AIM To investigate the patient-outcomes of newly developed pressure drop coefficient(CDP) in diagnosing epicardial stenosis(ES) in the presence of concomitant microvascular disease(MVD).METHODS Patients from our clini...AIM To investigate the patient-outcomes of newly developed pressure drop coefficient(CDP) in diagnosing epicardial stenosis(ES) in the presence of concomitant microvascular disease(MVD).METHODS Patients from our clinical trial were divided into two subgroups with:(1) cut-off of coronary flow reserve(CFR) < 2.0;and(2) diabetes.First,correlations were performed for both subgroups between CDP and hyperemic microvascular resistance(HMR),a diagnostic parameter for assessing the severity of MVD.Linear regression analysis was used for these correlations.Further,in each of the subgroups,comparisons were made between fractional flow reserve(FFR) < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events(MACE:Primary outcome).Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups.Two tailed chi-squared and Fischer's exact tests were performed for comparison of the primary outcomes,and the log-rank test was used to compare the Kaplan-Meier survival curves.P < 0.05 for all tests was considered statistically significant.RESULTS Significant linear correlations were observed between CDP and HMR for both CFR < 2.0(r = 0.58,P < 0.001) and diabetic(r = 0.61,P < 0.001) patients.In the CFR < 2.0 subgroup,the %MACE(primary outcomes) for CDP > 27.9 group(7.7%,2/26) was lower than FFR < 0.75 group(3/14,21.4%);P = 0.21.Similarly,in the diabetic subgroup,the %MACE for CDP > 27.9 group(12.5%,2/16) was lower than FFR < 0.75 group(18.2%,2/11);P = 0.69.Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group(n = 26) when compared with FFR < 0.75 group(n = 14);P = 0.10.Similarly,for the diabetic subgroup,CDP > 27.9 group(n = 16) showed higher survival times compared to FFR group(n = 11);P = 0.58.CONCLUSION CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR.These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.展开更多
BACKGROUND Madelung’s disease,also known as multiple symmetrical lipomatosis,is a rare,underrecognized disorder of fat metabolism that results in unusual accumulation of subcutaneous fat deposits around the neck,shou...BACKGROUND Madelung’s disease,also known as multiple symmetrical lipomatosis,is a rare,underrecognized disorder of fat metabolism that results in unusual accumulation of subcutaneous fat deposits around the neck,shoulders,upper arms,trunk,hips,and upper thighs.Our case demonstrates the importance of differential diagnosis and the value of a superb microvascular imaging technique for suspecting and confirming Madelung’s disease.Timely diagnosis and alcohol abstinence could prevent the progression of growing fatty masses and prevent surgery.CASE SUMMARY A 62-year-old male was admitted to the Rheumatology center complaining of symmetric subcutaneous tumors in the area of the parotid and submandibular salivary glands,small soft masses in the occiput and upper third of the forearm,rashes on calves.A high titer of rheumatoid factor and low concentrations of serum complements were detected.The high-end ultrasound and magnetic resonance imaging examinations of all affected areas of the soft tissues showed predominantly adipose tissue(lipomas)without suspicion of liposarcoma.The biopsy from the small salivary gland revealed no pathology.After evaluating the patient’s clinical presentation(symmetrical lipomatosis,cirrhosis,gynecomastia,anemia,hyperuricemia),Madelung’s disease,type I,along with the psoriatic rash and psoriatic arthritis and secondary liver cirrhosis were established.CONCLUSION Madelung’s disease consists of many co-occurring disorders imitating and overlapping with other conditions.Ultrasonography is the first choice for suspecting and confirming symmetrical lipomatosis.展开更多
In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation...In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation of P-glycoprotein.The amyloid cascade hypothesis describes amyloid-βas the central cause of Alzheimer’s disease neuropathology.Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-βand their potential association in the pathological process of Alzheimer’s disease is critical.Herein,we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age.The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age.Decreased sphingomyelin levels,increased ceramide levels,and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice.Similar results were observed in the Alzheimer’s disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42.In human cerebral microvascular endothelial cells,neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment.Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide.Together,these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway.These studies may serve as new pursuits for the development of anti-Alzheimer’s disease drugs.展开更多
Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less investigated.We sought to examine the association between NLR and new-onset ...Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less investigated.We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.Methods From a community cohort,we included 6,430 adults aged≥40 years without subclinical macrovascular and microvascular diseases at baseline.We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index(ABI),brachial-ankle pulse wave velocity(baPWV),and albuminuria.Results During a mean follow-up of 4.3 years,110 participants developed incident abnormal ABI,746 participants developed incident elevated baPWV,and 503 participants developed incident albuminuria.Poisson regression analysis indicated that NLR was significantly associated with an increased risk of newonset abnormal ABI,elevated baPWV,and albuminuria.Compared to overweight/obese participants,we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight.Furthermore,we found an interaction between the NLR and body mass index(BMI)on the risk of new-onset abnormal ABI(P for interaction:0.01).Conclusion NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population.Furthermore,in participants with normal weight,the association between NLR and subclinical vascular abnormalities was much stronger.展开更多
Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment （Jokinen et al., 2011）, declines in global functionality （Inzitari et al., 2009）, and even death （D...Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment （Jokinen et al., 2011）, declines in global functionality （Inzitari et al., 2009）, and even death （Debette and Markus, 2010）. Twenty years ago, estimations of the clinical incidence of ce- rebral microvascular disease approached 11 million per year in the US alone （Leary and Saver, 2003）. More recent estima- tions suggest the prevalence of diffuse white matter disease and silent brain infarction approaches 20% and increases dramatically in the presence of cardiovascular risk factors （Fanning et al., 2014）.展开更多
Pericytes are perivascular cells of microcirculation, which construct the barrier between the microcircula-tion and interstitial fluid with endothelial cell and basement membrane. Contractility and other multifunction...Pericytes are perivascular cells of microcirculation, which construct the barrier between the microcircula-tion and interstitial fluid with endothelial cell and basement membrane. Contractility and other multifunctional activities of pericytes are now being elucidated. Pericytes are pluripotential cells (i. e. as a source of other cell types)and take part in many biological and pathological procedures, such as vascularization, vascular remodeling , microvessel permeability and wound healing, etc. The functional interaction of pericytes with endothelial cells (EC) is now being established. The disfunction and population alteration of pericytes are characterized in many microvascular diseases, such as diabetic retinopa-thy, vascularization of tumors, hypertension,etc.展开更多
目的:探讨miR-455在宫颈癌中的表达及其与微血管密度(MVD)及血管内皮生长因子(VEGF)表达的关系。方法:采用实时荧光定量PCR技术检测68例宫颈癌患者和49例慢性宫颈炎(对照组)组织中miR-455的表达。免疫组化方法检测组织内MVD及VEGF蛋白...目的:探讨miR-455在宫颈癌中的表达及其与微血管密度(MVD)及血管内皮生长因子(VEGF)表达的关系。方法:采用实时荧光定量PCR技术检测68例宫颈癌患者和49例慢性宫颈炎(对照组)组织中miR-455的表达。免疫组化方法检测组织内MVD及VEGF蛋白表达水平。结果:宫颈癌组织内miR-455的相对表达量显著低于慢性宫颈炎(1.17±0.59 vs 2.58±0.83,P<0.01)。68例宫颈癌标本MVD表达的计数结果为30.45±7.9。Pearson相关分析结果显示,宫颈癌组织内miR-455表达水平与MVD呈负相关(r=-0.835,P<0.01。宫颈癌VEGF表达为阴性、弱阳性、中度阳性和强阳性组中,miR-455相对表达定量(RQ)分别为1.77±0.58、1.59±0.50、1.34±0.35和0.68±0.26,Spearman等级相关分析结果显示,miR-455表达水平与VEGF的表达呈负等级相关(r s=-0.857,P<0.01)。结论:miR-455低表达可能通过VEGF信号通路促进宫颈癌内微血管形成,是一个潜在的抑癌miRNA。展开更多
基金Supported by VA Merit Review Grant,Department of Veteran Affairs(PI:Dr.Rupak K Banerjee)No.I01CX000342-01
