Clinical characteristics of 290 foreign-imported cases infected with SARS-CoV-2 in Chengdu, China

Objective:To analyze the epidemiological and clinical characteristics of foreign-imported patients infected with SARS-CoV-2 in Chengdu City.Methods:A total of 290 foreign-imported patients infected with SARS-CoV-2 and discharged from Public Health Clinical Center of Chengdu were included in our study,they were divided into asymptomatic infection group(131 cases)and confirmed cases group(159 cases)in order to compare the epidemiology,clinical characteristics and laboratory tests between two groups.Multi-factor logistic regression analysis was used to investigate the influence factors of becoming a dominant infection after infected with SARS-CoV-2.Results:Among the 290 cases aged from 2 months to 68 years old,83.4%were males,62.1%came from Asia,and 43.8%were complicated with fatty liver disease,the age group of 14-49 years old had the largest number(247 cases).80.5%confirmed case group cases were general type,there was only 1 severe patient.Hospital stays in asymptomatic infection group was shorter than that in confirmed cases group,lymphocyte count,CD4+T count,CD8+T count,CD4+T/CD8+T creatine kinase in two groups half a month after discharge were relatively lower than those on admission,and alanine aminotransferase,aspartate aminotransferase,albumin,lactate dehydrogenase,creatine kinase isoenzyme were relatively higher than those on admission(P<0.05).Logistic regression analysis showed that increased age,decreased lymphocyte count on admission and increased lactate dehydrogenase on admission were associated with dominant infection.Chest CT of 13 general type cases indicated an increase in lesions compared with that at discharge and 3 of them had re-detectable positive RNA test.Conclusion:The majority of foreign-imported cases in Chengdu are mainly from Asia,fewer of them are severe patients.In the early stage of recovery,some SARS-CoV-2 infected patients still have intermittent viral replication.Early isolation and early treatment of imported patients is not only conducive to epidemic prevention and control,but also may change the natural course of the disease.

Analysis of laboratory and imaging examination results of patients with COVID-192 years after discharge in Chengdu

Objective:To summarize the follow-up results of laboratory examination,echocardiographic and chest CT of patients with COVID-19 at the time of 2 years after discharge in Chengdu.Methods:A total of 29 COVID-19 survivors who have participated in the 1-year follow-up and 2-year follow-up at Public Health Clinical Center of Chengdu were included in our study.Their blood laboratory tests,echocardiography and chest CT results were analyzed in order to evaluate the long-term recovery of COVID-19 survivors.Results:The most common abnormal laboratory test results at the 2-year follow-up were increased serum fibronectin(21 cases,72.4%)and decreased NK cell counts(19 cases,65.5%).Compared with laboratory test results at the 1-year follow-up,platelet count,hydroxybutyrate dehydrogenase and creatine kinase isoenzyme were decreased(all P<0.05),while serum fibrinogen,triglyceride,insulin and non-specific immunoglobulin A were increased(all P<0.05).Serum specific total SARS-CoV-2 antibody amount in COVID-19 survivors at half a year after COVID-19 vaccine was significantly higher than that before vaccination.More than half of patients(55.2%)had normal echocardiography results at the 2-year follow-up,the main abnormal results of them were valve regurgitation(7 cases,24.1%)and reduced left ventricular diastolic function(9 cases,31.0%).Compared with 1-year follow-up,7 patients had fewer abnormal cardiac ultrasound results.28 cases underwent chest CT at the 2-year follow-up,the mainly abnormal results were ground glass shadow(17.9%),pulmonary nodules(diameter<6mm)(32.1%)and scattered cable shadow(39.3%).71.4%(20/28)of them had no significant change between the two chest CT results.Conclusion:The mainly abnormal blood laboratory indicators in COVID-19 survivors at 2-year follow-up after discharge were increased serum fibronectin and decreased NK cell counts.Although echocardiography and chest CT results were no significant change between 1-year follow-up and 2-year follow-up among COVID-19 survivors,there were still some patients whose abnormal results were decreasing.Serum specific total SARS-CoV-2 antibody amount in COVID-19 survivors at half a year after COVID-19 vaccine was still significantly higher than that before vaccination,but the amount of specific antibody had a downward trend with time.

