Cardiac arrest(CA)is a life-threatening condition with complex pathophysiology and limited treatment options.To gain deeper insights into the pathological state of vital organs,we employed a proteomics analysis in rod...Cardiac arrest(CA)is a life-threatening condition with complex pathophysiology and limited treatment options.To gain deeper insights into the pathological state of vital organs,we employed a proteomics analysis in rodents to assess proteome alterations in the brain,heart,kidney,and liver using a rat model of CA.The brain displayed severe protein alterations in essential cellular pathways,including three major energy-generating pathways after CA,which worsened after resuscitation,resulting in the most significant overall protein changes among the organs.Conversely,the liver,experiencing the most substantial protein alterations post-CA,demonstrated significant recovery,presenting the least protein changes post-resuscitation.展开更多
Background Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events,the underlying mechanisms are still controversial.The aim of...Background Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events,the underlying mechanisms are still controversial.The aim of the study was to investigate the relationships between orthostatic changes and organ damage in subjects over 60 years old.Methods This is a prospective observational cohort study.One thousand nine hundred and ninety-seven subjects over 60 years old were enrolled.Participants were grouped according to whether they had a drop>20 mmHg in systolic or>10 mmHg in diastolic BP(orthostatic hypotension),an increase in mean orthostatic systolic blood pressure>20 mm Hg(orthostatic hypertension),or normal changes within 3 min of orthostatism.Multiple regression modeling was used to investigate the relationship between orthostatic hypotension,orthostatic hypertension and subclinical organ damage with adjustment for confounders.Results Orthostatic hypotension and orthostatic hypertension were found in 461(23.1%)and 189(9.5%)participants,respectively.Measurement of carotid intima-media thickness(IMT),brachial-ankle pulse wave velocity(baPWV),clearance of creatinine,and microalbuminuria were associated with orthostatic hypotension;measurement of IMT and baPWV were associated with orthostatic hypertension in a cruse model.After adjustment,IMT[odds ratio(OR),95%confidence interval(CI)per one-SD increment:1.385,1.052-1.823;P=0.02],baPWV(OR=1.627,95%CI:1.041-2.544;P=0.033)and microalbuminuria(OR=1.401,95%CI:1.002-1.958;P=0.049)were still associated with orthostatic hypotension,while orthostatic hypertension was only associated with IMT(OR=1.730,95%CI:1.143-2.618;P=0.009).Conclusions Orthostatic hypotension seems to be independently correlated with increased carotid atherosclerosis,arterial stiffness and renal damage in subjects over 60 years old.Orthostatic hypertension correlates with carotid atherosclerosis only.展开更多
Objectives To investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 yearswith true resistant hypertension (RH). Methods Patients aged ≥ 80 years with ...Objectives To investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 yearswith true resistant hypertension (RH). Methods Patients aged ≥ 80 years with hypertension (n = 1163) were included in this study. Theincluded participants attended a structured clinical examination and an evaluation of RH was carried out. The prevalence, clinical characteristicsand target organ damage of patients with RH were assessed. The associated clinical risk factors were analyzed by using logistic regression.Results The prevalence of RH diagnosis by 24-h ambulatory blood pressure monitoring assessment was 21.15%. End-diastolic left ven-tricular internal dimension, left ventricular mass index as well as prevalence of left ventricular hypertrophy were significantly greater in pa-tients with RH than in control group. The common carotid artery intimal media thickness, carotid walls thickness, common carotid arterydiameter and relative wall thickness were significant greater in RH group than in control. A relatively higher level of creatinine, estimatedglomerular filtration rate, microalbuminuria and retinal changes was found in RIt group than in control. A multivariate analysis showed thatpatients with a history of diabetes, higher body mass index (BMI) and lipid profiles were independent risk factors of RH. Conclusions Theprevalence of RH in patients aged ≥ 80 years was within the range of reported rates of the general population. Subjects with RH diagnosisshowed a higher occurrence of target organ damage than patients with well controlled blood pressure. Patients with diabetes, higher BMI andserum lipid profiles were independent risk factors for RH in patients aged ≥ 80 years.展开更多
