BACKGROUND/OBJECTIVES: Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients. SUBJECTS/METHODS: One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study. RESULTS: Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity.Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSHPx levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function. CONCLUSIONS IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.