Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integri...Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).展开更多
Objective Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate mar...Objective Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results In the analysis,average levels of indoor PM with aerodynamic diameters<2.5µm(PM2.5)decreased significantly by 59.2%(from 59.6 to 24.3µg/m3,P<0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by−84.6%(95%confidence interval[CI]:−90.7 to−78.6),growth differentiation factor-15 by−48.1%(95%CI:−31.2 to−25.6),osteoprotegerin by−65.4%(95%CI:−56.5 to−18.7),interleukin-4 by−46.6%(95%CI:−62.3 to−31.0)and myeloperoxidase by−60.3%(95%CI:−83.7 to−3.0),respectively.Conclusion Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable populations at risks.展开更多
Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying m...Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.展开更多
Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC ...Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.展开更多
Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it...Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.展开更多
The diagnosis of pulmonary hypertension(PH) should be made by combining clinical manifestations and echocardiographic probability.[1] Following the confirmation of PH, the classification should begin with the more com...The diagnosis of pulmonary hypertension(PH) should be made by combining clinical manifestations and echocardiographic probability.[1] Following the confirmation of PH, the classification should begin with the more common groups [group 2(PH due to left heart disease) and group 3(PH due to lung diseases and/or hypoxia)], then group 4(chronic thromboembolic PH and other pulmonary artery obstructions) and finally group 1(pulmonary arterial hypertension) and group 5(PH with unclear and/or multifactorial mechanisms).[1] In this case, we demonstrate a rare scenario of obstruction-caused group 4 PH.展开更多
Coronavirus disease 2019 is a major threat to public health globally.Though its pathogenesis has not been fully elucidated,angiotensin-converting enzyme 2(ACE2)has been recently identified as a receptor for the entry ...Coronavirus disease 2019 is a major threat to public health globally.Though its pathogenesis has not been fully elucidated,angiotensin-converting enzyme 2(ACE2)has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)into the cell.Here,we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism.As a receptor for coronavirus,ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus(SARS-CoV).The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans.On the other hand,ACE2 negatively regulates the renin-angiotensinaldosterone system(RAAS)primarily by converting angiotensinⅡto angiotensin 1-7.which exerts a beneficial effect on coronavirus-induced acute lung injury.Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection.The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor(ACEI)or angiotensinⅡtype 1 receptor blocker(ARB).To date,no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2,and hence,it is not advisable to discontinue such drugs in patients with cardiovascular disease.展开更多
The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer sc...The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale.However,many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging,owing to their unmatched absorption and emission wavelengths,small Stokes'shift,easy photo-bleaching,etc.Herein,we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor(D)-7c-acceptor(A)compound.The electron-rich carbazole group and the electron-poor pyridinium bromide group,linked by 7i-conjugated thiophen-bridge,ensure strong near infrared(NIR)emission with a Stokes'shift larger than 200 nm.The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer(CT)state(Φ<0.04)to highly emissive locally-excited(LE)state(Φ=0.57),giving rise to a fluorescence Turn-On probe.Together with large Stokes'shift,good photostability and high depletion efficiency,the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power.Moreover,the ex-vivo super-resolution imaging of(E)-1-butyl-4(2-(5-(9-ethyl-9Hcarbazol-3-yl)thiophen-2-yl)vinyl)pyridinium bromide(CTPB)probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated.This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism,providing a new approach to the development of future amyloid probes.展开更多
Dear editor,Wellens syndrome is characterized by electrocardiography(ECG)patterns of the biphasic or inverted T wave in the precordial leads with normal R wave progression and absence of Q waves,[1,2]which indicates o...Dear editor,Wellens syndrome is characterized by electrocardiography(ECG)patterns of the biphasic or inverted T wave in the precordial leads with normal R wave progression and absence of Q waves,[1,2]which indicates occlusive lesions of the proximal left anterior descending(LAD)coronary artery and warrants.[1]These ECG changes usually occur during a pain-free interval and turn to a fatal consequence if without urgent intervention therapy.[1,3]However,in some cases,coronary stenosis was absent and ECG patterns manifested as Wellens syndrome,which was defined as pseudo-Wellens syndrome.展开更多
