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AIM The global burden of chronic liver disease is substantial. Limited studies have reported the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis among middle-aged and older people. Therefore, we aimed to determine the nationwide prevalence of and associated factors for MAFLD and fibrosis in adults aged 45-79 years from the United States. METHODS This cross-sectional study utilized data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey conducted with a nationally representative sample of the civilian, noninstitutionalized US population. Hepatic steatosis and fibrosis were assessed by transient elastography with controlled attenuation parameter and liver stiffness measurement, respectively. RESULTS A total of 1186 eligible participants aged 45-79 years were finally included in the analyses. The estimated prevalence of MAFLD, significant fibrosis (F ≥ F2), and advanced fibrosis (F ≥ F3) was 48.6% (95% confidence interval [CI], 43.1%-54.0%), 9.5% (95% CI, 6.8%-12.7%), and 6.7% (95% CI, 4.1%-10.1%), respectively. Multivariable logistic regression revealed an increased MAFLD predisposition in subjects with metabolic disorders including overweight/obesity, abdominal obesity, hypertension, and diabetes mellitus. Moreover, the presence of depression was an independent and strong predictor of MAFLD risk (odds ratio = 3.23; 95% CI, 1.37-7.11). Elevated liver enzymes, hypertension, diabetes mellitus, hepatitis virus infection, and steatosis were associated with a high risk of significant fibrosis. CONCLUSIONS Newly defined MAFLD is highly prevalent in the US middle-aged and older population. Approximately 1 in 10 people has significant liver fibrosis. In addition to metabolic disorders, the presence of depression potentially increases the risk of MAFLD.

Type 2 diabetes (T2D) increases the risk of coronavirus disease (COVID-19). This study investigates the association between glucose control of COVID-19 patients with T2D in first 7 days after hospital admission and prognosis. A total of 252 infected inpatients with T2D in China were included. Well-controlled blood glucose was defined as stable fasting blood glucose (FBG) levels in the range of 3.9–7.8 mmol/L during first 7 days using indicators of average (FBGA), maximum (FBGM) or first-time (FBG1) FBG levels. The primary endpoint was admission to intensive care unit or death. Hazard ratio (HR) of poorly controlled glucose level group compared with well-controlled group were 4.96 (P = 0.021) for FBGM and 5.55 (P = 0.014) for FBGA. Well-controlled blood glucose levels in first 7 days could improve the prognosis of COVID-19 inpatients with diabetes.

Background: Cytokine storms are a common complication in severely ill patients with COVID-19, for which corticosteroid therapy (CsT) is used as adjuvant treatment. Therefore, we evaluated the efficacy and safety of CsT in patients with COVID-19.Methods: A single-center, retrospective cohort study was conducted in 1,392 severely ill patients with COVID-19 from Wuhan Huoshenshan Hospital. Patients received at least one dose (1–2 mg·kg-1·day-1 for 3–5 days) of methylprednisolone were divided into CsT group, whereas the rest were assigned into the non-CsT group. Results: Of 1,392 patients, 116 were assigned to the CsT group and 1,226 to the non-CsT group. Patients in the CsT group showed comparable mortality rate (1.8% vs. 1.2%, P > 0.99) and viral clearance time (44.5 days vs. 46.0 days, P = 0.48), but longer hospitalization time (21 days vs. 12 days, P < 0.001) than those in non-CsT group. During CsT, the proportion of lymphocytes was lower (14.7 % vs. 18.5 %, P = 0.01), while neutrophils was higher (77.1 % vs. 69.8 %, P < 0.001), than before treatment. The C-reactive protein (CRP) level was significantly lower after CsT (3.1 mg/L vs. 9.5 mg/L, P < 0.001). Furthermore, indicators of liver function (gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) and cardiac function (brain natriuretic peptide [BNP], α-hydroxybutyrate dehydrogenase [α-HBDH], and lactate dehydrogenase [LDH]) increased significantly during CsT but returned to normal after CsT. Patients who developed liver damage showed higher GGT, ALT, AST, LDH, Cre, and CRP; patients who developed heart injury had higher AST, LPH, CRP, lymphocyte (LYM), glucose, BNP, and α-HBDH; and patients who developed kidney failure had higher α-HBDH, LDH, CRP, and LYM values than before CsT. Additionally, patients who received CsT with cardiovascular disease showed a continuous elevation in D-dimer levels.Conclusions: CsT effectively attenuates the inflammatory response in severely ill patients with COVID-19 at a relatively low dose in a short duration; however, CsT increases the risk of hepatic and cardiac abnormalities.

Malignant melanoma (MM) is the most lethal cutaneous cancer and is associated with 80 % of skin cancer deaths. Recent progress into elucidating the role of the immune system in melanoma development and progression has led to promising treatments for patients with MM, including dendritic cell (DC) vaccination. Interferon-α2b is a commonly used adjuvant for MM that prolongs overall survival (OS) and progression-free survival (PFS). In the present study, we examined the impact of a DC-based vaccine with subsequent delivery of high-dose systemic interferon-α2b (HDI) on gene expression profiles and the immune response in MM patients. The results indicated that patients who were randomized to receive an HDI boost following DC vaccination had significantly higher OS and PFS rates compared with patients that received DC vaccination alone. Further analysis revealed that intradermal DC immunization did not significantly alter transcriptional profiles, whereas subsequent HDI injections enhanced B cell, T cell and natural killer cell-related gene expression. Analysis of the abundance of tumor-infiltrating immune cells revealed that HDI altered the immune cell profiles. Moreover, we determined that follicular helper T (Tfh) cells and eosinophils were associated with prolonged PFS in MM patients treated with the DC vaccine.

Glioblastoma expression subtypes have been previously been associated with genomic abnormalities, treatment response, and differences in tumor microenvironment. We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical, a revision of the previously reported TCGA subtypes. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and the presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Comparison of matching primary and recurrent gliomas elucidated treatment-induced phenotypic tumor evolution, including expression subtype switching, in 45% of our cohort as well as associations between microenvironmental components and treatment response. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence was associated with CD8+ T cell enrichment. Frequency of M2 macrophage detection was associated with short-term relapse after radiation therapy. Our study provides a comprehensive transcriptional and cellular landscape of IDH wild-type glioblastoma during treatment modulated tumor evolution. Characterization of the evolving glioblastoma transcriptome and tumor microenvironment aids in designing more effective immunotherapy trials.

We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ Tcell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.