文摘AIM To investigate the patient-outcomes of newly developed pressure drop coefficient(CDP) in diagnosing epicardial stenosis(ES) in the presence of concomitant microvascular disease(MVD).METHODS Patients from our clinical trial were divided into two subgroups with:(1) cut-off of coronary flow reserve(CFR) < 2.0;and(2) diabetes.First,correlations were performed for both subgroups between CDP and hyperemic microvascular resistance(HMR),a diagnostic parameter for assessing the severity of MVD.Linear regression analysis was used for these correlations.Further,in each of the subgroups,comparisons were made between fractional flow reserve(FFR) < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events(MACE:Primary outcome).Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups.Two tailed chi-squared and Fischer's exact tests were performed for comparison of the primary outcomes,and the log-rank test was used to compare the Kaplan-Meier survival curves.P < 0.05 for all tests was considered statistically significant.RESULTS Significant linear correlations were observed between CDP and HMR for both CFR < 2.0(r = 0.58,P < 0.001) and diabetic(r = 0.61,P < 0.001) patients.In the CFR < 2.0 subgroup,the %MACE(primary outcomes) for CDP > 27.9 group(7.7%,2/26) was lower than FFR < 0.75 group(3/14,21.4%);P = 0.21.Similarly,in the diabetic subgroup,the %MACE for CDP > 27.9 group(12.5%,2/16) was lower than FFR < 0.75 group(18.2%,2/11);P = 0.69.Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group(n = 26) when compared with FFR < 0.75 group(n = 14);P = 0.10.Similarly,for the diabetic subgroup,CDP > 27.9 group(n = 16) showed higher survival times compared to FFR group(n = 11);P = 0.58.CONCLUSION CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR.These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.
文摘BACKGROUND Madelung’s disease,also known as multiple symmetrical lipomatosis,is a rare,underrecognized disorder of fat metabolism that results in unusual accumulation of subcutaneous fat deposits around the neck,shoulders,upper arms,trunk,hips,and upper thighs.Our case demonstrates the importance of differential diagnosis and the value of a superb microvascular imaging technique for suspecting and confirming Madelung’s disease.Timely diagnosis and alcohol abstinence could prevent the progression of growing fatty masses and prevent surgery.CASE SUMMARY A 62-year-old male was admitted to the Rheumatology center complaining of symmetric subcutaneous tumors in the area of the parotid and submandibular salivary glands,small soft masses in the occiput and upper third of the forearm,rashes on calves.A high titer of rheumatoid factor and low concentrations of serum complements were detected.The high-end ultrasound and magnetic resonance imaging examinations of all affected areas of the soft tissues showed predominantly adipose tissue(lipomas)without suspicion of liposarcoma.The biopsy from the small salivary gland revealed no pathology.After evaluating the patient’s clinical presentation(symmetrical lipomatosis,cirrhosis,gynecomastia,anemia,hyperuricemia),Madelung’s disease,type I,along with the psoriatic rash and psoriatic arthritis and secondary liver cirrhosis were established.CONCLUSION Madelung’s disease consists of many co-occurring disorders imitating and overlapping with other conditions.Ultrasonography is the first choice for suspecting and confirming symmetrical lipomatosis.
基金supported by the National Key Research and Development Program of ChinaNos.2021YFC2 701800 and 2021YFC2 701805 (to QY)+2 种基金Open Research Fund of State Key Laboratory of Genetic EngineeringFudan UniversityNo.SKLGE-21 19 (to TXH and QY)
文摘In Alzheimer’s disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-βin the brain.Amyloid-βcorrelates with the sphingomyelin metabolism,and sphingomyelin participates in the regulation of P-glycoprotein.The amyloid cascade hypothesis describes amyloid-βas the central cause of Alzheimer’s disease neuropathology.Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-βand their potential association in the pathological process of Alzheimer’s disease is critical.Herein,we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age.The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age.Decreased sphingomyelin levels,increased ceramide levels,and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice.Similar results were observed in the Alzheimer’s disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42.In human cerebral microvascular endothelial cells,neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment.Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide.Together,these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway.These studies may serve as new pursuits for the development of anti-Alzheimer’s disease drugs.