Objective The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on car...Objective The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014‒2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results During the study period,24-hour average concentrations of ambient O3 were 47.4µg/m3(ranging from 1.0 to 165.9µg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95%confidence interval[CI]:1.95 to 2.32)and 5.47(95%CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74%of the risks of arrhythmias attributable to O3 exposure.Conclusion Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.展开更多
Polycyclic aromatic hydrocarbons(PAHs) have been of health concern due to its carcinogenesis and mutagenesis. In this study, we aimed to assess the variations, sources, and lifetime excessive cancer risk(ECR) attribut...Polycyclic aromatic hydrocarbons(PAHs) have been of health concern due to its carcinogenesis and mutagenesis. In this study, we aimed to assess the variations, sources, and lifetime excessive cancer risk(ECR) attributable to PAHs bound to ambient particulate matters with aerodynamic diameter less than 2.5 μm(PM_(2.5)) in metropolitan Beijing, China. We collected24-hour integrated PM_(2.5) samples on daily basis between November 2014 and June 2015 across both central heating(cold months) and non-heating(warm months) seasons, and further analyzed the PAH components in these daily PM_(2.5) samples. Our results showed that total concentrations of PM_(2.5)-bound PAHs varied between(88.6 ± 75.4) ng/m^3 in the cold months and(11.0 ± 5.9) ng/m^3 in the warm months. Benzo[a]pyrene(Ba P), the carcinogenic marker of PAHs,averaged at 5.7 and 0.4 ng/m^3 in the cold and warm months, respectively. Source apportionment analyses illustrated that gasoline, biomass burning, diesel, coal combustion and cooking were the major contributors, accounting for 12.9%, 17.8%, 24.7%, 24.3% and 6.4% of PM_(2.5)-bound PAHs, respectively. The BaP equivalent lifetime ECR from inhalation of PM_(2.5)-bound PAHs was 16.2 cases per million habitants. Our results suggested that ambient particulate reduction from energy reconstruction and adaption of clean fuels would result in reductions PM_(2.5)-bound PAHs and its associated cancer risks. However, as only particulate phased PAHs was analyzed in the present study, the concentration of ambient PAHs could be underestimated.展开更多
The many kinds of cell structures involved in cell-cell communication include tight junction,adherens junction and gap junction,but almost all are between adjacent cells.Recently,a general and dynamic membrane tether,...The many kinds of cell structures involved in cell-cell communication include tight junction,adherens junction and gap junction,but almost all are between adjacent cells.Recently,a general and dynamic membrane tether,termed tunneling nanotubes or membrane nanotubes(MNTs),was discovered to be involved in communication between distant cells.By facilitating intercellular communication,MNTs contribute to many biological functions and pathologic changes in cells.Many works have revealed the structure,formation and functional properties of MNTs.However,as novel structures,further research is needed.展开更多
With rapid economic development and urbanization in recent decades, China has experienced the worsening of ambient air quality. For better air quality management to protect human health, Chinese government revised nat...With rapid economic development and urbanization in recent decades, China has experienced the worsening of ambient air quality. For better air quality management to protect human health, Chinese government revised national ambient air quality standards (NAAQS) for particulate matter (PM) in 2012 (GB3095-2012). To assess the effectiveness of current NAAQS for PM on public health in Chinese population, we conducted a meta- analysis on published studies examining the mortality risk of short-term exposure to PM with aerodynamic diameters less than 10 and 2.5μm (PM10 and PM2.5) in China. The reported 24-hour concentrations of PM10 and PM2.5 in studies ranged from 43.5 to 150.1 μg/m^3 and 37.5 to 176.7 μg/m^3. In the pooled excess, mortality risk estimates of short-term exposure to PM. In specific, per 10 μg/m^3 increase in PM10, we observed increases of 0.40% (95%CI: 0.33%, 0.47%), 0.57% (95%CI: 0.44%, 0.70%) and 0.49% (95%CI: 0.40%, 0.58%) in total, respiratory and cardiovascular mortality, per 10/μg/m^3 increase in PM2.5, we observed increases of 0.51% (95% CI: 0.38%, 0.63%), 0.62% (95%CI: 0.52%, 0.73%) and 0.75% (95%CI: 0.54%, 0.95%) in total, respiratory and cardiovascular mortality. Finally, we derived 125 μg/m^3 for PM10 and 62.5 μg/ m^3 for PM2.5 as 24-hour recommendation values based on the pooled estimates. Our results indicated that current Chinese NAAQS for PM could be sufficient in mitigating the excess mortality risk from short-term exposure to ambient PM. However, future research on long-term exposure cohort studies in Chinese population is also essential in revising annual averages for PM in Chinese NAAQS.展开更多
文摘Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).
