Author
Jingmin Zhao
Bio: Jingmin Zhao is an academic researcher from Peking University. The author has contributed to research in topics: Medicine & Hepatocellular carcinoma. The author has an hindex of 9, co-authored 14 publications receiving 5799 citations.
Topics: Medicine, Hepatocellular carcinoma, Beam (structure), Fibrosis, Physics
Papers
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TL;DR: O surto do novo coronavÃrus (COVID-19) em Wuhan, China, iniciado em dezembro de 2019, evoluiu para se tornar uma pandemia global A.
6,850 citations
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TL;DR: Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectiously Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing; The Institute of Translational Hepatology, 302 Hospital of PLA, P Beijing, China.
Abstract: Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China; The Institute of Translational Hepatology, 302 Hospital of PLA, Peking University, Beijing, China; Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Institute for Viral Hepatitis, the Key Laboratory of Molecular Biology for Infectious Diseases, the second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Microbiology of Peking University Health Science Center, Beijing, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Serious Illness Medicine Inpatient Area, Beijing Youan Hospital, Capital Medical University, Beijing, China; Department of Pathology, 302 Hospital of PLA, Peking University, Beijing, China; Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Center of Infectious Diseases, West China Hospital of Sichuan University, Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China; Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China; Hepatology Institute, Peking University People’s Hospital, Beijing, China
255 citations
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TL;DR: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19 and could be used to predict disease deterioration and inform clinical interventions.
Abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.
224 citations
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TL;DR: The authors investigated the tumorigenic mechanism of this oncomir in the development of HCC and suggested that it is up‐regulated in hepatocellular carcinoma.
Abstract: BACKGROUND:
Recent research has suggested that the oncomir microRNA 155 (miR-155) is up-regulated in hepatocellular carcinoma (HCC). In this study, the authors investigated the tumorigenic mechanism of this oncomir in the development of HCC.
METHODS:
Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to analyze the expressions of miR-155 and its potential target genes in paired tumor tissues and adjacent tumor-free tissues and in disease-free liver tissue samples. The in silico predicted target genes of miR-155 were assessed by dual-luciferase reporting assay, real-time RT-PCR, and Western blot analyses. U6 promoters that drive miR-155 precursor overexpression and miR-155 tough decoy knock-down constructs were used to study its affects on cell proliferation in vitro and on tumor formation in nude mice.
RESULTS:
Quantitative RT-PCR demonstrated a gradual ascension of miR-155 expression in cirrhotic liver tissues and in HCC tumor tissues compared with low expression levels in normal liver tissues. Ectopic expression of miR-155 in HepG2 cells enhanced its tumorigenesis, whereas depletion of the endogenous miR-155 reversed these tumorigenic properties. Ectopic expression of sex-determining region Y box 6 (SOX6) was able to reverse the growth-promoting property of miR-155. Concordantly, the results demonstrated for the first time that SOX6 is a direct target of miR-155. Further analysis revealed that SOX6 reduced cell growth by up-regulating p21waf1/cip1 expression in a p53-dependent manner. In addition, a decline in p21waf1/cip1 expression caused by miR-155 could be reversed by SOX6 expression.
CONCLUSIONS:
The current data indicated that SOX6 is a novel target of miR-155 and that miR-155 enhances liver cell tumorigenesis at least in part through the novel miR-155/SOX6/p21waf1/cip1 axis. These findings suggest that miR-155 may be a potential target for HCC treatment. Cancer 2012. © 2011 American Cancer Society.
110 citations
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TL;DR: A multicenter study to validate the accuracy of LSM in the assessment of liver fibrosis in a large cohort of Chinese patients with chronic hepatitis B (CHB) is carried out.
Abstract: Background and Aim
Liver stiffness measurement (LSM) using transient elastography (FibroScan) is a useful tool to assess fibrosis in various chronic liver diseases. However, studies were mainly performed in Western countries and largely focused on chronic hepatitis C (CHC). We therefore carried out a multicenter study to validate the accuracy of LSM in the assessment of liver fibrosis in a large cohort of Chinese patients with chronic hepatitis B (CHB).
Methods
We compared LSM results to histological staging and serum fibrosis markers (five direct markers, APRI and FIB-4) using Spearman correlation analysis and area under receiver operating characteristic (ROC) curves (AUROCs).
Results
Four hundred sixty-nine patients were enrolled and eligible for statistical analysis. LSM in F0 to F4 was 5.5 ± 1.7, 5.8 ± 2.2, 7.6 ± 3.4, 14.5 ± 10.8, and 22.3 ± 13.6 kPa, respectively (correlation with fibrosis stage r = 0.522, P 5x the upper limit of normal values had significantly higher stiffness values than stage-matched patients with normal alanine aminotransferase.
Conclusion
Transient elastography is a reliable noninvasive technique to predict significant liver fibrosis in Chinese patients with CHB, being superior to current biomarker panels. However, enhanced inflammatory activity can lead to elevated stiffness values unrelated to histological fibrosis stage.
60 citations
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TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
20,189 citations
01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
4,408 citations
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TL;DR: The SARS-CoV-2 infection may affect primarily T lymphocytes particularly CD4+T and CD8+ T cells, resulting in decrease in numbers as well as IFN-γ production, which may be of importance due to their correlation with disease severity in COVID-19.
Abstract: BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).
3,488 citations
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TL;DR: This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19, the novel severe acute respiratory syndrome coronavirus 2 pandemic that has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.
3,371 citations
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TL;DR: The association between cardiac injury and mortality in patients with COVID-19 was analyzed and it was found that patients with cardiac injury had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings than those without cardiac injury.
Abstract: Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years;P Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.
3,360 citations