Li-Yao Zhu

Hepatitis C virus (HCV) infection is a major global health issue, associated with various metabolic disorders, including type 2 diabetes mellitus (T2DM). This study explores the impact of direct-acting antiviral agents (DAAs) on diabetes management in patients coinfected with HCV and T2DM. This study comprised a cross-sectional analysis of NHANES database (1999–2018) participants with HCV antibody-positive status and a retrospective cohort of T2DM patients achieving sustained virological response after DAAs treatment at The Fourth Hospital of Huai’an (2020–2023). We conducted Mendelian randomization analysis using expression Quantitative Trait Loci data (eQTLGen, GTEx) and protein quantitative trait loci data (Iceland Protein, UK Biobank) of DAAs target genes from blood and liver samples. The cross-sectional NHANES analysis assessed antiviral therapy effects on diabetes indicators, while the retrospective study evaluated changes in hemoglobin A1c (HbA1c) and fasting glucose at 6, 12, and 18 months post-DAA treatment. Mendelian randomization highlighted the potential role of the CXCL10 gene in modulating HbA1c levels. The cross-sectional NHANES study found no significant associations between interferon/ribavirin use and diabetes indicators. In the retrospective study, significant short-term improvements in HbA1c and fasting glucose were observed within 6 months of DAA therapy; however, these were not sustained over 12 to 18 months. Notably, patients with cirrhosis or abnormal BMI showed no short-term metabolic improvements. The study underscores the transient nature of the metabolic improvements following HCV eradication in T2DM patients and stresses the importance of comprehensive management strategies to sustain glycemic control in the long term.

Background: To investigate the predictive values of cytokeratin 18 for liver fibrosis in hepatitis C virus (HCV) infected patients with type 2 diabetes mellitus (T2DM). Methods: 252 HCV-infected patients with T2DM between January 2012 and August 2017 were retrospectively reviewed. Pearson/spearman correlation analysis was used to detect the correlation in the entire cohort. Multivariate linear regression was used to identify independent predictors and logistic regression was for establishing models. Combination models that incorporated CK18 and other methods (i.e. transient elastography, aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4)] were developed in a training cohort of 132 patients. Performance of models was evaluated through discrimination ability and clinical benefits. An internal validation was conducted in 120 consecutive patients. Results: CK18 was found significantly associated with fibrosis scores (r = 0.452, P < .001). CK18 and albumin were confirmed as independent predictors for fibrosis. For predicting significant fibrosis in the validation cohort, the observed AUC values of APRI + CK18 (AUC 0.83) and FIB-4 + CK18 (AUC 0.84) were higher than those of APRI (AUC 0.61) and FIB-4 (AUC 0.65). For predicting advanced fibrosis and cirrhosis, the AUC values of FIB-4 + CK18 (AUC 0.74 and 0.77, respectively) were significantly higher than those of FIB-4 (AUC 0.61 of both). Decision curve analysis confirmed the more clinical benefits can be provided by being combined with CK18. Conclusions: CK18 is an independent predictor of liver fibrosis for HCV-infected patients with T2DM. Noninvasive methods incorporate CK18 and other biomarker indices can have better performance for diagnosing fibrosis and help clinical decision-making.

(Aim) COVID-19 pandemic causes numerous death tolls till now. Chest CT is an effective imaging sensor system to make accurate diagnosis. (Method) This paper proposed a novel seven layer convolutional neural network based smart diagnosis model for COVID-19 diagnosis (7L-CNN-CD). We proposed a 14-way data augmentation to enhance the training set, and introduced stochastic pooling to replace traditional pooling methods. (Results) The 10 runs of 10-fold cross validation experiment show that our 7L-CNN-CD approach achieves a sensitivity of 94.44±0.73, a specificity of 93.63±1.60, and an accuracy of 94.03±0.80. (Conclusion) Our proposed 7L-CNN-CD is effective in diagnosing COVID-19 in chest CT images. It gives better performance than several state-of-the-art algorithms. The data augmentation and stochastic pooling methods are proven to be effective.

To evaluate the risk of first upper gastrointestinal bleeding by computerized tomoscanning (CT) for esophageal varices patients with cirrhotic portal hypertension.One hundred thirty two esophageal varices patients with cirrhotic portal hypertension who are also complicated with gastrointestinal bleeding were recruited as bleeding group, while another 132 patients without bleeding as non-bleeding group. The diameter of esophageal varices, number of vascular sections, and total area of blood vessels were measured by CT scanning. The sensitivity and specificity of these indicators were calculated, and Youden index was adjusted with the critical point.The diameter of esophageal varices was 7.832.76mm in bleeding group, and 6.57 +/- 3.42mm in non-bleeding group. The Youden index was 0.32 with the critical point 5.55mm. The area under the receiver operating characteristics (AUROC) was 0.72. The number of venous vessels was 4.5 +/- 2 in bleeding group, whereas being 4 +/- 2 in non-bleeding group. The Youden index was 0.35 with a critical point 4, and the area under the curve (AUC) was 0.68. The blood vessel area was 1.73 +/- 1.15cm(2) in bleeding group, and 1.12 +/- 0.89cm(2) in non-bleeding group. The Youden index was 0.48 with the critical point being 1.03cm(2), and corresponding AUC was 0.82.Among all 3 indicators of the total area, diameter, and number of sections of the esophageal varices, the total area of esophageal varices showed more accuracy as a potential and novel indicator for bleeding prediction.