On the basis of elastic-plastic damage model of cement consolidated soil,the authors took organic contents into reasonable damage variable evolution equation in order to seek relation between the organic contents and ...On the basis of elastic-plastic damage model of cement consolidated soil,the authors took organic contents into reasonable damage variable evolution equation in order to seek relation between the organic contents and parameters in the equation,and established the elastic-plastic damage model of cement consolidated soil considering organic contents.The results show that the parameters change correspondingly with difference of the organic contents.The higher the organic contents are,the less the valves of the parameters such as elastic modulus(E),material parameters(K,n) and damage evolution parameter(ε) become,but the larger strain damage threshold value(εd) of the sample is.Meanwhile,the calculation results obtained from established model are compared with the test data in the condition of common indoors test,which is testified with reliability.展开更多
Objective:To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS.Methods: A total of 78 patients with severe acut...Objective:To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS.Methods: A total of 78 patients with severe acute pancreatitis complicated by MODS who were treated in our hospital between June 2012 and March 2016 were selected and divided into control group (n=39) and observation group (n=39) according to random number table. Control group were treated with routine treatment, observation group were treated with conventional treatment plus continuous blood purification, and serum inflammatory factors, liver function indexes and renal function indexes were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of inflammatory factors, liver function indexes and renal function indexes were not statistically significant between two groups of patients. After treatment, serum inflammatory factors IL-6, IL-8, MCP-1 and HMGB1 levels of observation group were lower than those of control group, liver function indexes ALT, AST, TBIL and ALP levels of observation group were lower than those of control group, and renal function indexes Scr and BUN levels of observation group were lower than those of control group.Conclusion: Continuous blood purification can reduce the systemic inflammatory response as well as liver and kidney injury in patients with severe acute pancreatitis complicated by MODS.展开更多
Objective:To study the correlation between shock index and inflammation, oxidative stress as well as target organ damage in patients with sepsis.Methods: A total of 70 patients with sepsis treated in our hospital betw...Objective:To study the correlation between shock index and inflammation, oxidative stress as well as target organ damage in patients with sepsis.Methods: A total of 70 patients with sepsis treated in our hospital between March 2013 and May 2016 were collected and divided into no shock group (SI<0.5) (n=11), general shock group (0.5 SI 2) (n=42) and severe shock group (SI>2.0) (n=17) according to the shock index (SI). Immediately after admission, serum levels of inflammatory factors, oxidative stress indexes and liver function indexes were detected.Results:Serum interleukin-1β (IL-1β), interleukin-8 (IL-8), tumor necrosis factor (TNF-α), advanced oxidation protein products (AOPPs), total bilirubin (TB),γ-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) levels of severe shock group and general shock group were higher than those of no shock group while anti-inflammatory factors interleukin-10 (IL-10), interleukin-13 (IL-13), soluble tumor necrosis factor receptorⅠ(sTNF-RI), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and catalase (CAT) levels were lower than those of no shock group;serum IL-1β, IL-8, TNF-α, AOPPs, TB, GGT and ALT levels of severe shock group were higher than those of general shock group while IL-10, IL-13, sTNF-RI, CAT, GSH-Px and SOD levels were lower than those of general shock group.Conclusion:The higher the shock index in patients with sepsis, the more severe the inflammation, oxidative stress and target organ damage, and the two are positively correlated.展开更多
