Self-Efficacy's Mediating Role in the Relationship Between Self-Perceived Burden and Health-Related Quality of Life Among Older-Adult Inpatients in China: A Cross-Sectional Study.

Purpose: This study investigated the current state of self-efficacy and the association between self-perceived burden (SPB) and health-related quality of life (HRQoL) among Chinese older-adult inpatients. Methods: A cross-sectional study was conducted using convenience sampling to survey Chinese older-adult inpatients. Data regarding demographic characteristics, self-efficacy, SPB, and HRQoL were collected. Pearson's correlation analysis was used to examine the correlations among the research variables. SPSS® Statistics V26.0, and SPSS® PROCESS Macro Model 4 were used to analyze the available data. The bootstrap method was used to analyze the mediating role of self-efficacy. Results: Survey participants included 514 older-adult inpatients, with a mean age of 72.28±5.58 years. Self-efficacy (r=0.471, p<0.01) was positively correlated with HRQoL, whereas self-efficacy (r=-0.891, p<0.01) and HRQoL (r=-0.516, p<0.01) were negatively correlated with SPB. The mediating effect analysis revealed that self-efficacy either completely or partially mediated the effect of SPB on HRQoL, with the indirect effect accounting for 30.2% of the total. Conclusion: This study provides a mediating model suggesting that SPB exerts both direct and indirect effects on the HRQoL of older-adult inpatients through self-efficacy.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese: a randomized, double-blind, placebo-controlled, multiple-dose phase 1b study.

BACKGROUND: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. METHODS: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18-75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. RESULTS: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 µg*h/mL, and AUC0-inf ranged from 159 to 340 µg*h/mL. TG103 had a half-life of 110-116 h, with a median Tmax of 36-48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. CONCLUSIONS: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.

Peak ground acceleration prediction for on-site earthquake early warning with deep learning.

Rapid and accurate prediction of peak ground acceleration (PGA) is an important basis for determining seismic damage through on-site earthquake early warning (EEW). The current on-site EEW uses the feature parameters of the first arrival P-wave to predict PGA, but the selection of these feature parameters is limited by human experience, which limits the accuracy and timeliness of predicting peak ground acceleration (PGA). Therefore, an end-to-end deep learning model is proposed for predicting PGA (DLPGA) based on convolutional neural networks (CNNs). In DLPGA, the vertical initial arrival 3-6 s seismic wave from a single station is used as input, and PGA is used as output. Features are automatically extracted through a multilayer CNN to achieve rapid PGA prediction. The DLPGA is trained, verified, and tested using Japanese seismic records. It is shown that compared to the widely used peak displacement (Pd) method, the correlation coefficient of DLPGA for predicting PGA has increased by 12-23%, the standard deviation of error has decreased by 22-25%, and the error mean has decreased by 6.92-19.66% with the initial 3-6 s seismic waves. In particular, the accuracy of DLPGA for predicting PGA with the initial 3 s seismic wave is better than that of Pd for predicting PGA with the initial 6 s seismic wave. In addition, using the generalization test of Chilean seismic records, it is found that DLPGA has better generalization ability than Pd, and the accuracy of distinguishing ground motion destructiveness is improved by 35-150%. These results confirm that DLPGA has significant accuracy and timeliness advantages over artificially defined feature parameters in predicting PGA, which can greatly improve the effect of on-site EEW in judging the destructiveness of ground motion.

A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility.

Disulfidptosis, a novel type of programmed cell death, has attracted researchers' attention worldwide. However, the role of disulfidptosis-related lncRNAs (DRLs) in liver hepatocellular carcinoma (LIHC) not yet been studied. We aimed to establish and validate a prognostic signature of DRLs and analyze tumor microenvironment (TME) and drug susceptibility in LIHC patients. RNA sequencing data, mutation data, and clinical data were obtained from the Cancer Genome Atlas Database (TCGA). Lasso algorithm and cox regression analysis were performed to identify a prognostic DRLs signature. Kaplan-Meier curves, principal component analysis (PCA), nomogram and calibration curve, function enrichment, TME, immune dysfunction and exclusion (TIDE), tumor mutation burden (TMB), and drug sensitivity analyses were analyzed. External datasets were used to validate the predictive value of DRLs. qRT-PCR was also used to validate the differential expression of the target lncRNAs in tissue samples and cell lines. We established a prognostic signature for the DRLs (MKLN1-AS and TMCC1-AS1) in LIHC. The signature could divide the LIHC patients into low- and high-risk groups, with the high-risk subgroup associated with a worse prognosis. We observed discrepancies in tumor-infiltrating immune cells, immune function, function enrichment, and TIDE between two risk groups. LIHC patients in the high-risk group were more sensitive to several chemotherapeutic drugs. External datasets, clinical tissue, and cell lines confirmed the expression of MKLN1-AS and TMCC1-AS1 were upregulated in LIHC and associated with a worse prognosis. The novel signature based on the two DRLs provide new insight into LIHC prognostic prediction, TME, and potential therapeutic strategies.

