioral variant frontotemporal dementia(bv FTD)using transcranial magnetic stimulati...Objective To investigate the changes in cortical excitability and inhibitory circuits of patients with Alzheimer’s disease(AD)or behavioral variant frontotemporal dementia(bv FTD)using transcranial magnetic stimulation(TMS).Methods Forty-four patients with AD,30 patients with bv FTD and 44 healthy controls were enrolled in the study.The epidemiological data展开更多
Liver cancer is one of the world's most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma(HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathog...Liver cancer is one of the world's most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma(HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel smallmolecule inhibitors. This review will focus on illustrativeexamples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts,drug discovery, and drug-induced toxic liver injury.展开更多
In remote ischemic conditioning(RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ...In remote ischemic conditioning(RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site(remote ischemic preconditioning), during the ischemic insult(remote ischemic perconditioning) or at the onset of reperfusion(remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.展开更多
AIM:To evaluate when Helicobacter pylori(H.pylori)eradication therapy(ET)should be started in patients with peptic ulcer bleeding(PUB).METHODS:Clinical data concerning adults hospitalizedwith PUB were retrospectively ...AIM:To evaluate when Helicobacter pylori(H.pylori)eradication therapy(ET)should be started in patients with peptic ulcer bleeding(PUB).METHODS:Clinical data concerning adults hospitalizedwith PUB were retrospectively collected and analyzed.Age,sex,type and stage of peptic ulcer,whether endoscopic therapy was performed or not,methods of H.pylori detection,duration of hospitalization,and specialty of the attending physician were investigated.Factors influencing the confirmation of H.pylori infection prior to discharge were determined using multiple logistic regression analysis.The H.pylori eradication rates of patients who received ET during hospitalization and those who commenced ET as outpatients were compared.RESULTS:A total of 232 patients with PUB were evaluated for H.pylori infection by histology and/or rapid urease testing.Of these patients,53.7%(127/232)had confirmed results of H.pylori infection prior to discharge.In multivariate analysis,duration of hospitalization and ulcer stage were factors independently influencing whether H.pylori infection was confirmed before or after discharge.Among the patients discharged before confirmation of H.pylori infection,13.3%(14/105)were lost to follow-up.Among the patients found to be H.pylori-positive after discharge,41.4%(12/29)did not receive ET.There was no significant difference in the H.pylori eradication rate between patients who received ET during hospitalization a n d t h o s e w h o c o m m e n c e d E T a s o u t p a t i e n t s[intention-to-treat:68.8%(53/77)vs 60%(12/20),P=0.594;per-protocol:82.8%(53/64)vs 80%(12/15),P=0.723].CONCLUSION:Because many patients with PUB who were discharged before H.pylori infection status was confirmed lost an opportunity to receive ET,we should confirm H.pylori infection and start ET prior to discharge.展开更多
We have read with interest the paper by Roman C.and colleagues discussing the relationship between gastroesophageal reflux disease and atrial fibrillation.The review is presenting the available evidence for the common...We have read with interest the paper by Roman C.and colleagues discussing the relationship between gastroesophageal reflux disease and atrial fibrillation.The review is presenting the available evidence for the common pathogenic mechanisms.However,from a cardiologist perspective,some available data were not highlighted in the review,cardiovascular involvement in gastroesophageal reflux is less assessed.Hypertension,obesity or diabetes mellitus are substrate for left atrial remodeling that initiate and sustained atrial fibrillation development.One of the pathophysiologic mechanisms in atrial fibrillation is the presence of a trigger.Gastroesophageal reflux could be only a trigger for this arrhythmia.We believe that atrial fibrillation should be considered as possible extraesophageal syndrome in the gastroesophageal reflux classification.展开更多
Immunoglobulin G4(Ig G4)-related disease is a rare systemic diseases. A 67-year-old male presented at our institution with mild upper abdominal pain and jaundice for 20 d. Laboratory results revealed high levels of Ig...Immunoglobulin G4(Ig G4)-related disease is a rare systemic diseases. A 67-year-old male presented at our institution with mild upper abdominal pain and jaundice for 20 d. Laboratory results revealed high levels of Ig G4(15.4 g/L,range: 0.08-1.4 g/L). Computed tomography(CT) showed significant enlargement of the entire pancreas and a capsule-like low-density rim surrounding the whole pancreas. Positron emission tomography/CT revealed increased uneven metabolism of the entire pancreas. Both magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed stenosis of the distal common bile duct and proximal main pancreatic duct,and dilation of the proximal common bile duct and extra- and intra-hepatic bile ducts. He was diagnosed with Ig G4-related autoimmune pancreatitis. The patient was treated with prednisone for 14 mo. The patient responded well to prednisone but upon cessation of the corticosteroid developed enlargement of the submandibular gland. The patient's serum Ig G4 was elevated at 23.9 g/L. It is important to maintain treatment,so the patient was again treated with prednisone and had a good response. Follow-up of Ig G4-related disease is thus necessary.展开更多
