Around 71% of the Earth’s surface is covered by oceans with depths that exceed several kilometers, while continents are geographically enclosed by these vast bodies of water. The principle of fluid mechanics stipulat...Around 71% of the Earth’s surface is covered by oceans with depths that exceed several kilometers, while continents are geographically enclosed by these vast bodies of water. The principle of fluid mechanics stipulates that water yields pressure everywhere in the container that holds it, and the water pressure against the wall of container generates force. Ocean basins are naturally gigantic containers of water, in which continents form the walls of the containers. In this study, we present that the ocean water pressure against the walls of continents generates enormous force, and determine the distribution of this force around continents and estimate its amplitude to be of the order of 1017 N per kilometer of continent width. Our modelling suggests that the stresses yielded by this force are mostly concentrated on the upper part of the continental crust, and their magnitudes reach up to 2.0 - 6.0 MPa. Our results suggest that the force may have significantly impacted the dynamics of continent (lithospheric plate) and its evolution.展开更多
Plate motion representing a remarkable Earth process is widely attributed to several primary forces such as ridge push and slab pull. Recently, we have presented that the ocean water pressure against the wall of conti...Plate motion representing a remarkable Earth process is widely attributed to several primary forces such as ridge push and slab pull. Recently, we have presented that the ocean water pressure against the wall of continents may generate enormous force on continents. Continents are physically fixed on the top of the lithosphere that has been already broken into individual plates, this attachment enables the force to be laterally transferred to the lithospheric plates. In this study, we combine the force and the existing plate driving forces (i.e., ridge push, slab pull, collisional, and shearing) to account for plate motion. We show that the modelled movements for the South American, African, North American, Eurasian, Australian, Pacific plates are well agreement with the observed movements in both speed and azimuth, with a Root Mean Square Error (RMSE) of the modelled speed against the observed speed of 0.91, 3.76, 2.77, 2.31, 7.43, and 1.95 mm/yr, respectively.展开更多
This paper deals with the co-existence of mixed aleatory and epistemic uncertainties in a wind turbine geared system for more reliable and robust vibration analyses.To this end,the regression-based polynomial chaos ex...This paper deals with the co-existence of mixed aleatory and epistemic uncertainties in a wind turbine geared system for more reliable and robust vibration analyses.To this end,the regression-based polynomial chaos expansion(PCE)is used to track aleatory uncertainties,and the polynomial surrogate approach(PSA)is developed to treat the epistemic uncertainties.This non-intrusive dual-layer framework shares the same collocation pool,which is extracted from the Legendre series.Moreover,the regression technique has been implemented in both layers to enhance calculation efficiency.Numerical validation is carried out to show the effectiveness of the proposed method.New vibration behaviors of the geared transmission system are observed,and the mechanism behind is discussed in detail.The findings of this paper will contribute to the insightful understanding of such wind turbine geared systems under hybrid uncertainties and are beneficial for the condition monitoring.展开更多
Purpose: To compare the dosimetric impact of coplanar intensity modulated radiation therapy (IMRT) and non-coplanar IMRT for the esophageal carcinoma. Methods: There are forty-five esophageal carcinoma patients, fifte...Purpose: To compare the dosimetric impact of coplanar intensity modulated radiation therapy (IMRT) and non-coplanar IMRT for the esophageal carcinoma. Methods: There are forty-five esophageal carcinoma patients, fifteen of whom were cervical and upper thoracic (Group 1) and thirty were middle and lower thoracic (Group 2). Gross tumor volume (GTV), clinical target volume (CTV), and organs at risk (OAR) were contoured by the chief physician in the CMS-XiO treatment planning system. For each patient, one coplanar plan and two non-coplanar plans have been created using the same physical objective function. A detailed dose-volume histogram (DVH) comparison among three plans was then carried out in a tabulated format. Results: 1) In Group 1 patients with PTV volume less than 100cc, the mean dose and dose gradient of non-coplanar plan were much better than those in coplanar plan. 2) In Group 2 patients, the conformity index (CI) for coplanar and two non-coplanar plans were 0.69 ± 0.13, 0.41 ± 0.13, and 0.68 ± 0.15, respectively. The V5, V10, V20, and the mean dose to the lung were lower in the non-coplanar plans compared to ones in coplanar plan. However, the non-coplanar plans resulted in an increase in a dose to the heart, but the dose was still within heart toxicity tolerance. Conclusion: For Group 1 patients, the non-coplanar IMRT plan had less dose gradient and better mean dose than the coplanar IMRT plan. For Group 2 patients, the non-coplanar IMRT could the decrease dose to the lung tissue, thus lowering the probability of radiation pneumonia to esophageal cancer patients. The drawback of non-coplanar IMRT is that, even within toxicity tolerance, it could deliver a higher dose to the heart and spinal cord compared to the coplanar plan. Therefore, for patients with cardiology and neurology concern, non-coplanar IMRT should be used with caution.展开更多