Optimal Timing of Antiretroviral Therapy Initiation in Acquired Immunodeficiency Syndrome-Associated Toxoplasmic Encephalitis:A Prospective Observational Multicenter Study in China

Background:Toxoplasmic encephalitis(TE)is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome(AIDS).However,the optimal timing of antiretroviral therapy(ART)initiation in these patients remains controversial.This study aims to investigate the differences in outcomes of ART initiation at different times,in order to help clarify the treatment timing of AIDS-associated TE.Methods:This multicenter prospective observational study included 87 patients recruited from 11 research centers in China(from March 2019 to December 2022).Of the patients,38 were assigned to the early ART group(initiating ART within 2 weeks after anti-Toxoplasma treatment initiation),and the remaining 49 patients received deferred ART(initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation).The main outcomes includedmortality and emergence of immune reconstitution inflammatory syndrome(IRIS).Human immunodeficiency virus(HIV)-1 viral load and CD4^(+)T-cell counts at weeks 24 and 48 were observed.Results:The number of deaths(1 vs.5,P=0.225)and incidence of IRIS(2.6%vs.0,P=0.437)were not significantly different between the early and deferred ART groups at week 48.Early ART initiation did not contribute significantly to HIV-1 viral load control(<50 copies/mL,n=8 vs.n=3 at week 24,P=0.142;n=7 vs.n=7 atweek 48,P=1.000).The median CD4^(+)T-cell counts between the two groups were not significantly different,either at week 24(155 vs.91 cells/mm^(3),P=0.837)or atweek 48(181 vs.146 cells/mm^(3),P=0.219).Conclusion:In patients with AIDS-associated TE,early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality,IRIS,and HIV virological and immunological outcomes.Trial registration:This study was registered(registration number:ChiCTR1900021195)as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry(chictr.gov)on February 1,2019.Enrollment for this study began inMarch 2019.

Evaluating patients' perception of service quality at hospitals in nine Chinese cities by use of the ServQual scale

Objective: To investigate patients' perception of service quality at hospitals in nine Chinese cities and propose some measures for improvement. Methods: The ServQ ual scale method was used in a survey involving patients at out-patient and in-patient facilities in Shanghai, Chongqing, Chengdu, Nanning, Guilin and Laibin of Guangxi, Honghezhou of Yunnan, Wulumuqi of Xinjiang and Zhongshan of Guangdong. The data collected were entered and analyzed using SPSS 20.0. Statistical analyses included descriptive statistics, factor analyses, reliability analyses, product-moment correlations, independent-sample t-tests, One-way ANOVA and regression analyses. Results: The Kaiser-Meyer-Olkin value for the factor analysis of the scale was 0.979. The Cronbach's α for the reliability analysis was 0.978. All the Pearson correlation coei cients were positive and statistically signii cant. Visitors to out-patient facilities reported more positive perception tacilities on tangibles(t = 4.168, P(t = 1.979, P <han visitors to in-patient f 0.05). Patients of 60 years of age and above reported mor< 0.001) and reliability e positive perception th<an those between 40 and 49 on reliability(F = 3.311, P = 0.010), assurances(F = 2.751, P 0.05) and empathy(F = 4.009, P = 0.003). For the i ve dimensions of the scale, patients in Laibin, Guangxi reported the most positive perceived service quality, followed by patients in Shanghai. On the other hand, patients in Chongqing and Nanning and Guilin of Guangxi reported relatively poor perceptions of service quality. Standardized regression coei cients showed statistically significant(P < 0.001) positive values for all Serv Qual dimensions. Empathy(β = 0.267) and reliability(β uality. = 0.239) most strongly predicted perception of service qConclusions: Chinese patients perceived service quality as satisfactory. Hospitals in various regions of China should enhance their awareness and ability to serve their patients.

