Clinical and radiographic characteristics, management and short-term outcomes of patients with COVID-19 in Wenzhou, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging viral disease. Here, we report the clinical features, management, and short-term outcomes of COVID-19 patients in Wenzhou, China, an area outside Wuhan. METHODS: Patients admitted to the Infectious Diseases Department of Ruian People's Hospital in Wenzhou, from January 21 to February 7, 2020, were recruited. Medical data on epidemiological history, demographics, clinical characteristics, laboratory tests, chest computerized tomography (CT) examination, treatment, and short-term outcomes were retrospectively reviewed. Blood biochemistry and routine tests were examined using standard methods and automatic machines. CT examination was performed several times during hospitalization as necessary. RESULTS: A total of 67 confirmed COVID-19 cases were diagnosed; 64 (95.4%) were common cases and three (4.5%) were severe cases. The most common symptoms at admission were fever (86.6%), cough (77.6%), productive cough (52.2%), chest distress (17.9%), and sore throat (11.9%), followed by diarrhea (7.4%), headache (7.4%), shortness of breath (6.0%), dizziness (4.5%), muscular soreness (4.5%), and running nose (4.5%). Thirty patients (47.8%) had increased C-reactive protein levels. The CT radiographs at admission showed abnormal findings in 54 (80.6%) patients. The patients were treated mainly by oxygen therapy and antiviral drugs. By March 3, 2020, all 67 patients completely recovered and had negative nucleic acid tests. The patients were discharged from the hospital and transferred to a medical observation isolation center for further observation. CONCLUSION: Cases of COVID-19 in Wenzhou are milder and have a better prognosis, compared to those in Wuhan. Timely and appropriate screening, diagnosis, and treatment are the key to achieve good outcomes.

Long noncoding RNA hypoxia-inducible factor 1 alpha-antisense RNA 1 promotes tumor necrosis factor-α-induced apoptosis through caspase 3 in Kupffer cells.

Kupffer cells (KCs) play a crucial role in the pathogenesis of acute-on-chronic liver failure (ACLF) which is characterized by acute and severe disease in patients with preexisting liver disease and shows high mortality. Long noncoding RNAs (lncRNAs) are recently found to be involved in gene regulation. However, the mechanisms of how KCs are regulated by inflammatory factors, tumor necrosis factor-α (TNF-α), and whether lncRNAs are involved in the process remain largely unknown. Hence, we investigated the role of lncRNAs in the cytotoxicity of TNF-α on KCs.lncRNA array (The lncRNAs in the array are apoptosis-related lncRNAs reported in some research papers.) was used to identify lncRNAs related with liver fibrosis. Annexin V/protease inhibitor (PI) staining was used for detection of cell apoptosis. Real time-polymerase chain reaction was utilized for analysis of mRNA levels of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 1 (HIF1A-AS1) and apoptosis-related genes. Western blot was implied to the determination of lymphoid enhancer factor-1 (LEF-1).In this study, we found that HIF1A-AS1 could be upregulated by TNF-α by lncRNA array analysis and knockdown of HIF1A-AS1 significantly rescued cell apoptosis induced by TNF-α. Moreover, inhibition of HIF1A-AS1 markedly reduced mRNA level of caspase 3 which can be significantly enhanced by TNF-α. Furthermore, HIF1A-AS1 showed binding sites for LEF-1 and siRNA-mediated downregulation of LEF-1 decreased HIF1A-AS1 level in KCs treated with TNF-α.This study elucidates a new role of HIF1A-AS1 in TNF-α-induced cell apoptosis and provides potential therapeutic targets for ACLF.

A novel system for predicting liver histopathology in patients with chronic hepatitis B.

There is currently a lack of reliable, reproducible, and easily applied methods for assessing changes in liver histology in patients in the gray zone phase of chronic hepatitis B (CHB). Therefore, we aimed to develop a novel predictive scoring system to detect significant liver histological changes in these patients.A total of 388 patients in the gray zone phase of CHB who underwent liver biopsy were divided into a training group and a validation group, and their clinical and routinely available laboratory parameters were analyzed using univariate analysis, Spearman correlation analysis, and logistic modeling. A novel scoring system, termed the Significant Histological Model (SHM), was constructed using logistic modeling. The diagnostic accuracy of our novel scoring system was evaluated by the receiving operating characteristic (ROC) method, sensitivity, specificity, and positive and negative predictive values (NPVs).We established the novel SHM scoring system using serum aspartate transaminase (AST), platelet counts (PLTs), albumin (ALB), and hepatitis B virus (HBV) DNA (log10 IU/mL) levels. The area under the ROC curve of the SHM scoring system was 0.763 in the training group and 0.791 in the validation group. For patients with a score of -1.0 or less and no significant histological changes, the sensitivity was 78.9%, specificity was 51.5%, positive predictive value (PPV) was 46.4%, and NPV was 82.0%. In the validation set, the sensitivity, specificity, PPV, and NPV were 80.0%, 66.6%, 56.3%, and 86.2%, respectively.This novel scoring system using AST, PLT, ALB, and HBV DNA (log10 IU/mL) levels identifies patients in the gray zone phase of CHB with and without histological changes with a high degree of accuracy. Here, we provide the experimental basis for the initiation of clinical antiviral treatment without the need for liver biopsy.

