Determinants of HPV vaccine uptake intentions in Chinese clinical interns: an extended theory of planned behavior approach.

Background: This study aims to utilize the extended Theory of Planned Behavior (TPB) model to examine the intentions of clinical interns in China towards Human papillomaviruses (HPV) vaccination. It also fills a significant gap in the literature concerning vaccine acceptance in this specific population. Methods: This cross-sectional study was carried out with clinical interns in Shandong Province, China, with a total of 1,619 participants. Data were collected through self-reported questionnaires, including demographic characteristics, TPB variables, and HPV-related health knowledge. Hierarchical regression analysis was employed to identify key factors influencing vaccination intentions, and Structural Equation Modeling (SEM) was used to analyze the interrelationships between these factors. Results: This study initially identified key predictors affecting clinical interns' intentions to receive the HPV vaccine through hierarchical regression analysis. The preliminary model, which accounted for demographic factors, revealed foundational impacts of household income and HPV-related clinical experience on intentions. After integrating TPB variables-attitude, subjective norm, perceived behavioral control, and HPV-related health knowledge-the model's explanatory power was enhanced to 37.30%. SEM analysis focused on the interplay among TPB constructs and extended variables, confirming their significance in forming vaccination intentions, with subjective norm having the most substantial impact (ß = 0.375, p < 0.001). The extended TPB model explained over half of the variance in vaccination intentions, substantiating the hypotheses and revealing the psychological determinants behind clinical interns' decision-making for HPV vaccination. Conclusion: The extended TPB model from this study effectively explains the vaccination intentions among clinical interns for HPV, offering theoretical support for public health strategies and educational interventions targeting this group. These findings are of significant importance for public health practice and future health promotion strategies.

Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis.

Background: Given that immune-related rash was the most frequently reported PD-1 or PD-L1-related skin toxicity, this systematic review and meta-analysis were conducted to elucidate its incidence risk. Methods: The meta-analysis was carried out according to the PRISMA guidelines. The random effect model was used in the process of all analyses. Skin rash of all grades and grades 3-5 were calculated and gathered in the final comprehensive analyses. Results: The study included 86 clinical trials classified into 15 groups. Compared with chemotherapy, PD-1 or PD-L1 inhibitors significantly strengthened the risk of developing rash across all grades (OR = 1.66, 95% CI: [1.31, 2.11]; p < 0.0001). This trend was significantly stronger when the control group was placebo (OR = 2.62, 95% CI: [1.88, 3.65]; p < 0.00001). Similar results were observed when PD-1 or PD-L1 inhibitors were given together with chemotherapy (OR = 1.87, 95% CI: [1.59, 2.20]; p < 0.00001), even in patients with grades 3-5. As with other combination therapies, the risk of developing rash for all grades was enhanced when PD-1 or PD-L1 was given together with chemotherapy as the second-line option (OR = 2.98, 95% CI: [1.87, 4.75]; p=0.05). No statistically significant differences could be found in skin rash between the PD-1 and PD-L1-related subgroups. Conclusion: Whether PD-1 or PD-L1 inhibitors were given alone or together with others, the risk of developing rash would be enhanced. Furthermore, the risk of developing rash appeared to be higher when PD-1 or PD-L1 inhibitors together with other antitumor drugs were given as the second-line options. No statistically significant results of developing rash between PD-1 and PD-L1 subgroups were obtained owing to the participation of PD-1 or PD-L1 inhibitors.

Association between glucagon-like peptide-1 receptor gene polymorphism and treatment response to GLP1R agonists in Chinese patients with type 2 diabetes: a prospective cohort study.

PURPOSE: Clinical response to glucagon-like peptide-1 receptor agonists (GLP1RAs) varies considerably among patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to examine the potential association between the genetic variants in GLP1R gene polymorphism with the therapeutic efficacy as well as gastrointestinal adverse drug reactions (ADRs) of GLP1RAs in Chinese T2DM patients. METHODS: Adult T2DM patients were eligible to participate in this prospective cohort study. Subjects received 12-week treatment with either exenatide (20 µg/day) or liraglutide (1.2 mg/day). GLP1R rs10305420 and rs3765467 genotyping was performed using the Sanger sequencing method. Clinical response to GLP1RAs was assessed in the patients who completed the 12-week treatment and defined by the change of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and body mass index (BMI) from the baseline. RESULTS: A total of 176 subjects (mean age 50.9 ± 12.7 years, 111 men) were enrolled. The planned 12-week treatment was completed by 156 patients. HbA1c reduction was significantly larger in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (1.7% ± 2.4% vs. 0.8% ± 1.8%; P = 0.002). Similarly, the 7.0% target HbA1c attainment rate was significantly higher in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (50.9% vs. 23.8%; P = 0.002). Gastrointestinal ADRs did not differ significantly among different genotypes. CONCLUSION: GLP1R rs3765467 polymorphism is associated with therapeutic response to GLP1RAs in Chinese T2DM patients. HbA1c reduction is more pronounced in subjects with the GG genotype.

Significance of CD8+ T cell infiltration-related biomarkers and the corresponding prediction model for the prognosis of kidney renal clear cell carcinoma.