3-to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge:Results from a Prospective,Multicenter Study

Objective Coronavirus disease 2019(COVID-19)and tuberculosis(TB)are major public health and social issues worldwide.The long-term follow-up of COVID-19 with pulmonary TB(PTB)survivors after discharge is unclear.This study aimed to comprehensively describe clinical outcomes,including sequela and recurrence at 3,12,and 24 months after discharge,among COVID-19 with PTB survivors.Methods From January 22,2020 to May 6,2022,with a follow-up by August 26,2022,a prospective,multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China.Clinical outcomes,including sequela,recurrence of COVID-19,and PTB survivors,were collected via telephone and face-to-face interviews at 3,12,and 24 months after discharge.Results Thirty-two COVID-19 with PTB survivors were included.The median age was 52(45,59)years,and 23(71.9%)were men.Among them,nearly two-thirds(62.5%)of the survivors were moderate,three(9.4%)were severe,and more than half(59.4%)had at least one comorbidity(PTB excluded).The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6%at 3 months to 15.8%at 24 months,with anxiety having a higher proportion over a follow-up.Cough and amnesia recovered at the 12-month follow-up,while anxiety,fatigue,and trouble sleeping remained after 24months.Additionally,one(3.1%)case presented two recurrences of PTB and no re-positive COVID-19during the follow-up period.Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time,while nearly one in six still experience persistent symptoms with a higher proportion of anxiety.The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China

Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.Results Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two weeks.Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

A Follow-up Study for Chinese Chronic Hepatitis C Patients Treated with the Combination of PEG-IFNα-2a(PEGASYS) and Ribavirin

Objective To compare the efficacy of peginterferon alfa-2a(PEGASYS) plus ribavirin(RBV) with interferon alfa-2a plus RBV, and evaluate the safety. Methods Total of 117 patients with chronic hepatitis C were enrolled to receive either PEGASYS(135 μg or 180 μg) subcutaneously once per week, plus RBV(800 mg-1 200 mg) per day for 48 weeks(79 patients, PEGASYS group), or 5 million units of interferon alfa-2a subcutaneously every other day, plus RBV as above dosage for 48 weeks(38 patients, IFNα group). Results Sixty-three of 79(79.7%) patients reached sustained virological response(SVR) in PEGASYS group, while 14 of 38(36.8%) patients reached SVR in IFNα group. PEGASYS group was associated with a higher rate of virologic response than IFNα group at week 4, 12, 36, 48 and week 72. Sustained normalization of serum ALT concentrations at week 36, 48 and week 72 was also more common in PEGASYS group than in IFNα group. Baseline levels of ALT and HCV RNA had no effect on SVR in either PEGASYS group or IFNα group. Both groups were similar in the frequency and severity of adverse events. Conclusions PEGASYS plus RBV produced similar adverse events but higher rate of SVR. Meanwhile, complications should be prevented and treated promptly in order to increase compliances and effects.

Glucose metabolism continuous deteriorating in male patients with human immunodeficiency virus accepted antiretroviral therapy for 156 weeks

BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.

Drug resistance and pathogenic spectrum of patients coinfected with nontuberculous mycobacteria and human-immunodeficiency virus in Chengdu, China