Objective: To study the effect of continuous blood purification on inflammatory response, immune response and target organ damage in patients with sepsis. Methods: A total of 78 patients with sepsis who were treated i...Objective: To study the effect of continuous blood purification on inflammatory response, immune response and target organ damage in patients with sepsis. Methods: A total of 78 patients with sepsis who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to the random number table method, 39 cases in each group. Control group received conventional therapy for sepsis, and observation group received continuous blood purification on the basis of conventional therapy. The differences in inflammatory response, immune response and target organ damage were compared between the two groups before and after treatment. Results: Before treatment, difference in serum inflammatory factor contents, peripheral blood Th17/Treg cellular immunity levels and serum myocardial injury marker contents were not statistically significant between the two groups. After treatment, serum IL-2, IL-6, PCT, CRP, NT-prBNP, CK, CK-MB, TnT and TnI contents as well as peripheral bloodTh17 and Treg cell levels and Th17/Treg proportion of both groups of patients were lower than those before treatment, and serum IL-2, IL-6, PCT, CRP, NT-prBNP, CK, CK-MB, TnT and TnI contents as well as peripheral blood Th17 and Treg cell levels and Th17/Treg proportion of observation group were lower than those of control group. Conclusion: Continuous blood purification can effectively reduce systemic inflammatory response, inhibit immune response, and reduce myocardial injury in patients with sepsis.展开更多
Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about...Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.展开更多
AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and ...AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.展开更多
Abstract:Objective To determine the role of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), and evaluate the progress from SIRS to MODS and the therapeutic strategies for...Abstract:Objective To determine the role of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), and evaluate the progress from SIRS to MODS and the therapeutic strategies for acute necrotizing pancreatitis (ANP).Methods Rat ANP models were made by retrograde injection of 3.5% sodium taurocholate 2.5?ml/kg into the pancreatic duct. Serum interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNFα), amylase, endotoxin, and albumin were examined. The morphology and pathology of the pancreas, liver, lung, kidney and heart after ANP were observed. Finally, TNFα mRNA in the liver, lung, kidney and heart after ANP were observed by reverse transcriptase-polymerase chain reactions, and the efficiency of somatostatin and growth hormone were also observed in this experiment.Results ANP led to remarkable elevation of the inflammatory mediators which were positively correlated with the development of ANP and MODS. Somatostatin and growth hormone inhibited inflammatory mediators and TNFα mRNA overexpressions, reduced the risk of MODS, corrected hypoalbuminemia, reversed negative nitrogen balance, and controlled the reduction of cell groups with functions and reasonably intervened SIRS caused by ANP.Conclusion TNFα mRNA plays an important role in ANP progression. The amelioration of ANP by combination treatment with somatostatin and growth hormone leads to the reduction of complications and marked increase in survival.展开更多
目的探讨心电向量图(vectorcardiogram,VCG)对高血压心脏电活动异常的诊断价值,并分析早期心脏靶器官损害的影响因素。方法选取昆明市中医医院心血管病科2022年1月至2023年2月的高血压病住院患者80例,经超声心动图(ultrasound cardiogra...目的探讨心电向量图(vectorcardiogram,VCG)对高血压心脏电活动异常的诊断价值,并分析早期心脏靶器官损害的影响因素。方法选取昆明市中医医院心血管病科2022年1月至2023年2月的高血压病住院患者80例,经超声心动图(ultrasound cardiogram,UCG)排外心脏结构异常。比较心电图(electrocardiogram,ECG)与VCG对异常心室除极与复极指标的检出情况。按心电向量检查结果将80例病例分为正常组(n=40)与异常组(n=40),比较2组早期心脏损害的相关影响因素指标,将差异有统计学意义的因素做二元Logistic回归分析,筛选出早期心脏损害的独立影响因素。结果VCG检出异常心室复极指标较ECG有优势(P<0.05),二者对异常除极指标的检出差异无统计学意义(P>0.05)。正常组与异常组比较,在年龄、规律服药、家族史、糖尿病、24 h平均收缩压(24 h average systolic blood pressure,24 h SBP)、白昼平均收缩压(daytime average systolic blood pressure,DSBP)、夜间平均收缩压(night average systolic blood pressure,NSBP)、血压负荷值、清晨血压、脉压差等指标上,差异有统计学意义(P<0.05)。二元Logistic回归分析显示,年龄[OR(95%CI)=0.891,0.998]、夜间平均收缩压[OR(95%CI)=1.018,2.10]、家族史[OR(95%CI)=0.029,0.499]、糖尿病[OR(95%CI)=0.042,0.916]是高血压早期心脏损害的独立影响因素。结论VCG为高血压早期心脏靶器官损害的有效检测手段。展开更多
基金the National Research Foundation of Korea grant funded by the Korea government(Ministry of Science and ICT(MSIT),Grant No.:2021R1F1A1061840).