基金This work was supported by Beijing Natural Science Foundation(7222246)Royal Dutch Philips Electronics Ltd.(Grant NL18-2100478471).
文摘Objective Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results In the analysis,average levels of indoor PM with aerodynamic diameters<2.5µm(PM2.5)decreased significantly by 59.2%(from 59.6 to 24.3µg/m3,P<0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by−84.6%(95%confidence interval[CI]:−90.7 to−78.6),growth differentiation factor-15 by−48.1%(95%CI:−31.2 to−25.6),osteoprotegerin by−65.4%(95%CI:−56.5 to−18.7),interleukin-4 by−46.6%(95%CI:−62.3 to−31.0)and myeloperoxidase by−60.3%(95%CI:−83.7 to−3.0),respectively.Conclusion Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable populations at risks.
基金The study was supported by grants from the National Natural Science Foundation of China (No. 81300076, 81400833), Beijing Natural Science Foundation (No. 7132195) and Discovery Cardiovascular Research Grant, Chinese Medical Doctor Association (No. DFCMDA201306).
基金supported by the National Key Research and Development Program of China(No.2017YFC1700400,2017YFC1700405)the National Natural Science Foundation of China(No.81921001,82122073)。
文摘Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.
基金supported by the National Key Research and Development Program of China(Grant No.2020YFA0803700)the National Natural Science Foundation of China(Grant Nos.91639108,81770272,and 81970425)+1 种基金the Beijing Natural Science Foundation(Grant No.7212044)the Beijing Hospital Authority Youth Program(Grant No.QML20190306)。
文摘Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.
基金This work was supported by the National Natural Science Foundation of China(81970425)by the National High Technology Research and Development Program of China(2020YFA0803700),and by Hangzhou Qianjiang Distinguished Expert Project(Prof.Lemin Zheng).
文摘Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.
基金supported by the National Natural Science Foundation of China(Nos90913004 and 30821001)the Natural Science Foundation of Beijing(No7082101)+1 种基金Program for New Century Excellent Talents in UniversityBeijing Talents Foundation Beijing National Laboratory for Molecular Sciences
文摘在 telomere 和 oncogene 倡导者区域从 G 富有的海滨形成的 G 四倍在癌症治疗被认为是新有希望的目标。在信号变换器的下游的 flanking 区域和抄写 3 的使活跃之物(STAT3 )G 四倍的 A 基因被探索。它的合拢的模式被建议是由由 CD 光谱学的变化分析的 3:2:2 和 3:3:1 环异构体。结构被分子的当模特儿的方法构造并且精制。
文摘The diagnosis of pulmonary hypertension(PH) should be made by combining clinical manifestations and echocardiographic probability.[1] Following the confirmation of PH, the classification should begin with the more common groups [group 2(PH due to left heart disease) and group 3(PH due to lung diseases and/or hypoxia)], then group 4(chronic thromboembolic PH and other pulmonary artery obstructions) and finally group 1(pulmonary arterial hypertension) and group 5(PH with unclear and/or multifactorial mechanisms).[1] In this case, we demonstrate a rare scenario of obstruction-caused group 4 PH.