Background: Autoimmune hepatitis (AIH) is a hepatocyte injury characterized by a dis-regulated immune system, inflammation of the liver with interface hepatitis, serum antibodies and elevated gamma-globulins. Currentl...Background: Autoimmune hepatitis (AIH) is a hepatocyte injury characterized by a dis-regulated immune system, inflammation of the liver with interface hepatitis, serum antibodies and elevated gamma-globulins. Currently, it exists 2 mainly types on autoimmune hepatitis, based on the presentation of their autoantibodies: type 1 and 2. Type 1 is the one of interest in this review. Autoimmune hepatitis type 1 is an indolent inflammatory disease mediated by abnormal autoimmune reaction, commonly seeing in women (4:1), with no preference of age, however typically present in 4th and 6th decade’s individuals, and a good response to immunosuppressive therapy. Autoimmune hepatitis is known to present not specific symptoms which can go from inexistent to fulminant or exacerbate presentation. The incidence of autoimmune hepatitis in western country is 1/5000 - 1/10,000. Although the detection rate of AIH increasing, especially in China, autoimmune hepatitis diagnosis and treatment remain challenging. Most AIH case do not present pathognomonic biomarkers, however the diagnostic has to considerate other features, which had been codified into validated diagnosis scoring systems. Regarding the treatment, based on prior literature autoimmune hepatitis is mostly sensitive to prednisone or azathioprine, however the use of other immunosuppressive agent or event their combination had offer distinct advantages. Autoimmune hepatitis presents a great life threatening disorder especially because of the delay in the early stage on the disease, the not specific presentations, and the large overlap syndrome associate with it. A deep knowledge in its identification, specific diagnostic criteria, and its therapeutic strategy is much needed. Conclusion: Autoimmune hepatitis is a systemic disease that is difficult to recognize because of its variable clinical presentation and histological features that are not strictly specific. Several new autoantibodies as well as recently simplified diagnostic criteria may allow the primary care physician to progress in the diagnostic process. This is all the more important as undiagnosed and therefore untreated autoimmune hepatitis has a poor prognosis and immunosuppressive treatment leads to remission in a large majority of cases.展开更多
The coal resources are abundant in Huainan City,but with development and utilization of coal mine,the water surface formed by mining subsidence increases gradually,and more and more people pay great attention on the r...The coal resources are abundant in Huainan City,but with development and utilization of coal mine,the water surface formed by mining subsidence increases gradually,and more and more people pay great attention on the research of the wetland in the subsidence area. Through on-site review,the status of the wetland resources is explored,and wetland ecosystem of the region is analyzed. In this paper,the red line delimitation,functional zoning,overall layout and basic engineering planning and design of Suocao Bay Wetland Park are carried out. The planning and design of Suocao Bay Wetland Park mean to provide new support for ecological protection,accelerate the ecological restoration in Maoji Experimental Area,vigorously carry forward the wetland culture,and make it become an important wetland demonstration base in coal mine subsidence area.展开更多
There are many types of wetlands around the Chaohu Lake,and wetland biodiversity is rich. The protection of wetland biodiversity is of great significance for regional sustainable development. In this paper,the wetland...There are many types of wetlands around the Chaohu Lake,and wetland biodiversity is rich. The protection of wetland biodiversity is of great significance for regional sustainable development. In this paper,the wetlands around the Chaohu Lake are taken as the research objects. Based on the investigation and analysis of the biodiversity in the wetlands,combing the threats to the biodiversity of the wetland around the Chaohu Lake at the present stage,the biodiversity protection countermeasures of the wetlands around the Chaohu Lake are put forward.展开更多
Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fum...Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.展开更多