New role and molecular mechanism of Gadd45a in hepatic fibrosis.

AIM: To investigate the role of Gadd45a in hepatic fibrosis and the transforming growth factor (TGF)-ß/Smad signaling pathway. METHODS: Wild-type male BALB/c mice were treated with CCl4 to induce a model of chronic liver injury. Hepatic stellate cells (HSCs) were isolated from the liver of BALB/c mice and were treated with small interfering RNAs (siRNAs) targeting Gadd45a or the pcDNA3.1-Gadd45a recombinant plasmid. Cellular α-smooth muscle actin (α-SMA), ß-actin, type I collagen, phospho-Smad2, phospho-Smad3, Smad2, Smad3, and Smad4 were detected by Western blots. The mRNA levels of α-SMA, ß-actin, and type I collagen were determined by quantitative real-time (qRT)-PCR analyses. Reactive oxygen species production was monitored by flow cytometry using 2,7-dichlorodihydrofluorescein diacetate. Gadd45a, Gadd45b, anti-Gadd45g, type I collagen, and SMA local expression in liver tissue were measured by histologic and immunohistochemical analyses. RESULTS: Significant downregulation of Gadd45a, but not Gadd45b or Gadd45g, accompanied by activation of the TGF-ß/Smad signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl4 treatment. Overexpression of Gadd45a reduced the expression of extracellular matrix proteins and α-SMA in HSCs, whereas transient knockdown of Gadd45a with siRNA reversed this process. Gadd45a inhibited the activity of a plasminogen activator inhibitor-1 promoter construct and (CAGA)9 MLP-Luc, an artificial Smad3/4-specific reporter, as well as reduced the phosphorylation and nuclear translocation of Smad3. Gadd45a showed protective effects by scavenging reactive oxygen species and upregulating antioxidant enzymes. CONCLUSION: Gadd45a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-ß/Smad signaling.

Combination lamivudine and adefovir versus entecavir for the treatment of naïve chronic hepatitis B patients: a pilot study.

BACKGROUND: The aim of this study was to compare the effect of combination lamivudine (LAM) and adefovir dipivoxil (ADV) versus entecavir (ETV) monotherapy for naïve HBeAg-positive chronic hepatitis B (CHB) patients. MATERIAL/METHODS: Fifty enrolled patients with CHB were evenly divided into 2 groups: a group treated with of lamivudine (LAM) (100 mg/day) plus adefovir (ADV) (10 mg/day) combination, and a group treated with entecavir (ETV) (0.5 mg/day). Serum levels of ALT, AST, creatinine, bilirubin, HBsAg, HBeAg and HBV viral load, and genotypic resistance were analyzed at 0, 12, 24, 52, and 104 weeks. HBV DNA levels were determined by real-time PCR and HBsAg and HBeAg by chemiluminescence. Serum levels of ALT, AST, creatinine, and bilirubin were measured by an automatic biochemical analyzer. Data analysis was performed with SPSS 12.0 software. RESULTS: There were no significant differences in the virological response (VR) rates between LAM+ADV and ETV cohorts at 24, 52, and 104 weeks (P>0.05). The HBeAg seroconversion rates were 28% and 20%, and the biochemical response (BR) rates were 88% and 84% at week 104 in the LAM+ADV and ETV groups, respectively. The rates of undetectable HBV DNA, HBeAg seroconversion, and ALT normalization rates were similar in both cohorts. No virological breakthrough or serious adverse effects were noted for any patient during the study period. CONCLUSIONS: Both LAM+ADV combination therapy and ETV monotherapy were effective and safe in the treatment of -naïve HBeAg-positive CHB patients. However, further studies are needed to obtain long-term results.