Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China

Background: Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks.Methods: Eight hundred recruits(722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus(Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for Adv Ig G antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38℃ and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR.Results: Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 Adv were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits(incidence rate of 4.9%) and 5 cases of Adv were detected(positive rate of 12.8%). Genotyping showed 3 cases of type 4 Adv and 2 of type 3 Adv. No type 7, 14 or 55 Adv was detected. The Adv-Ig G positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-Ig G positive.Conclusion: The pathogen carrier rate in recruits was low, and only group C Adv, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 Adv.

Exploring an Integrative Therapy for Treating COVID-19:A Randomized Controlled Trial

Objectives:To develop a new Chinese medicine(CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome(ARDS)in COVID-19 patients.Methods:A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized,controlled two-arm trial.The two arms of the trial consist of a control therapy(alpha interferon inhalation,50(x g twice daily;and lopinavir/ritonavir,400 and 100 mg twice daily,respectively)and a testing therapy(control therapy plus Keguan-119.4 g twice daily)by random number table at 1:1 ratio with 24 cases each group.After 2-week treatment,adverse events,time to fever resolution,ARDS development,and lung injury on newly diagnosed COVID-19 patients were assessed.Results:An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events.Based on this result,the study was expanded to include a total of 48 participants(24 cases each arm).The results show that compared with the control arm,the testing arm exhibited a significant improvement in time to fever resolution(P=0.035),and a significant reduction in the development of ARDS(P=0.048).Conclusions:Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients.(Trial registration No.NCT 04251871 at www.clinicaltrials.gov).

Neutrophils in liver diseases:pathogenesis and therapeutic targets

Previously,it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions.However,recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation.The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer,inflammatory disorders,infections,and other diseases.Currently,neutrophils,with their autocrine,paracrine,and immune modulation functions,have been shown to be involved in liver diseases,including viral hepatitis,nonalcoholic steatohepatitis,alcoholic liver disease,liver fibrosis,cirrhosis,liver failure,and liver cancer.Accordingly,this review summarizes the role of neutrophils in liver diseases.

Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS:a multicenter randomized controlled trial

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell(hUC-MSC)infusion for immune nonresponder(INR)patients with chronic HIV-1 infection,who represent an unmet medical need even in the era of efficient antiretroviral therapy(ART).Seventy-two INR patients with HIV were enrolled in this phase II randomized,double-blinded,multicenter,placebo-controlled,dose-determination trial(NCT01213186)from May 2013 to March 2016.They were assigned to receive high-dose(1.5 x 106/kg body weight)or low-dose(0.5 x 106/kg body weight)hUC-MSC,or placebo.Their clinical and immunological parameters were monitored during the 96-week follow-up study.We found that hUC-MSC treatment was safe and well-tolerated.Compared with baseline,there was a statistical increase in CD4+T counts in the high-dose(P<0.001)and low-dose(P<0.001)groups after 48-week treatment,but no change was observed in the control group.Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group(95.8%vs.70.8%,P=0.00A).However,no significant changes in CD4/CD84-T counts and CD4/CD8 ratios were observed among the three groups.In summary,hUC-MSC treatment is safe.However,the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.

A survey of knowledge about hepatitis B among new military recruits in China

Background: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus(HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of and behaviours towards the transmission and prevention of hepatitis B of new military recruits in China.Methods: A cross-sectional study was conducted among 800 new military recruits. A self-administered, structured questionnaire was used to collect information, and 727 questionnaires were returned completed. Analysis was performed using SPSS 18.0, and P<0.05 was considered statistically significant.Results: Of the respondents, 665(91.5%) were male and 62(8.5%) were female. The mean age was 18.9±1.7 years. A total of 608 respondents(83.6%) demonstrated poor knowledge and 119(16.4%) adequate knowledge about HBV. Older age, female and higher education level were statistically associated with a higher mean knowledge score. Multivariate logistic regression showed that age(OR=3.040, 95%CI 1.724–5.359, P<0.001) and gender(OR=1.791, 95%CI 1.325–2.421, P<0.001) were significantly associated with appropriate behavioural practices towards prevention of HBV.Conclusion: Against a backdrop of high HBV prevalence in China, new military recruits had poor knowledge of HBV. New recruits need better education about HBV to assist in reducing and preventing HBV infection.

Increased circulating level of interleukin-6 and CD8+T cell exhaustion are associated with progression of COVID-19