Dear Editor:Lung cancer has the highest incidence rate among malignancies and remains the primary contributor to cancer-related mortality on a global scale[1].Early detection is the most efficacious approach for enhan...Dear Editor:Lung cancer has the highest incidence rate among malignancies and remains the primary contributor to cancer-related mortality on a global scale[1].Early detection is the most efficacious approach for enhancing the prognosis and mitigating the mortality of patients with lung cancer[2].Currently,diagnosis of lung cancer is mainly by different types of imaging including low-dose spiral computed tomography(LDCT)combined with pathological assessment of biopsy,but prevalence of false-positive results and associated expenses may impede its becoming a standard screening technique[3].展开更多
To the Editor:China provides free antiretroviral therapy(ART)for people with human immunodeficiency virus(HIV),typically using two nucleoside reverse transcriptase inhibitors(NRTIs)and one non-nucleoside reverse trans...To the Editor:China provides free antiretroviral therapy(ART)for people with human immunodeficiency virus(HIV),typically using two nucleoside reverse transcriptase inhibitors(NRTIs)and one non-nucleoside reverse transcriptase inhibitor(NNRTI).This regimen has significantly reduced mortality and slowed HIV spread over the past 20 years.展开更多
To determine whether repetitive transcranial magnetic stimulation(rTMS)of the visual cortex(VC)provides effective and welltolerated treatment and whether magnetic resonance imaging(MRI)measures functional change of th...To determine whether repetitive transcranial magnetic stimulation(rTMS)of the visual cortex(VC)provides effective and welltolerated treatment and whether magnetic resonance imaging(MRI)measures functional change of the VC as a biomarker of therapeutic effect in major depressive disorder(MDD),we performed a sham-controlled,double-blind,randomized,three-arm VC rTMS treatment study in 74 MDD patients.Neuronavigated rTMS(10 Hz,90%of resting motor threshold,1,600 pulses over20 min twice per day)was performed over the VC for five days.Clinical outcome was measured by Hamilton Depression Rating Scale(HAMD-24)at days 0,1,3,5 and after terminating rTMS,with follow-up at four weeks.MRI was measured at days 0 and5.The individualized group exhibited the greatest change in HAMD-24 scores after VC rTMS for 5 days(F=5.53,P=0.005),which were maintained during follow-up period(F=4.22,P=0.016).All patients reported good tolerance.Changes in VC taskrelated functional MRI correlated with symptomatic reduction in the individualized group.Treatment reduced the initially abnormal increase in resting state functional connectivity from the VC to the pre/subgenual anterior cingulate cortex at day 5,especially in the individualized group.We demonstrated therapeutic potential and good tolerance of VC rTMS in MDD patients,indicated by biomarkers of f MRI measurement.展开更多
Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China...Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.展开更多
Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year...Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.展开更多
Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable ...Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.展开更多
Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed th...Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.展开更多
Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms.The heterogeneity can be attributed to genetic,transc...Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms.The heterogeneity can be attributed to genetic,transcriptional,and epigenetic parameters.Here,we established a multi-omics atlas,integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing.We investigated their differences in genetic amplification,cellular compositions,and expression modules.We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells,and had distinct cellular composition modules associated with poor survival of lung cancer.Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression.Moreover,we identified subclusters with proliferating and differentiating properties in AT2 and basal cells.Overexpression assays of ten genes,including sub-cluster markers AQP5 and KPNA2,further indicated their functional roles,providing potential targets for early diagnosis and treatment in lung cancer.展开更多
Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV ...Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis Huiying Rao1,Xingxiang Yang2,Youwen Tan3,Qin Ning4,Daokun Yang5,Jiefei Wang6,Yongfeng Yang7,Sujun Zheng8,Dongliang Yang9,Jinlin Hou10,Qing Xie11,Caiyan Zhao12,Lunli Zhang13,Xiaorong Mao14,Tong Sun15,Lang Bai16,Fuchun Zhang17,Jinglan Jin18,Yingren Zhao19,Maorong Wang20,Wen Xie21,Yingjie Ma22,Jun Quan23,Xuebing Yan24,Ping An25,Feng Lin26,Jidong Jia27,Xiaoxuan Hu28,Zuojiong Gong29,Jie Wu30,Yongping Chen31,Zhansheng Jia32,Minghua Lin33,Guiqiang Wang34,Yueyong Zhu35,Yingjun Zhang*,36,Hongming Xie36,Lin Luo36,Qingyun Ren36,Rui Huang1 and Lai Wei*,37 Author information Journal of Clinical and Translational Hepatology 2020;8(3):255-261DOI:10.14218/JCTH.2020.00031 Abstract Background and Aims:Emitasvir is a new type of hepatitis C virus(HCV)nonstructural protein 5A(NS5A)inhibitor,and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance.We conducted this phase 3 trial to further verify the efficacy and safety.Methods:We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate(100 mg)combined with sofosbuvir(400 mg)once daily in non-cirrhotic patients with genotype 1 HCV infection.The primary endpoint was a sustained virological response at 12 weeks(SVR12)after the end of treatment.Results:Of the 362 patients enrolled in the trial,39.8%were male,99.2%had HCV genotype 1b,0.8%had genotype 1a and 79.8%were treatment-naïve.The average age was 47.2 years.All patients completed the treatment and follow-up.All 3 patients with genotype 1a achieved SVR.Two genotype 1b treatment-naïve patients experienced virologic relapse.The rate of SVR12 was 99.7%(358/359),and SVR24 was 99.4%(357/359)in genotype 1b.Overall,36.2%had resistance-associated substitutions(RASs)in NS5A and 98.3%had RASs in NS5B at baseline.The RASs at baseline had no effect on the rates of response.Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir.Most adverse events did not require therapy.Conclusions:The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis,who had not been treated or who had been treated with interferon-based regimen previously.展开更多
Considering the aircraft and its external components are subjected to complex and variable aerodynamic loads during the working process,the missile-frame clearance system of the airborne external missile is investigat...Considering the aircraft and its external components are subjected to complex and variable aerodynamic loads during the working process,the missile-frame clearance system of the airborne external missile is investigated.The random vibration characteristics of the airborne external components are analyzed by finite element method.The finite element model is optimized with reference to the test results,and the effects of different clearance on the dynamic response of the missile-frame system are compared.The result shows that the frequency response curves of the same position and the resonant peak frequencies are consistent under different clearances.The acceleration response at both ends of the missile is large and the amplitude near the center of mass is gentle.The results can be used to predict reasonable missile-frame clearance and make guidance to the structural design and reliability analysis of the missile-frame system.展开更多
The growth of flue-cured tobacco is sensitive to changes in environmental conditions.Excellent tobacco leaf production is strictly restricted by regional cultivated lands.For the purpose of reasonable utilization and ...The growth of flue-cured tobacco is sensitive to changes in environmental conditions.Excellent tobacco leaf production is strictly restricted by regional cultivated lands.For the purpose of reasonable utilization and scientific management of Sanmenxia tobacco fields,it is meaningful to evaluate the soil fertility suitability of tobacco crops quantitatively and objectively.In this study,the global positioning system(GPS)technology was used to obtain sample point information automatically.Based on the analysis of fertility properties of soil samples collected from the Sanmenxia tobacco planting regions in Henan Province,we present the index system of soil fertility suitability for tobacco crops.The integrated evaluation of soil fertility suitability was studied with six indices,including organic matter,pH value,available nitrogen(N),available phosphorus(P),available potassium(K),and chlorine(Cl–1)content of surface soil.The subjective grade value was calculated according to S-type and parabola-type functions of the effect of evaluation factors on tobacco crops.Further,the weight value of soil fertility suitability indices was calculated by the method of Hiberarchy analysis.The soil fertility suitability level was evaluated and classified.The suitability map of the Sanmenxia tobacco planting regions in Henan Province was then drawn with the geographic information system(GIS)software mapGIS.It was found that highly suitable fields were mainly distributed in the high mountains in the Southwestern part of the investigated regions where soil pH value and the contents of organic matter were medium,but the contents of available P and available K were higher,accounting for 79.36% of the whole area.Suitable fields were 17% of the whole area,mainly distributed in the middle part of the investigated regions where soil pH value was higher.Unsuitable fields existed in the northern-east and middle part of the Sanmenxia where the contents of soil Cl^(–)was very high,accounting for 3.51%of the whole regions.展开更多
文摘Around 71% of the Earth’s surface is covered by oceans with depths that exceed several kilometers, while continents are geographically enclosed by these vast bodies of water. The principle of fluid mechanics stipulates that water yields pressure everywhere in the container that holds it, and the water pressure against the wall of container generates force. Ocean basins are naturally gigantic containers of water, in which continents form the walls of the containers. In this study, we present that the ocean water pressure against the walls of continents generates enormous force, and determine the distribution of this force around continents and estimate its amplitude to be of the order of 1017 N per kilometer of continent width. Our modelling suggests that the stresses yielded by this force are mostly concentrated on the upper part of the continental crust, and their magnitudes reach up to 2.0 - 6.0 MPa. Our results suggest that the force may have significantly impacted the dynamics of continent (lithospheric plate) and its evolution.