文摘Cardiac arrest(CA)is a life-threatening condition with complex pathophysiology and limited treatment options.To gain deeper insights into the pathological state of vital organs,we employed a proteomics analysis in rodents to assess proteome alterations in the brain,heart,kidney,and liver using a rat model of CA.The brain displayed severe protein alterations in essential cellular pathways,including three major energy-generating pathways after CA,which worsened after resuscitation,resulting in the most significant overall protein changes among the organs.Conversely,the liver,experiencing the most substantial protein alterations post-CA,demonstrated significant recovery,presenting the least protein changes post-resuscitation.
基金supported in part by the Beijing Health System High Level Health Technology Talent Cultivation Plan—2015-3-028Beijing Chaoyang 1351 Talent Cultivation Plan—CYXX-2017-03+2 种基金National Natural Science Foundation of China—81200194,81770253Beijing Municipal Natural Science Foundation—7122072National Major Research Plan Training Program of China—91849111
文摘Background Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events,the underlying mechanisms are still controversial.The aim of the study was to investigate the relationships between orthostatic changes and organ damage in subjects over 60 years old.Methods This is a prospective observational cohort study.One thousand nine hundred and ninety-seven subjects over 60 years old were enrolled.Participants were grouped according to whether they had a drop>20 mmHg in systolic or>10 mmHg in diastolic BP(orthostatic hypotension),an increase in mean orthostatic systolic blood pressure>20 mm Hg(orthostatic hypertension),or normal changes within 3 min of orthostatism.Multiple regression modeling was used to investigate the relationship between orthostatic hypotension,orthostatic hypertension and subclinical organ damage with adjustment for confounders.Results Orthostatic hypotension and orthostatic hypertension were found in 461(23.1%)and 189(9.5%)participants,respectively.Measurement of carotid intima-media thickness(IMT),brachial-ankle pulse wave velocity(baPWV),clearance of creatinine,and microalbuminuria were associated with orthostatic hypotension;measurement of IMT and baPWV were associated with orthostatic hypertension in a cruse model.After adjustment,IMT[odds ratio(OR),95%confidence interval(CI)per one-SD increment:1.385,1.052-1.823;P=0.02],baPWV(OR=1.627,95%CI:1.041-2.544;P=0.033)and microalbuminuria(OR=1.401,95%CI:1.002-1.958;P=0.049)were still associated with orthostatic hypotension,while orthostatic hypertension was only associated with IMT(OR=1.730,95%CI:1.143-2.618;P=0.009).Conclusions Orthostatic hypotension seems to be independently correlated with increased carotid atherosclerosis,arterial stiffness and renal damage in subjects over 60 years old.Orthostatic hypertension correlates with carotid atherosclerosis only.
文摘Objectives To investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 yearswith true resistant hypertension (RH). Methods Patients aged ≥ 80 years with hypertension (n = 1163) were included in this study. Theincluded participants attended a structured clinical examination and an evaluation of RH was carried out. The prevalence, clinical characteristicsand target organ damage of patients with RH were assessed. The associated clinical risk factors were analyzed by using logistic regression.Results The prevalence of RH diagnosis by 24-h ambulatory blood pressure monitoring assessment was 21.15%. End-diastolic left ven-tricular internal dimension, left ventricular mass index as well as prevalence of left ventricular hypertrophy were significantly greater in pa-tients with RH than in control group. The common carotid artery intimal media thickness, carotid walls thickness, common carotid arterydiameter and relative wall thickness were significant greater in RH group than in control. A relatively higher level of creatinine, estimatedglomerular filtration rate, microalbuminuria and retinal changes was found in RIt group than in control. A multivariate analysis showed thatpatients with a history of diabetes, higher body mass index (BMI) and lipid profiles were independent risk factors of RH. Conclusions Theprevalence of RH in patients aged ≥ 80 years was within the range of reported rates of the general population. Subjects with RH diagnosisshowed a higher occurrence of target organ damage than patients with well controlled blood pressure. Patients with diabetes, higher BMI andserum lipid profiles were independent risk factors for RH in patients aged ≥ 80 years.