Chronic hepatitis C virus(HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk f...Chronic hepatitis C virus(HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases(CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct rolein altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease. HCV core protein plays an essential role in promoting insulin resistance and oxidative stress. On the other hand, atherosclerosis is a common disease in which the artery wall thickens due to accumulation of fatty deposits. The main step in the formation of atherosclerotic plaques is the oxidation of low density lipoprotein particles, together with the increased production of proinflammatory markers [tumor necrosis factor-α, interleukin(IL)-6, IL-18 or C-reactive protein]. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus. Consequently, the number of studies evaluating this association is growing. Data derived from these studies have demonstrated the strong link between HCV infection and the atherogenic process, showing a higher risk of coronary heart disease, carotid atherosclerosis, peripheral artery disease and, ultimately, CVD-related mortality.展开更多
Protein Klotho,beyond its role as a regulator of the phosphatemia,is also involved in the maintaining of the cardiovascular health,being associated its alterations with the development of cardiovascular damage and inc...Protein Klotho,beyond its role as a regulator of the phosphatemia,is also involved in the maintaining of the cardiovascular health,being associated its alterations with the development of cardiovascular damage and increased morbi-mortality. For all this,nowadays Klotho is the subject of a thorough research which is focused on uncover its intimate mechanisms of action,and in analyzing the utility of its modulation as a potential strategy with clinical applicability. Molecular mechanisms of Klotho are not well understood but an emerging research area links Klotho deficiency with vascular pathology. Changes in this protein have been associated with cardiovascular-related complications like inflammation,vascular calcification,and endothelial dysfunction. All this is particularly relevant if considering the recent discovery of Klotho expression in vascular tissue.展开更多
Ebola virus disease(EVD)is a rare,highly contagious and a deadly disease with a variable fatality rate ranging from 30%to 90%.Over the past two decades,Ebola pandemic has severely affected the sub-Sahara region includ...Ebola virus disease(EVD)is a rare,highly contagious and a deadly disease with a variable fatality rate ranging from 30%to 90%.Over the past two decades,Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo(DRC),and Uganda.The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus(ZEBOV),Sudan Ebolavirus(SUDV)and Bundibugyo Ebolavirus(BDBV).In recent years,significant strides have been made in therapeutic interventions.Notably,the US Food and Drug Administration has approved two monoclonal antibodies:InmazebTM(REGN-EB3)and Ansuvimab or EbangaTM.Additionally,many small molecules are currently in the developmental stage,promising further progress in medical treatment.Addressing the critical need for preventive measures,this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno(Ad26.ZEBOV)and Mvabea(MVA-BN-Filo)as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies.These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease.The current treatment landscape for EVD encompasses both nutritional(supportive)and drug therapies.The review comprehensively details the origin,pathogenesis,and epidemiology of EVD,shedding light on the ongoing efforts to combat this devastating disease.It explores small molecules in various stages of the development,discusses patents filed or granted,and delves into the clinical and supportive therapies that form the cornerstone of EVD management.This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention,treatment,and control of EVD.展开更多
Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks ofAlzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs It wasreported that cyclin-dependent kinase...Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks ofAlzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs It wasreported that cyclin-dependent kinase5 (Cdk-5) could phosphorylate tau atmost AD-related epitopesin vivo. In this study, we investigated the effect of cdk-5 overexpression on tauhyperphosphbrylation in neuroblastoma N2a cells. We demonstrated that Overexpression of cdk-5 whichresulted in a 3.5-fold Cdk-5 activation in thetransfected cells induced a dramatic increase inphosphorylation of tau at severalphosphorylatiosites. Overexpression of cdk-5 led to a reducedstaining with antibody Tau-1 and an enhanced staining with antibody PHF-1, suggestinghy-perphosphorylation of tau at Serl99/202 and Ser396/404 sites. It implies that in vitroOverexpression of cdk-5 leads to Cdk-5 overactivation and tau hyperphosphorylation may be theunderline mechanism.展开更多
Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 pa...Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.展开更多