文摘Plate motion representing a remarkable Earth process is widely attributed to several primary forces such as ridge push and slab pull. Recently, we have presented that the ocean water pressure against the wall of continents may generate enormous force on continents. Continents are physically fixed on the top of the lithosphere that has been already broken into individual plates, this attachment enables the force to be laterally transferred to the lithospheric plates. In this study, we combine the force and the existing plate driving forces (i.e., ridge push, slab pull, collisional, and shearing) to account for plate motion. We show that the modelled movements for the South American, African, North American, Eurasian, Australian, Pacific plates are well agreement with the observed movements in both speed and azimuth, with a Root Mean Square Error (RMSE) of the modelled speed against the observed speed of 0.91, 3.76, 2.77, 2.31, 7.43, and 1.95 mm/yr, respectively.
基金Project supported by the National Natural Science Foundation of China(Nos.12072263 and 11972295)the Fundamental Research Funds for the Central Universities(No.G2021KY0601)。
文摘This paper deals with the co-existence of mixed aleatory and epistemic uncertainties in a wind turbine geared system for more reliable and robust vibration analyses.To this end,the regression-based polynomial chaos expansion(PCE)is used to track aleatory uncertainties,and the polynomial surrogate approach(PSA)is developed to treat the epistemic uncertainties.This non-intrusive dual-layer framework shares the same collocation pool,which is extracted from the Legendre series.Moreover,the regression technique has been implemented in both layers to enhance calculation efficiency.Numerical validation is carried out to show the effectiveness of the proposed method.New vibration behaviors of the geared transmission system are observed,and the mechanism behind is discussed in detail.The findings of this paper will contribute to the insightful understanding of such wind turbine geared systems under hybrid uncertainties and are beneficial for the condition monitoring.
文摘Purpose: To compare the dosimetric impact of coplanar intensity modulated radiation therapy (IMRT) and non-coplanar IMRT for the esophageal carcinoma. Methods: There are forty-five esophageal carcinoma patients, fifteen of whom were cervical and upper thoracic (Group 1) and thirty were middle and lower thoracic (Group 2). Gross tumor volume (GTV), clinical target volume (CTV), and organs at risk (OAR) were contoured by the chief physician in the CMS-XiO treatment planning system. For each patient, one coplanar plan and two non-coplanar plans have been created using the same physical objective function. A detailed dose-volume histogram (DVH) comparison among three plans was then carried out in a tabulated format. Results: 1) In Group 1 patients with PTV volume less than 100cc, the mean dose and dose gradient of non-coplanar plan were much better than those in coplanar plan. 2) In Group 2 patients, the conformity index (CI) for coplanar and two non-coplanar plans were 0.69 ± 0.13, 0.41 ± 0.13, and 0.68 ± 0.15, respectively. The V5, V10, V20, and the mean dose to the lung were lower in the non-coplanar plans compared to ones in coplanar plan. However, the non-coplanar plans resulted in an increase in a dose to the heart, but the dose was still within heart toxicity tolerance. Conclusion: For Group 1 patients, the non-coplanar IMRT plan had less dose gradient and better mean dose than the coplanar IMRT plan. For Group 2 patients, the non-coplanar IMRT could the decrease dose to the lung tissue, thus lowering the probability of radiation pneumonia to esophageal cancer patients. The drawback of non-coplanar IMRT is that, even within toxicity tolerance, it could deliver a higher dose to the heart and spinal cord compared to the coplanar plan. Therefore, for patients with cardiology and neurology concern, non-coplanar IMRT should be used with caution.
