Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Effect of garlic essential oil in 97 patients hospitalized with covid-19: A multi-center experience.

To observe the synergistic effect of garlic essential oil in patients with novel coronavirus disease (COVID-19), in addition to the routine treatment, we used garlic essential oil in COVID-19 patients with mild to moderate symptoms and compared their results to those of patients who did not receive the essential oil. We conducted a quasi-experimental study with COVID-19 patients from 3 hospitals. In the experimental group, 97 patients received garlic essential oil combined with conventional treatment. In the control group, 100 patients received only the conventional treatment for COVID-19. The effectiveness and safety of the garlic essential oil were assessed. Compared to the control group, the group receiving garlic essential oil showed a shorter duration of symptoms, shorter time to negative nucleic acid testing (NAT) results and shorter time to improvement on the computed tomography (CT). In the same period, the experimental group showed an increase in the rate of the disappearance of symptoms and the improvement rates of NAT and CT. Due to its effectiveness and safety in patients with COVID-19, garlic essential oil is recommended as a preventive measure or a supportive therapy during the COVID-19 pandemic.

Early detection of hepatocellular carcinoma via no end-repair enzymatic methylation sequencing of cell-free DNA and pre-trained neural network.

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC. METHODS: We developed a low DNA damage and high-fidelity methylation detection method called No End-repair Enzymatic Methyl-seq (NEEM-seq). We further developed a read-level neural detection model called DeepTrace that can better identify HCC-derived sequencing reads through a pre-trained and fine-tuned neural network. After pre-training on 11 million reads from NEEM-seq, DeepTrace was fine-tuned using 1.2 million HCC-derived reads from tumor tissue DNA after noise reduction, and 2.7 million non-tumor reads from non-tumor cfDNA. We validated the model using data from 130 individuals with cfDNA whole-genome NEEM-seq at around 1.6X depth. RESULTS: NEEM-seq overcomes the drawbacks of traditional enzymatic methylation sequencing methods by avoiding the introduction of unmethylation errors in cfDNA. DeepTrace outperformed other models in identifying HCC-derived reads and detecting HCC individuals. Based on the whole-genome NEEM-seq data of cfDNA, our model showed high accuracy of 96.2%, sensitivity of 93.6%, and specificity of 98.5% in the validation cohort consisting of 62 HCC patients, 48 liver disease patients, and 20 healthy individuals. In the early stage of HCC (BCLC 0/A and TNM I), the sensitivity of DeepTrace was 89.6 and 89.5% respectively, outperforming Alpha Fetoprotein (AFP) which showed much lower sensitivity in both BCLC 0/A (50.5%) and TNM I (44.7%). CONCLUSIONS: By combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications. DeepTrace: https://github.com/Bamrock/DeepTrace.

A visual method for determination of hepatitis C virus RNAs based on a 3D nanocomposite prepared from graphene quantum dots.

Sensitive and specific assay of hepatitis C virus (HCV) RNA has a great clinical significance for the diagnosis of hepatitis C in window period. A colorimetric assay is described for determination of the RNA of hepatitis C virus. The method is based on the in situ synthesis of graphene quantum dot-silver nano-composites (GQD/Ag NCs), magnetic separation and catalyzed hairpin assembly reaction (CHA). The silver component of GQD/Ag NCs react with H2O2 generated by glucose oxidase, which are induced via CHA. Then the light-yellow solution turns into colorless transparent in the presence of the target RNAs. The method has a linear response in the 25-500 pM RNA concentration range, and the detection limit is 24.84 pM. The method is simple, stable and sensitive and might be extend to the assay of other RNA viruses. The retro-transcription free and visual distinguishable properties endow this strategy a promising application in the screening of HCV.

Hepatic venous pressure gradient (HVPG) predicts liver failure after transjugular intrahepatic portal shunt: a retrospective cohort study.

Background: Esophagogastric variceal bleeding is a serious complication of decompensated cirrhosis. Transjugular intrahepatic portal shunt (TIPS) is a salvage treatment with clear hemostatic results. However, various complications may occur after TIPS, including postoperative liver failure, and the prognosis is very poor once occurs. Liver failure is a common symptom of severe liver disease with a high mortality rate. This study investigated the incidence of liver failure after TIPS treatment for varicose bleeding. Methods: We analyzed the data of patients admitted to the First Affiliated Hospital of Soochow University between January 2013 and December 2018 with portal hypertension with an episode of acute gastroesophageal variceal bleeding. A total of 121 patients were referred to the regional liver unit for TIPS. Hepatic venous pressure gradient (HVPG) and clinical data were collected. Patients with incomplete data were excluded, and 93 patients were ultimately enrolled in the study. Primary outcomes were morbidity and hospital mortality within 4 weeks of surgery. The data were retrospectively and consecutively collected and evaluated by univariate and multivariate analyses to identify risk factors of liver failure. Results: The patients included 58 males (62.37%) and 35 females (37.63%), and the mean age was 58.43±11.85 years. The main cause was hepatitis B virus (HBV), which was found in 50.54% of patient. The overall surgical success rate was 83.87% (78/93). Of 15 treatment-failure patients, 9 (9.68%) died in hospital. Four patients died of liver failure, accounting for 44.44% of postoperative all-cause deaths. Univariate logistic regression analysis showed that only hepatic venous pressure gradient (HVPG) was an independent risk factor for post-TIPS morbidity [relative risk (RR) 1.156; 95% confidence interval (CI): 1.041 to 1.283; P=0.006]. In addition, HVPG was an independent risk factor for hospital mortality within 4 weeks (RR 1.133; 95% CI: 1.021 to 0.539; P=0.016). Conclusions: Post-TIPS liver failure is a serious complication in patients with cirrhosis. Pre-TIPS HVPG level may be used as a predictor of potential short-term postoperative adverse events.

Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways.

In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg(-1)) and dexamethasone (2 mg·kg(-1)), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg(-1) markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.