Background:Human-immunodeficiency virus (HIV) infection is increasing worldwide and nontuberculous mycobacteria (NTM) is an established microbiologic cause of pulmonary disease,lymphadenitis,and disseminated disease in cases of advanced immune suppression.Data on patients coinfected with HIV and NTM are limited.Thus,this study aimed to analyze the clinical characteristics,drug resistance,and pathogen spectrum of patients coinfected with both HIV and NTM in the Chengdu area of China.Methods:Data of 59 patients coinfected with both HIV and NTM collected from the Public Health Clinical Center of Chengdu,between January 2014 and December 2018,were analyzed.NTM drug sensitivity testing was performed using the microporous plate ratio method.Data were analyzed using SPSS 19.0,and the change in drug resistance rate was analyzed using the chi-square (x2) test.Results:Seven species/complex of NTM were identified from patients coinfected with HIV and NTM in this study,with Mycobacterium avium-intracellulare complex (52.5%) and M.kansasii (27.1%) as the predominant species.Male patients were more affected 50/59 (84.7%);the mean age of the 59 cases was 45 years.The clinical characteristics mainly included anemia (86.4%),cough and expectoration (79.7%).The baseline CD4 count was <50 cells/μL (84.7%).Patients were mainly in advanced acquired immunodeficiency syndrome (AIDS) stage.Chest imaging mainly showed patchy shadows (42.4%) and nodules (32.2%),with various degrees of AIDS-defining diseases.The drug resistance of NTM was severe,and the rate of isoniazid resistance (100.0%) was the highest,followed by rifampicin (94.9%),streptomycin (94.9%),ofloxacin (93.2%),and others.Ethambutol (52.5%) and clarithromycin (33.9%) were relatively low.No significant difference was found in the drug resistance rate of NTM strain against nine antituberculosis drugs in 5 years (P > 0.05).Condusions:The immune level of patients coinfected with HIV and NTM is low in advanced AIDS stage;more male are affected in patients who are mainly infected with MAC and M.kansasii and with serious drug resistance,The drug resistance rate of ethambutol and clarithromycin is relatively low.

Three Cases of COVID-19 Variant Delta With and Without Vaccination——Chengdu City,Sichuan Province,April-May,2021

On April 26,2021,a 33-year-old male Chinese sailor returning from India via Kathmandu,Nepal,tested positive for the coronavirus disease 2019(COVID-19)by Chengdu Customs and was confirmed positive by Chengdu CDC(Case A).On May 2,2021,a housewife in the same flight tested positive for COVID-19 by Pengzhou CDC in Sichuan Province during her quarantine period and was confirmed positive by Chengdu CDC the next day(Case B).

Sequentially responsive size reduction and drug release of core-satellite nanoparticles to enhance tumor penetration and effective tumor suppression

Poor tumor accumulation remains a serious challenge for nanomedicines to achieve ideal antitumor outcomes.The different size preferences for systematic circulation,tumor retention and deep permeation have attracted great attention when designing antineoplastic nano-delivery system.Herein,we developed a nano-system which can shrink its size in tumor microenvironment to achieve better tumor retention and penetration.In this work,the cationic bovine serum albumin-protected,doxorubicin-loaded gold nanoclusters(CAuNC-DOX)and amino-functionalized mesoporous silica nanoparticles(MSN)are connected by Fe^(2+)and are further coated with hyaluronic acid(HA)to obtain a core-satellite MSN-Fe-CAuNCDOX@HA nano system(MFADH).When reaching the tumor site,the HA shell,which endows the system with both good biocompatibility and preferable tumor targeting ability,was disintegrated,followed by acid-stimulated release of small-sized pharmacological unit—CAuNC-DOX for further tumor penetration.As demonstrated in both in vitro and in vivo results,MFADH showed excellent antitumor effect,providing a proof of concept for the feasibility of shrinkable nanoplatforms in tumor treatment.

Value of Non-tumoral Liver Volume in the Prognosis of Large Hepatocellular Carcinoma Patients After R0 Resection