Baseline Data and HLA Alleles and Haplotypes Diversity and Panel Reactive Antibody in Kidney Transplant Candidates in Southwest China.

BACKGROUND: To investigate the baseline data characteristic, human leukocyte antigen (HLA) polymorphisms, and panel reactive antibody (PRA) in end-stage kidney disease (ESKD) patients awaiting kidney transplantation in Southwest China. METHODS: HLA genotyping was performed using the real-time PCR sequence-specific primer. PRA was detected by enzyme-linked immunosorbent assay. The patients' medical records were extracted from the hospital information database. RESULTS: A total of 281 kidney transplant candidates with ESKD were analyzed. The average age was 35.7 ± 13.8 years. There were 61.6% patients had hypertension, 40.2% patients had dialysis ≥ 3 times per week, 47.3% patients had moderate or severe anemia, 30.2% patients with albumin < 35 g/L, 49.1% patients had serum ferritin < 200 ng/mL, 40.5% patients had serum calcium in target range (2.23 - 2.80 mmol/L), 43.4% patients had serum phosphate in target range (1.45 - 2.10 mmol/L), and 93.6% patients with parathyroid hormone > 88.00 pg/mL. In total, 15 HLA-A, 28 HLA-B, 15 HLA-DRB1, and 8 HLA-DQB1 allelic groups were identified. The most frequent alleles for each locus were HLA-A*02 (33.63%), HLA-B*46 (14.41%), HLA-DRB1*15 (21.89%), and HLA-DQB1*05 (39.50%). The most frequent haplotypes were HLA-A*33-B*58-DRB1*17-DQB1*02. A total of 9.60% of patients tested positive for PRAs - Class I or Class II. CONCLUSIONS: The data from this study provide some new insights into baseline data, the distribution of HLA polymorphisms, and PRA results in the population of Southwest China. This is of great significance in this region, and indeed in the country as a whole, in comparison with other populations and in the process of organ transplant allocation.

Versatile Biocatalytic C(sp3 )-H Oxyfunctionalization for the Site- Selective and Stereodivergent Synthesis of α- and ß-Hydroxy Acids.

C(sp3 )-H oxyfunctionalization, the insertion of an O-atom into C(sp3 )-H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3 )-H oxyfunctionalization has the potential to overcome limitations inherent to small-molecule-mediated approaches by delivering catalyst-controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3 )-H bonds, providing concise synthetic routes towards four types of 92 α- and ß-hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.

Antioxidants-related nuclear factor erythroid 2-related factor 2 gene variants associated with HBV-related liver disease.

BACKGROUND: Accumulating evidence demonstrated that nuclear factor erythroid 2-related factor 2 (NRF2) expression plays a crucial role in the proliferation, invasion and metastasis of hepatocellular carcinoma (HCC). However, research on the effect of NRF2 genetic polymorphism on the development of chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and HCC is still missing. METHODS: A total of 673 individuals were included in the study and classified into four groups: 110 CHB cases, 86 LC cases, 260 HCC cases, and 217 healthy controls. ​The polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing method were used to detect rs6721961 and rs6726395 polymorphisms. RESULTS: Patients carrying the T allele in rs6721961 were at a higher risk of HCC than individuals with the G allele compared to CHB patients (OR = 1.561, 95%CI: 1.003-2.430, P = 0.048). The statistically significant differences were also found in the rs6721961 GT genotype (OR = 2.298, 95% CI: 1.282-4.119, P = 0.005) and dominant model (OR = 2.039, 95% CI: 1.184-0.510, P = 0.010). Subgroup analysis also detected a significant association between the rs6721961 T allele and the development of HCC in older subjects (≥ 50 years) (OR = 2.148, 95% CI: 1.208-3.818, P = 0.009). Statistical analysis results indicated that subjects carrying haplotype G-A had a lower risk of HCC (OR = 0.700, 95% CI: 0.508-0.965, P = 0.028). CONCLUSIONS: For the first time, our findings provide evidence that the NRF2 gene rs6721961 variation is a potential genetic marker of susceptibility to HCC.