Objective: to study the effect and safety of laparoscopic surgery in the treatment of acute gastroduodenal ulcer perforation. Methods: 68 patients with acute perforation of gastroduodenal ulcer were divided into 2 gro...Objective: to study the effect and safety of laparoscopic surgery in the treatment of acute gastroduodenal ulcer perforation. Methods: 68 patients with acute perforation of gastroduodenal ulcer were divided into 2 groups by "number random grouping method", 34 cases in experimental group and 34 cases in control group. Control group received routine surgical intervention;The experimental group was treated with laparoscopic surgical intervention. The length of hospital stay of patients with acute gastroduodenal ulcer perforation was recorded and the incidence of complications was compared between the two groups. Results: the experimental group of hospitalized patients with acute gastroduodenal ulcer perforation disease duration (6.19-1.86) days shorter than the control group, and group contrast between two groups of patients with acute gastroduodenal ulcer perforation disease incidence of concurrent disease, the experimental group patients concurrent disease incidence of 2.94% lower than the control group (p < 0.05), the difference is statistically significant. Conclusion: in the treatment of patients with acute gastroduodenal ulcer perforation, laparoscopic surgical intervention can effectively shorten the length of hospital stay and reduce the incidence of complications, with high safety.展开更多
Objective To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. Methods The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) prolifer...Objective To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. Methods The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) proliferation was measured with 3 H-TdR incorporation and was confirmed with histological analysis. Results Northern blot analysis showed that HRG-1 mRNA was expressed not only in VSMC, but also in various rat tissues (heart, brain, lung, kidney, and liver). In addition, the expression of HRG-1 mRNA in heart, brain, kidney and liver of spontaneously hypertensive rat (SHR) was lower than that in the same tissues of Wistar-Kyotorat (WKY). Semi-quantitative RT-PCR and histological analysis showed that the expression of HRG-1 mRNA in ApoE-knockout mice and in animal models of restenosis was decreased and neointimal formation was observed in both models. ET, AII, and IL-1 stimulating VSMC proliferation reduced the expression of HRG-1 mRNA of VSMC. Atrial natriuretic factor (ANF), calcitonin gene-related peptide and adrenomedullin, inhibited VSMC proliferation and elevated the expression of HRG-1 mRNA. These effects could be blocked or attenuated by their corresponding antagonists or antibodies. Conclusion HRG-1 is a gene related to VSMC proliferation. It may play an important role in several occlusive cardiovascular diseases including atherosclerosis, restenosis and hypertension.展开更多
Objective:The frontal lobe may be involved in circuits associated with depression,apathy,aggression,and other psychiatric symptoms.Although white matter changes(WMC)are related to the severity of behavioral and psycho...Objective:The frontal lobe may be involved in circuits associated with depression,apathy,aggression,and other psychiatric symptoms.Although white matter changes(WMC)are related to the severity of behavioral and psychological symptoms of dementia(BPSD)in patients with Alzheimer’s disease(AD),it is unclear which part of the WMC may play the most important role in BPSD.This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients.Methods:Among patients diagnosed with Alzheimer’s disease between 2009 and2014,387 patients were retrospectively reviewed after those with pre‐existing organic brain syndrome,psychiatric diseases,or toxic‐metabolic encephalopathy were excluded.Patients’demographic and laboratory data,WMC measured with brain computed tomography and scored using the age‐related white matter changes(ARWMC)scale,and neuropsychological tests,including the cognitive abilities screening instrument(CASI),the Mini‐Mental State Examination(MMSE),the clinical dementia rating scale with sum‐box(CDR‐SB),and the neuropsychiatric inventory(NPI)were analyzed.Results:There was no significant difference in the NPI between patients with and without a history of stroke,hypertension,and diabetes.No significant difference in the NPI was identified between different sexes or different Apolipoprotein E(APOE)alleles.The NPI score was significantly correlated with the duration of education(r=–0.4515,P=0.0172),CASI(r=–0.2915,P<0.0001),MMSE(r=–0.8476,P<0.0001),and CDR‐SB(r=2.2839,P<0.0001).WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC(P=0.0255).After adjusting for age,duration of education,and CASI,WMC in the right frontal lobe remained significantly associated with the NPI score(β=3.8934,P=0.042).Conclusions:WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis.Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.展开更多
文摘Objective To investigate the changes in cortical excitability and inhibitory circuits of patients with Alzheimer’s disease(AD)or behavioral variant frontotemporal dementia(bv FTD)using transcranial magnetic stimulation(TMS).Methods Forty-four patients with AD,30 patients with bv FTD and 44 healthy controls were enrolled in the study.The epidemiological data
基金Supported by Grants from the National Science Council,NSC102-2314-B-002-142-MY3 and NSC-102-2628-B-002-029-MY3,Taiwan
文摘Liver cancer is one of the world's most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma(HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel smallmolecule inhibitors. This review will focus on illustrativeexamples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts,drug discovery, and drug-induced toxic liver injury.
