BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untran...BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.展开更多
AIM:To investigate the biological role of mi R-1290 in esophageal squamous cell carcinoma(ESCC) progression and invasion and the underlying mechanism.METHODS:Quantitative real-time polymerase chain reaction(q RT-PCR) ...AIM:To investigate the biological role of mi R-1290 in esophageal squamous cell carcinoma(ESCC) progression and invasion and the underlying mechanism.METHODS:Quantitative real-time polymerase chain reaction(q RT-PCR) was performed to evaluate mi R-1290 expression in ESCC tissue samples.The roles of mi R-1290 in cell proliferation,migration and invasion were identified using mi R-1290 mimic-transfected cells.In addition,the regulatory effect of mi R-1290 on suppressor of cancer cell invasion(SCAI) was evaluated using q RT-PCR,Western blot analysis and a dual luciferase reporter assay.RESULTS:mi R-1290 was significantly upregulated in ESCC tissue samples compared with normal adjacent tissues(9.213 ± 1.150 vs 1.000 ± 0.0),(P < 0.01).Upregulation of mi R-1290 was associated with tumor differentiation(P = 0.021),N classification(P = 0.006) and tumor-node-metastasis stage(P = 0.021) in ESCC patients.Moreover,ectopic mi R-1290 expression potently promoted ESCC cell growth(P < 0.01),migration(P < 0.01) and invasion(P < 0.01) in vitro.mi R-1290 overexpression in ESCC cell lines decreased SCAI expression at the translational level and reduced SCAI-driven luciferase-reporter activity(P < 0.01).CONCLUSION:Our findings suggested that mi R-1290 may play an oncogenic role in cellular processes of ESCC.展开更多
BACKGROUND Listeria monocytogenes(L. monocytogenes), a Gram-positive facultatively intracellular bacterium, is the causative agent of human listeriosis. Listeria infection is usually found in immunocompromised patient...BACKGROUND Listeria monocytogenes(L. monocytogenes), a Gram-positive facultatively intracellular bacterium, is the causative agent of human listeriosis. Listeria infection is usually found in immunocompromised patients, including elderly people, pregnant women, and newborns, whereas it is rare in healthy people. L.monocytogenes may cause meningitis, meningoencephalitis, and some very rare and severe complications, such as hydrocephalus and intracranial hemorrhage,which cause high mortality and morbidity worldwide. Up to now, reports on hydrocephalus and intracranial hemorrhage due to L. monocytogenes are few.CASE SUMMARY We herein report a case of rhombencephalitis caused by L. monocytogenes in a 29-year-old man. He was admitted to the hospital with a 2-d history of headache and fever. He consumed unpasteurized cooked beef two days before appearance.His medical history included type 2 diabetes mellitus, and contaminated beef intake 2 d before onset. Cerebrospinal fluid analysis revealed Gram-positive rod infection, and blood culture was positive for L. monocytogenes. Magnetic resonance imaging findings suggested rhombencephalitis and hydrocephalus.Treatment was started empirically and then modified according to the blood culture results. Repeated CT images were suggestive of intracranial hemorrhage.Although the patient underwent aggressive external ventricular drainage, he died of a continuing deterioration of intracranial conditions.CONCLUSION Hydrocephalus, intracranial hemorrhage, and inappropriate antimicrobial treatment are the determinations of unfavorable outcomes.展开更多
BACKGROUND: The treatment of acute myocardial infarction(AMI) is thought to restore antegrade blood flow in the infarct-related artery(IRA) and minimize ischemic damage to the myocardium as soon as possible. The prese...BACKGROUND: The treatment of acute myocardial infarction(AMI) is thought to restore antegrade blood flow in the infarct-related artery(IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-refl ow in patients with AMI after primary percutaneous coronary intervention(PCI).METHODS: A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were:(i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or(ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were:(i) coronary artery spasm;(ii) diameter stenosis of the culprit lesion was ≤50% and coronary blood f low was normal;(iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction(TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography f indings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-ref low.RESULTS: Fifty-four(17.3%) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure(SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump(IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow(P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95% confi dence interval(CI) 1.460–1.490, P=0.007], long time from onset to reperfusion >6 hours(OR=1.270, 95%CI 1.160–1.400, P=0.001), low SBP on admission <100 mmHg(OR=1.910, 95%CI 1.018–3.896, P=0.004), IABP use before PCI(OR= 1.949, 95%CI 1.168–3.253, P=0.011), low(≤1) TIMI fl ow grade before primary PCI(OR=1.100, 95%CI 1.080–1.250, P<0.001), high thrombus burden(OR=1.600, 95%CI 1.470–2.760, P=0.030), and long target lesion(OR=1.948, 95%CI 1.908–1.990, P=0.019) on angiography were independent predictors of no-refl ow.CONCLUSION: The occurrence of no-refl ow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.展开更多