Asymmetric C1 Extension of Aldehydes through Biocatalytic Cascades for Stereodivergent Synthesis of Mandelic Acids.

The development of mild, efficient, and enantioselective methods for preparing chiral building blocks from simple, renewable carbon units has been a long-term goal of the sustainable chemical industry. Mandelate derivatives are valuable pharmaceutical intermediates and chiral resolving agents, but their manufacture relies heavily on highly toxic cyanide. Herein, we report (S)-4-hydroxymandelate synthase (HmaS)-centered biocatalytic cascades for the synthesis of mandelates from benzaldehydes and glycine. We show that HmaS can be engineered to perform R-selective hydroxylation by single-point mutation, empowering the stereodivergent synthesis of both (S)- and (R)-mandelate derivatives. These biocatalytic cascades enabled the production of various mandelate derivatives with high atom economy as well as excellent yields (up to 98 %) and ee values (up to >99 %). This methodology offers an effective cyanide-free technology for greener and sustainable production of mandelate derivatives.

Biomarkers of PEGylated Liposomal Doxorubicin-Induced Hypersensitivity Reaction in Breast Cancer Patients Based on Metabolomics.

This study aimed to analyze and discuss the biomarkers of PEGylated liposomal doxorubicin (PLD) injection-induced hypersensitivity reactions (HSRs) in advanced breast cancer patients. Fourteen patients from Sun Yat-sen Memorial Hospital were included in the study between April 15th, 2020 and April 14th, 2021. Patient plasma was collected 30 min before PLD injection. HSRs were found to occur in a total of 9 patients (64.3%). No association was found between HSRs and various patient characteristics such as age, body surface area, anthracycline treatment history, IgE, and complement 3 and 4 (p > 0.05). Non-targeted metabolomics analysis of patient plasma was performed, and several metabolites showed significant association with HSRs. In particular, l-histidine (fold change = 91.5, p = 0.01) showed significantly higher levels in the immediate HSR group, while myristicin (fold change = 0.218, p = 0.003), urocanic acid (fold change = 0.193, p = 0.007), and d-aldose (fold change = 0.343, p = 0.003) showed significantly lower levels in the same group. In vivo experiments showed that exogenous histidine aggravated HSRs and increased IgE plasma levels in rats following the injection of PLD. Histidine can be decarboxylated to histamine by histidine decarboxylase. Histidine decarboxylase inhibitor 4-bromo-3-hydroxybenzoic acid improved symptoms and IgE levels in vivo. These findings suggested that l-histidine can be a potential biomarker for PLD-induced HSR. Moreover, an antihistamine drug, histidine decarboxylase inhibitor, or dietary histidine management could be used as potential preventive measures. Furthermore, metabolomics research could serve as a powerful method to explore biomarkers or uncover mechanisms of drug side effects.

Relationship between the red cell distribution width-to-platelet ratio and in-hospital mortality among critically ill patients with acute myocardial infarction: a retrospective analysis of the MIMIC-IV database.

OBJECTIVES: We aimed to investigate the association between red cell distribution width-to-platelet ratio (RPR), and in-hospital mortality in critically ill patients with acute myocardial infarction (AMI). DESIGN: A retrospective cohort study. SETTING: Data were collected from the Medical Information Mart for Intensive Care database (MIMIC-IV) consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Centre in Boston. PARTICIPANTS: A total of 5067 patients with AMI were enrolled from the MIMIC-IV database. PRIMARY AND SECONDARY OUTCOME: In-hospital mortality. RESULTS: A total of 4034 patients survived, while 1033 died. In a multiple regression analysis adjusted for age, weight and ethnicity, RPR also showed a positive correlation with in-hospital mortality (HR 1.91, 95% CI 1.42 to 2.56, p<0.0001). Moreover, after adjusting for additional confounding factors, obvious changes were observed (HR 1.63, 95% CI 1.03 to 2.57, p=0.0357). In model 2, the high ratio quartile remained positively associated with hospital mortality compared with the low ratio quartile (HR 1.20, 95% CI 1.01 to 1. 43), with a p-value trend of 0.0177. Subgroup analyses showed no significant effect modifications on the association between RPR and in-hospital mortality in the different AMI groups (p>0.05). CONCLUSION: RPR is an independent predictor of in-hospital mortality in critically ill patients with AMI.

