Ductular proliferation in liver tissues with severe chronic hepatitis B: An immunohistochemical study

AIM： To clarify the pathogenesis of ductular proliferation and its possible association with oval cell activation and hepatocyte regeneration. METHODS： Immunohistochemical staining and image analysis of the ductular structures in the liver tissues from 11 patients with severe chronic hepatitis B and 2 healthy individuals were performed. The liver specimens were sectioned serially, and then cytokeratin 8 （CK8）, CK19, OV6, proliferating cell nuclear antigens （PCNA）, glutathione-S-transferase （GST）, α-fetal protein （AFP） and albumin were stained immunohistochemically. RESULTS： Typical and atypical types of ductular proliferation were observed in the portal tracts of the liver tissues in all 11 patients. The proliferating ductular cells were positive for CKS, CK19, OV6 and PCNA staining. Some atypical ductular cells displayed the morphological and immunohistochemical characteristics of hepatic oval cells. Some small hepatocyte-like cells were between hepatic oval cells and mature hepatocytes morphometrically and immunohistochemically. CONCLUSION： The proliferating ductules in the liver of patients with severe chronic liver disease may have different origins. Some atypical ductular cells are actually activated hepatic oval cells. Atypical ductular proliferation is related to hepatocyte regeneration and small hepatocyte-like cells may be intermediate transient cells between hepatic oval cells and mature hepatocytes.

Effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19:A retrospective cohort study

BACKGROUND The effectiveness of adjunctive corticosteroid use in patients with coronavirus disease 2019(COVID-19)remains inconclusive.AIM To investigate the effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19.METHODS We conducted a retrospective analysis of the difference in several outcomes between patients with severe COVID-19 who received corticosteroid therapy(the corticosteroid group)and patients with severe COVID-19 who did not receive corticosteroid therapy(the non-corticosteroid group).RESULTS Seventy-five patients were included in this study.Of these,47 patients were in the corticosteroid group and 28 patients were in the non-corticosteroid group.There were no differences between the two groups in the total length of hospital stay,the length of intensive care unit stay,high-flow oxygen days,non-invasive ventilator days,invasive ventilation days,and mortality rate.Total lesion volume ratio,consolidation volume ratio and ground-glass opacity volume ratio in the corticosteroid group decreased significantly on day 14,while those in the noncorticosteroid group did not show a significant decrease.CONCLUSION Our results show that adjunctive corticosteroid use did not significantly improveclinical outcomes in severe COVID-19 patients,but might promote the absorptionof pulmonary lesions.Larger multicenter randomized controlled studies may beneeded to confirm this.

Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019:protocol of a randomized controlled trial

Background:At the end of 2019,a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus(2019-nCoV).The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear,and warrants further investigation.Methods:The present study will be conducted as an open-labeled,randomized,controlled trial.We will enrol 48 subjects from Chongqing Public Health Medical Center.Each eligible subject will be assigned to an intervention group(methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days)or a control group(no glucocorticoid use)randomly,at a 1:1 ratio.Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points.We will use the clinical improvement rate as our primary endpoint.Secondary endpoints include the timing of clinical improvement after intervention,duration of mechanical ventilation,duration of hospitalization,overall incidence of adverse events,as well as rate of adverse events at each visit,and mortality at 2 and 4 weeks.Discussion:The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades.Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past.However,there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease,or indeed in other types of severe respiratory disease.In this study,we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.

Potential therapeutic options for coronavirus disease 2019:using knowledge of past outbreaks to guide future treatment

In December 2019,initial cases of the novel coronavirus(2019-nCoV)infection,termed coronavirus disease 2019(COVID-19),were first reported in Wuhan,China.[1]In humans,infections with the human coronavirus 229E,OC43,NL63,and HKU1 usually result in mild,selflimiting upper respiratory tract infections.However,other variants have rapid transmission rates and can cause severe respiratory syndrome and death.These variants include severe acute respiratory syndrome coronavirus(SARSCoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and the current 2019-nCoV.

The clinical and immunological features of pediatric COVID-19 patients in China

In December 2019,the corona virus disease 2019(COVID-19)caused by novel coronavirus(SARS-CoV-2)emerged in Wuhan,China and rapidly spread worldwide.Few information on clinical features and immunological profile of COVID-19 in paediatrics.The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed.The immunological features of children patients was investigated and compared with twenty adult patients.The median age was 14.5-years(range from 0.64 to 17),and six of the patients were male.The average incubation period was 8 days.Clinically,cough(9/12,75%)and fever(7/12,58.3%)were the most common symptoms.Four patients(33.3%)had diarrhea during the disease.As to the immune profile,children had higher amount of total T cell,CD8t T cell and B cell but lower CRP levels than adults(P<0.05).Ground-glass opacity(GGO)and local patchy shadowing were the typical radiological findings on chest CT scan.All patients received antiviral and symptomatic treatment and the symptom relieved in 3e4 days after admitted to hospital.The paediatric patients showed mild symptom but with longer incubation period.Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level,which might ascribed to the mild clinical symptom.We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs:a promising therapeutic strategy for HIV cure

Many seminal advances have been made in human immunodeficiency virus(HIV)/AIDS research over the past four decades.Treatment strategies,such as gene therapy and immunotherapy,are yielding promising results to effectively control HIV infection.Despite this,a cure for HIV/AIDS is not envisioned in the near future.A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS,referred to as“selective elimination of host cells capable of producing HIV”(SECH).Similar to the“shock and kill strategy,”the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs.Herein,we comprehensively review the specific mechanisms targeted by the SECH strategy.Briefly,the suggested cocktail of drugs should contain(i)latency reversal agents to promote the latency reversal process in replication-competent reservoir cells,(ii)pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways,and finally(iii)drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells,and by HIV integrase inhibitor drugs.Finally,we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

Asymptomatic cryptococcal antigenemia in HIV-infected patients:a review of recent studies

The prevalence of asymptomatic cryptococcal antigenemia(ACA)in human immunodeficiency virus(HIV)infected individuals has been observed to be elevated.The prevalence of ACA ranges from 1.3%to 13%,with different rates of prevalence in various regions of the world.We reviewed studies conducted internationally,and also referred to two established expert consensus guideline documents published in China,and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4+T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines,although it is likely that this recommendation may change in the future.Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis,and is lifesaving.Further studies are warranted to explore issues related to the optimal management of ACA.

