The efficient transmission of severe acute respiratory syndrome-2 coronavirus(SARS-CoV-2)from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak.On the...The efficient transmission of severe acute respiratory syndrome-2 coronavirus(SARS-CoV-2)from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak.On the basis of clinical practice and in-vitro studies,we postulated that post-exposure prophylaxis(PEP)using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection.We conducted a retrospective cohort study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and chest computed tomography(CT)from January 1 to January 16,2020.The last follow-up date was Feb.26,2020.The emergence of fever and/or respiratory symptoms after exposure to the primary case was collected.The correlations between post-exposure prophylaxis and infection in household contacts and health care workers were respectively analyzed.A total of 66 members in 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19.The Cox regression based on the data of the family members and health care workers with Arbidol or not showed that Arbidol PEP was a protective factor against the development of COVID-19(HR 0.025,95%CI 0.003-0.209,P=0.0006 for family members and HR 0.056,95%CI 0.005-0.662,P=0.0221 for health care workers).Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings.This treatment should be promoted for PEP use and should be the subject of further investigation.展开更多
Objective: Lung cancer has emerged as a leading cause of cancer death in the world. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. RNA interference (RNAi) has sh...Objective: Lung cancer has emerged as a leading cause of cancer death in the world. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. RNA interference (RNAi) has shown promise in gene silencing in vitro, the potential of which in developing new methods for the therapy of non-small-cell lung cancer (NSCLC) needs to be further tested in vivo. In this study, chemically synthesized double-stranded RNA (dsRNA) targeting epidermal growth factor receptor (EGFR) was transfected into NSCLC cell line SPC-A1 cells and established the tumor burdened athymic nude mice model to investigate whether dsRNA could induce gene silencing in NSCLC cells in vivo. Methods: SPC-A1 was transfected with EGFR sequence-specific dsRNA formulated with Lipofectamine 2000. SPC-A1 cells (1 × 107/ mL) in 200 pL were injected s.c. into the left flank area of the mice to establish the tumor burdened athymic nude mice model. Calculate the tumor growth inhibition rate by measuring the diameter and the weight of the tumor. Immunohistochemistry and Westem blot were used to monitor the reduction in the production of the EGFR protein. Realtime RT-PCR was used to detect the silencing of the EGFR mRNA level. Results: It displayed that EGFR sequence specific dsRNA (dsRNA-EGFR) significantly inhibited the tumor growth in vivo. The tumor growth inhibition rate was 75.03%. The dsRNA-EGFR sequence specifically silenced EGFR with 53.6% of down-regulation of EGFR protein production and 32.3% of silencing of EGFR mRNA level. Conclusion: DsRNA-EGFR showed a blockbuster effect in downregulation of EGFR mRNA level and protein production, and inhibition of tumor growth in vivo.展开更多
Background and purpose COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2).Apart from respiratory complications,acute cerebrovascular disease(CVD)has been observed i...Background and purpose COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2).Apart from respiratory complications,acute cerebrovascular disease(CVD)has been observed in some patients with COVID-19.Therefore,we described the clinical characteristics,laboratory features,treatment and outcomes of CVD complicating SARS-CoV-2 infection.Materials and methods Demographic and clinical characteristics,laboratory findings,treatments and clinical outcomes were collected and analysed.Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.Results Of 219 patients with COVID-19,10(4.6%)developed acute ischaemic stroke and 1(0.5%)had intracerebral haemorrhage.COVID-19 with new onset of CVD were significantly older(75.7±10.8 years vs 52.1±15.3 years,p<0.001),more likely to present with severe COVID-19(81.8%vs 39.9%,p<0.01)and were more likely to have cardiovascular risk factors,including hypertension,diabetes and medical history of CVD(all p<0.05).In addition,they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein(51.1(1.3-127.9)vs 12.1(0.1-212.0)mg/L,p<0.05)and D-dimer(6.9(0.3-20.0)vs 0.5(0.1-20.0)mg/L,p<0.001).Of 10 patients with ischemic stroke;6 received antiplatelet treatment with aspirin or clopidogrel;and 3 of them died.The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.As of 24 March 2020,six patients with CVD died(54.5%).Conclusion Acute CVD is not uncommon in COVID-19.Our findings suggest that older patients with risk factors are more likely to develop CVD.The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.展开更多
Coronavirus disease 2019(COVID‐19)has become a pandemic disease globally.Although COVID-19 directly invades lungs,it also involves the nervous system.Therefore,patients with nervous system involvement as the presenti...Coronavirus disease 2019(COVID‐19)has become a pandemic disease globally.Although COVID-19 directly invades lungs,it also involves the nervous system.Therefore,patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed.They become silent contagious sources or‘virus spreaders’.In order to help neurologists to better understand the occurrence,development and prognosis,we have developed this consensus of prevention and management of COVID‐19.It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.展开更多
Coronavirus disease-2019(COVID‐19)has become a global pandemic.COVID-19 runs its course in two phases,the initial incubation phase and later clinical symptomatic phase.Patients in the initial incubation phase often h...Coronavirus disease-2019(COVID‐19)has become a global pandemic.COVID-19 runs its course in two phases,the initial incubation phase and later clinical symptomatic phase.Patients in the initial incubation phase often have insidious clinical symptoms,but they are still highly contagious.At the later clinical symptomatic phase,the immune system is fully activated and the disease may enter the severe infection stage in this phase.Although many patients are known for their respiratory symptoms,they had neurological symptoms in their first 1-2 days of clinical symptomatic phase,and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase.The key is to prevent a patient from progressing to this severe infection from mild infection.We are sharing our experience on prevention and management of COVID-19.展开更多
Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely relate...Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.展开更多
文摘The efficient transmission of severe acute respiratory syndrome-2 coronavirus(SARS-CoV-2)from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak.On the basis of clinical practice and in-vitro studies,we postulated that post-exposure prophylaxis(PEP)using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection.We conducted a retrospective cohort study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and chest computed tomography(CT)from January 1 to January 16,2020.The last follow-up date was Feb.26,2020.The emergence of fever and/or respiratory symptoms after exposure to the primary case was collected.The correlations between post-exposure prophylaxis and infection in household contacts and health care workers were respectively analyzed.A total of 66 members in 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19.The Cox regression based on the data of the family members and health care workers with Arbidol or not showed that Arbidol PEP was a protective factor against the development of COVID-19(HR 0.025,95%CI 0.003-0.209,P=0.0006 for family members and HR 0.056,95%CI 0.005-0.662,P=0.0221 for health care workers).Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings.This treatment should be promoted for PEP use and should be the subject of further investigation.