文摘Background: Autoimmune hepatitis (AIH) is a hepatocyte injury characterized by a dis-regulated immune system, inflammation of the liver with interface hepatitis, serum antibodies and elevated gamma-globulins. Currently, it exists 2 mainly types on autoimmune hepatitis, based on the presentation of their autoantibodies: type 1 and 2. Type 1 is the one of interest in this review. Autoimmune hepatitis type 1 is an indolent inflammatory disease mediated by abnormal autoimmune reaction, commonly seeing in women (4:1), with no preference of age, however typically present in 4th and 6th decade’s individuals, and a good response to immunosuppressive therapy. Autoimmune hepatitis is known to present not specific symptoms which can go from inexistent to fulminant or exacerbate presentation. The incidence of autoimmune hepatitis in western country is 1/5000 - 1/10,000. Although the detection rate of AIH increasing, especially in China, autoimmune hepatitis diagnosis and treatment remain challenging. Most AIH case do not present pathognomonic biomarkers, however the diagnostic has to considerate other features, which had been codified into validated diagnosis scoring systems. Regarding the treatment, based on prior literature autoimmune hepatitis is mostly sensitive to prednisone or azathioprine, however the use of other immunosuppressive agent or event their combination had offer distinct advantages. Autoimmune hepatitis presents a great life threatening disorder especially because of the delay in the early stage on the disease, the not specific presentations, and the large overlap syndrome associate with it. A deep knowledge in its identification, specific diagnostic criteria, and its therapeutic strategy is much needed. Conclusion: Autoimmune hepatitis is a systemic disease that is difficult to recognize because of its variable clinical presentation and histological features that are not strictly specific. Several new autoantibodies as well as recently simplified diagnostic criteria may allow the primary care physician to progress in the diagnostic process. This is all the more important as undiagnosed and therefore untreated autoimmune hepatitis has a poor prognosis and immunosuppressive treatment leads to remission in a large majority of cases.
文摘The coal resources are abundant in Huainan City,but with development and utilization of coal mine,the water surface formed by mining subsidence increases gradually,and more and more people pay great attention on the research of the wetland in the subsidence area. Through on-site review,the status of the wetland resources is explored,and wetland ecosystem of the region is analyzed. In this paper,the red line delimitation,functional zoning,overall layout and basic engineering planning and design of Suocao Bay Wetland Park are carried out. The planning and design of Suocao Bay Wetland Park mean to provide new support for ecological protection,accelerate the ecological restoration in Maoji Experimental Area,vigorously carry forward the wetland culture,and make it become an important wetland demonstration base in coal mine subsidence area.
文摘There are many types of wetlands around the Chaohu Lake,and wetland biodiversity is rich. The protection of wetland biodiversity is of great significance for regional sustainable development. In this paper,the wetlands around the Chaohu Lake are taken as the research objects. Based on the investigation and analysis of the biodiversity in the wetlands,combing the threats to the biodiversity of the wetland around the Chaohu Lake at the present stage,the biodiversity protection countermeasures of the wetlands around the Chaohu Lake are put forward.
文摘Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
基金supported by the National Natural Science Foundation of China (Grant No.82200078)the Interdisciplinary Innovation Project Fund of West China Hospital of Sichuan University (Grant No.ZYJC21054).
文摘Dear Editor:Lung cancer has the highest incidence rate among malignancies and remains the primary contributor to cancer-related mortality on a global scale[1].Early detection is the most efficacious approach for enhancing the prognosis and mitigating the mortality of patients with lung cancer[2].Currently,diagnosis of lung cancer is mainly by different types of imaging including low-dose spiral computed tomography(LDCT)combined with pathological assessment of biopsy,but prevalence of false-positive results and associated expenses may impede its becoming a standard screening technique[3].
基金This study was funded in part by the project of Nanjing Infectious Disease Clinical Medical Center and the project of Innovation center for infectious disease of Jiangsu Province(NO.CXZX202232)the Jiangsu Provincial Health Commission Medical Research Foundation(No.M2022030)+1 种基金the Nanjing Medical Science and Technique Development Foundation(No.ZKX21037)the Research Project of Nantong Municipal Health Commission(No.MS2023077).
文摘To the Editor:China provides free antiretroviral therapy(ART)for people with human immunodeficiency virus(HIV),typically using two nucleoside reverse transcriptase inhibitors(NRTIs)and one non-nucleoside reverse transcriptase inhibitor(NNRTI).This regimen has significantly reduced mortality and slowed HIV spread over the past 20 years.