Background and Aims:Hepatectomy is an effective treatment for selected patients with large hepatocellular carcinoma(HCC).This study aimed to develop a nomogram in-corporating non-tumoral liver volume(non-TLV)and liver function markers to predict the patients’overall survival(OS)and disease-free survival(DFS).Methods:Data of 198 consecutive large HCC patients who underwent hepa-tectomy at the Zhongshan Hospital Xiamen University were collected.Another 68 patients from the Mengchao Hepatobil-iary Surgery Hospital served as an external validation cohort.The nomograms were developed based on the independent prognostic factors screened by multivariate Cox regression analyses.Concordance index(C-index),calibration curves,and time-dependent receiver operating characteristic(ROC)curves were used to measure the discrimination and predic-tive accuracy of the models.Results:High HBV DNA level,low non-TLV/ICG,vascular invasion,and a poorly differenti-ated tumor were confirmed as independent risk factors for both OS and DFS.The model established in this study pre-dicted 5-year post-operative survival and DFS in good agree-ment with the actual observation confirmed by the calibra-tion curves.The C-indexes of the nomograms in predicting OS and DFS were 0.812 and 0.823 in the training cohort,0.821 and 0.846 in the internal validation cohort,and 0.724 and 0.755 in the external validation cohort.The areas under the ROC curves(AUCs)of nomograms for predicted OS and DFS at 1,3,and 5 year were 0.85,0.86,0.83 and 0.76,0.76,0.63,respectively.Conclusions:Nomograms with non-TLV/ICG predicted the prognosis of single large HCC patients ac-curately and effectively.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B:Study Protocol for a Multi-Center,Double-Blind Randomized-Controlled Trial

Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine （CHM） is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule （调肝益脾颗粒, TGYP） or Tiaogan-Jianpi-Jiedu Granule （调肝健脾解毒颗粒, TGJPJD） plus entecavir tablet （ETV） was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods： The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1：1 ratio via central randomization system： experimental group （EG） and control group （CG）. Subjects in EG received CM formulae （TGYP or TGJPJD, 50 g per dose, twice daily） plus ETV tablet （or ETV placebo） 0.5 mg per day in the first 24 weeks （stage 1）, and CHM granule plus ETV tablet （0.5 mg per day） from week 25 to 108 （stage 2）. Subjects in CG received CHM Granule placebo plus E＇IV tablet （0.5 mg per day） for 108 weeks throughout the trial. The assessments of primary outcomes （HBV serum markers and HBV-DNA） were conducted by a third-party College of American Pathologists （CAP） qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion： The study was designed to compare the curative effect of CM plus E＇IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as ＂a valuable endpoint＂. We believe this trial could provide a reliable status for patients＇ ＂joumey＂ towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry （No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23）.

Are tuberculosis patients adherent to prescribed treatments in China? Results of a prospective cohort study

Background:Tuberculosis(TB)patients face numerous difficulties adhering to the long-term,rigorous TB treatment regimen.Findings on TB patients’treatment adherence vary across existing literature and official reports.The present study attempted to determine the actual treatment adherence of new TB patients and to identify factors leading to non-adherence.Methods:A prospective cohort of 481 newly confirmed TB patients from three counties in western China were enrolled during June to December 2012 and was followed until June 2013.Patients who missed at least one dose of drugs or one follow-up re-examination during the treatment course were deemed as non-adherent.Influencing factors were identified using a logistic regression model.Results:A total of 173(36.0%)patients experienced non-adherence and the loss to follow-up cases reached 136(28.2%).Only 13.9%of patients took drugs under direct observation,and 60.5%of patients were supervised by phone calls.Factor analyses suggested that patients who were observed by family members(OR:5.54,95%CI:2.87–10.69)and paying monthly service expenses above 450 RMB(OR:2.08,95%CI:1.35–3.19)were more likely to be non-adherent,while supervision by home visit(OR:0.06,95%CI:0.01–0.28)and phone calls(OR:0.27,95%CI:0.17–0.44)were protective factors.Conclusions:Despite recent efforts,a large proportion of newly confirmed TB patients could not adhere to standard TB treatment,and patients’lost to follow-up was still a serious problem.Poor treatment supervision and heavy financial burden might be the main causes for non-adherence.More needs to be done to enhance treatment supervision policies and financial supports to both health providers and TB patients.

