MiR-155 regulates M2 polarization of hepatitis B virus-infected tumour-associated macrophages which in turn regulates the malignant progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) initiated by hepatitis B virus (HBV) infection is a complicated process. MiR-155 can alter the immune microenvironment to affect the host's anti-infective ability. This study investigated the mechanism by which miR-155 affects tumour-associated macrophage (TAM) polarization at a molecular level, thus affecting the malignant progression of HBV+ HCC. MiR-155 and TAM-related cytokine expression were analysed by qRT-PCR. The distribution of TAMs was detected by immunohistochemistry. The effect of the aberrant miR-155 expression on macrophage polarization was examined by flow cytometry. The targeted relationship was verified by dual-luciferase assay, and the protein level of src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was detected by western blot. The proliferation of HCC cells was examined by CCK-8 and colony formation assays. Invasion and migration of HCC cells were detected by transwell assay. In HBV+ HCC tissues, miR-155 was significantly highly expressed and the number of CD206-positive TAM (CD206+ TAM) and CD68-positive TAM (CD68+ TAM) were higher than those in HBV- HCC tissues. In addition, miR-155 overexpression significantly promoted M2-type macrophage polarization, whilst miR-155 silencing expression significantly promoted M1-type macrophage polarization. Besides, the miR-155/SHIP1 axis accelerated HCC cell invasion, proliferation and migration by inducing M2-type macrophage polarization. MiR-155 accelerates HCC cell proliferation, migration and invasion by targeting SHIP1 expression and inducing macrophage M2 polarization. This finding provides new insights into the development of novel therapeutic strategies for combatting HBV+ HCC and a new reference for exploring anti-tumour immunotherapy.

Inactivated vaccines prevent severe COVID-19 in patients infected with the Delta variant: A comparative study of the Delta and Alpha variants from China.

The Delta variant has gradually replaced the Alpha variant as the major strain of SARS-COV-2 infection worldwide. We extracted the clinical characteristics and outcomes information about 381 hospitalized patients infected with Delta variant and compared them with 856 patients diagnosed with Alpha variant infection in Zhejiang Province. The majority (85.3%) of patients infected with the Delta variant had received inactivated vaccine. The patients' condition was generally mild. Most of them were mild (35.7%) and common (62.7%) types. Only six patients (1.5%) were severe/critical types. During the follow-up period, patients infected with the Delta variant had longer hospital stays than the Alpha variant (24 [21-26] vs. 18 [14-24], p < 0.001). In addition, the unvaccinated patients infected with the Delta variant had a higher proportion of severe/critical cases than vaccinated patients (11.11% vs. 0.92%, p = 0.024) and a higher usage rate of glucocorticoids (38.89 vs. 14.77%, p = 0.017) and antibiotics (55.56% vs. 32.31%, p = 0.042) during hospitalization. The vaccine's efficacy against severe COVID-19 did not diminish over time for patients who received two doses of the inactivated vaccine. The disease types and clinical manifestations were generally mild in patients infected with the Delta variant, possibly associated with widespread vaccination with inactivated vaccines in China.

Association of single nucleotide polymorphisms in the nuclear respiratory factor-2 beta subunit-encoding the GABPB1 gene within the occupational environment.

GABPB1, known as nuclear respiratory factor 2 (Nrf2), activates the mitochondrial genes that are responsible for antioxidant action and detoxification. Two single nucleotide polymorphisms (SNPs) of GABPB1, such as rs7181866 and rs8031031, were reported to be associated with the prevention of the increasing cancer risk caused by environmental deterioration. Between March 1 and May 1, 2018, human peripheral blood mononuclear cells (PBMCs) from a cohort of 300 volunteers working in adverse occupational environments were genotyped for the two SNPs in the present study. The SNP rs7181866 was found to be significantly greater in the male group than in the female group. Frequencies of SNP rs7181866 and bi-allele SNPs (rs7181866 + rs8031031) were significantly different between the <35-year-old group and the ≥35-year-old group. Further, multinomial logistic regression analysis of the occupational environments revealed the highest predictive frequency of SNPs for four environmental factors, of which chemical factors accounted for 15.33% rs7181866, physical factors accounted for 34.79% rs7181866 + rs8031031, physical + chemical factors accounted for 39.5% rs8031031, and unknown factors accounted for 26.5% rs7181866 + rs8031031. In conclusion, the G allele of rs7181866 was found to be significantly more susceptible than the rs8031031 allele under adverse occupational environmental factors, and physical factors such as noise, which appear to play vital roles in causing SNP mutations.

Cross-sectional retrospective analysis of clinical characteristics of chronic hepatitis B patients with oral antiviral treatment in eastern China.

BACKGROUND: In China, more than 20 million patients with chronic hepatitis B need antiviral treatment. Side effects of antiviral treatment such as renal complications can be problematic, particularly in an aging population. METHODS: The data were retrospectively extracted from the hospital medical charts of five centers in eastern China from January 1 to December 31, 2018. RESULTS: A total of 8309 patients with CHB was enrolled in this study. The median age of the patients was 46 years. The prevalence of diabetes mellitus, hypertension, and hepatic cirrhosis was respectively 3.49%, 4.42%, and 23.72%. The prevalence of these comorbidities increased with age (P < 0.001). Of the patients with CHB, 5332 had complete renal function results. Among them, patients with an estimated glomerular filtration rate of < 60 mL/min/1.73m2 accounted for 4.14%, and those with proteinuria for 8.33%. According to the definition of chronic kidney disease, the proportion of patients with chronic kidney disease was 11.37%. The prevalence of chronic kidney disease increased with age (P < 0.001). In a multivariate analysis, age group [odds ratio (OR) = 2.387], diabetes mellitus (OR = 1.486), hypertension (OR = 2.557), hepatic cirrhosis (OR = 1.295), and a history of exposure to adefovir dipivoxil (OR = 1.644) were significantly associated with CKD (P < 0.05). Among patients with CKD, 17.66% (107/606) had a history of lamivudine exposure, and 34.65% (210/606) had a history of nucleotide analogue exposure CONCLUSION: The management of Chinese patients with CHB should take into consideration age, previous medication history, and renal impairment.