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR‐1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull‐down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR‐1301, and it was shown that miR‐1301 mimics significantly suppressed STAT3 in HCC cells. Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR‐1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR‐1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.

Objective: To investigate the correlation between serum protein level of insulin growth factor 1 (IGF‐1) and the degree of liver fibrosis in patients with chronic hepatitis C (CHC) combined with type 2 diabetes mellitus (T2DM).Methods: The cases are divided into four groups. Then serum levels of IFG‐1, alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C virus (HCV) RNA, and HCV genotypes were detected simultaneously in patients with hepatitis C, liver stiffness measurement (LSM) was measured by transient elastography, and aspartate aminotransferase platelet ratio (APRI) score was determined.Results: There was no significant difference between CHC with T2DM group and CHC group in diabetes family history (P > 0.05), but the difference between the two groups were significantly lower than that of T2DM group ( P < 0.05). The levels of fasting insulin and homeostatic model assessment of insulin resistance (HOMA‐IR) in CHC group with T2DM group were significantly higher than those in the other two groups ( P < 0.05), while the IGF‐1 RNA and the serum protein level in the two groups were significantly lower than those in the CHC group, and were lower than those in the control group ( P < 0.05). The level of serum IGF‐1 was negatively correlated with HOMA‐IR, LSM, and APRI score in CHC with T2DM group ( r = −0.71, −0.75, and −0.69; P < 0.01).Conclusion: The degree of hepatic fibrosis in patients with CHC combined with T2DM was higher than that in non‐T2DM patients with CHC, which was mainly related to insulin resistance (IR) induced by 1b genotype HCV infection. IR can lead to impaired synthesis of IGF‐1, and the degree of damage has a corresponding relationship with hepatic fibrosis.

Purpose: To further observe and verify the effect of nonalcoholic fatty liver disease (NAFLD) on the response to antiviral therapy in patients with chronic hepatitis B (CHB) and investigate the relationship between the virologic response and insulin resistance. Patients and methods: A retrospective study was adopted and 61 NAFLD patients with HBeAg-positive CHB were included as the observation group (group A), and 64 patients with simple CHB were included as the control group (group B). Results: After 12 weeks of treatment with entecavir, the total virologic response rate in group A was statistically significantly lower than that in group B (P0.05). In weeks 48 and 96, there was no significant difference in the HBeAg seroconversion rates between the two groups (P>0.05). In weeks 12 and 24, there was also no significant difference in the alanine transaminase (ALT) normalization rate between the two groups (P>0.05). Then, in weeks 48 and 96, the ALT normalization rate of group A was obviously lower than that of group B (PM) according to the median value (M=2.79) of the baseline homeostatic model assessment method insulin resistance levels. In weeks 48 and 96, the ALT normalization rate of group A1 was significantly higher than that of group A2 (Pr) of the baseline homeostatic model assessment method insulin resistance level and the severity of fatty liver in group A was 0.426 (P=0.001). Conclusion: NAFLD cannot affect the long-term total virologic response rate and HBeAg seroconversion rate in CHB patients treated with entecavir but can reduce the long-term biochemical response rate, which has a positive correlation with the severity of fatty liver and the insulin resistance index.

Liver cancer is one of the most common malignant tumors, and most of which is hepatocellular carcinoma (HCC). We aim to study the characteristic changes of numerous genes and their roles in HCC through systematical analysis of the characteristics of expression spectrum of HCC. Firstly, we made systematic clustering of the HCC samples according to the RNAseq data from TCGA (The Cancer Genome Atlas) and newly classified HCC. Then the characteristic genes in different molecular subtypes were found out and further analyzed combing with methylation and SNP 6.0 chip. Finally, these genes were subjected to do functional annotation and abnormal signaling pathways of HCC in various molecular subtypes and were screened out. There were 3843 differential genes screened; among which, 689 genes were enriched into 13 KEGG-related pathways, and the expression of 27 and 924 genes showed positive and negative correlation to methylation level, respectively, while the expression of 43 genes showed positive correlation to variation level of copy number. The methylation degree of ZSCAN18 may be considered as a marker for prognosis evaluation, and ABHD6 could be a potential anti-oncogene.

Objective: To investigate effects of hydrogen‐rich water (HRW) on oxidative stress, liver function and HBV DNA in patients with chronic hepatitis B (CHB).Methods: Sixty patients with CHB were randomly assigned into routine treatment group or hydrogen treatment group in which patients received routine treatment alone or additional oral HRW (1200–1800 mL/day, twice daily), respectively, for 6 consecutive weeks. Serum oxidative stress, liver function, and HBV DNA level were detected before and after treatment. Thirty healthy subjects served as controls.Results: When compared with controls, oxidative stress was obvious in CHB patients, and the liver function also significantly impaired. After treatment, the oxidative stress remained unchanged in routine treatment group, but markedly improved in hydrogen treatment group. The liver function was improved significantly and the HBV DNA reduced markedly after corresponding treatments. Although a significant difference was noted in the oxidative stress between two groups after treatment, the liver function and HBV DNA level were comparable after treatment and both had improved tendencies.Conclusion: HRW significantly attenuates oxidative stress in CHB patients, but further study with long‐term treatment is required to confirm the effect of HRW on liver function and HBV DNA level. Clin Trans Sci 2013; Volume #: 1–4