文摘In remote ischemic conditioning(RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site(remote ischemic preconditioning), during the ischemic insult(remote ischemic perconditioning) or at the onset of reperfusion(remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.
文摘AIM:To evaluate when Helicobacter pylori(H.pylori)eradication therapy(ET)should be started in patients with peptic ulcer bleeding(PUB).METHODS:Clinical data concerning adults hospitalizedwith PUB were retrospectively collected and analyzed.Age,sex,type and stage of peptic ulcer,whether endoscopic therapy was performed or not,methods of H.pylori detection,duration of hospitalization,and specialty of the attending physician were investigated.Factors influencing the confirmation of H.pylori infection prior to discharge were determined using multiple logistic regression analysis.The H.pylori eradication rates of patients who received ET during hospitalization and those who commenced ET as outpatients were compared.RESULTS:A total of 232 patients with PUB were evaluated for H.pylori infection by histology and/or rapid urease testing.Of these patients,53.7%(127/232)had confirmed results of H.pylori infection prior to discharge.In multivariate analysis,duration of hospitalization and ulcer stage were factors independently influencing whether H.pylori infection was confirmed before or after discharge.Among the patients discharged before confirmation of H.pylori infection,13.3%(14/105)were lost to follow-up.Among the patients found to be H.pylori-positive after discharge,41.4%(12/29)did not receive ET.There was no significant difference in the H.pylori eradication rate between patients who received ET during hospitalization a n d t h o s e w h o c o m m e n c e d E T a s o u t p a t i e n t s[intention-to-treat:68.8%(53/77)vs 60%(12/20),P=0.594;per-protocol:82.8%(53/64)vs 80%(12/15),P=0.723].CONCLUSION:Because many patients with PUB who were discharged before H.pylori infection status was confirmed lost an opportunity to receive ET,we should confirm H.pylori infection and start ET prior to discharge.
基金Supported by A grant from University of Medicine and Pharmacy Grigore T.Popa Iasi,Romania,No.POSDRU/159/1.5/S/133377
文摘We have read with interest the paper by Roman C.and colleagues discussing the relationship between gastroesophageal reflux disease and atrial fibrillation.The review is presenting the available evidence for the common pathogenic mechanisms.However,from a cardiologist perspective,some available data were not highlighted in the review,cardiovascular involvement in gastroesophageal reflux is less assessed.Hypertension,obesity or diabetes mellitus are substrate for left atrial remodeling that initiate and sustained atrial fibrillation development.One of the pathophysiologic mechanisms in atrial fibrillation is the presence of a trigger.Gastroesophageal reflux could be only a trigger for this arrhythmia.We believe that atrial fibrillation should be considered as possible extraesophageal syndrome in the gastroesophageal reflux classification.
