Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially whe...Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.展开更多
The evolution of microstructure and mechanical properties of A356 aluminum alloy subjected to hot spinning process has been investigated. The results indicated that the deformation process homogenized microstructure a...The evolution of microstructure and mechanical properties of A356 aluminum alloy subjected to hot spinning process has been investigated. The results indicated that the deformation process homogenized microstructure and improved mechanical properties of the A356 aluminum alloy. During the hot spinning process, eutectic Si particles and Fe-rich phases were fragmented, and porosities were eliminated. In addition, recrystallization of Al matrix and precipitation of Al Si Ti phases occurred. The mechanical property testing results indicated that there was a significant increase of ductility and a decrease of average microhardness in deformed alloy over die-cast alloy. This is attributed to uniform distribution of finer spherical eutectic Si particles, the elimination of casting defects and to the recrystallized finer grain structure.展开更多
Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are ...Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are rarely described.A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province.A total of 25 confirmed pediatric cases of COVID-19 were collected.The demographic data,epidemiological history,underlying discascs,clinical mani festations,laboratory and radiological data,treatments,and outcomes were analyzcd.Of 25 hospitalized patients with COVID-19,the boy to girl ratio was 1.27:1.The median age was 3 years.COVID-19 cases in children aged<3 years,3-6 years,and≥6-years patients were 10(40%),6(24%),and 9(36%),respectively.The most common symptoms at onset of ilness were fever(13[52%]),and dry cough(11[44%]).Chest CT images showed essential normal in 8 cases(33.3%),unilateral involvement of lungs in 5 cases(20.8%),and bilateral involvement in 11 cases(45.8%).Clinical diagnoses included upper respiratory tract infection(n=8),mild pneumonia(n=15),and critical cases(n=2).Two critical cases(8%)were given invasive mechanical ventilation,corticosteroids,and immunoglobulin.The symptoms in 24(96%)of 25 patients were alleviated and one patient had been discharged.It was concluded that children were susceptible to COVID-19 like adults,while the clinical presentations and outcomes were more favorable in children.However,children less than 3 years old accounted for majority cases and critical cases lied in this age group,which demanded extra attentions during home caring and hospitalization treatment.展开更多
The peroxisomal matrix proteins involved in many important biological metabolism pathways in eukaryotic cells are encoded by nucleal genes, synthesized in the cytoplasm and then transported into the organelles. Target...The peroxisomal matrix proteins involved in many important biological metabolism pathways in eukaryotic cells are encoded by nucleal genes, synthesized in the cytoplasm and then transported into the organelles. Targeting and import of these proteins depend on their two peroxisomal targeting signals (PTS1 and PTS2) in sequence as we have known so far. The vectors of the fluorescent fusions with PTS, i.e., green fluorescence protein (GFP)-PTS1, GFP-PTS2 and red fluorescence protein (RFP)-PTS1, were constructed and introduced into Magnaporthe oryzae Guy11 cells. Transformants containing these fusions emitted fluorescence in a punctate pattern, and the locations of the red and green fluorescence overlapped exactly in RFP-PTS1 and GFP-PTS2 co-transformed strains. These data indicated that both PTS1 and PTS2 fusions were imported into peroxisomes. A probable higher efficiency of PTS1 machinery was revealed by comparing the fluorescence backgrounds in GFP-PTS1 and GFP-PTS2 transformants. By introducing both RFP-PTS1 and GFP-PTS2 into Δmgpex6 mutants, the involvement of MGPEX6 gene in both PTS1 and PTS2 pathways was proved. In addition, using these transformants, the inducement of peroxisomes and the dynamic of peroxisomal number during the pre-penetration processes were investigated as well. In summary, by the localization and co-localization of PTS1 and PTS2, we provided a useful tool to evaluate the biological roles of the peroxisomes and the related genes.展开更多