In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an ...In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.展开更多
Flash flood hazard mapping is a supporting component of non-structural measures for flash flood prevention. Pilot case studies are necessary to develop more practicable methods for the technical support systems of fla...Flash flood hazard mapping is a supporting component of non-structural measures for flash flood prevention. Pilot case studies are necessary to develop more practicable methods for the technical support systems of flash flood hazard mapping. In this study, the headwater catchment of the Xiapu River Basin in central China was selected as a pilot study area for flash flood hazard mapping. A conceptual distributed hydrological model was developed for flood calculation based on the framework of the Xinanjiang model, which is widely used in humid and semi-humid regions in China. The developed model employs the geomorphological unit hydrograph method, which is extremely valuable when simulating the overland flow process in ungauged catchments, as compared with the original Xinanjiang model. The model was tested in the pilot study area, and the results agree with the measured data on the whole. After calibration and validation, the model is shown to be a useful tool for flash flood calculation. A practicable method for flash flood hazard mapping using the calculated peak discharge and digital elevation model data was presented, and three levels of flood hazards were classified. The resulting flash flood hazard maps indicate that the method successfully predicts the spatial distribution of flash flood hazards, and it can meet the current requirements in China.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the etiologic agent responsible for the global coronavirus disease 2019(COVID-19)pandemic.Numerous studies have demonstrated that cardiovascular disease m...Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the etiologic agent responsible for the global coronavirus disease 2019(COVID-19)pandemic.Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression.In the present study,we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-Co V-2.Results revealed that SARS-Co V-2 replication was delayed in hypertensive mouse lungs.In contrast,SARS-Co V-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-Co V-2-infected normotensive mice.展开更多
A facile self-assembly strategy to labricate vitamin E-tocopheryl polyethylene glycol succinate (TPGS) based nanoparticles with a high drug loading level for co-delivery of multiple drugs was developed. To overcome ...A facile self-assembly strategy to labricate vitamin E-tocopheryl polyethylene glycol succinate (TPGS) based nanoparticles with a high drug loading level for co-delivery of multiple drugs was developed. To overcome multi-drug resistance, a chemotherapeutic agent (paclitaxel, PTX) and a drug resistance inhibitor (tariq- uidar, TQR) were co-loaded in the vitamin E-TPGS based nanoparticle to obtain TPGS/PTX/TQR nanoparticles. The sizes of mono-drug loaded TPGS/PTX nanoparticles and dual-drug loaded TPGS/PTX/TQR nanoparticles were below 150 nm with relatively narrow size distributions. The efficiencies of the drug delivery systems on tumor cells inhibition and reversal of drug resistance were evaluated in drug resistant cancer cells (MCF-7/ADR) as compared with nonresistant cells (HeLa). Due to the effective inhibition of the P-gp efflux by TQR, the dual-drug loaded nanoparticles exhibited significantly improved tumor cell inhibitory efficiency. To study the immunostimulatory effect, the effect of the drug delivery system on the production of IL- 10, a cytokine related to tumor development, in the drug resistant cells was determined. After the treatment by the drug delivery systems, the concentration of IL-10 in the cell supernatant decreased. The multi-drug loaded vitamin E-TPGS nanoparticles for synergistic drug delivery have promising applications in reversal of drug resistance in tumor treatments.展开更多
The corrosion evolution processes of steel reinforced concrete under simulated tidal and immersion zones of marine environment were investigated by using electrochemical measurements and corrosion morphology observati...The corrosion evolution processes of steel reinforced concrete under simulated tidal and immersion zones of marine environment were investigated by using electrochemical measurements and corrosion morphology observations. The results indicate that the corrosion of rebar in concrete under both environments experiences the deterioration from passivation to pitting corrosion and then to general corrosion. Specially, the pitting plays the major role only in the early stage of corrosion, and the general corrosion replaces the dominate role of pitting during the long-term corrosion. In addition, both the pitting depth on local surface and the rust thickness on the overall surface of rebar in the tidal condition are larger than those in immersion condition, which is attributed to the faster corrosion rate in tidal zone caused by the concentrated chloride ions and sufficient oxygen supply.展开更多