Cytotoxic T cells expressing cell surface CD8 played a key role in anti-cancer immunotherapy, including kidney renal clear cell carcinoma (KIRC). Here we set out to comprehensively analyze and evaluate the significance of CD8+ T cell-related markers for patients with KIRC. We checked immune cell response in KIRC and identified cell type-specific markers and related pathways in the tumor-infiltrating CD8+ T (TIL-CD8T) cells. We used these markers to explore their prognostic signatures in TIL-CD8+ T by evaluating their prognostic efficacy and group differences at various levels. Through pan-cancer analysis, 12 of 63 up-regulated and 162 of 396 down-regulated genes in CD8+ T cells were found to be significantly correlated with the survival prognosis. Based on our highly integrated multi-platform analyses across multiple datasets, we constructed a 6-gene risk scoring model specific to TIL-CD8T. In this model, high TIL-CD8 sig score was corresponding to a higher incidence frequency of copy number variation and drug sensitivity to sorafenib. Moreover, the prognosis of patients with the same or similar immune checkpoint gene levels could be distinguished from each other by TIL-CD8 sig score.

Population pharmacokinetics and dosing optimization of metformin in Chinese patients with type 2 diabetes mellitus.

Approximately 35% of patients fail to attain ideal initial blood glucose control under metformin monotherapy. The objective of this observational study is to simulate the optimal protocol of metformin according to the different renal function.The population pharmacokinetics of metformin was performed in 125 subjects with type 2 diabetes mellitus. Plasma concentrations of metformin were quantified by high-performance liquid chromatography. A population pharmacokinetic model of metformin was developed using NONMEN (version 7.2, Icon Development Solutions, USA). Monte Carlo simulation was used to simulate the concentration-time profiles for doses of metformin for 1000 times at different stages of renal function.The mean population pharmacokinetic parameters were apparent clearance 53.0 L/h, apparent volume of distribution 438 L, absorption rate constant 1.4 hour and lag-time 0.91 hour. Covariate analyses revealed that estimated glomerular filtration rate (eGFR) and bodyweight as individual factors influencing the apparent oral clearance: CL/F = 53.0 × ( bodyweight/75) × (eGFR/102.5)EXP(0.1797). The results of the simulation showed that patients should be prescribed metformin 2550 mg/d (t.i.d.) vs 3000 mg/d (b.i.d.) as the minimum doses for patients with augmented renal clearance.eGFR had a significant impact on metformin pharmacokinetics. Patients administered metformin twice a day require higher total daily doses than those with a regimen of 3 times a day at each stage of kidney function.

SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study.

BACKGROUND: Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment. METHODS: This cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment. RESULTS: Fasting plasma glucose (FPG) levels, HbA1c levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele (P < 0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (P=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (P=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA1c (r = 0.629, P < 0.001) and negatively associated with Lg10 FPG (r = -0.708, P < 0.001). CONCLUSIONS: The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.

Dietary Copper Plays an Important Role in Maintaining Intestinal Barrier Integrity During Alcohol-Induced Liver Disease Through Regulation of the Intestinal HIF-1α Signaling Pathway and Oxidative Stress.

Impaired intestinal barrier function and oxidative stress injury play critical roles in the pathogenesis of alcoholic liver disease (ALD), and recent investigations have revealed a role for dietary copper in the liver and intestinal barrier function. Therefore, the current study investigates the mechanisms and role of dietary copper in alcohol induced liver diseases. C57BL/6 mice were used to create an alcoholic liver disease model with a Lieber-DeCarli diet containing 5% alcohol and were fed with different concentrations of dietary copper of adequate (6 ppm, CuA), marginal (1.5 ppm, CuM), or supplemental (20 ppm, CuS) amounts. Caco-2 cells were also exposed to ethanol and different concentrations of copper. Damages of the liver and intestine were evaluated by transaminases, histology staining, and protein and mRNA level, as well as cell proliferation, oxidative stress, and mitochondrial membrane potential. In animal experiments, the results indicate that an alcohol diet causes liver injury and disruption of intestinal barrier function as well as decreasing the expression of genes such as HIF-1α, occludin, SOD1, and GPX1. Supplemental dietary copper can revert these changes except for SOD1, but marginal dietary copper can worsen these changes. The in vitro cell experiments showed that proper copper supplementation can promote cell growth and reduce reactive oxygen species (ROS) production. In conclusion, supplemental dietary copper has beneficial effects on alcohol-induced intestine and liver injury, and marginal dietary copper shows detrimental effects on these parameters.