The cast Al-Si alloy was fabricated using the Additive Pressure Casting(APC)method.The effects of holding pressure from 50 to 400 k Pa on the density,cooling rate,and mechanical properties of the alloy,and the corresp...The cast Al-Si alloy was fabricated using the Additive Pressure Casting(APC)method.The effects of holding pressure from 50 to 400 k Pa on the density,cooling rate,and mechanical properties of the alloy,and the corresponding mechanism were discussed.The results indicate that the application of high holding pressure(300 k Pa)enhances the feeding ability of the alloy,leading to an increase of the density.Meanwhile,the cooling rate of the alloy is increased by 100%.In addition,the tensile testing results show that the increase of holding pressure from 50 to 300 k Pa improves the tensile strength and elongation of the alloy by 6.2%and 81.3%,respectively.However,excessive holding pressure(400 k Pa)might lower the density and cooling rate of the alloy due to the feeding channels being blocked.展开更多
Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated...Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca2+-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca2+ sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy.展开更多
Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely st...Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study,we created a MHV-A59 temperature sensitive (ts) mutant Wu"-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu"-ts18(cd) were indistinguishable from the reported ts mutant Wu"-ts18. Then we cultured the ts mutant Wu"-ts18(cd) at non-permissive temperature 39.5°C,which "forced" the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu"-ts18 (cd) to non-ts phenotype,an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.展开更多
BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory d...BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory distress syndrome (ARDS).METHODS: ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilatedwith neurally adjusted ventilatory assistance (NAVA) with a tidal volume (VT) of 6 mL/kg and theelectrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation ofthe bilateral vagus nerve trunk, the rabbits were randomized into two groups: sham operation (SHAM)group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanicswere detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively.Pulmonary permeability index, pathological changes and infl ammatory response were also measured.RESULTS: Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased signifi cantly2 and 3 hours after ventilation (P〈0.05). There was no significant difference in PaCO2 betweenthe SHAM and VAG groups (P〉0.05), and the VAG group had a high VT, peak pressure (Ppeak),and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P〈0.05).Compared to the SHAM group, dead space fraction (VD/VT) and respiratory system elastance (Ers)in the VAG group increased (P〈0.05) and static pulmonary compliance (Cst) decreased markedly(P〈0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injuryscore (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-# (TNF-#) (779±372 pg/mL vs. 355±130 pg/mL)and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG groupcompared with the SHAM group (P〈0.05).CONCLUSION: Lung injury is aggravated after bilateral vagotomy, demonstrating thatpulmonary stretch refl ex may have protective effect on the lung.展开更多
Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to eva...Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.展开更多
The influence of emulsified oil, suspended solids, Fe3+, Fe2+, cationic water clarifier and sulfate-reducing (SR) bacteria on the aggregation behavior of residual hydrophobic modified polyacrylamide in treated oil...The influence of emulsified oil, suspended solids, Fe3+, Fe2+, cationic water clarifier and sulfate-reducing (SR) bacteria on the aggregation behavior of residual hydrophobic modified polyacrylamide in treated oily wastewater from polymer flooding was studied by fluorescence spectroscopy and dynamic light scattering. The result of I1/I3 showed that the polarity of hydrophobic microdomains increased, whereas the size of the hydrophobic microdomains may be decreased, where the value of I1/I3 represents the ratio of the intensity of peak 11 (374.0 nm) to that of peak/3 (385.0 nm) of the vibration fine structure of pyrene monomer emission in residual polymer solution. The results of the ratio of I1 at 48 h to I1 at 0 h (I1,48h/I1,0h) indicated that oil and cationic water clarifier could inhibit the aggregation to some extent, while Fe2+ and suspended solids were helpful for aggregation, and Fe3+ and SR bacteria had no significant influence on the aggregation of polymer.展开更多
Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage...Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage of sibling donors,and lack of resources to support the HSCT.In addition,some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis.Considering the disease condition,economics and other factors,the present study designed a new and relatively mild treatment strategy:cyclosporine A plus pulsed high-dose prednisone(CsA+HDP).Methods The present study retrospectively analyzed 11 VSAA patients,who were treated with CsA+HDP in our hospital from August 2017 to August 2019.Results The median follow-up time for these patients was 24.9 months.The overall response rate was 54.5%(6/11)at six months after the initiation of IST and 81.8%(9/11)at deadline.Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up.The median time to response for responders was 110 days.Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor.Recurrence and clonal evolution were not found in any of these patients.The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0%and 72.7%,respectively.In addition,the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients.Conclusion The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies,who have no serious life-threatening infections or bleeding at the time of initial diagnosis.展开更多
The effect of La addition(0,0.1,0.2,0.4,wt.%)on the microstructure,tensile properties and fracture behavior of Al-7Si alloy was investigated systematically.It is found that the La appears in the Al-7Si alloy in the fo...The effect of La addition(0,0.1,0.2,0.4,wt.%)on the microstructure,tensile properties and fracture behavior of Al-7Si alloy was investigated systematically.It is found that the La appears in the Al-7Si alloy in the form of Al4La and Al2Si2La phases.La addition can refine the secondary dendrite arm spacing(SDAS)and eutectic Si particles,which are decreased by 7.9%and 7%,respectively,with the optimal La content of 0.1wt.%.Because when 0.1wt.%La is added,a relatively higher nucleation undercooling of 37.47℃ is observed.Higher undercooling degree suggests that nucleation is accelerated and subsequent growth is restrained.After T6 heat treatment,compared with the without La,the ultimate tensile strength of the alloy with 0.1wt.%La is enhanced by 5.2%from 333 MPa to 350.2 MPa and the elongation increases by 73%from 7.37%to 12.75%,correspondingly.The fracture mode evolves from the ductile-brittle mixed fracture to ductile fracture mode.However,when La element content reaches a certain value of 0.4wt.%,serious segregation takes place during the solidification process.The formed brittle phases deteriorate the tensile properties of the alloy and the fracture mode of Al-7Si-0.2/0.4 La changes to mixed ductile-brittle fracture mode.展开更多
Objective: To explore the clinical significance of serum S100B in chronic heart failure (CHF). Methods: A total of 300 patients with CHF of cardiac function levels II–IV were divided into three groups, and 300 normal...Objective: To explore the clinical significance of serum S100B in chronic heart failure (CHF). Methods: A total of 300 patients with CHF of cardiac function levels II–IV were divided into three groups, and 300 normal cases were selected as controls. Serum S100B, B-type natriuretic peptide (BNP), LVEF(%) and LVEDD were detected and analyzed. CHF patients were followed up for 1 year. Statistical analysis was performed using SPSS and Microsoft Excel. Results: The level of S100B in CHF patients was significantly increased, and the serum level was positively correlated with BNP. The serum S100B level was positively correlated with heart failure classification, and the area under ROC curve was 0.84. The sensitivity and specificity were 81.2% and 71.5%, respectively. Patients with high serum S100B were at higher risk of major cardiovascular events. Conclusion: Serum S100B level is significantly increased in patients with chronic heart failure, and is negatively correlated with the patients' cardiac function. It is an independent risk factor for the occurrence and development of chronic heart failure, and it has implications for the prognosis of patients with chronic heart failure.展开更多
The M-test has been in common use and widely studied in testing the linear hypotheses in linear models. However, the critical value for the test is usually related to the quantities of the unknown error distribution a...The M-test has been in common use and widely studied in testing the linear hypotheses in linear models. However, the critical value for the test is usually related to the quantities of the unknown error distribution and the estimate of the nuisance parameters may be rather involved, not only for the M-test method but also for the existing bootstrap methods. In this paper we suggest a random weighting resampling method for approximating the null distribution of the M-test statistic. It is shown that, under both the null and the local alternatives, the random weighting statistic has the same asymptotic distribution as the null distribution of the M-test. The critical values of the M-test can therefore be obtained by the random weighting method without estimating the nuisance parameters. A distinguished feature of the proposed method is that the approximation is valid even the null hypothesis is not true and the power evaluation is possible under the local alternatives.展开更多
Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficien...Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficient mice were shown to be susceptible to HAV infection.Herein,we sought to determine the infection and replication dynamics of the H2 in Ifnar^(-/-)mice that lack type Ⅰ IFN receptor.Following intravenous injection,the H2 failed to cause obvious clinical symptoms in Ifnar^(-/-)mice,and no significant upregulation in serum alanine aminotransferase(ALT)levels was observed.Notably,the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area,but no focal necrosis was observed in liver tissues.Viral RNAs sustained in the liver,and the infectious virus could be recovered from the liver tissue until 42 days post-infection.More importantly,H2 infection induced obvious viremia and persistent viral shedding in feces.In addition,robust HAV-specific humoral immune responses were induced in Ifnar^(-/-)mice.Overall,our study revealed the safety profile of H2 in Ifnar^(-/-)mice,which not only helps understand the attenuation mechanism of H2,but also expands the application of the Ifnar^(-/-)mouse model for HAV studies.展开更多
Acute pulmonary embolism(APE)is a challenging condition with frequently missed or delayed diagnosis,and thus may be fatal.In emergency patients with a history of coronary heart disease,the electrocardiogram(ECG)result...Acute pulmonary embolism(APE)is a challenging condition with frequently missed or delayed diagnosis,and thus may be fatal.In emergency patients with a history of coronary heart disease,the electrocardiogram(ECG)results are often not specific,and APE is difficult to diagnose.Consequently,the patients tend to be diagnosed with acute coronary syndrome(ACS),and either undergo reexamination with myocardial enzyme observations in the emergency department,or are admitted to the hospital for coronary angiography.The 2008 European Society of Cardiology(ESC)guidelines on the diagnosis and management of acute pulmonary embolism stated that the clinical risk assessment of APE should be based on the Wells score.[1]However,despite this official recommendation,the Wells score is not widely used in emergency medicine,especially for patients with coronary heart disease and concomitant APE.The present study analyzed the predictive value of the Wells score combined with the D-dimer level in identifying APE in patients with coronary heart disease.展开更多
基金the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNLH-201907)the Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019Q041)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(No.2021-I2M-1-009).
文摘Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.
基金supported by the National Key Research Project(No.2016YFB0300901)
文摘The evolution of microstructure and mechanical properties of A356 aluminum alloy subjected to hot spinning process has been investigated. The results indicated that the deformation process homogenized microstructure and improved mechanical properties of the A356 aluminum alloy. During the hot spinning process, eutectic Si particles and Fe-rich phases were fragmented, and porosities were eliminated. In addition, recrystallization of Al matrix and precipitation of Al Si Ti phases occurred. The mechanical property testing results indicated that there was a significant increase of ductility and a decrease of average microhardness in deformed alloy over die-cast alloy. This is attributed to uniform distribution of finer spherical eutectic Si particles, the elimination of casting defects and to the recrystallized finer grain structure.
文摘Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are rarely described.A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province.A total of 25 confirmed pediatric cases of COVID-19 were collected.The demographic data,epidemiological history,underlying discascs,clinical mani festations,laboratory and radiological data,treatments,and outcomes were analyzcd.Of 25 hospitalized patients with COVID-19,the boy to girl ratio was 1.27:1.The median age was 3 years.COVID-19 cases in children aged<3 years,3-6 years,and≥6-years patients were 10(40%),6(24%),and 9(36%),respectively.The most common symptoms at onset of ilness were fever(13[52%]),and dry cough(11[44%]).Chest CT images showed essential normal in 8 cases(33.3%),unilateral involvement of lungs in 5 cases(20.8%),and bilateral involvement in 11 cases(45.8%).Clinical diagnoses included upper respiratory tract infection(n=8),mild pneumonia(n=15),and critical cases(n=2).Two critical cases(8%)were given invasive mechanical ventilation,corticosteroids,and immunoglobulin.The symptoms in 24(96%)of 25 patients were alleviated and one patient had been discharged.It was concluded that children were susceptible to COVID-19 like adults,while the clinical presentations and outcomes were more favorable in children.However,children less than 3 years old accounted for majority cases and critical cases lied in this age group,which demanded extra attentions during home caring and hospitalization treatment.