Understanding the pathological features of severe acute respiratory syn drome coronavirus 2(SARS-CoV-2)infect io n in an animal model is crucial for the treatment of coronavirus disease 2019(COVID-19).Here,we compared...Understanding the pathological features of severe acute respiratory syn drome coronavirus 2(SARS-CoV-2)infect io n in an animal model is crucial for the treatment of coronavirus disease 2019(COVID-19).Here,we compared imnnunopathological changes in young and old rhesus macaques(RMs)before and after SARS-CoV-2 infection at the tissue level.Quantitative analysis of multiplex immunofluoresce nee staining images of formali n-fixed paraffi n-embedded(FFPE)sections showed that SARS-CoV-2 infectio n specifically induced elevated levels of apoptosis,autophagy,and nuclear factor kappa-B(NF-kB)activation of angiotensirv convert!ng enzyme 2(ACE2)+cells,and increased interferon a(IFN-a)-and interleukin 6(IL-6)-secreting cells and C-X-C motif chemokine receptor 3(CXCR3)+cells in lung tissue of old RMs.This pathological pattern,which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens,was significantly correlated with the systemic accumulation of CXCR3+cells in lungs,spleens,and peripheral blood.Furthermore,the ratio of CXCR3+to T-box protein expression in T cell(T-bet)+(CXCR3+/T-bet+ratio)in CD8+cells may be used as a predictor of severe COVID-19.These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+cells in predicting severe COVID-19.展开更多
SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast c...SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast cells(MCs)are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations.In this study,we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury.SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques,and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells;MC degranulation altered various signaling pathways in alveolar epithelial cells,particularly,the induction of pro-inflammatory factors and consequential disruption of tight junctions.Importantly,the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury.These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation,and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.展开更多
The number of elderly people living with HIV is increasing globally,and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection.However,the impact of HIV infection...The number of elderly people living with HIV is increasing globally,and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection.However,the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear.Here,we used the simian immunodeficiency virus mac239(SIVmac239)strain to infect six young and six old Chinese rhesus macaques(ChRMs)and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes.The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes,especially when a large number of CD8+T cells infiltrated the follicles and germinal centers.STAT3 in these follicular CXCR5+CD8+T cells was highly activated,with high expression of granzyme B,which might be caused by the severe inflammatory milieu in the follicles of old ChRMs.This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues,affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+cells.展开更多
基金Supported by General Program of National Natural Science Foundation of China,No.81770197Scientific and Technological Research Major Program of Chongqing Municipal Education Commission,No.KJZD-M202312802+1 种基金Chongqing Natural Science Foundation of China,No.CSTB2022NSCQ-MSX0190,No.CSTB2022NSCQ-MSX0176,and No.cstc2020jcyj-msxmX0051Xinqiao Young Postdoc Talent Incubation Program,No.2022YQB098.
文摘BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.
基金Supported by grants from Innovative Team Project of Jiangsu Province,China,No.CXZZ11_0705
文摘AIM:To investigate the biological role of mi R-1290 in esophageal squamous cell carcinoma(ESCC) progression and invasion and the underlying mechanism.METHODS:Quantitative real-time polymerase chain reaction(q RT-PCR) was performed to evaluate mi R-1290 expression in ESCC tissue samples.The roles of mi R-1290 in cell proliferation,migration and invasion were identified using mi R-1290 mimic-transfected cells.In addition,the regulatory effect of mi R-1290 on suppressor of cancer cell invasion(SCAI) was evaluated using q RT-PCR,Western blot analysis and a dual luciferase reporter assay.RESULTS:mi R-1290 was significantly upregulated in ESCC tissue samples compared with normal adjacent tissues(9.213 ± 1.150 vs 1.000 ± 0.0),(P < 0.01).Upregulation of mi R-1290 was associated with tumor differentiation(P = 0.021),N classification(P = 0.006) and tumor-node-metastasis stage(P = 0.021) in ESCC patients.Moreover,ectopic mi R-1290 expression potently promoted ESCC cell growth(P < 0.01),migration(P < 0.01) and invasion(P < 0.01) in vitro.mi R-1290 overexpression in ESCC cell lines decreased SCAI expression at the translational level and reduced SCAI-driven luciferase-reporter activity(P < 0.01).CONCLUSION:Our findings suggested that mi R-1290 may play an oncogenic role in cellular processes of ESCC.