基金Supported by Projects of National Natural Science Foundation of China(Nos.40372122, 40672180)Education Reform and Development Fund of Jilin University (No.498020200029)
文摘On the basis of elastic-plastic damage model of cement consolidated soil,the authors took organic contents into reasonable damage variable evolution equation in order to seek relation between the organic contents and parameters in the equation,and established the elastic-plastic damage model of cement consolidated soil considering organic contents.The results show that the parameters change correspondingly with difference of the organic contents.The higher the organic contents are,the less the valves of the parameters such as elastic modulus(E),material parameters(K,n) and damage evolution parameter(ε) become,but the larger strain damage threshold value(εd) of the sample is.Meanwhile,the calculation results obtained from established model are compared with the test data in the condition of common indoors test,which is testified with reliability.
文摘Objective:To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS.Methods: A total of 78 patients with severe acute pancreatitis complicated by MODS who were treated in our hospital between June 2012 and March 2016 were selected and divided into control group (n=39) and observation group (n=39) according to random number table. Control group were treated with routine treatment, observation group were treated with conventional treatment plus continuous blood purification, and serum inflammatory factors, liver function indexes and renal function indexes were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of inflammatory factors, liver function indexes and renal function indexes were not statistically significant between two groups of patients. After treatment, serum inflammatory factors IL-6, IL-8, MCP-1 and HMGB1 levels of observation group were lower than those of control group, liver function indexes ALT, AST, TBIL and ALP levels of observation group were lower than those of control group, and renal function indexes Scr and BUN levels of observation group were lower than those of control group.Conclusion: Continuous blood purification can reduce the systemic inflammatory response as well as liver and kidney injury in patients with severe acute pancreatitis complicated by MODS.
文摘Objective:To study the correlation between shock index and inflammation, oxidative stress as well as target organ damage in patients with sepsis.Methods: A total of 70 patients with sepsis treated in our hospital between March 2013 and May 2016 were collected and divided into no shock group (SI<0.5) (n=11), general shock group (0.5 SI 2) (n=42) and severe shock group (SI>2.0) (n=17) according to the shock index (SI). Immediately after admission, serum levels of inflammatory factors, oxidative stress indexes and liver function indexes were detected.Results:Serum interleukin-1β (IL-1β), interleukin-8 (IL-8), tumor necrosis factor (TNF-α), advanced oxidation protein products (AOPPs), total bilirubin (TB),γ-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) levels of severe shock group and general shock group were higher than those of no shock group while anti-inflammatory factors interleukin-10 (IL-10), interleukin-13 (IL-13), soluble tumor necrosis factor receptorⅠ(sTNF-RI), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and catalase (CAT) levels were lower than those of no shock group;serum IL-1β, IL-8, TNF-α, AOPPs, TB, GGT and ALT levels of severe shock group were higher than those of general shock group while IL-10, IL-13, sTNF-RI, CAT, GSH-Px and SOD levels were lower than those of general shock group.Conclusion:The higher the shock index in patients with sepsis, the more severe the inflammation, oxidative stress and target organ damage, and the two are positively correlated.