基金the National Natural Science Foundation of China (Nos. 30671351 and 30810033the Natural Science Foundation of Zhejiang Province of China (No. Y306638)
文摘The peroxisomal matrix proteins involved in many important biological metabolism pathways in eukaryotic cells are encoded by nucleal genes, synthesized in the cytoplasm and then transported into the organelles. Targeting and import of these proteins depend on their two peroxisomal targeting signals (PTS1 and PTS2) in sequence as we have known so far. The vectors of the fluorescent fusions with PTS, i.e., green fluorescence protein (GFP)-PTS1, GFP-PTS2 and red fluorescence protein (RFP)-PTS1, were constructed and introduced into Magnaporthe oryzae Guy11 cells. Transformants containing these fusions emitted fluorescence in a punctate pattern, and the locations of the red and green fluorescence overlapped exactly in RFP-PTS1 and GFP-PTS2 co-transformed strains. These data indicated that both PTS1 and PTS2 fusions were imported into peroxisomes. A probable higher efficiency of PTS1 machinery was revealed by comparing the fluorescence backgrounds in GFP-PTS1 and GFP-PTS2 transformants. By introducing both RFP-PTS1 and GFP-PTS2 into Δmgpex6 mutants, the involvement of MGPEX6 gene in both PTS1 and PTS2 pathways was proved. In addition, using these transformants, the inducement of peroxisomes and the dynamic of peroxisomal number during the pre-penetration processes were investigated as well. In summary, by the localization and co-localization of PTS1 and PTS2, we provided a useful tool to evaluate the biological roles of the peroxisomes and the related genes.
基金National Key Research Project of China(No.2016YFB0300901).
文摘The cast Al-Si alloy was fabricated using the Additive Pressure Casting(APC)method.The effects of holding pressure from 50 to 400 k Pa on the density,cooling rate,and mechanical properties of the alloy,and the corresponding mechanism were discussed.The results indicate that the application of high holding pressure(300 k Pa)enhances the feeding ability of the alloy,leading to an increase of the density.Meanwhile,the cooling rate of the alloy is increased by 100%.In addition,the tensile testing results show that the increase of holding pressure from 50 to 300 k Pa improves the tensile strength and elongation of the alloy by 6.2%and 81.3%,respectively.However,excessive holding pressure(400 k Pa)might lower the density and cooling rate of the alloy due to the feeding channels being blocked.
文摘Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca2+-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca2+ sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy.
基金Research Grants from State Key Laboratory of Pathogen and Biosecurity (SKLPBS0918)
文摘Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study,we created a MHV-A59 temperature sensitive (ts) mutant Wu"-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu"-ts18(cd) were indistinguishable from the reported ts mutant Wu"-ts18. Then we cultured the ts mutant Wu"-ts18(cd) at non-permissive temperature 39.5°C,which "forced" the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu"-ts18 (cd) to non-ts phenotype,an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.
文摘BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory distress syndrome (ARDS).METHODS: ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilatedwith neurally adjusted ventilatory assistance (NAVA) with a tidal volume (VT) of 6 mL/kg and theelectrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation ofthe bilateral vagus nerve trunk, the rabbits were randomized into two groups: sham operation (SHAM)group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanicswere detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively.Pulmonary permeability index, pathological changes and infl ammatory response were also measured.RESULTS: Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased signifi cantly2 and 3 hours after ventilation (P〈0.05). There was no significant difference in PaCO2 betweenthe SHAM and VAG groups (P〉0.05), and the VAG group had a high VT, peak pressure (Ppeak),and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P〈0.05).Compared to the SHAM group, dead space fraction (VD/VT) and respiratory system elastance (Ers)in the VAG group increased (P〈0.05) and static pulmonary compliance (Cst) decreased markedly(P〈0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injuryscore (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-# (TNF-#) (779±372 pg/mL vs. 355±130 pg/mL)and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG groupcompared with the SHAM group (P〈0.05).CONCLUSION: Lung injury is aggravated after bilateral vagotomy, demonstrating thatpulmonary stretch refl ex may have protective effect on the lung.
