Short-term entecavir versus lamivudine therapy for HBeAg-negative patients with acute-on-chronic hepatitis B liver failure

BACKGROUND: Selection of drugs for antiviral therapy of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains difficult. This study was undertaken to evaluate the short-term efficacy of entecavir versus lamivudine on hepatitis B e antigen (HBeAg)-negative patients with ACLF. METHODS: The data of 182 HBeAg-negative patients with ACLF were retrospectively collected from patient profiles of the hospital. In these patients, 93 HBeAg-negative patients with ACLF were treated orally with 0.5 mg of entecavir and 89 were treated orally with 100 mg of lamivudine every day. The gender and age were matched between the two groups. Biochemical items, the model for end-stage liver disease (MELD) score, and HBV DNA level were matched at baseline between the two groups and monitored during treatment. The 3-month mortalities of the two groups were compared. RESULTS: No significant differences were found in biochemical items, MELD score, and HBV DNA level at baseline (P】0.05). HBV DNA level decreased within 3 months in both groups (P【0.05), regardless of the pretreatment MELD score. In patients with the same range of pretreatment MELD scores, treatment duration, posttreatment HBV DNA levels, percentage of HBV DNA level 【2.7 lg copies/mL, biochemical items, MELD scores and 3-month mortality were similar in the two groups (all P】0.05). Pretreatment MELD score was not related to posttreatment HBV DNA levels (P】0.05), but related to a 3-month mortality in both groups (both P【0.001).CONCLUSIONS: In HBeAg-negative patients with ACLF, the short-term efficacy of entecavir versus lamivudine was similar. The degree of pretreatment liver failure significantly affected the outcome of treatment.

Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia

Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in complete remission（CR）.Methods：Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3＋,CD4＋ and CD8＋ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results：A significantly higher percentage of PD-1＋ cells were found for CD3＋ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1＋ CD8＋ T cells,but not PD-1＋ CD4＋,was found for CD3＋ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244＋ CD4＋,CD244＋ CD8＋,CD57＋ CD4＋ and CD57＋ CD8＋ T cells was found in CD3＋ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1＋ CD244＋ and PD-1＋ CD57＋ coexpression was found for CD4＋ and CD8＋ T cells in the de novo AML group compared with healthy controls.Conclusions：We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8＋ T cells,suggesting a poor anti-leukemia immune response in these patients.

Development and validation of the Nurse’s Workplace Mental Health Questionnaire

Objectives:This study aimed to develop and validate the Nurse’sWorkplace Mental Health Questionnaire(NWMHQ).Methods:The questionnaire was developed based on the two continua model of mental illness and health proposed by Keyes.The initial questionnaire was generated through literature review,two rounds of Delphi expert consultation,followed by a pilot survey.Finally,the reliability and validity of the questionnaire were validated through an online survey of 2,815 registered nurses selected from the public hospitals in 11 provinces from June to July 2020.Results:The item-content validity index(I-CVI)of the questionnaire ranged from 0.750 to 1.000 and the average scale-level content validity index(S-CVI/Ave)was 0.906.Cronbach’s a coefficient was 0.948 and test-retest reliability was 0.850.The self-rating depression scale score was negatively related to the NWMHQ score(r=0.664,P<0.01).The exploratory factor analysis(EFA)yielded six factors(emotional status,psychological security,positive relationship,resilience,self-efficacy,and subjective well-being),consisting of 32 items.The cumulative variance contribution rate was 65.58%.Confirmatory factor analysis(CFA)showed an acceptable fit.Conclusion:The NWMHQ developed in this study showed good reliability and validity.This questionnaire may help assess the mental health status of nurses and help nursing managers to develop appropriate targeted psychological interventions.