基金supported by grants from the National Key Research and Development Program of China(2016YFC1306700 to ZJZ,2016YFC1306704 to HXZ)the National Natural Science Key Foundation of China(81830040 to ZJZ)+2 种基金Science and Technology Program of Guangdong(2018B030334001 to ZJZ)Program of Excellent Talents in Medical Science of Jiangsu Province(JCRCA2016006 to ZJZ)the Program for Innovative Research Team in Science and Technology in University of Henan Province(18IRTSTHN025 to HXZ)。
文摘To determine whether repetitive transcranial magnetic stimulation(rTMS)of the visual cortex(VC)provides effective and welltolerated treatment and whether magnetic resonance imaging(MRI)measures functional change of the VC as a biomarker of therapeutic effect in major depressive disorder(MDD),we performed a sham-controlled,double-blind,randomized,three-arm VC rTMS treatment study in 74 MDD patients.Neuronavigated rTMS(10 Hz,90%of resting motor threshold,1,600 pulses over20 min twice per day)was performed over the VC for five days.Clinical outcome was measured by Hamilton Depression Rating Scale(HAMD-24)at days 0,1,3,5 and after terminating rTMS,with follow-up at four weeks.MRI was measured at days 0 and5.The individualized group exhibited the greatest change in HAMD-24 scores after VC rTMS for 5 days(F=5.53,P=0.005),which were maintained during follow-up period(F=4.22,P=0.016).All patients reported good tolerance.Changes in VC taskrelated functional MRI correlated with symptomatic reduction in the individualized group.Treatment reduced the initially abnormal increase in resting state functional connectivity from the VC to the pre/subgenual anterior cingulate cortex at day 5,especially in the individualized group.We demonstrated therapeutic potential and good tolerance of VC rTMS in MDD patients,indicated by biomarkers of f MRI measurement.
基金Ascletis BioScience Co.,Ltd.provided financial support for this study
文摘Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.
基金This study was sponsored by Gilead Sciences,Inc.
文摘Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.
基金Ascletis Pharmaceuticals Co.,Ltd.provided financial support for this study(MANASA)
文摘Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.
基金supported by the National Natural Science Foundation of China(81321004,81621064,Jiandong Jiang81322050,Zonggen Peng)+2 种基金National Mega-Project for “R&D for Innovative drugs”,Ministry of Science and Technology,China(2012ZX09301-002-001,Jiandong Jiang,2018ZX09711001-003-010,Zonggen Peng)Ministry of Education,China(NCET-12-0072,Zonggen Peng)CAMS Innovation Fund for Medical Sciences,China(CIFMS)(2017-I2M-3-012,Zonggen Peng)
文摘Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.
基金This study was funded by the National Key Research and Development Program of China,Stem Cell and Translational Research(2017YFA0106800 and 2017YFA0106500)the National Natural Science Foundation of China(grants 81974363,81772478,81871890,81722004 and 91859203).
文摘Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms.The heterogeneity can be attributed to genetic,transcriptional,and epigenetic parameters.Here,we established a multi-omics atlas,integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing.We investigated their differences in genetic amplification,cellular compositions,and expression modules.We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells,and had distinct cellular composition modules associated with poor survival of lung cancer.Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression.Moreover,we identified subclusters with proliferating and differentiating properties in AT2 and basal cells.Overexpression assays of ten genes,including sub-cluster markers AQP5 and KPNA2,further indicated their functional roles,providing potential targets for early diagnosis and treatment in lung cancer.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirteenth Five-Year Plan Period of China(Nos.2017ZX09201006004 and 2017ZX09201006009)the Chinese National Research Grant of the Thirteenth Five-Year Plan for the Key Projects in Infectious Diseases(No.2017ZX10202202)+1 种基金the Key Research and Development Program of Guangdong(No.2019B02021002)funded by Sunshine Lake Pharma Co.,Ltd.(ClinicalTrials.gov number,NCT 03487107).