基金Supported by a grant from the Natural Science Foundation of Shanghai (No. 03ZR14004).
文摘Objective: Lung cancer has emerged as a leading cause of cancer death in the world. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. RNA interference (RNAi) has shown promise in gene silencing in vitro, the potential of which in developing new methods for the therapy of non-small-cell lung cancer (NSCLC) needs to be further tested in vivo. In this study, chemically synthesized double-stranded RNA (dsRNA) targeting epidermal growth factor receptor (EGFR) was transfected into NSCLC cell line SPC-A1 cells and established the tumor burdened athymic nude mice model to investigate whether dsRNA could induce gene silencing in NSCLC cells in vivo. Methods: SPC-A1 was transfected with EGFR sequence-specific dsRNA formulated with Lipofectamine 2000. SPC-A1 cells (1 × 107/ mL) in 200 pL were injected s.c. into the left flank area of the mice to establish the tumor burdened athymic nude mice model. Calculate the tumor growth inhibition rate by measuring the diameter and the weight of the tumor. Immunohistochemistry and Westem blot were used to monitor the reduction in the production of the EGFR protein. Realtime RT-PCR was used to detect the silencing of the EGFR mRNA level. Results: It displayed that EGFR sequence specific dsRNA (dsRNA-EGFR) significantly inhibited the tumor growth in vivo. The tumor growth inhibition rate was 75.03%. The dsRNA-EGFR sequence specifically silenced EGFR with 53.6% of down-regulation of EGFR protein production and 32.3% of silencing of EGFR mRNA level. Conclusion: DsRNA-EGFR showed a blockbuster effect in downregulation of EGFR mRNA level and protein production, and inhibition of tumor growth in vivo.
基金This study was funded by the National Key Research and Development Program of China(number 2018YFC1312200 to BH)the National Natural Science Foundation of China(number 81820108010 to BH).
文摘Background and purpose COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2).Apart from respiratory complications,acute cerebrovascular disease(CVD)has been observed in some patients with COVID-19.Therefore,we described the clinical characteristics,laboratory features,treatment and outcomes of CVD complicating SARS-CoV-2 infection.Materials and methods Demographic and clinical characteristics,laboratory findings,treatments and clinical outcomes were collected and analysed.Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.Results Of 219 patients with COVID-19,10(4.6%)developed acute ischaemic stroke and 1(0.5%)had intracerebral haemorrhage.COVID-19 with new onset of CVD were significantly older(75.7±10.8 years vs 52.1±15.3 years,p<0.001),more likely to present with severe COVID-19(81.8%vs 39.9%,p<0.01)and were more likely to have cardiovascular risk factors,including hypertension,diabetes and medical history of CVD(all p<0.05).In addition,they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein(51.1(1.3-127.9)vs 12.1(0.1-212.0)mg/L,p<0.05)and D-dimer(6.9(0.3-20.0)vs 0.5(0.1-20.0)mg/L,p<0.001).Of 10 patients with ischemic stroke;6 received antiplatelet treatment with aspirin or clopidogrel;and 3 of them died.The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.As of 24 March 2020,six patients with CVD died(54.5%).Conclusion Acute CVD is not uncommon in COVID-19.Our findings suggest that older patients with risk factors are more likely to develop CVD.The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.
基金supported by the National Key Research and Development Program of China(No.2018YFC1312200 to BH)the National Natural Science Foundation of China(No.81820108010 to BH,No.81974182 to LM and No.81671147 to HJ)major refractory diseases pilot project of clinical collaboration with Chinese and Western Medicine(SATCM-20180339).
文摘Coronavirus disease 2019(COVID‐19)has become a pandemic disease globally.Although COVID-19 directly invades lungs,it also involves the nervous system.Therefore,patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed.They become silent contagious sources or‘virus spreaders’.In order to help neurologists to better understand the occurrence,development and prognosis,we have developed this consensus of prevention and management of COVID‐19.It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.
基金supported by the National Key Research and Development Program of China(No.2018YFC1312200 to BH)the National Natural Science Foundation of China(No.81820108010 to BH).
文摘Coronavirus disease-2019(COVID‐19)has become a global pandemic.COVID-19 runs its course in two phases,the initial incubation phase and later clinical symptomatic phase.Patients in the initial incubation phase often have insidious clinical symptoms,but they are still highly contagious.At the later clinical symptomatic phase,the immune system is fully activated and the disease may enter the severe infection stage in this phase.Although many patients are known for their respiratory symptoms,they had neurological symptoms in their first 1-2 days of clinical symptomatic phase,and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase.The key is to prevent a patient from progressing to this severe infection from mild infection.We are sharing our experience on prevention and management of COVID-19.
基金supported by a grant from the Strategic CAS Project(XDB38000000)a grant from the National Natural Science Foundation of China(81561128018).
文摘Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.