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders:a brief report

Background:Allogeneic natural killer(NK)cell immunotherapy is recognized as a promising anti-tumor strategy,but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1(HIV-1)infected patients is unknown.This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders(INRs)receiving antiretroviral therapy(ART).Methods:From February to April 2018,a prospective,randomized,controlled,open-label clinical trial,which enrolled 20 HIV-1 INRs following specific inclusion criteria,was conducted at Nankai University Second People’s Hospital.Participants were randomly allocated(simple randomization 1:1)to either the combined treatment(NK+ART)group(n=10)or the control(ART)group(n=10).The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor(KIR)/human leukocyte antigen(HLA)-Cw mismatched healthy donor were prepared(108 cells in each injection)and intravenously infused to each recruited patient of NK+ART group in three courses.Key immune parameters(CD4 count,CD8 count,CD4/CD8 ratio),laboratory tests(count of blood cells,biochemistry panel)and symptoms at baseline and at month 1,3,6,9,12,and 24 were measured/collected to analyze the safety and efficacy of the therapy.Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance(ANOVA)test.Generalized estimating equations(GEE)model was performed to evaluate the overall effect of the NK+ART group vs.the ART group.Results:From baseline to 24 months,we noted a mean CD4 count augmentation(139 to 243 cells/μL)in the NK+ART group and(144 to 176 cells/μL)in the ART group(difference,67;95%CI,10 to 124;P=0.024).Our estimations revealed that NK+ART group could improve CD4 level(β=54.59,P=0.006)and CD8 level(β=322.47,P=0.010)on average among the six measurements compared with the ART group.Only two(2/10,20%)participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs,allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio.The practical effects,however,need long-term follow-up observations.Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912(No.ChiCTR1900020634).

Detection of serum IgM and IgG for COVID-19 diagnosis

Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 remains ongoing and was linked to more than 80,000 infected patients and more than 3,000 deaths in China as of March 7,2020(Holshue et al.,2020).

Two Cases of COVID-19 with Persistently Positive SARS-CoV-2- Specific IgM During One-Year Follow-Up-Sichuan Province,China,February 2021

On January 22,2020,a 41-year-old male(Patient A)developed a fever with a maximum temperature of 38°C after returning to Chengdu City from Wuhan City.He was admitted to the Public Health Clinical Center of Chengdu on January 26,2020,after being confirmed to be positive for coronavirus disease 2019(COVID-19)by Chengdu CDC.Chest computed tomography(CT)revealed multiple plaque-like,ground-glass shadows in the upper,middle,and lower lobes of the right lung and upper and lower lobes of the left lung,as well as a small amount of pericardial effusion.

MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury

Background and Aims:The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury(ALI).Methods:Lipopolysaccharide(LPS)was used to induce an ALI cellular model in HL7702 cells,in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced.A series of experiments were performed to determine their roles in liver injury,oxidative stress injury,and cell biological processes.The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified.Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay.Results:MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model.MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation,and reduced ALI.Functionally,MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression.Moreover,MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway.Conclusion:Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Dynamic blood single-cell immune responses in patients with COVID-19

The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5'gene expression,T cell receptor(TCR),and B cell receptors(BCR)V(D)J transcriptome analysis at a single-cell resolution.We obtained single-cell mRNA sequencing(scRNA-seq)data of 341,420 peripheral blood mononuclear cells(PBMCs)and 185,430 donotypic T cells and 28,802 donotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies.In addition,we used three control samples.We found expansion of dendritic cells(DCs),CD14+monocytes,and megakaryocytes progenitor cells(MP)/platelets and a reduction of naive CD4+T lymphocytes in patients with COVID-19,along with a significant decrease of CD8+T lymphocytes,and natural killer cells(NKs)in patients in critical condition.The type I interferon(IFN-I),mitogen-activated protein kinase(MAPK),and ferroptosis pathways were activated while the disease was active,and recovered gradually after patient conditions improved.Consistent with this finding,the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls.The concentration of interferon-a(IFN-a)in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls,further suggesting the important role of the IFN-I pathway in the immune response of COVID-19.TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens.Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection,providing clues for therapeutic potentials in treating COVID-19.