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Introduction: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug–drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. Methods: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. Results: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17–6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. Conclusion: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. Trial registration: ClinicalTrials.gov; identifier, NCT06019273. [ABSTRACT FROM AUTHOR]

The roles of cytokines and chemokines in HIV‐associated cryptococcal meningitis (HCM) and HIV‐associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV‐infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)‐12p40, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α and TNF‐β and Th2 (IL‐2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV‐infected patients without central nervous system (CNS) infection. Furthermore, the IL‐1Ra, IL‐12p40, IL‐17α and monocyte chemotactic protein‐1 (MCP‐1) levels were higher in HCM patients, while the IFN‐γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferon‐inducible protein‐10 (IP)‐10 levels were higher in HTBM patients. Elevated CSF concentrations of IL‐17a, TNF‐β, IL‐5, IL‐12p40 and IL‐1Rα were closely related to meningitis, but elevated IP‐10, MCP‐1, RANTES and IFN‐γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV‐infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP‐1, RANTES, IFN‐γ and IP‐10 in CSF are protective factors against HCM but not HTBM. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a crucial risk factor for hepatocellular carcinoma (HCC). However, its underlying mechanism remains understudied. Methods: Microarray analysis was conducted to compare the genes and miRNAs in liver tissue from HBV-positive and HBV-negative HCC patients. Biological functions of these biomarkers in HBV-related HCC were validated via in vitro and in vivo experiments. Furthermore, we investigated the effect of HBV on the proliferation and migration of tumor cells in HBV-positive HCC tissue. Bioinformatics analysis was then performed to validate the clinical value of the biomarkers in a large HCC cohort. Results: We found that a gene, MINPP1 from the glycolytic bypass metabolic pathway, has an important biological function in the development of HBV-positive HCC. MINPP1 is down-regulated in HBV-positive HCC and could inhibit the proliferation and migration of the tumor cells. Meanwhile, miRNA-30b-5p was found to be a stimulator for the proliferation of tumor cell through glycolytic bypass in HBV-positive HCC. More importantly, miRNA-30b-5p could significantly downregulate MINPP1 expression. Metabolic experiments showed that the miRNA-30b-5p/MINPP1 axis is able to accelerate the conversion of glucose to lactate and 2,3-bisphosphoglycerate (2,3-BPG). In the HBV-negative HCC cells, miRNA-30b-5p/MINPP1 could not regulate the glycolytic bypass to promote the tumorigenesis. However, once HBV was introduced into these cells, miRNA-30b-5p/MINPP1 significantly enhanced the proliferation, migration of tumor cells, and promoted the glycolytic bypass. We further revealed that HBV infection promoted the expression of miRNA-30b-5p through the interaction of HBV protein P (HBp) with FOXO3. Bioinformatics analysis on a large cohort dataset showed that high expression of MINPP1 was associated with favorable survival of HBV-positive HCC patients, which could lead to a slower progress of this disease. Conclusion: Our study found that the HBp/FOXO3/miRNA-30b-5p/MINPP1 axis contributes to the development of HBV-positive HCC cells through the glycolytic bypass. We also presented miRNA-30b-5p/MINPP1 as a novel biomarker for HBV-positive HCC early diagnosis and a potential pharmaceutical target for antitumor therapy. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the associated coronavirus disease (COVID‐19) have spread throughout China. Previous studies predominantly focused on its place of origin, Wuhan, causing over estimation of the disease severity due to selection bias. We analyzed 465 confirmed cases in Zhejiang province to determine the epidemiological, clinical, and virological characteristics of COVID‐19. Methods: Epidemiological, demographic, clinical, laboratory, and management data from qRT‐PCR confirmed COVID‐19 patients from January 17, 2020, to January 31, 2020, were collected, followed by multivariate logistic regression analysis for independent predictors of severe/critical‐type COVID‐19 and bioinformatic analysis for features of SARS‐CoV‐2 from Zhejiang province. Results: Among 465 COVID‐19 patients, median age was 45 years, while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical‐type of COVID‐19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms, while diarrhea/vomiting was reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID‐19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS‐CoV‐2 from Zhejiang province, with more similarity to humans than to viruses. Conclusions: SARS‐CoV‐2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable. [ABSTRACT FROM AUTHOR]

The viral RNA shedding time (VST) for severe acute respiratory syndrome coronavirus 2 has not been well characterized. Clinical data were collected and compared between patients with short and long VSTs (in the lower and upper quartiles, respectively). The probability of recurrent positive reverse-transcription polymerase chain reaction results decreased sharply to 4.8% after 3 consecutive negative results. A series of ≥3 consecutive negative results was suitable as a criterion for the end of viral RNA shedding. The VST for shedding from the respiratory tract was significantly shorter in patients with normal B-cell counts on admission than in those with decreased B-cell counts (median [interquartile range], 11 [9-13] vs 16 [12-20] days, respectively; P = .001). [ABSTRACT FROM AUTHOR]

Background: Studies on Epstein-Barr virus (EBV) have focused mostly on neoplastic disease. Few studies have considered immunocompetent patients who are not severely immunocompromised. Liver cirrhosis is associated with various levels of immune dysfunction. In the current study, we determined EBV infection rates, the influence on liver function, and analyzed the risk factors for death in patients with liver cirrhosis.Methods: The medical records of patients diagnosed with liver cirrhosis between 1 January 2014 and 31 December 2016 were reviewed. Patients who were or were not infected with EBV were enrolled in this study. Liver functions were compared. The risk factors for 28-, 90-, and 180-day mortality rates were analyzed by univariate and multivariate logistic regression.Results: The medical records hospitalized patients diagnosed with liver cirrhosis were reviewed. Of these patients, 97 had assessed EBV deoxyribonucleic acid (DNA) and 36 (37.1%) patients were EBV DNA-positive. The age of the EBV-infected patients was older than patients not infected with EBV. EBV-infected patients had a lower level of albumin, and a lower albumin-to-globulin ratio (P = 0.019 and P = 0.013, respectively). EBV-infected patients had higher Child-Pugh scores (P = 0.033) and higher acute-on-chronic liver failure (ACLF) rate (P = 0.050). The Child-Pugh score and ACLF were the risk factors for the 28-, 90-, and 180-day mortality rates.Conclusions: This study revealed that patients with liver cirrhosis had higher EBV infection rates, especially patients > 60 years of age, which likely reflected viral reactivation. And liver injury was aggravated in EBV-infected patients. Thus, EBV infection indirectly influenced the prognosis of EBV-infected patients by increasing the Child-Pugh score and ACLF rate. [ABSTRACT FROM AUTHOR]