Background: Coronavirus disease 2019(COVID-19)is pandemic.It is critical to identify COVID-19 patients who are most likely to develop a severe disease.This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.Methods:: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing,China from December 27,2019 to March 12,2020 were enrolled in this study and followed-up to March 16,2020.Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by theχ2 test or the Fisher exact test(categorical variables)and independent group t test or Mann–Whitney U test(continuous variables).The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.Results: The mean incubation was 8.67(95%confidence interval,6.78–10.56)days.Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38(9.86–12.90)days.Compared to pneumonia-free patients,pneumonia patients were 16.5 years older and had higher frequencies of having hypertension,fever,and cough and higher circulating levels of neutrophil proportion,interleukin-6,low count(<190/µl)of CD8+T cells,and neutrophil/lymphocyte ratio.Thirteen patients deteriorated during hospitalization.Cox regression analysis indicated that older age and higher serum levels of interleukin-6,C-reactive protein,procalcitonin,and lactate at admission significantly predicted the progression of COVID-19.During hospitalization,circulating counts of T lymphocytes,CD4+T cells,and CD8+T cells were lower,whereas neutrophil proportion,neutrophil/lymphocyte ratio,and the circulating levels of interleukin-6,C-reactive protein,and procalcitonin were higher,in pneumonia patients than in pneumonia-free patients.CD8+lymphocyte count in pneumonia patients did not recover when discharged.Conclusions: Older age and higher levels of C-reactive protein,procalcitionin,interleukin-6,and lactate might predict COVID-19 progression.T lymphocyte,especially CD8+cell-mediated immunity is critical in recovery of COVID-19.This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）

High levels of circulating GM-CSF^(+) CD4^(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study

Granulocyte colony-stimulating factor(GM-CSF),produced by CD4^(+)T cells,has recently been implicated in the pathogenesis of inflammatory diseases,such as multiple sclerosis and juvenile arthritis.However,the role of GM-CSF-producing CD4^(+)T cells in sepsis remains unknown.This study reports peripheral changes in GM-CSF-producing CD4^(+)T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis.Forty-three septic patients,20 SIRS patients,and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality.We measured the peripheral frequency of GM-CSF^(+)CD4^(+)T cells and recorded their associated relationship with disease progression.Our data demonstrated that peripheral GM-CSF-producing CD4^(+)T cells were significantly higher in septic patients than in both SIRS patients and healthy controls.These cells exhibit a memory phenotype and impaired IFN-γ-secreting capacity in sepsis patients.Using a receiver operating curve analysis with 8.01%as a cut-off point,the percentage of GM-CSF^(+)CD4^(+)T cells could predict the outcome of septic patients.Combined with the increase in GM-CSF-producing CD4^(+)T cells,inflammatory cytokines IL-1βand IL-6 were also upregulated.Using an in vitro neutrophil model,we found that GM-CSF inhibited C3aR expression,while inducing IL-8 production.Furthermore,this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an anti-GM-CSF antibody.These results indicate that GM-CSF-producing CD4^(+)T cells may serve as a marker of sepsis severity.Thus,targeting GM-CSF overproduction may benefit sepsis patients.

Is aberrant CD8+ T cell activation by hypertension associated with cardiac injury in severe cases of COVID-19?

COVID-19 global pandemic,caused by severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),1 has swept 185 countries and regions with more than 2,824,728 confirmed cases,and 197,667 death as on April 25,2020 according the Coronavirus Resource Center at Johns Hopkins University.Accumulating data suggest that hypertension,diabetes,and cardiovascular diseases are the most frequent comorbidities in COVID-19 patients,and case mortality rates tended to be high in these individuals.

An immunopathogenic perspective of interleukin-1 signaling

Interleukin-1(IL-1),referred to as two distinct proteins,IL-1αand IL-1β,was first described almost 50 years ago.1 IL-1αand IL-1βrepresent immediate early innate cytokines critically involved in alarming and activating the host defense system.2 Therefore,any impairment of IL-1 signaling pathways often leads to devastating outcomes,such as autoimmunity and autoinflammation,dysmetabolism,cardiovascular disorders,and cancer.2 Many advances in targeting IL-1 in immune therapies have been achieved;for example,the IL-1-blocking agents anakinra(IL-1 receptor antagonist,IL-1Ra),canakinumab(anti-IL-1βmAb),and MABp1(anti-IL-1αmAb)have been approved for clinical use or are being evaluated.2 Remarkably,the CANTOS study,which included over 10,000 patients,showed that blocking IL-1βnot only reduced atherosclerosis-related cardiovascular mortality but was also effective in inflammatory diseases related to lung cancer,arthrosis,and gout.3.

HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed AIDS patients

Severely immunosuppressed AIDS patients with recurrent opportunistic infections(Ols)represent an unmet medical need even in the era of antiretroviral therapy(ART).Here we report the development of a human leukocyte antigen(HLA)-mismatched allogeneic adaptive immune therapy(AAIT)for severely immunosuppressed AIDS patients.Twelve severely immunosuppressed AIDS patients with severe Ols were enrolled in this single-arm study.Qualified donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate hematopoiesis.Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients.Clinical,immunological,and virological parameters were monitored during a 12-month follow-up period.We found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients.Improvements in clinical symptoms were evident throughout the study period.All patients exhibited a steady increase of peripheral CD4^(+)T cells from a median 10.5 to 207.5 cells/μl.Rapid increase in peripheral CD8^(+)T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of AAIT.In addition,their inflammatory cytokine levels and HIV RNA viral load decreased.A short-term microchimerism with donor cells was found.There were no adverse events associated with graft-versus-host disease throughout the study period.Overall,AAIT treatment was safe,and might help severely immunosuppressed AIDS patients to achieve a better immune restoration.A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.