文摘Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis Huiying Rao1,Xingxiang Yang2,Youwen Tan3,Qin Ning4,Daokun Yang5,Jiefei Wang6,Yongfeng Yang7,Sujun Zheng8,Dongliang Yang9,Jinlin Hou10,Qing Xie11,Caiyan Zhao12,Lunli Zhang13,Xiaorong Mao14,Tong Sun15,Lang Bai16,Fuchun Zhang17,Jinglan Jin18,Yingren Zhao19,Maorong Wang20,Wen Xie21,Yingjie Ma22,Jun Quan23,Xuebing Yan24,Ping An25,Feng Lin26,Jidong Jia27,Xiaoxuan Hu28,Zuojiong Gong29,Jie Wu30,Yongping Chen31,Zhansheng Jia32,Minghua Lin33,Guiqiang Wang34,Yueyong Zhu35,Yingjun Zhang*,36,Hongming Xie36,Lin Luo36,Qingyun Ren36,Rui Huang1 and Lai Wei*,37 Author information Journal of Clinical and Translational Hepatology 2020;8(3):255-261DOI:10.14218/JCTH.2020.00031 Abstract Background and Aims:Emitasvir is a new type of hepatitis C virus(HCV)nonstructural protein 5A(NS5A)inhibitor,and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance.We conducted this phase 3 trial to further verify the efficacy and safety.Methods:We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate(100 mg)combined with sofosbuvir(400 mg)once daily in non-cirrhotic patients with genotype 1 HCV infection.The primary endpoint was a sustained virological response at 12 weeks(SVR12)after the end of treatment.Results:Of the 362 patients enrolled in the trial,39.8%were male,99.2%had HCV genotype 1b,0.8%had genotype 1a and 79.8%were treatment-naïve.The average age was 47.2 years.All patients completed the treatment and follow-up.All 3 patients with genotype 1a achieved SVR.Two genotype 1b treatment-naïve patients experienced virologic relapse.The rate of SVR12 was 99.7%(358/359),and SVR24 was 99.4%(357/359)in genotype 1b.Overall,36.2%had resistance-associated substitutions(RASs)in NS5A and 98.3%had RASs in NS5B at baseline.The RASs at baseline had no effect on the rates of response.Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir.Most adverse events did not require therapy.Conclusions:The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis,who had not been treated or who had been treated with interferon-based regimen previously.
基金funded by National Natural Science Foundation of China(No.11972295)the Key Laboratory of Vibration and Control of Aero-Propulsion System Ministry of Education,Northeastern University(No.VCAME201803)+1 种基金Aeronautical Science Foundation of China(Nos.20182953025,2016ZD12032)Graduate Innovation Fund of Northwestern Polytechnical University(No.ZZ2019126)。
文摘Considering the aircraft and its external components are subjected to complex and variable aerodynamic loads during the working process,the missile-frame clearance system of the airborne external missile is investigated.The random vibration characteristics of the airborne external components are analyzed by finite element method.The finite element model is optimized with reference to the test results,and the effects of different clearance on the dynamic response of the missile-frame system are compared.The result shows that the frequency response curves of the same position and the resonant peak frequencies are consistent under different clearances.The acceleration response at both ends of the missile is large and the amplitude near the center of mass is gentle.The results can be used to predict reasonable missile-frame clearance and make guidance to the structural design and reliability analysis of the missile-frame system.
文摘The growth of flue-cured tobacco is sensitive to changes in environmental conditions.Excellent tobacco leaf production is strictly restricted by regional cultivated lands.For the purpose of reasonable utilization and scientific management of Sanmenxia tobacco fields,it is meaningful to evaluate the soil fertility suitability of tobacco crops quantitatively and objectively.In this study,the global positioning system(GPS)technology was used to obtain sample point information automatically.Based on the analysis of fertility properties of soil samples collected from the Sanmenxia tobacco planting regions in Henan Province,we present the index system of soil fertility suitability for tobacco crops.The integrated evaluation of soil fertility suitability was studied with six indices,including organic matter,pH value,available nitrogen(N),available phosphorus(P),available potassium(K),and chlorine(Cl–1)content of surface soil.The subjective grade value was calculated according to S-type and parabola-type functions of the effect of evaluation factors on tobacco crops.Further,the weight value of soil fertility suitability indices was calculated by the method of Hiberarchy analysis.The soil fertility suitability level was evaluated and classified.The suitability map of the Sanmenxia tobacco planting regions in Henan Province was then drawn with the geographic information system(GIS)software mapGIS.It was found that highly suitable fields were mainly distributed in the high mountains in the Southwestern part of the investigated regions where soil pH value and the contents of organic matter were medium,but the contents of available P and available K were higher,accounting for 79.36% of the whole area.Suitable fields were 17% of the whole area,mainly distributed in the middle part of the investigated regions where soil pH value was higher.Unsuitable fields existed in the northern-east and middle part of the Sanmenxia where the contents of soil Cl^(–)was very high,accounting for 3.51%of the whole regions.