Six weeks into the 2019 coronavirus disease outbreak:it is time to consider strategies to impede the emergence of new zoonotic infections

Coronaviruses have in the past been known to be the etiologic agents of mild upper respiratory infections in humans,similar to the ubiquitous and relatively benign"common cold"-type upper respiratory illnesses induced by the human rhinoviruses in adults and children.Subsequent to the severe acute respiratory syndrome(SARS)outbreak in China 2003,and the Middle East respiratory syndrome(MERS)outbreak in the Middle East in 2012,global concerns regarding the pathogenicity and epidemic/pandemic potential of novel human coronaviruses began to emerge,with some experts predicting that novel coronaviruses could likely again cross the species barrier and present humans with future pandemic-potential infections.[1]These concerns have proven prescient with the emergence,late in 2019,of the 2019 coronavirus disease(COVID-19)or novel coronavirus pneumonia.

Comparative effectiveness and safety of ribavirin plus interferon-alpha,lopinavir/ritonavir plus interferon-alpha,and ribavirin plus lopinavir/ritonavir plus interferon-alpha in patients with mild to moderate novel coronavirus disease 2019:study protocol

To the Editor:At the end of 2019,an outbreak of novel coronavirus disease 2019(COVID-19),caused by 2019-nCov,causing widespread novel coronavirus disease.This outbreak of COVID-19 occurred during the period of the 2020 Spring Festival in China,a period known for massive population movements within China.This has resulted in large numbers of infected patients as a consequence of multiple human contact episodes in individual travelers.

Consensus statement on human immunodeficiency virus pre-exposure prophylaxis in China

Introduction Although the global human immunodeficiency virus(HIV)epidemic has been effectively curbed,preventing and managing HIV infection in high-risk populations remains challenging.[1]In China,HIV is primarily transmitted through sexual contact.[1,2]Pre-exposure prophylaxis(PrEP)is a new and effective method for preventing HIV infection using antiretroviral drugs[3];data from multiple clinical trials worldwide have shown that using antiretroviral drugs for PrEP can limit HIV transmission.[4,5,6,7]The World Health Organization(WHO)issued guidelines in 2015 recommending PrEP in populations with an HIV incidence above 3/100 person-years(PY)and in individuals engaging in high-risk behaviors.[3]According to existing studies,the HIV incidence among key populations in China was 5.6/100 PY for men who have sex with men(MSM),[8]1.6/100 PY for intravenous drug users(IDUs),[9]and 1.4/100 PY for female sex workers.[10,11]As of July 2020,54 countries and regions have issued PrEP guidelines for adults to prevent HIV infection,and 36 of these have also published guidelines for children and adolescents.However,there are no PrEP guidelines or related consensus statement in China.As such,there is a strong need for standardized guidance on the implementation of PrEP pertaining to medical selection criteria,PrEP timing,drug safety,and consultation and testing programs.Here we present the consensus statement on the implementation of PrEP in China based on the opinions and suggestions of health policy-makers,scientists,clinical experts,community-based organizations of key populations,and the latest reports in PrEP researches.

Moxibustion versus non-moxibustion for immune reconstitution inflammatory syndrome in patients with HIV:A 48-week prospective cohort study

Objective:To assess the effects of moxibustion on immune reconstitution inflammatory syndrome(IRIS)in patients with acquired immune deficiency syndrome(AIDS)by tracking T-cell subsets over a 48-week prospective cohort study.Methods:Patients with AIDS who had low viral loads and weakened immune systems were divided into a moxibustion group and a non-moxibustion group.The non-moxibustion group received standard western treatment,including 48 weeks of antiretroviral therapy(ART).The moxibustion group received ART combined with moxibusion therapy,administered three times weekly.Each treatment lasted 10 weeks,with four courses completed over 48 weeks,separated by 2-week breaks.At different time points,plasma levels of CD4^(+),CD8^(+),CD45RAt,CD45RO^(+),CD4^(+)CD28^(+),CD8^(+)CD38^(+),and CD4^(+)CD38^(+)were compared between the two groups.Results:A total of 200 eligible patients were included and divided into two groups,with 100 in the non-moxibustion group and 100 in the moxibustion group.At Week 24,the CD4^(+)T cell count was(180.71±79.62)cells/μL in the non-moxibustion group and(218.22±82.02)cells/μL in the moxibustion group.By Week 36,the counts were(204.83±96.78)cells/μuL and(239.35±81.90)cells/μL,respectively.At Weeks 24 and 48,the CD8^(+)T cell and CD45RO^(+)counts were higher in the moxibustion group than in the non-moxibustion group(P<0.05).By Week 48,the CD45RA^(+)count was also higher in the moxibustion group(P<0.05).At Week 24,the CD4^(+)CD25^(+)count was lower in the moxibustion group than in the non-moxibustion group(P<0.05).