基金supported by the grants from the National Key R&D Program of China[2017YFC1310700,2016YFC1305600,2016YFC0901200,2016YFC1305202,2016YFC1304904,2018YFC1311800,2018YFC1311705]the National Natural Science Foundation of China[81870560,81561128019,81621061,81700764,81941017,81770842]+9 种基金the Chinese Academy of Medical Sciences[2018PT32017,2019PT330006]the Shanghai Municipal Government[18411951800]the Shanghai Shenkang Hospital Development Center[SHDC12019101]Shanghai Municipal Commission of Health and Family Planning[20174Y0014]National Major Scientific and Technological Special Project for“Significant New Drugs Development”[2017ZX09304007]Shanghai Rising-Star Program[21QA1408100]the Scientific and Technological Committee of Shanghai[19411964200]Innovative research team of high-level local universities in Shanghaithe Shanghai Jiaotong University School of Medicine[DLY201801,20161301,20161307]the Ruijin Hospital[2018CR002]。
文摘Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less investigated.We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.Methods From a community cohort,we included 6,430 adults aged≥40 years without subclinical macrovascular and microvascular diseases at baseline.We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index(ABI),brachial-ankle pulse wave velocity(baPWV),and albuminuria.Results During a mean follow-up of 4.3 years,110 participants developed incident abnormal ABI,746 participants developed incident elevated baPWV,and 503 participants developed incident albuminuria.Poisson regression analysis indicated that NLR was significantly associated with an increased risk of newonset abnormal ABI,elevated baPWV,and albuminuria.Compared to overweight/obese participants,we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight.Furthermore,we found an interaction between the NLR and body mass index(BMI)on the risk of new-onset abnormal ABI(P for interaction:0.01).Conclusion NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population.Furthermore,in participants with normal weight,the association between NLR and subclinical vascular abnormalities was much stronger.
基金support from the Larry L.Hillblom Foundation (GX)NIH NS083740 (JDH)the United States Department of Veterans Affairs Greater Los Angeles Healthcare System (JDH)
文摘Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment （Jokinen et al., 2011）, declines in global functionality （Inzitari et al., 2009）, and even death （Debette and Markus, 2010）. Twenty years ago, estimations of the clinical incidence of ce- rebral microvascular disease approached 11 million per year in the US alone （Leary and Saver, 2003）. More recent estima- tions suggest the prevalence of diffuse white matter disease and silent brain infarction approaches 20% and increases dramatically in the presence of cardiovascular risk factors （Fanning et al., 2014）.
文摘Pericytes are perivascular cells of microcirculation, which construct the barrier between the microcircula-tion and interstitial fluid with endothelial cell and basement membrane. Contractility and other multifunctional activities of pericytes are now being elucidated. Pericytes are pluripotential cells (i. e. as a source of other cell types)and take part in many biological and pathological procedures, such as vascularization, vascular remodeling , microvessel permeability and wound healing, etc. The functional interaction of pericytes with endothelial cells (EC) is now being established. The disfunction and population alteration of pericytes are characterized in many microvascular diseases, such as diabetic retinopa-thy, vascularization of tumors, hypertension,etc.
文摘目的:探讨miR-455在宫颈癌中的表达及其与微血管密度(MVD)及血管内皮生长因子(VEGF)表达的关系。方法:采用实时荧光定量PCR技术检测68例宫颈癌患者和49例慢性宫颈炎(对照组)组织中miR-455的表达。免疫组化方法检测组织内MVD及VEGF蛋白表达水平。结果:宫颈癌组织内miR-455的相对表达量显著低于慢性宫颈炎(1.17±0.59 vs 2.58±0.83,P<0.01)。68例宫颈癌标本MVD表达的计数结果为30.45±7.9。Pearson相关分析结果显示,宫颈癌组织内miR-455表达水平与MVD呈负相关(r=-0.835,P<0.01。宫颈癌VEGF表达为阴性、弱阳性、中度阳性和强阳性组中,miR-455相对表达定量(RQ)分别为1.77±0.58、1.59±0.50、1.34±0.35和0.68±0.26,Spearman等级相关分析结果显示,miR-455表达水平与VEGF的表达呈负等级相关(r s=-0.857,P<0.01)。结论:miR-455低表达可能通过VEGF信号通路促进宫颈癌内微血管形成,是一个潜在的抑癌miRNA。