Association between WNT-1-inducible signaling pathway protein-1 (WISP1) genetic polymorphisms and the risk of gastric cancer in Guangxi Chinese.

BACKGROUND: WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of ß-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship. METHODS: Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls. RESULTS: Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14-0.78; TT vs. CC: OR = 0.29, 95%CI 0.11-0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14-0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35-0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively. CONCLUSIONS: The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.

Identification and characterization of a subpopulation of CD133+ cancer stem-like cells derived from SK-UT-1 cells.

BACKGROUND: Uterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus. Cancer stem cells (CSCs) are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure. However, little is known about CSCs and their associated-markers in ULMS. We aimed to characterize and identify a subpopulation of CD133+ cancer stem-like cells derived from SK-UT-1 cell line. METHODS: SK-UT-1 cells were sphere-forming cultured in vitro. We also sorted the CD133+ cells derived from SK-UT-1 cell line by immunomagnetic beads. CD133+ subpopulation and apoptotic cells were detected by flow cytometry. Self-renewal and anchorage-independent growth capabilities were examined using sphere and colony formation assays. The tumorigenicity of the fourth-passage spheres and parental SK-UT-1 cells was used by mouse xenograft model in vivo. Cell proliferation ability and sensitivity to doxorubicin (DXR) were assessed by CCK-8 assay. Cell migration and invasion were tested by wound healing assay or Transwell migration and invasion assays. Expressions of CSC-related marker were analyzed by Western blotting. RESULTS: The fourth-passage spheres were defined as a CD133+ cell population, which was accompanied by increase of sphere and colony forming rate, migration and invasion abilities, as well as drug-resistant properties in vitro. Moreover, the fourth-passage spheres showed a stronger tumorigenic potential in vivo. CD133+ cell population sorted from SK-UT-1 line showed an increased ability in sphere and colony formation, proliferation, migration, invasion, resistance to apoptosis after treatment with doxorubicin (DXR) compared with CD133- cell population. The expression levels of CSCs-related markers (e.g., CD44, ALDH1,BMI1, and Nanog), were significantly elevated in CD133+ cells compared with those in CD133- cells. CONCLUSIONS: Collectively, our findings indicated that CD133 may be a significant marker for cancer stem-like cells, and it may be a potential therapeutic target for human ULMS.

Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.

HBV promotes the recruitment of IL-17 secreting T cells via chemokines CCL22 and CCL17.

BACKGROUND AND AIMS: Little is known about the mechanisms of IL-17 secreting T cells accumulation in HBV-transfected livers. Here, we investigated the role of the chemokines CCL17, CCL20 and CCL22 in this process. METHODS: Peripheral blood and liver tissues were obtained from 30 chronic hepatitis B (CHB) patients and 15 healthy volunteers and were evaluated by flow cytometric analysis and immunohistochemistry. Chemokine production by monocyte-derived dendritic cells (MoDCs) cocultured with HBV-transfected or untransfected Huh7 cells was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The chemotactic activity of the culture supernatants was also tested. RESULTS: The proportions of IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells were both increased in liver and peripheral blood mononuclear cells of CHB patients compared to those in HVs. CHB patients showed higher intrahepatic levels of CCL17 mRNA, CCL22 mRNA, CCR6 mRNA and CCR4 mRNA than HVs. The expression of CCR6 and CCR4 on the surface of Th17 and Tc17 cells in CHB patients was also significantly higher than that in HVs. Significant correlations existed between the CCR4/CCR6 levels and both the alanine transaminase levels and HBV DNA loads. Contact between MoDCs and pBlue-HBV-transfected Huh7 cells induced the expression of CCL17 and CCL22 dependent on the dose of HBV DNA. However, CCL20 expression was lower in CHB patients than in HVs. Transwell experiments showed that upregulation of CCL17 and CCL22 enhanced the migration of IL-17 secreting T cells. CONCLUSIONS: Contact of HBV-transfected cells with MoDCs induces CCL17 and CCL22 chemokine production, which may favour the recruitment of Th17 and Tc17 cells to liver tissue in CHB. Our results reveal the mechanism of IL-17 secreting T cells recruitment to liver tissue and thus provide new immunotherapy targets for CHB patients.