文摘Coronavirus disease 2019 is a major threat to public health globally.Though its pathogenesis has not been fully elucidated,angiotensin-converting enzyme 2(ACE2)has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)into the cell.Here,we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism.As a receptor for coronavirus,ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus(SARS-CoV).The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans.On the other hand,ACE2 negatively regulates the renin-angiotensinaldosterone system(RAAS)primarily by converting angiotensinⅡto angiotensin 1-7.which exerts a beneficial effect on coronavirus-induced acute lung injury.Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection.The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor(ACEI)or angiotensinⅡtype 1 receptor blocker(ARB).To date,no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2,and hence,it is not advisable to discontinue such drugs in patients with cardiovascular disease.
基金This work was supported by the Ministry of Science and Technology of China(Nos.2017YFA0204503 and 2018YFA0704805)the National Natural Science Foundation of China(Nos.21503139,21573251,21673144,21873065,21833005,81970425 and 21790364)+5 种基金the Beijing Natural Science Foundation of China(No.2192011)the High-level Teachers in Bejing Municipal Universities in the Period of 13^th Five-year Plan(Nos.IDHT20180517 and CIT&TCD20180331)the Open Fund of the State Key Laboratory of Integrated Optoelectronics(No.IOSKL2019KF01)Capacity Building for Sci-Tech Innovation-Fundamental Scientific Research Funds(Nos.025185305000/210,009/19530050162 and 19530012018)Youth Innovative Research Team of Capital Normal University(No,009/19530050148)Beijing Advanced Innovation Center for Imaging Theory and Technology(No.009/19530011009).
文摘The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale.However,many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging,owing to their unmatched absorption and emission wavelengths,small Stokes'shift,easy photo-bleaching,etc.Herein,we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor(D)-7c-acceptor(A)compound.The electron-rich carbazole group and the electron-poor pyridinium bromide group,linked by 7i-conjugated thiophen-bridge,ensure strong near infrared(NIR)emission with a Stokes'shift larger than 200 nm.The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer(CT)state(Φ<0.04)to highly emissive locally-excited(LE)state(Φ=0.57),giving rise to a fluorescence Turn-On probe.Together with large Stokes'shift,good photostability and high depletion efficiency,the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power.Moreover,the ex-vivo super-resolution imaging of(E)-1-butyl-4(2-(5-(9-ethyl-9Hcarbazol-3-yl)thiophen-2-yl)vinyl)pyridinium bromide(CTPB)probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated.This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism,providing a new approach to the development of future amyloid probes.
文摘Dear editor,Wellens syndrome is characterized by electrocardiography(ECG)patterns of the biphasic or inverted T wave in the precordial leads with normal R wave progression and absence of Q waves,[1,2]which indicates occlusive lesions of the proximal left anterior descending(LAD)coronary artery and warrants.[1]These ECG changes usually occur during a pain-free interval and turn to a fatal consequence if without urgent intervention therapy.[1,3]However,in some cases,coronary stenosis was absent and ECG patterns manifested as Wellens syndrome,which was defined as pseudo-Wellens syndrome.
基金This work was supported by China Postdoctoral Science Foundation(2021M690249)Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research(BMU20140467).
文摘Objective The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014‒2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results During the study period,24-hour average concentrations of ambient O3 were 47.4µg/m3(ranging from 1.0 to 165.9µg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95%confidence interval[CI]:1.95 to 2.32)and 5.47(95%CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74%of the risks of arrhythmias attributable to O3 exposure.Conclusion Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.