基金Young Teacher Foundation of Wuhan University,China,No.2042017kf0142Guidance Fund of Renmin Hospital of Wuhan University,China,No.RMYD2018M19
文摘BACKGROUND Listeria monocytogenes(L. monocytogenes), a Gram-positive facultatively intracellular bacterium, is the causative agent of human listeriosis. Listeria infection is usually found in immunocompromised patients, including elderly people, pregnant women, and newborns, whereas it is rare in healthy people. L.monocytogenes may cause meningitis, meningoencephalitis, and some very rare and severe complications, such as hydrocephalus and intracranial hemorrhage,which cause high mortality and morbidity worldwide. Up to now, reports on hydrocephalus and intracranial hemorrhage due to L. monocytogenes are few.CASE SUMMARY We herein report a case of rhombencephalitis caused by L. monocytogenes in a 29-year-old man. He was admitted to the hospital with a 2-d history of headache and fever. He consumed unpasteurized cooked beef two days before appearance.His medical history included type 2 diabetes mellitus, and contaminated beef intake 2 d before onset. Cerebrospinal fluid analysis revealed Gram-positive rod infection, and blood culture was positive for L. monocytogenes. Magnetic resonance imaging findings suggested rhombencephalitis and hydrocephalus.Treatment was started empirically and then modified according to the blood culture results. Repeated CT images were suggestive of intracranial hemorrhage.Although the patient underwent aggressive external ventricular drainage, he died of a continuing deterioration of intracranial conditions.CONCLUSION Hydrocephalus, intracranial hemorrhage, and inappropriate antimicrobial treatment are the determinations of unfavorable outcomes.
文摘BACKGROUND: The treatment of acute myocardial infarction(AMI) is thought to restore antegrade blood flow in the infarct-related artery(IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-refl ow in patients with AMI after primary percutaneous coronary intervention(PCI).METHODS: A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were:(i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or(ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were:(i) coronary artery spasm;(ii) diameter stenosis of the culprit lesion was ≤50% and coronary blood f low was normal;(iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction(TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography f indings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-ref low.RESULTS: Fifty-four(17.3%) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure(SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump(IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow(P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95% confi dence interval(CI) 1.460–1.490, P=0.007], long time from onset to reperfusion >6 hours(OR=1.270, 95%CI 1.160–1.400, P=0.001), low SBP on admission <100 mmHg(OR=1.910, 95%CI 1.018–3.896, P=0.004), IABP use before PCI(OR= 1.949, 95%CI 1.168–3.253, P=0.011), low(≤1) TIMI fl ow grade before primary PCI(OR=1.100, 95%CI 1.080–1.250, P<0.001), high thrombus burden(OR=1.600, 95%CI 1.470–2.760, P=0.030), and long target lesion(OR=1.948, 95%CI 1.908–1.990, P=0.019) on angiography were independent predictors of no-refl ow.CONCLUSION: The occurrence of no-refl ow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.
基金supported by a grant from the NIH:DK32333supported by the National Natural Science Foundation of China (81070693 and 81200647)
文摘In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.
基金supported by the Key Project in the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(Grant No.2012BAK10B04)the Specific Research Fund of the China Institute of Water Resources and Hydropower Research(Grant No.JZ0145B032014)
文摘Flash flood hazard mapping is a supporting component of non-structural measures for flash flood prevention. Pilot case studies are necessary to develop more practicable methods for the technical support systems of flash flood hazard mapping. In this study, the headwater catchment of the Xiapu River Basin in central China was selected as a pilot study area for flash flood hazard mapping. A conceptual distributed hydrological model was developed for flood calculation based on the framework of the Xinanjiang model, which is widely used in humid and semi-humid regions in China. The developed model employs the geomorphological unit hydrograph method, which is extremely valuable when simulating the overland flow process in ungauged catchments, as compared with the original Xinanjiang model. The model was tested in the pilot study area, and the results agree with the measured data on the whole. After calibration and validation, the model is shown to be a useful tool for flash flood calculation. A practicable method for flash flood hazard mapping using the calculated peak discharge and digital elevation model data was presented, and three levels of flood hazards were classified. The resulting flash flood hazard maps indicate that the method successfully predicts the spatial distribution of flash flood hazards, and it can meet the current requirements in China.
基金supported by the National Key R&D Program of China(2020YFC0842000)National Natural Science Foundation of China(81960662)Science and Technology Department of Yunnan Province(202001AS070034)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)is the etiologic agent responsible for the global coronavirus disease 2019(COVID-19)pandemic.Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression.In the present study,we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-Co V-2.Results revealed that SARS-Co V-2 replication was delayed in hypertensive mouse lungs.In contrast,SARS-Co V-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-Co V-2-infected normotensive mice.