Burden and depression in caregivers of patients with rheumatoid arthritis in China.

AIM: Caregivers of patients with rheumatoid arthritis (RA) often experience a sense of burden and depression. This study aimed to determine the degree of burden and depression on caregivers of RA patients and identify characteristics of both patients and caregivers that may contribute to that distress. METHODS: A convenience sample of 195 patients with RA and their caregivers completed a demographic questionnaire, Zarit Care Burden Scale, Center Depression Self Rating Scale, Health Assessment Questionnaire Disability Index, and the Short Form Health Survey. Univariate and multivariate regression analysis were used to evaluate contributing factors. RESULTS: Overall, caregivers' feelings of burden and depression were moderate, with 52 (26.7%) feeling depression and 156 (80%) feeling burdened. Caregivers with poorer health (OR = 4.393; 95% CI = 1.155-16.708; P = 0.030) and less education (OR = 6.458; 95% CI = 1.675-24.895; P = 0.007) experienced greater burdens than those with better health and more education. The greatest degree of stress occurred during the first 6 months of providing care and after 5 years of caregiving. CONCLUSIONS: Overall occurrence of depression among caregivers is low. Caregivers with poorer health, less education and closer relationship with the patient bear a heavier burden. Healthcare professionals should be aware of these potential problems and provide information and support to ensure the best quality of life for both RA patients and their caregivers.

Genetic polymorphisms in complement receptor 1 gene and its association with HBV-related liver disease: A case-control study.

BACKGROUND: Several investigators have reported that complement receptor 1 (CR1) likely play a role in the pathogenesis of tumors, autoimmune and inflammatory diseases. However, the association of genetic polymorphisms of CR1 with risk of hepatitis B virus (HBV)-related liver disease remains unexplored. METHODS: In a case-control study of 399 HBV-related liver disease patients and 227 healthy controls, we genotyped two SNPs in CR1 (rs3811381 and rs2274567) and assessed their associations with risk of HBV-related liver disease. RESULTS: No significant differences were observed in the frequency distribution of genotypes or alleles between CR1 rs3811381 and rs2274567 polymorphisms in patients and controls. However, stratification analysis indicated that these two CR1 polymorphisms may contribute to the risk of HBV- hepatocellular carcinoma (HCC) and chronic hepatitis B (CHB) in subgroups of males, alcohol drinkers and nonsmokers. Further, our results showed that the rs3811381 polymorphism may contribute to HBV-HCC risk in subgroups of older and younger subjects, while the G allele, AG and the combined AG + GG genotypes of rs2274567 may be risk factors for HBV-HCC in younger subjects. In addition, our results indicated that subjects who carried the rs3811381 G allele and the rs2274567 AG genotype were at decreased risk of HBV- liver cirrhosis (LC) in subgroups of females. CONCLUSIONS: Our results support the hypothesis that the CR1 gene rs3811381 and rs2274567 polymorphisms may contribute to HBV-HCC and HBV-CHB risk, particularly in subgroups of males, alcohol drinkers, nonsmokers, while these two CR1 polymorphisms were found to associate with decreased risk of HBV-LC, particularly in females. Further validation of these results is warranted.

P-glycoprotein gene MDR1 polymorphisms and susceptibility to systemic lupus erythematosus in Guangxi population: a case-control study.