基金supported by Beijing Natural Science Foundation(L150001)Peking University Health Science Center "100 Talent Young Investigator" ProgramPeking University Infrastructure Fund for Clinical Research(2013-3-02)
文摘Polycyclic aromatic hydrocarbons(PAHs) have been of health concern due to its carcinogenesis and mutagenesis. In this study, we aimed to assess the variations, sources, and lifetime excessive cancer risk(ECR) attributable to PAHs bound to ambient particulate matters with aerodynamic diameter less than 2.5 μm(PM_(2.5)) in metropolitan Beijing, China. We collected24-hour integrated PM_(2.5) samples on daily basis between November 2014 and June 2015 across both central heating(cold months) and non-heating(warm months) seasons, and further analyzed the PAH components in these daily PM_(2.5) samples. Our results showed that total concentrations of PM_(2.5)-bound PAHs varied between(88.6 ± 75.4) ng/m^3 in the cold months and(11.0 ± 5.9) ng/m^3 in the warm months. Benzo[a]pyrene(Ba P), the carcinogenic marker of PAHs,averaged at 5.7 and 0.4 ng/m^3 in the cold and warm months, respectively. Source apportionment analyses illustrated that gasoline, biomass burning, diesel, coal combustion and cooking were the major contributors, accounting for 12.9%, 17.8%, 24.7%, 24.3% and 6.4% of PM_(2.5)-bound PAHs, respectively. The BaP equivalent lifetime ECR from inhalation of PM_(2.5)-bound PAHs was 16.2 cases per million habitants. Our results suggested that ambient particulate reduction from energy reconstruction and adaption of clean fuels would result in reductions PM_(2.5)-bound PAHs and its associated cancer risks. However, as only particulate phased PAHs was analyzed in the present study, the concentration of ambient PAHs could be underestimated.
基金supported by the National Basic Research Program of China(2013CB933701)the Projects of International Cooperation and Exchanges of the National Natural Science Foundation of China(30910103902)the National Natural Science Foundation of China(81270159)
文摘The many kinds of cell structures involved in cell-cell communication include tight junction,adherens junction and gap junction,but almost all are between adjacent cells.Recently,a general and dynamic membrane tether,termed tunneling nanotubes or membrane nanotubes(MNTs),was discovered to be involved in communication between distant cells.By facilitating intercellular communication,MNTs contribute to many biological functions and pathologic changes in cells.Many works have revealed the structure,formation and functional properties of MNTs.However,as novel structures,further research is needed.
基金supported by the Beijing Natural Science Foundation (No. L150001)National Natural Science Foundation of China (No. 81773381)Ministry of Environmental Protection of the People's Republic of China Fund for National Environmental Criteria Management (No. 2110105)
文摘With rapid economic development and urbanization in recent decades, China has experienced the worsening of ambient air quality. For better air quality management to protect human health, Chinese government revised national ambient air quality standards (NAAQS) for particulate matter (PM) in 2012 (GB3095-2012). To assess the effectiveness of current NAAQS for PM on public health in Chinese population, we conducted a meta- analysis on published studies examining the mortality risk of short-term exposure to PM with aerodynamic diameters less than 10 and 2.5μm (PM10 and PM2.5) in China. The reported 24-hour concentrations of PM10 and PM2.5 in studies ranged from 43.5 to 150.1 μg/m^3 and 37.5 to 176.7 μg/m^3. In the pooled excess, mortality risk estimates of short-term exposure to PM. In specific, per 10 μg/m^3 increase in PM10, we observed increases of 0.40% (95%CI: 0.33%, 0.47%), 0.57% (95%CI: 0.44%, 0.70%) and 0.49% (95%CI: 0.40%, 0.58%) in total, respiratory and cardiovascular mortality, per 10/μg/m^3 increase in PM2.5, we observed increases of 0.51% (95% CI: 0.38%, 0.63%), 0.62% (95%CI: 0.52%, 0.73%) and 0.75% (95%CI: 0.54%, 0.95%) in total, respiratory and cardiovascular mortality. Finally, we derived 125 μg/m^3 for PM10 and 62.5 μg/ m^3 for PM2.5 as 24-hour recommendation values based on the pooled estimates. Our results indicated that current Chinese NAAQS for PM could be sufficient in mitigating the excess mortality risk from short-term exposure to ambient PM. However, future research on long-term exposure cohort studies in Chinese population is also essential in revising annual averages for PM in Chinese NAAQS.