Comparison of Telbivudine and Entecavir Therapy on Nephritic Function and Drug Resistance in Patients with Hepatitis B Virus-Related Compensated Cirrhosis.

BACKGROUND: To compare the impact of telbivudine (LDT) and entecavir (ETV) administration on nephritic function. METHOD: One hundred thirty patients diagnosed with hepatitis B virus (HBV)-related compensated cirrhosis were randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups. RESULTS: The drug resistance rate was higher following LDT treatment compared to ETV treatment (16.9% vs. 1.5%, P=0.0006). The mean creatinine level decreased compared to baseline in the LDT group (0.81 vs. 0.94 mg/dl, P=0.000). The change in median glomerular filtration rate (eGFR) compared to baseline in the LTD and ETV groups was 22.3 and -3.3, respectively, at 2 years (P=0.000). In patients with mild nephritic injury (eGFR< 90 ml/min/1.73m2), the median eGFR increased by 28.0 ml/min/1.73m2 in the LDT group and decreased by 4.3 ml/min/1.73m2 in the ETV group (p=0.000). The eGFR in 88.5% of patients (23/26) from the LDT group increased > 90 ml/min/1.73m2. The percentage of patients with an eGFR > 90 ml/min/1.73m2 increased from 60.0% to 92.3% in the LDT group and from 64.6% to 69.2% in the ETV group. CONCLUSION: In patients with HBV-related compensated cirrhosis, LDT treatment was more effective in protecting nephritic function and was associated with a higher drug resistance rate, but did not contribute to a better outcome compared with ETV treatment.

miR-202 functions as a tumor suppressor in hepatocellular carcinoma by targeting HK2.

Recent evidence has suggested that microRNAs (miRNAs) can participate in metabolic reprogramming. Additionally, aerobic glycolysis is associated with tumor progression in hepatocellular carcinoma (HCC). In the present study, miRNA (miR)-202 expression levels were found to be significantly lower in HCC tissues compared with the corresponding adjacent non-cancerous tissue samples using reverse transcription-quantitative PCR analysis in 56 patients with HCC. Lower miR-202 expression levels were identified to be associated with tumor size, vascular invasion, Tumor, Node and Metastasis stages and poor overall survival rates in patients with HCC. In vitro, upregulation of miR-202 expression was revealed to significantly suppress the cell glucose uptake, lactate production and cell proliferation in liver cancer cells. In addition, dual luciferase reporter analysis and western blot assays suggested that hexokinase 2 (HK2) was a direct target of miR-202. Upregulation of miR-202 expression could inhibit cell proliferation by regulating HK2 expression in HCC. Therefore, the results from the present study suggested that miR-202 may serve as a potential target for HCC treatment.

Clinical characteristics of 16 patients with COVID-19 infection outside of Wuhan, China: a retrospective, single-center study.

BACKGROUND: Since early December 2019, the 2019 novel coronavirus (COVID-19) has emerged in Wuhan and spread rapidly in China. We aimed to describe the clinical characteristics of hospitalized patients with confirmed COVID-19 infection in Shaoxing, and provide an insight into the treatment of COVID-19 across China and elsewhere. METHODS: In this retrospective, single-center, study, we enrolled 16 patients with laboratory-confirmed COVID-19 admitted to the Affiliated Hospital of Shaoxing University between February 24 and January 25, 2020. Epidemiological, demographic, clinical, laboratory, radiological feature, and treatment data were all collected. Outcomes were followed up until March 16, 2020. RESULTS: Among the 16 patients with COVID-19 infection, 11 patients (68.8%) had traveled or lived in Wuhan or surrounding areas, and 2 (12.5%) patients had exposure to patients with confirmed COVID-19 infection. The average age of the patients was 44.1 (16.5) years, and there were 10 women (62.5%) and 6 men (37.5%). More than half had chronic diseases [9 (56.3%)]. The most common symptoms at onset of COVID-19 infection were fever [12 (75%)] and cough [8 (50%)]; 11 (68.8%) patients had lymphopenia, and 12 (75%) had elevated C-reactive protein. On admission, abnormalities in computed tomography (CT) or chest X-ray images were revealed among all patients, and 11 (68.8%) of 16 patients had bilateral involvement. All patients were given psychological counseling, 15 (93.8%) patients were administered with antiviral therapy, 8 (50%) received empirical antibiotic treatment, and 5 (31.3%) patients were given systematic corticosteroids. Complications included acute respiratory distress syndrome (ARDS) requiring non-invasive mechanical ventilation [1 (6.3%)], acute respiratory injury [4 (25%)], acute renal injury [1 (6.3%)], septic shock [1 (6.3%)], liver dysfunction [5 (31.3%)], electrolyte disturbance [8 (50.0%)], and hospital-acquired pneumonia [3 (18.8%)]. None of the 16 patients died of COVID-19 pneumonia. CONCLUSIONS: Compared with the symptoms of the initial patients with COVID-19 infection in Wuhan, the symptoms of the patients from Shaoxing city were relatively mild. Currently, there is no effective drug treatment or vaccine for COVID-19, and psychological counseling cannot be ignored. Drugs and vaccines against COVID-19 infection need to be developed as soon as possible.