The multidrug resistance 1 gene (MDR1) encodes for P-glycoprotein (P-gp), which plays a pathophysiological role in the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Herein, we aimed to investigate the relationship between MDR1 gene polymorphisms and SLE susceptibility in the Chinese Guangxi population. The genotypes of rs1128503 and rs1045642 in MDR1 gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method in 283 SLE patients and 247 healthy controls from Guangxi. Direct sequencing method was used to verify the results. Binary logistic regression analyses adjusting for gender and age indicated that subjects carrying the rs1128503 T-allele and TT genotype were at increased risk of SLE when compared to carriers of the C allele and CC genotype, with adjusted ORs of 1.36 (95% CI 1.07-1.74; P = 0.014) and 1.77 (95% CI 1.08-2.88; P = 0.022), respectively. In addition, the risk allele T had a recessive effect (OR 1.49, 95% CI 1.04-2.14, P = 0.029). Subgroup analyses revealed effect modification by age for the presence of the rs1128503 T allele, yielding a significant positive association with SLE in older (≥40 years) subjects (T vs. C allele: OR 1.41, 95% CI 1.01-1.96; P = 0.041; TT vs. CC genotype: OR 1.74, 95% CI 1.07-2.79; P = 0.021). For the first time, we demonstrated that MDR1 rs1128503 polymorphisms were associated with SLE susceptibility in Chinese Guangxi population.

Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case-control study.

BACKGROUND: To investigate the influence of polymorphisms in the receptor for advanced glycation end products (RAGE) gene and circulating soluble RAGE (sRAGE) levels on susceptibility to gastric cancer, and identify whether these polymorphisms were correlated with serum sRAGE levels. METHODS: We performed a hospital-based case-control study involving 200 gastric cancer patients and 207 cancer-free controls. Four well-characterized RAGE genetic polymorphisms, namely, rs1800624, rs1800625, rs184003, and rs2070600 were genotyped by PCR-RFLP. RESULTS: The rs2070600 AG genotype might play a predominant role in the development of gastric cancer (adjusted OR 1.62, 95% CI 1.03-2.58). In contrast, the rs184003 GT genotype represented significantly reduced risk for gastric cancer (adjusted OR 0.62, 95% CI 0.39-0.99). Subgroup analysis demonstrated that rs2070600 AG variant genotype enhanced the gastric cancer risk among nonsmokers (OR 1.71, 95% CI 1.01-2.91), nondrinkers (OR 1.75, 95% CI 1.03-2.97), and patients with tumor stage III (OR 2.00, 95% CI 1.13-3.56). The average sRAGE levels in the gastric cancer patients were significantly decreased compared with those of the healthy controls. Subjects carrying the rs2070600 AG genotype had a decreased ability to produce sRAGE. Subjects carrying the rs184003 T variant allele had an increased ability to sRAGE. CONCLUSIONS: These findings suggested that the variant genotypes of rs184003 and rs2070600 in the RAGE gene exhibit significant associations with gastric cancer risk and circulating sRAGE levels inverse change simultaneously, leading to a marked causal estimate between lowered sRAGE levels and increased gastric cancer risk.

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study.

OBJECTIVE: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC). METHOD: A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005). CONCLUSIONS: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

Association of IL-17A and IL-17F gene polymorphisms with chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: A case-control study.

BACKGROUND: Interleukin (IL)-17 has been shown to play an important role in tissue inflammation and in the pathogenesis of immune-related liver damage. Genetic variations in IL-17 gene may be associated with the development of hepatitis B virus (HBV) infection. However, literature is scanty regarding their association. METHODS: We conducted a case-control study including 433 subjects (171 healthy controls, 130 patients with chronic hepatitis B [CHB]; and 132 patients with HBV-related liver cirrhosis [HBV-LC] to assess the association between IL-17A rs4711998, IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk of CHB and HBV-LC. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS: Our results revealed a statistically significant association between IL-17A rs4711998 G allele and increased risk of HBV-LC risk (OR=1.541, 95% CI 1.057-2.246, P=0.025). Subjects carrying the IL-17A rs4711998 AG genotype were 1.75 times more likely to develop HBV-LC (OR=1.757, 95% CI 1.096-2.817, P=0.026). Stratification analysis indicated that IL-17A rs4711998 G allele and AG genotype enhanced the risk of HBV-LC development among men and older age (≥50years) subject groups. In addition, we found that GCT haplotype also might be a risk factor for HBV-LC (OR=2.448, 95% CI 1.137-5.271, P=0.019). Furthermore, no significant association between IL-17A rs2275913 and IL-17F rs763780 polymorphisms and CHB, HBV-LC risk was observed (P>0.05). CONCLUSION: Our data provide the first evidence that the IL-17A rs4711998 genetic variant may contribute to HBV-LC susceptibility in a Chinese population.