Associations of Urinary Nickel with NAFLD and Liver Fibrosis in the USA: A Nationwide Cross­Sectional Study.

Despite the robust correlation between metabolic disorders and heavy metals, there has been limited research on the associations between nickel levels and non-alcoholic fatty liver disease (NAFLD) as well as liver fibrosis. This study aimed to examine the associations among urinary nickel, NAFLD, and liver fibrosis. The data utilized in this study were obtained from the National Health and Nutrition Examination Survey 2017-2020. A comprehensive screening process was conducted, resulting in the inclusion of a total of 3169 American adults in the analysis. The measurement of urinary nickel was conducted through inductively coupled-plasma mass spectrometry. Vibration-controlled transient elastography was employed to assess the controlled attenuation parameter and liver stiffness measurement as indicators for NAFLD and liver fibrosis, respectively. Multivariable logistic regression models were employed to evaluate the associations among urinary nickel, NAFLD, and liver fibrosis. Restricted cubic splines were employed to explored the nonlinear associations. After adjusting for all covariates, the correlation between the highest quartile of urinary nickel and NAFLD was found to be significant (OR = 1.65; 95% CI, 1.19-2.27). Subgroup analysis revealed that the correlation was significant only in men. A significant association occurred between the second quartile of urinary nickel and liver fibrosis (OR 1.88; 95% CI, 1.22-2.90). Restricted cubic spline showed that the relationship was linear between urinary nickel and NAFLD and non-monotonic, inverse U-shaped between urinary nickel and liver fibrosis. This cross-sectional study indicated that the risk of NAFLD is associated with urinary nickel, and this correlation was only present among males.

MicroRNA-34a Mediates High-Fat-Induced Hepatic Insulin Resistance by Targeting ENO3.

The etiology of numerous metabolic disorders is characterized by hepatic insulin resistance (IR). Uncertainty surrounds miR-34a's contribution to high-fat-induced hepatic IR and its probable mechanism. The role and mechanism of miR-34a and its target gene ENO3 in high-fat-induced hepatic IR were explored by overexpressing/suppressing miR-34a and ENO3 levels in in vivo and in vitro experiments. Moreover, as a human hepatic IR model, the miR-34a/ENO3 pathway was validated in patients with non-alcoholic fatty liver disease (NAFLD). The overexpression of hepatic miR-34a lowered insulin signaling and altered glucose metabolism in hepatocytes. In contrast, reducing miR-34a expression significantly reversed hepatic IR indices induced by palmitic acid (PA)/HFD. ENO3 was identified as a direct target gene of miR-34a. Overexpression of ENO3 effectively inhibited high-fat-induced hepatic IR-related indices both in vitro and in vivo. Moreover, the expression patterns of members of the miR-34a/ENO3 pathway in the liver tissues of NAFLD patients was in line with the findings of both cellular and animal studies. A high-fat-induced increase in hepatic miR-34a levels attenuates insulin signaling and impairs glucose metabolism by suppressing the expression of its target gene ENO3, ultimately leading to hepatic IR. The miR-34a/ENO3 pathway may be a potential therapeutic target for hepatic IR and related metabolic diseases.

Treatment response and safety of immunotherapy for advanced non-small cell lung cancer with comorbid chronic obstructive pulmonary disease: a retrospective cohort study.