基金supported by the National Natural Science Foundation of China(No.81700147 and No.82070172).
文摘Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.
基金supported by the Scientific Research Project of CNOOC(China)(Grant No.CNOOC-KJ 125 ZDXM 06 LTD NFGC 2014-01)
文摘The influence of emulsified oil, suspended solids, Fe3+, Fe2+, cationic water clarifier and sulfate-reducing (SR) bacteria on the aggregation behavior of residual hydrophobic modified polyacrylamide in treated oily wastewater from polymer flooding was studied by fluorescence spectroscopy and dynamic light scattering. The result of I1/I3 showed that the polarity of hydrophobic microdomains increased, whereas the size of the hydrophobic microdomains may be decreased, where the value of I1/I3 represents the ratio of the intensity of peak 11 (374.0 nm) to that of peak/3 (385.0 nm) of the vibration fine structure of pyrene monomer emission in residual polymer solution. The results of the ratio of I1 at 48 h to I1 at 0 h (I1,48h/I1,0h) indicated that oil and cationic water clarifier could inhibit the aggregation to some extent, while Fe2+ and suspended solids were helpful for aggregation, and Fe3+ and SR bacteria had no significant influence on the aggregation of polymer.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.21906061).
文摘Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage of sibling donors,and lack of resources to support the HSCT.In addition,some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis.Considering the disease condition,economics and other factors,the present study designed a new and relatively mild treatment strategy:cyclosporine A plus pulsed high-dose prednisone(CsA+HDP).Methods The present study retrospectively analyzed 11 VSAA patients,who were treated with CsA+HDP in our hospital from August 2017 to August 2019.Results The median follow-up time for these patients was 24.9 months.The overall response rate was 54.5%(6/11)at six months after the initiation of IST and 81.8%(9/11)at deadline.Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up.The median time to response for responders was 110 days.Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor.Recurrence and clonal evolution were not found in any of these patients.The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0%and 72.7%,respectively.In addition,the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients.Conclusion The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies,who have no serious life-threatening infections or bleeding at the time of initial diagnosis.
基金the Fundamental Research Funds for the Central Universities(Grant number FRF-TP-19-083A1)the Guangxi Special Funding Programme for Innovation-Driven Development(Grant number GKAA17202008)。
文摘The effect of La addition(0,0.1,0.2,0.4,wt.%)on the microstructure,tensile properties and fracture behavior of Al-7Si alloy was investigated systematically.It is found that the La appears in the Al-7Si alloy in the form of Al4La and Al2Si2La phases.La addition can refine the secondary dendrite arm spacing(SDAS)and eutectic Si particles,which are decreased by 7.9%and 7%,respectively,with the optimal La content of 0.1wt.%.Because when 0.1wt.%La is added,a relatively higher nucleation undercooling of 37.47℃ is observed.Higher undercooling degree suggests that nucleation is accelerated and subsequent growth is restrained.After T6 heat treatment,compared with the without La,the ultimate tensile strength of the alloy with 0.1wt.%La is enhanced by 5.2%from 333 MPa to 350.2 MPa and the elongation increases by 73%from 7.37%to 12.75%,correspondingly.The fracture mode evolves from the ductile-brittle mixed fracture to ductile fracture mode.However,when La element content reaches a certain value of 0.4wt.%,serious segregation takes place during the solidification process.The formed brittle phases deteriorate the tensile properties of the alloy and the fracture mode of Al-7Si-0.2/0.4 La changes to mixed ductile-brittle fracture mode.
基金Hainan Natural Science Foundation Project.Project No:817336.