Pseudo-hyperaldosteronism caused by compound glycyrrhizin tablets: a case report

Compound glycyrrhizin tablets(CGT)is a glycyrrhizin-containing preparation for the treatment of chronic hepatic diseases,it contained Glycyrrhizin,Monoammonium Glycyrrhizinate,Aminoacetic Acid and Methionine.CGT has been shown to have anti-inflammatory,anti-oxidative,and anti-viral effects.Although pseudo-hyperaldosteronism was reported as its important side effects,the frequency was unknown.A 59-year-old male patient with tuberculous pleurisy received CGT to prevent impairment in liver function which was caused by antituberculosis drugs.After more than one month,it appeared edema in the lower extremity,blood pressure increased,serum potassium lowed,serum sodium raised at the normal high limit.Finally,it was improved by suspending the CGT and diuretic treatment.

A network pharmacology analysis on Jiawei Buhuanjin Zhengqi powder against COVID-19 in children

Background:To clarify the effectiveness and potential mechanism of Jiawei Buhuanjin Zhengqi powder(JBZP)for the prevention and treatment of coronavirus disease 2019(COVID-19)in children based on network pharmacology.Methods:The active ingredients and action targets of Jiawei Buhuanjin Zhengqi powder formulas were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Genes related to COVID-19 were found on the GeneCards database.The active ingredients-target network map was constructed by Cytoscape.The action mechanisms of these genes were predicted using a Gene Ontology-based functional enrichment and annotation tool and the Kyoto Encyclopedia of Genes and Genomes.Results:Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,187 eligible compounds and 12,921 targets of Jiawei Buhuanjin Zhengqi powder were identified.A total of 257 genes related to Jiawei Buhuanjin Zhengqi powder and 401 genes related to COVID-19 in children were screened and 59 common target genes were obtained.The network analysis showed that the predicted seven main active components were Quercetin,Luteolin,Wogonin,Kaempferol,Irisolidone,Nobiletin and Licochalcone a.Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that key targets were associated with regulating immunological function or glycosylation through the biological processes.Conclusion:The potential mechanisms of Jiawei Buhuanjin Zhengqi powder on COVID-19 in children might be related to anti-inflammatory,virus infection,and immunomodulatory signaling pathway.

Effect of Ramipril on Renin-Angiotensin-Aldosterone System of Young and Middle-Aged Patients with Hypertension

Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking treatment in the hospital between August 2017 and August 2018 were selected and randomly divided into a control group and an observation group according to the random number table,with 45 cases in each group.The control group received Amlodipine for treatment,whereas the observation group was given Amlodipine combined with Ramipril for treatment.The hemodynamic indexes,blood lipid,blood pressure,angiotensinⅡ(AngⅡ),plasma renin(PRA),aldosterone(ALD)levels and incidence of adverse reactions during the medication in the two groups were compared before and after treatment.Results After treatment,thefibrinogen,plasma viscosity and whole blood viscosity in the observation group were significantly higher than those in the control group,with statistically significant difference between the two groups(P<0.05);total cholesterol(TC),triacylglycerol(TG)and low density lipoprotein cholesterin(LDL-C)in the observation group were significantly lower than those in the control group,and statistically significant difference was registered between the two groups(P<0.05);the diastolic pressure and systolic pressure in the observation group were decreased more significantly compared with the control group,with statistically significant difference shown between the two groups(P<0.05);the AngⅡ,ALD and PRA levels in the observation group were significantly lower than the control group,and the difference between two groups were statistically significant(P<0.05);during the medication,no significant bleeding or liver and kidney function damages occurred in the two groups.Conclusions For young and middle-aged patients with hypertension,the treatment with Ramipril,which is of high safety,can effectively improve the activity of their renin-angiotensin-aldosterone system,reduce the level of blood pressure and AngⅡ,ALD and PRA levels.

High percentage of bone marrow CD8^(+)tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia

Tissue-resident memory T(TRM)cells infiltrating solid tumors could influence tumor progression and the response to immune therapies.However,the proportion and prognostic value of TRM cells in the bone marrow(BM)of patients with acute myeloid leukemia(AML)are unclear.In this study,we used flow cytometry to assay the phenotype of 49 BM samples from patients newly diagnosed with AML(ND-AML).We found that the BM CD8^(+)effector memory(TEM)cells highly expressed CD69(CD8^(+)TRM-like T cells),and their percentage was significantly increased in patients with ND-AML compared with that in healthy individuals(HI).The high percentage of CD8^(+)TRM-like subset was associated with poor overall survival in our ND-AML cohort.The Kaplan–Meier Plotter database verified a significantly reduced survival rate among patients with high expression of CD8^(+)TRM-like T cell characteristic genes(CD8A,CD69,and TOX),especially the M4 and M5 subtypes.Phenotypic analysis revealed that the BM CD8^(+)TRM-like subpopulation exhibited exhausted T cell characteristics,but its high expression of CD27 and CD28 and low expression of CD57 suggested its high proliferative potential.The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8^(+)T cells in the BM of patients with AML and verified the high expression of immune checkpoints and costimulatory molecules.In conclusion,we found that the accumulation of BM CD8^(+)TRM-like cells could be an immune-related survival prediction marker for patients with AML.

Double Plasma Molecular Adsorption System with Sequential Low-dose Plasma Exchange in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure:A Prospective Study

Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods:Clinical data of patients with HBVACLF were prospectively collected,including patients in a DPMAS with sequential LPE(DPMAS+LPE)group and those in a standard medical treatment(SMT)group.The primary endpoint was death or liver transplantation(LT)at 12 weeks of follow-up.Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups.Results:After 2 weeks,total bilirubin,alanine aminotransferase,blood urea nitrogen levels,and Chinese Group on the Study of Severe Hepatitis B score,were significantly lower in the DPMAS+LPE group than those in the SMT group(p<0.05).After 4 weeks,laboratory parameters of the two groups were similar.The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks(97.9%vs.85.4%,p=0.027),but not at 12 weeks(85.4%vs.83.3%,p=0.687).Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group(p<0.05).Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes,regulation of immune effect response,regulation of endotoxin response,and glial cell proliferation.Conclusion:DPMAS+LPE significantly improved the 4-week cumulative survival rate,and ameliorated the inflammatory response in patients.DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.

Efficacy and safety of low-dose rifampicin in patients with benign intrahepatic cholestasis

Background and aim:Some previous studies supported that rifampicin was an effective treatment for benign intrahepatic cholestasis.However,the efficacy and safety of rifampicin remain unclear.Therefore,this study aimed to evaluate its efficacy and safety on benign intrahepatic cholestasis.Methods:A retrospective,single-center,observational study was conducted on patients diagnosed with benign intrahepatic cholestasis between 2019 and 2021,who were administered 150 mg of rifampicin orally once a day.We collected and analyzed the data at baseline and post-treatment,including total bilirubin(TBIL),direct bilirubin(DBIL),total bile acid(TBA),gamma-glutamyl transferase(GGT),alkaline phosphatase,aspartate aminotransferase,and alanine aminotransferase levels.Statistical analysis was performed using appropriate tests.Results:A total of 17 rifampicin-treated patients were enrolled in the study from January 2019 to January 2021.Among them,14 patients(82%)improved,with significantly decreased TBIL,DBIL,and TBA levels after 3 weeks of treatment(all P<0.05),whereas the remaining 3 had no improvement.Moreover,GGT levels of the former were significantly lower than those of the latter(34(12-227)U/L vs.244(76-293)U/L,P=0.023)at baseline.No severe adverse effect was observed during treatment.Conclusions:Low-dose rifampicin(150 mg per day)was an effective and safe treatment for benign intrahepatic cholestasis.Low GGT level at baseline and a significant decrease of TBIL,DBIL,and TBA levels within the first 3 weeks of treatment may lead to the good curative effect.

Tris(Znsalen) cryptand minimizes Znsalen aggregation arising from intermolecular Zn…O interaction

Exploring the factors to control Znsalen aggregation is of importance to design functional materials in catalysis, optical materials and biological imaging. In this work, we synthesized and characterized four cryptand type tri Znsalen complexes and found that cryptand structure could efficiently minimize intermolecular Zn…O interaction. More importantly, encapsulated by PLGA nanoparticles, cryptand tri Znsalen 1 displayed visible intracellular fluorescence whereas monomeric Znsalen 5 could not. These results provide a new access to design new luminescent materials with the potential application in optics and biological studies.