Background: Immunotherapy has provided a novel therapeutic option for lung cancer but studies involving patients with advanced non-small cell lung cancer (NSCLC) coupled with various degrees of comorbid chronic obstructive pulmonary disease (COPD) are limited. Thus, we performed a retrospective cohort study to optimize the use of immunotherapy in this special population. Methods: We enrolled a total of 99 patients with advanced (stage IIIB/C-IV) NSCLC with comorbid COPD who had received immune checkpoint inhibitors (ICIs) according to the inclusion and exclusion criteria. They were divided into four groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline criteria as follows: no COPD group (n1=19), mild COPD group (n2=24), moderate COPD group (n3=31), and severe COPD group (n4=25). Routine blood, imaging characteristics, related cytokines including interleukin (IL)-6, IL-8, IL-10, etc., Krebs Von den Lungen (KL)-6, and corresponding indicators of immune-related adverse events (irAEs), incidence of irAEs, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were recorded and analyzed. Comparability of baseline factors above and clinical characteristics were evaluated. Results: There were statistically significant differences in the incidence of irAEs among the four groups (P=0.003). The incidence of irAEs in patients with no COPD (n1, 21.1%) and mild to moderate COPD (n2/3, 8.3%, 32.3%) was lower than that in patients with severe COPD (n4, 56.0%) (P=0.003). The median PFS of the mild to moderate COPD group was significantly longer than the severe COPD group (19.0 vs. 8.00 months, log-rank P=0.004). A significant increase of both ORR (P=0.004) and DCR (P=0.037), as well as higher IL-6 (P=0.000), IL-8 (P=0.026), and IL-10 (P=0.010) levels, have been observed in the mild to moderate COPD group compared with severe COPD group. IL-6 level was an independent factor influencing PFS [P=0.007, 95% confidence interval (95% CI): 1.000-1.002] and COPD grading was an independent predictor of irAEs (P=0.037, 95% CI: 1.035-3.039). Conclusions: Immunotherapy should be selected with caution for advanced NSCLC patients with comorbid severe COPD, considering the limited efficacy and the increased risk of immune-related adverse events related to the immune-checkpoint inhibitors administration in this special population.

Relationship between leisure-time physical activity and depressive symptoms under different levels of dietary inflammatory index.

Depressive symptoms are major public health problems. Leisure-time Physical activity (LPA) and dietary inflammatory preference are emerging factors that tends to affect the mental health status. There is limited evidence regarding the joint influence of LPA and dietary status on the prevalence of depression. This study was a cross-sectional study, which used a nationwide represented sample from the National Health and Nutrition Examination Survey (NHANES) to assess the relationship among LPA, diet status and depression. Depression and LPA status was reported by the 9-item Patient Health Questionnaire (PHQ-9) and Physical Activity Questionnaire (PAQ), respectively. To assess dietary inflammatory preferences, dietary inflammatory index (DII) was applied based on a 24-h dietary recall interview. A total of 11,078 subjects was included in this study and weighted participants were 89,682,020. Weighted multivariable linear regression showed that DII was negatively associated with LPA after full adjustment, with ß (95% CI): -0.487 (-0.647, -0.327). Weighted multivariable logistic regression showed that LPA was significantly associated with depressive symptoms after full adjustment, with odds ratios OR (95% CIs): 0.986 (0.977, 0.995). By DII stratification analysis, this phenomenon was also existed in groups with anti-inflammatory diet. Mediation effect analysis was further performed, which showed that DII significantly mediating the association between LPA and depression with proportion mediated as 3.94%. Our findings indicated the mediating role of DII in the association between LPA condition and incident depression. More well-designed studies are still needed to validate the causal relationship.

Maternal Anxiety Symptoms and Chinese Adolescents' Mental Health During the COVID-19 Pandemic: The Protective Role of Adolescents' Self-Compassion.

The COVID-19 outbreak triggered dramatic changes to family life. Parents, especially mothers, were found to experience more psychological distress during the pandemic, which may have had an impact on their children's mental health. The primary goal of this study was to examine the potential protective role of adolescents' self-compassion in the relationship between maternal anxiety and adolescents' mental health during the COVID-19 pandemic. Participants included 5,720 adolescents (48.9% girls; M age = 11.60, SD age = 1.36) and their mothers from Zhengzhou city, Henan province, in Mainland China. Adolescents reported their level of self-compassion, PTSD symptoms, and negative affect during the COVID-19 pandemic. Mothers reported their own anxiety symptoms and their children's depression and anxiety symptoms. Results indicated that older female adolescents reported higher levels of PTSD symptoms and negative affect and lower levels of self-compassion than their counterparts. Maternal anxiety during the COVID-19 pandemic was consistently positively associated with adolescents' psychological maladjustment. These associations were buffered by adolescents' self-compassion. Specifically, adolescents with higher levels of self-compassion were found to be less psychologically affected by their mothers' anxiety during the COVID-19 pandemic. Findings highlighted the possibility of improving adolescents' mental health through fostering their self-compassion during the COVID-19 pandemic.