基金supported by the National Natural Science Foundation of China (21274113 and 51533006)
文摘A facile self-assembly strategy to labricate vitamin E-tocopheryl polyethylene glycol succinate (TPGS) based nanoparticles with a high drug loading level for co-delivery of multiple drugs was developed. To overcome multi-drug resistance, a chemotherapeutic agent (paclitaxel, PTX) and a drug resistance inhibitor (tariq- uidar, TQR) were co-loaded in the vitamin E-TPGS based nanoparticle to obtain TPGS/PTX/TQR nanoparticles. The sizes of mono-drug loaded TPGS/PTX nanoparticles and dual-drug loaded TPGS/PTX/TQR nanoparticles were below 150 nm with relatively narrow size distributions. The efficiencies of the drug delivery systems on tumor cells inhibition and reversal of drug resistance were evaluated in drug resistant cancer cells (MCF-7/ADR) as compared with nonresistant cells (HeLa). Due to the effective inhibition of the P-gp efflux by TQR, the dual-drug loaded nanoparticles exhibited significantly improved tumor cell inhibitory efficiency. To study the immunostimulatory effect, the effect of the drug delivery system on the production of IL- 10, a cytokine related to tumor development, in the drug resistant cells was determined. After the treatment by the drug delivery systems, the concentration of IL-10 in the cell supernatant decreased. The multi-drug loaded vitamin E-TPGS nanoparticles for synergistic drug delivery have promising applications in reversal of drug resistance in tumor treatments.
基金financially supported by the National Natural Science Foundation of China (Nos. 51501201, 51501204 and 51671200)the National Key Research and Development Program of China (No. 2017YFB0702302)
文摘The corrosion evolution processes of steel reinforced concrete under simulated tidal and immersion zones of marine environment were investigated by using electrochemical measurements and corrosion morphology observations. The results indicate that the corrosion of rebar in concrete under both environments experiences the deterioration from passivation to pitting corrosion and then to general corrosion. Specially, the pitting plays the major role only in the early stage of corrosion, and the general corrosion replaces the dominate role of pitting during the long-term corrosion. In addition, both the pitting depth on local surface and the rust thickness on the overall surface of rebar in the tidal condition are larger than those in immersion condition, which is attributed to the faster corrosion rate in tidal zone caused by the concentrated chloride ions and sufficient oxygen supply.
基金supported by the National Key Research and Development Program of China(2020YFC0842000,2020YFC0847000).
文摘Understanding the pathological features of severe acute respiratory syn drome coronavirus 2(SARS-CoV-2)infect io n in an animal model is crucial for the treatment of coronavirus disease 2019(COVID-19).Here,we compared imnnunopathological changes in young and old rhesus macaques(RMs)before and after SARS-CoV-2 infection at the tissue level.Quantitative analysis of multiplex immunofluoresce nee staining images of formali n-fixed paraffi n-embedded(FFPE)sections showed that SARS-CoV-2 infectio n specifically induced elevated levels of apoptosis,autophagy,and nuclear factor kappa-B(NF-kB)activation of angiotensirv convert!ng enzyme 2(ACE2)+cells,and increased interferon a(IFN-a)-and interleukin 6(IL-6)-secreting cells and C-X-C motif chemokine receptor 3(CXCR3)+cells in lung tissue of old RMs.This pathological pattern,which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens,was significantly correlated with the systemic accumulation of CXCR3+cells in lungs,spleens,and peripheral blood.Furthermore,the ratio of CXCR3+to T-box protein expression in T cell(T-bet)+(CXCR3+/T-bet+ratio)in CD8+cells may be used as a predictor of severe COVID-19.These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+cells in predicting severe COVID-19.
文摘SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast cells(MCs)are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations.In this study,we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury.SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques,and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells;MC degranulation altered various signaling pathways in alveolar epithelial cells,particularly,the induction of pro-inflammatory factors and consequential disruption of tight junctions.Importantly,the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury.These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation,and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.
基金The work was supported by the National Key R&D Program of China(2021YFC2301703)National Natural Science Foundation of China(81771770,81671627,U1802284,81971548,82071847)National Resource Center for Non-Human Primates.
文摘The number of elderly people living with HIV is increasing globally,and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection.However,the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear.Here,we used the simian immunodeficiency virus mac239(SIVmac239)strain to infect six young and six old Chinese rhesus macaques(ChRMs)and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes.The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes,especially when a large number of CD8+T cells infiltrated the follicles and germinal centers.STAT3 in these follicular CXCR5+CD8+T cells was highly activated,with high expression of granzyme B,which might be caused by the severe inflammatory milieu in the follicles of old ChRMs.This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues,affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+cells.