文摘Objective: To explore the clinical significance of serum S100B in chronic heart failure (CHF). Methods: A total of 300 patients with CHF of cardiac function levels II–IV were divided into three groups, and 300 normal cases were selected as controls. Serum S100B, B-type natriuretic peptide (BNP), LVEF(%) and LVEDD were detected and analyzed. CHF patients were followed up for 1 year. Statistical analysis was performed using SPSS and Microsoft Excel. Results: The level of S100B in CHF patients was significantly increased, and the serum level was positively correlated with BNP. The serum S100B level was positively correlated with heart failure classification, and the area under ROC curve was 0.84. The sensitivity and specificity were 81.2% and 71.5%, respectively. Patients with high serum S100B were at higher risk of major cardiovascular events. Conclusion: Serum S100B level is significantly increased in patients with chronic heart failure, and is negatively correlated with the patients' cardiac function. It is an independent risk factor for the occurrence and development of chronic heart failure, and it has implications for the prognosis of patients with chronic heart failure.
基金This work was partially supported by the National Natural Science Foundation of China (Grant No. 10471136) Ph. D. Program Foundation of the Ministry of Education of China, Special Foundations of the Chinese Academy of Sciences and USTCIMS Program-Semi-parametric Methods for Survival and Longitudinal Data in National University of Singapore.
文摘The M-test has been in common use and widely studied in testing the linear hypotheses in linear models. However, the critical value for the test is usually related to the quantities of the unknown error distribution and the estimate of the nuisance parameters may be rather involved, not only for the M-test method but also for the existing bootstrap methods. In this paper we suggest a random weighting resampling method for approximating the null distribution of the M-test statistic. It is shown that, under both the null and the local alternatives, the random weighting statistic has the same asymptotic distribution as the null distribution of the M-test. The critical values of the M-test can therefore be obtained by the random weighting method without estimating the nuisance parameters. A distinguished feature of the proposed method is that the approximation is valid even the null hypothesis is not true and the power evaluation is possible under the local alternatives.
基金supported by the National Natural Science Fund for Distinguished Young Scholar (No.81925025)the Innovative Research Group (No. 81621005) from the National Natural Science Foundation of Chinathe Innovation Fund for Medical Sciences (No. 2019-I2M-5-049) from the Chinese Academy of Medical Sciences
文摘Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficient mice were shown to be susceptible to HAV infection.Herein,we sought to determine the infection and replication dynamics of the H2 in Ifnar^(-/-)mice that lack type Ⅰ IFN receptor.Following intravenous injection,the H2 failed to cause obvious clinical symptoms in Ifnar^(-/-)mice,and no significant upregulation in serum alanine aminotransferase(ALT)levels was observed.Notably,the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area,but no focal necrosis was observed in liver tissues.Viral RNAs sustained in the liver,and the infectious virus could be recovered from the liver tissue until 42 days post-infection.More importantly,H2 infection induced obvious viremia and persistent viral shedding in feces.In addition,robust HAV-specific humoral immune responses were induced in Ifnar^(-/-)mice.Overall,our study revealed the safety profile of H2 in Ifnar^(-/-)mice,which not only helps understand the attenuation mechanism of H2,but also expands the application of the Ifnar^(-/-)mouse model for HAV studies.
文摘Acute pulmonary embolism(APE)is a challenging condition with frequently missed or delayed diagnosis,and thus may be fatal.In emergency patients with a history of coronary heart disease,the electrocardiogram(ECG)results are often not specific,and APE is difficult to diagnose.Consequently,the patients tend to be diagnosed with acute coronary syndrome(ACS),and either undergo reexamination with myocardial enzyme observations in the emergency department,or are admitted to the hospital for coronary angiography.The 2008 European Society of Cardiology(ESC)guidelines on the diagnosis and management of acute pulmonary embolism stated that the clinical risk assessment of APE should be based on the Wells score.[1]However,despite this official recommendation,the Wells score is not widely used in emergency medicine,especially for patients with coronary heart disease and concomitant APE.The present study analyzed the predictive value of the Wells score combined with the D-dimer level in identifying APE in patients with coronary heart disease.