Randomized phase III study comparing the first-line chemotherapy regimens in patients with driver mutation-negative advanced non-small cell lung cancer and poor performance status complicated with chronic obstructive pulmonary disease.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD) with poor performance status (PS) are common in clinical practice with few related studies. Present studies have found that weekly low-dose docetaxel or gemcitabine combined with platinum is suitable for elderly or poor PS patients with advanced NSCLC. METHODS: Untreated advanced driver mutation-negative NSCLC patients with COPD and PS ≥2 were enrolled in this double-blind randomized trial. Both groups controlled their COPD symptoms according to the GOLD guidelines. The anti-tumor regimens included docetaxel (37.5 mg/m2, D1, D8)/carboplatin (AUC 5.0) (DC group) and gemcitabine (1,000 mg/m2, D1, D8)/carboplatin (AUC 5.0) (GC group) were used every 3 weeks with continuous chemotherapy for 4-6 cycles or until disease progression. The primary endpoints were progression-free survival (PFS), and overall survival (OS). RESULTS: Among the 52 patients (DC, n=25; GC, n=27), the median follow-up time was 12.3 months. There was no significant difference in tumor overall response rate (ORR; DC, 20.0% vs. GC, 22.2%, P=0.845) and disease control rate (DCR; DC, 72.0% vs. GC, 74.1%, P=0.064) between the 2 groups. The median PFS (GC, 6.5 vs. DC, 5.5 months; P=0.296) and the median OS (GC, 14.9 vs. DC, 12.3 months; P=0.548) of the GC group was slightly longer than the DC group. The main adverse reactions were myelosuppression and there were few adverse reactions of grade 3-4. Compared with the anti-tumor therapy only group in previous literature, the median PFS in this study was longer (6.2 months, 95% CI: 3.533-6.733 vs. 3.5 months, 95% CI: 2.432-4.568; P=0.589). There was also no significant difference in median OS and median PFS between the 2 groups (14.0 vs. 15.0 months, P=0.718). Chemotherapy cycle (P<0.001) was an independent prognostic factor for PFS, while chemotherapy cycle (P=0.011) and PS (P=0.041) were independent prognostic factors for OS. CONCLUSIONS: Weekly low-dose docetaxel or gemcitabine combined with carboplatin chemotherapy regimens can yield survival benefits and a tolerable safety profile in patients with driver mutation-negative advanced NSCLC and poor PS complicated with COPD, with no significant difference between the two regimens. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-15006164.

Moderately decreasing fertilizer in fields does not reduce populations of cereal aphids but maximizes fitness of parasitoids.

Examination of the tradeoff between the extent of decreasing nitrogen input and pest suppression is crucial for maintaining the balance between essential yield and an efficient, sustainable pest control strategy. In this study, an experiment with four manipulated nitrogen fertilizer levels (70, 140, 210, and 280 kg N ha-1 = conventional level) was conducted to explore the effects of decreasing nitrogen on cereal aphids (Sitobion avenae and Rhopalosiphum padi) (Hemiptera: Aphididae), Aphidiinae parasitoids (Hymenoptera: Braconidae: Aphidiinae), and body sizes of parasitoids. The results indicated that nitrogen application, in the range of 70-280 kg N ha-1, has the potential to impact the populations of cereal aphids and their parasitoids. However, both differences between densities of cereal aphids and their parasitoids in moderate (140-210 kg N ha-1) and those in high nitrogen input (280 kg N ha-1) were not significant, and the parasitism rate was also unaffected. A higher parasitism rate reduced population growth of the cereal aphid (S. avenae). Additionally, a moderate decrease of nitrogen fertilizer from 280 to 140-210 kg N ha-1 maximized the body sizes of Aphidiinae parasitoids, indicating that a moderate decrease of nitrogen fertilizer could facilitate biocontrol of cereal aphid by parasitoids in the near future. We conclude that a moderate decrease in nitrogen application, from 280 to 140-210 kg N ha-1, does not quantitatively impact the densities of cereal aphids or the parasitism rate but can qualitatively maximize the fitness of the parasitoids.