文摘Objective: To study the effect of continuous blood purification on inflammatory response, immune response and target organ damage in patients with sepsis. Methods: A total of 78 patients with sepsis who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to the random number table method, 39 cases in each group. Control group received conventional therapy for sepsis, and observation group received continuous blood purification on the basis of conventional therapy. The differences in inflammatory response, immune response and target organ damage were compared between the two groups before and after treatment. Results: Before treatment, difference in serum inflammatory factor contents, peripheral blood Th17/Treg cellular immunity levels and serum myocardial injury marker contents were not statistically significant between the two groups. After treatment, serum IL-2, IL-6, PCT, CRP, NT-prBNP, CK, CK-MB, TnT and TnI contents as well as peripheral bloodTh17 and Treg cell levels and Th17/Treg proportion of both groups of patients were lower than those before treatment, and serum IL-2, IL-6, PCT, CRP, NT-prBNP, CK, CK-MB, TnT and TnI contents as well as peripheral blood Th17 and Treg cell levels and Th17/Treg proportion of observation group were lower than those of control group. Conclusion: Continuous blood purification can effectively reduce systemic inflammatory response, inhibit immune response, and reduce myocardial injury in patients with sepsis.
文摘Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.
文摘AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.
文摘Abstract:Objective To determine the role of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), and evaluate the progress from SIRS to MODS and the therapeutic strategies for acute necrotizing pancreatitis (ANP).Methods Rat ANP models were made by retrograde injection of 3.5% sodium taurocholate 2.5?ml/kg into the pancreatic duct. Serum interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNFα), amylase, endotoxin, and albumin were examined. The morphology and pathology of the pancreas, liver, lung, kidney and heart after ANP were observed. Finally, TNFα mRNA in the liver, lung, kidney and heart after ANP were observed by reverse transcriptase-polymerase chain reactions, and the efficiency of somatostatin and growth hormone were also observed in this experiment.Results ANP led to remarkable elevation of the inflammatory mediators which were positively correlated with the development of ANP and MODS. Somatostatin and growth hormone inhibited inflammatory mediators and TNFα mRNA overexpressions, reduced the risk of MODS, corrected hypoalbuminemia, reversed negative nitrogen balance, and controlled the reduction of cell groups with functions and reasonably intervened SIRS caused by ANP.Conclusion TNFα mRNA plays an important role in ANP progression. The amelioration of ANP by combination treatment with somatostatin and growth hormone leads to the reduction of complications and marked increase in survival.
文摘目的探讨心电向量图(vectorcardiogram,VCG)对高血压心脏电活动异常的诊断价值,并分析早期心脏靶器官损害的影响因素。方法选取昆明市中医医院心血管病科2022年1月至2023年2月的高血压病住院患者80例,经超声心动图(ultrasound cardiogram,UCG)排外心脏结构异常。比较心电图(electrocardiogram,ECG)与VCG对异常心室除极与复极指标的检出情况。按心电向量检查结果将80例病例分为正常组(n=40)与异常组(n=40),比较2组早期心脏损害的相关影响因素指标,将差异有统计学意义的因素做二元Logistic回归分析,筛选出早期心脏损害的独立影响因素。结果VCG检出异常心室复极指标较ECG有优势(P<0.05),二者对异常除极指标的检出差异无统计学意义(P>0.05)。正常组与异常组比较,在年龄、规律服药、家族史、糖尿病、24 h平均收缩压(24 h average systolic blood pressure,24 h SBP)、白昼平均收缩压(daytime average systolic blood pressure,DSBP)、夜间平均收缩压(night average systolic blood pressure,NSBP)、血压负荷值、清晨血压、脉压差等指标上,差异有统计学意义(P<0.05)。二元Logistic回归分析显示,年龄[OR(95%CI)=0.891,0.998]、夜间平均收缩压[OR(95%CI)=1.018,2.10]、家族史[OR(95%CI)=0.029,0.499]、糖尿病[OR(95%CI)=0.042,0.916]是高血压早期心脏损害的独立影响因素。结论VCG为高血压早期心脏靶器官损害的有效检测手段。