文摘Immunoglobulin G4(Ig G4)-related disease is a rare systemic diseases. A 67-year-old male presented at our institution with mild upper abdominal pain and jaundice for 20 d. Laboratory results revealed high levels of Ig G4(15.4 g/L,range: 0.08-1.4 g/L). Computed tomography(CT) showed significant enlargement of the entire pancreas and a capsule-like low-density rim surrounding the whole pancreas. Positron emission tomography/CT revealed increased uneven metabolism of the entire pancreas. Both magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed stenosis of the distal common bile duct and proximal main pancreatic duct,and dilation of the proximal common bile duct and extra- and intra-hepatic bile ducts. He was diagnosed with Ig G4-related autoimmune pancreatitis. The patient was treated with prednisone for 14 mo. The patient responded well to prednisone but upon cessation of the corticosteroid developed enlargement of the submandibular gland. The patient's serum Ig G4 was elevated at 23.9 g/L. It is important to maintain treatment,so the patient was again treated with prednisone and had a good response. Follow-up of Ig G4-related disease is thus necessary.
文摘Chronic hepatitis C virus(HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases(CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct rolein altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease. HCV core protein plays an essential role in promoting insulin resistance and oxidative stress. On the other hand, atherosclerosis is a common disease in which the artery wall thickens due to accumulation of fatty deposits. The main step in the formation of atherosclerotic plaques is the oxidation of low density lipoprotein particles, together with the increased production of proinflammatory markers [tumor necrosis factor-α, interleukin(IL)-6, IL-18 or C-reactive protein]. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus. Consequently, the number of studies evaluating this association is growing. Data derived from these studies have demonstrated the strong link between HCV infection and the atherogenic process, showing a higher risk of coronary heart disease, carotid atherosclerosis, peripheral artery disease and, ultimately, CVD-related mortality.
文摘Protein Klotho,beyond its role as a regulator of the phosphatemia,is also involved in the maintaining of the cardiovascular health,being associated its alterations with the development of cardiovascular damage and increased morbi-mortality. For all this,nowadays Klotho is the subject of a thorough research which is focused on uncover its intimate mechanisms of action,and in analyzing the utility of its modulation as a potential strategy with clinical applicability. Molecular mechanisms of Klotho are not well understood but an emerging research area links Klotho deficiency with vascular pathology. Changes in this protein have been associated with cardiovascular-related complications like inflammation,vascular calcification,and endothelial dysfunction. All this is particularly relevant if considering the recent discovery of Klotho expression in vascular tissue.
文摘Ebola virus disease(EVD)is a rare,highly contagious and a deadly disease with a variable fatality rate ranging from 30%to 90%.Over the past two decades,Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo(DRC),and Uganda.The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus(ZEBOV),Sudan Ebolavirus(SUDV)and Bundibugyo Ebolavirus(BDBV).In recent years,significant strides have been made in therapeutic interventions.Notably,the US Food and Drug Administration has approved two monoclonal antibodies:InmazebTM(REGN-EB3)and Ansuvimab or EbangaTM.Additionally,many small molecules are currently in the developmental stage,promising further progress in medical treatment.Addressing the critical need for preventive measures,this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno(Ad26.ZEBOV)and Mvabea(MVA-BN-Filo)as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies.These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease.The current treatment landscape for EVD encompasses both nutritional(supportive)and drug therapies.The review comprehensively details the origin,pathogenesis,and epidemiology of EVD,shedding light on the ongoing efforts to combat this devastating disease.It explores small molecules in various stages of the development,discusses patents filed or granted,and delves into the clinical and supportive therapies that form the cornerstone of EVD management.This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention,treatment,and control of EVD.
基金Supported by the National Natural Science Foundation of China (39925012 30100057+1 种基金30170221) the Science and Technology Founda tion Committee Foundurion of China(G1999054007) and National Youth Sci ence Foundation of China(39925012)
文摘Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks ofAlzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs It wasreported that cyclin-dependent kinase5 (Cdk-5) could phosphorylate tau atmost AD-related epitopesin vivo. In this study, we investigated the effect of cdk-5 overexpression on tauhyperphosphbrylation in neuroblastoma N2a cells. We demonstrated that Overexpression of cdk-5 whichresulted in a 3.5-fold Cdk-5 activation in thetransfected cells induced a dramatic increase inphosphorylation of tau at severalphosphorylatiosites. Overexpression of cdk-5 led to a reducedstaining with antibody Tau-1 and an enhanced staining with antibody PHF-1, suggestinghy-perphosphorylation of tau at Serl99/202 and Ser396/404 sites. It implies that in vitroOverexpression of cdk-5 leads to Cdk-5 overactivation and tau hyperphosphorylation may be theunderline mechanism.