Effects of Transcutaneous Neuromuscular Electrical Stimulation on Swallowing Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the study was to evaluate the efficacy of transcutaneous neuromuscular electrical stimulation on swallowing disorders. DESIGN: MEDLINE/PubMed, Embase, CENTRAL, Web of science, and PEDro were searched from their earliest record to August 1, 2019. All randomized controlled trials and quasi-randomized controlled trial were identified, which compared the efficacy of neuromuscular electrical stimulation plus traditional therapy with traditional therapy in swallowing function. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to evaluate the quality of evidence. RESULTS: Eight randomized controlled trials and three quasi-randomized controlled trials were included. These studies demonstrated a significant, moderate pooled effect size (standard mean difference = 0.62; 95% confidence interval = 0.06 to 1.17). Studies stimulating suprahyoid muscle groups revealed a negative standard mean difference of 0.17 (95% confidence interval = -0.42, 0.08), whereas large effect size was observed in studies stimulating the infrahyoid muscle groups (standard mean difference = 0.89; 95% confidence interval = 0.47 to 1.30) and stimulating the suprahyoid and infrahyoid muscle groups (standard mean difference = 1.4; 95% confidence interval = 1.07 to 1.74). Stimulation lasting 45 mins or less showed a large, significant pooled effect size (standard mean difference = 0.89; 95% confidence interval = 0.58 to 1.20). The quality of evidences was rated as low to very low. CONCLUSIONS: There is no firm evidence to conclude on the efficacy of neuromuscular electrical stimulation on swallowing disorders. Larger-scale and well-designed randomized controlled trials are needed to reach robust conclusions.

Exposure to organochlorine pesticides and the risk of type 2 diabetes in the population of East China.

Organochlorine pesticides (OCPs) have been reported to be associated with an elevated risk of type 2 diabetes, although no study has focused on such associations in Chinese populations. In this case-control study, we aimed to explore the associations between OCPs and type 2 diabetes and their potential mechanisms in a population from East China. Participants diagnosed with type 2 diabetes and nondiabetic participants from Shandong Province, East China, were enrolled in this case-control study. Six OCPs (ß-HCH, trans-chlordane, trans-nonachlor, p,p'-DDE, p,p'-DDT and mirex/kepone) were detected in more than 75% of serum samples. Logistic regression analysis and multiple linear regression analysis were used to assess the associations between OCP exposure and the outcomes. After adjusting for potential confounding factors such as age, sex and body mass index, all six OCPs showed positive associations with type 2 diabetes in a linear dose-response manner. Serum concentrations of ß-HCH and p,p'-DDE were associated with higher levels of fasting plasma glucose in participants without diabetes, although no OCPs showed significant associations with hemoglobin A1c. In addition, certain OCPs showed significantly positive associations with triglycerides, total cholesterol, and low-density lipoprotein cholesterol and negative relationships with high-density lipoprotein cholesterol in nondiabetics, indicating that OCP exposure may disrupt lipid metabolism. Findings in the current study indicated that OCPs may be a diabetogenic factor in the population of this study. To our knowledge, this is the first study to investigate the associations between OCP exposure and type 2 diabetes in a Chinese population.

microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation.

Autoimmune hepatitis (AIH) is a chronic liver disease due to autoimmune system attacks hepatocytes and causes inflammation and fibrosis. Intracellular signalling and miRNA may play an important role in regulation of liver injury. This study aimed to investigate the potential roles of microRNA 143 in a murine AIH model and a hepatocyte injury model. Murine AIH model was induced by hepatic antigen S100, and hepatocyte injury model was induced by LPS. Mice and AML12 cells were separated into six groups with or without the treatment of miRNA-143. Inflammation and fibrosis as well as gene expression were examined by different cellular and molecular techniques. The model was successfully established with the elevation of ALT and AST as well as inflammatory and fibrotic markers. Infection or transfection of mir-143 in mice or hepatocytes significantly attenuated the development of alleviation of hepatocyte injury. Moreover, the study demonstrated phosphorylation of TAK1-mediated miRNA-143 regulation of hepatic inflammation and fibrosis as well as hepatocyte injury. Our studies demonstrated a significant role of miRNA-143 in attenuation of liver injury in AIH mice and hepatocytes. miRNA-143 regulates inflammation and fibrosis through its regulation of TAK1 phosphorylation, which warrants TAK1 as a target for the development of new therapeutic strategy of autoimmune hepatitis.

Psychological and behavioral intervention improves the quality of life and mental health of patients suffering from differentiated thyroid cancer treated with postoperative radioactive iodine-131.

BACKGROUND: We examined the effects of psychological and behavioral intervention on health-related quality of life and mental health among patients suffering from differentiated thyroid cancer (DTC) treated with postoperative radioactive iodine-131 (RAI). METHODS: Sixty patients with DTC, undergoing RAI, were randomly assigned to receive either conventional nursing (n=30) or a 1-year psychological and behavioral intervention based on conventional nursing (n=30). Health-related quality of life and mental health issues, depression, and anxiety were measured using the Quality of Life Core Questionnaire, Self-rating Depression Scale, and Self-rating Anxiety Score, respectively. RESULTS: After RAI treatment, patients in both groups showed improved functional capacities (ie, physical, role, cognitive, emotional, and social) and global quality of life, along with reduced depression and anxiety (P<0.05). At 1-year follow-up, compared with patients in the routine nursing group, those in the psychological and behavioral intervention group demonstrated greater improvements in functional capacities, global quality of life, and depression and anxiety symptoms (P<0.05). CONCLUSION: Psychological and behavioral interventions for patients with DTC undergoing RAI facilitated positive outcomes, suggesting that nursing care models that include psychological and behavioral interventions may be a complementary strategy for this patient population.