文摘Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.
文摘Objective: to study the effect and safety of laparoscopic surgery in the treatment of acute gastroduodenal ulcer perforation. Methods: 68 patients with acute perforation of gastroduodenal ulcer were divided into 2 groups by "number random grouping method", 34 cases in experimental group and 34 cases in control group. Control group received routine surgical intervention;The experimental group was treated with laparoscopic surgical intervention. The length of hospital stay of patients with acute gastroduodenal ulcer perforation was recorded and the incidence of complications was compared between the two groups. Results: the experimental group of hospitalized patients with acute gastroduodenal ulcer perforation disease duration (6.19-1.86) days shorter than the control group, and group contrast between two groups of patients with acute gastroduodenal ulcer perforation disease incidence of concurrent disease, the experimental group patients concurrent disease incidence of 2.94% lower than the control group (p < 0.05), the difference is statistically significant. Conclusion: in the treatment of patients with acute gastroduodenal ulcer perforation, laparoscopic surgical intervention can effectively shorten the length of hospital stay and reduce the incidence of complications, with high safety.
基金ThisprojectwassupportedbyNationalNaturalScienceFoundationofChina (No 39870 35 5 )
文摘Objective To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. Methods The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) proliferation was measured with 3 H-TdR incorporation and was confirmed with histological analysis. Results Northern blot analysis showed that HRG-1 mRNA was expressed not only in VSMC, but also in various rat tissues (heart, brain, lung, kidney, and liver). In addition, the expression of HRG-1 mRNA in heart, brain, kidney and liver of spontaneously hypertensive rat (SHR) was lower than that in the same tissues of Wistar-Kyotorat (WKY). Semi-quantitative RT-PCR and histological analysis showed that the expression of HRG-1 mRNA in ApoE-knockout mice and in animal models of restenosis was decreased and neointimal formation was observed in both models. ET, AII, and IL-1 stimulating VSMC proliferation reduced the expression of HRG-1 mRNA of VSMC. Atrial natriuretic factor (ANF), calcitonin gene-related peptide and adrenomedullin, inhibited VSMC proliferation and elevated the expression of HRG-1 mRNA. These effects could be blocked or attenuated by their corresponding antagonists or antibodies. Conclusion HRG-1 is a gene related to VSMC proliferation. It may play an important role in several occlusive cardiovascular diseases including atherosclerosis, restenosis and hypertension.
文摘Objective:The frontal lobe may be involved in circuits associated with depression,apathy,aggression,and other psychiatric symptoms.Although white matter changes(WMC)are related to the severity of behavioral and psychological symptoms of dementia(BPSD)in patients with Alzheimer’s disease(AD),it is unclear which part of the WMC may play the most important role in BPSD.This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients.Methods:Among patients diagnosed with Alzheimer’s disease between 2009 and2014,387 patients were retrospectively reviewed after those with pre‐existing organic brain syndrome,psychiatric diseases,or toxic‐metabolic encephalopathy were excluded.Patients’demographic and laboratory data,WMC measured with brain computed tomography and scored using the age‐related white matter changes(ARWMC)scale,and neuropsychological tests,including the cognitive abilities screening instrument(CASI),the Mini‐Mental State Examination(MMSE),the clinical dementia rating scale with sum‐box(CDR‐SB),and the neuropsychiatric inventory(NPI)were analyzed.Results:There was no significant difference in the NPI between patients with and without a history of stroke,hypertension,and diabetes.No significant difference in the NPI was identified between different sexes or different Apolipoprotein E(APOE)alleles.The NPI score was significantly correlated with the duration of education(r=–0.4515,P=0.0172),CASI(r=–0.2915,P<0.0001),MMSE(r=–0.8476,P<0.0001),and CDR‐SB(r=2.2839,P<0.0001).WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC(P=0.0255).After adjusting for age,duration of education,and CASI,WMC in the right frontal lobe remained significantly associated with the NPI score(β=3.8934,P=0.042).Conclusions:WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis.Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.
