Non-linear association of liver enzymes with cognitive performance in the elderly: A cross-sectional study.

BACKGROUND: Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance. METHODS: In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects. RESULTS: The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L. CONCLUSIONS: There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.

Application of a core genome sequence typing (cgMLST) pipeline for surveillance of Clostridioides difficile in China.

Introduction: Clostridioides difficile (C. difficile) is a nosocomial bacterial pathogen that causes antibiotic-associated diarrhea mediated by cellular exotoxins secreted into the intestine during bacterial growth. Multilocus sequence typing (MLST) and PCR ribotyping are the main molecular typing for C. difficile. Whole genome sequencing (WGS) core genome multilocus sequence typing (cgMLST) was developed for genetic evolution and outbreak investigation of C. difficile with higher precision and accuracy. Methods: A total of 699 whole (complete and draft) genome sequences of distinct C. difficile strains were used in this study to identify core gene set (2469 core genes) and the cgMLST scheme for the phylogeny analysis of C. difficile. This cgMLST pipeline was then carried the Chinese Pathogen Identification Net (China PIN) for surveillance of C. difficile in China. Within the China PIN, 195 WGS of C. difficile and an outbreak of CDI with 12 WGS of C. difficile were used to evaluate the cgMLST pipeline. Results: The result displayed that mostly tested C. difficile isolates could be successfully divided into 5 classic clades and the outbreak event was also successfully identified. Discussion: The results are meaningful and offer a practicable pipeline for a national-wide surveillance of C. difficile in China.

Genetic Diversity, Antibiotic Resistance, and Pathogenicity of Aeromonas Species from Food Products in Shanghai, China.

Objective: Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. Methods: Aeromonas isolates ( n = 79) collected from food samples were analyzed using concatenated gyrB- cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using ß-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. Results: Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [ tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr -1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. Conclusion: The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.

Comparative Study of the Genetic Diversity, Antimicrobial Resistance, and Pathogenicity of Aeromonas Isolates from Clinical Patients and Healthy Individuals.

OBJECTIVE: This study was performed to compare the genetic diversity, virulence, and antimicrobial resistance of Aeromonas strains isolated from patients and healthy individuals. METHODS: A total of 38 clinical strains and 19 strains from healthy individuals were isolated from the samples collected in Ma'anshan City, Anhui Province. Their taxonomy was investigated using concatenated gyrB- cpn60 sequences, and their resistance to 12 antibiotics was evaluated. The pathogenicity of these strains was examined through beta-hemolysis, protease activity, and virulence gene assays. RESULTS: The 57 Aeromonas strains were divided into 55 sequence types. Of these types, 21 were novel, suggesting that their genetic diversity was high. These Aeromonas isolates could be divided into 7 species, and the positive rates of beta-hemolysis and protease activity were 49.1% and 73.7%, respectively. The detection rate of clinical patients in terms of beta-hemolysis and protease activity was higher than that of healthy individuals. Among the four most common Aeromonas strains, A. dhakensis had the highest detection rate of virulence genes. The multidrug resistance rate of the clinical isolates was much higher than that of the strains isolated from healthy individuals. CONCLUSIONS: The taxonomy, virulence properties, and antibiotic resistance of Aeromonas isolates from patients differ from those of the isolates from healthy individuals.

Genetic Diversity, Antimicrobial Resistance, and Virulence Genes of Aeromonas Isolates from Clinical Patients, Tap Water Systems, and Food.

OBJECTIVE: This study aimed to evaluate the genetic diversity, virulence, and antimicrobial resistance of Aeromonas isolates from clinical patients, tap water systems, and food. METHODS: Ninety Aeromonas isolates were obtained from Ma'anshan, Anhui province, China, and subjected to multi-locus sequence typing (MLST) with six housekeeping genes. Their taxonomy was investigated using concatenated gyrB-cpn60 sequences, while their resistance to 12 antibiotics was evaluated. Ten putative virulence factors and several resistance genes were identified by PCR and sequencing. RESULTS: The 90 Aeromonas isolates were divided into 84 sequence types, 80 of which were novel, indicating high genetic diversity. The Aeromonas isolates were classified into eight different species. PCR assays identified virulence genes in the isolates, with the enterotoxin and hemolysin genes act, aerA, alt, and ast found in 47 (52.2%), 13 (14.4%), 22 (24.4%), and 12 (13.3%) of the isolates, respectively. The majority of the isolates (≥ 90%) were susceptible to aztreonam, imipenem, cefepime, chloramphenicol, gentamicin, tetracycline, and ciprofloxacin. However, several resistance genes were detected in the isolates, as well as a new mcr-3 variant. CONCLUSIONS: Sequence type, virulence properties, and antibiotic resistance vary in Aeromonas isolates from clinical patients, tap water systems, and food.

Two Cases of Multi-antibiotic Resistant Cronobacter spp. Infections of Infants in China.

Infections by Cronobacter spp. are hazardous to infants since they can lead to neonatal meningitis, bacteremia, and necrotizing enterocolitis. Cronobacter spp. are frequently resistant to ß-lactam derivatives, macrolides, and aminoglycosides. In addition, multi-resistant strains have also been detected. In China, the isolation rate of Cronobacter spp. from commercial powdered infant formula (PIF) or follow-up formula (FUF) is relatively high. Nevertheless, clinical cases of Cronobacter infection have been ignored to date. Here we describe two cases of Cronobacter infection detected at the Wuhan Women and Children Medical Care Center Hospital (Wuhan City, China). We provide the genomic analysis of the isolates and the antibiotic-resistance profiles of the two strains. The Cronobacter strains identified in this study were not susceptible to third-generation cephalosporins, aminoglycoside, and/or trimethoprim-sulfamethoxazole. Whole genome sequencing revealed various genes known to encode antibiotic resistance. Future studies are needed to determine whether the genes predicted in this study are functional. As with Enterobacter spp., the antibiotic resistance of Cronobacter is a serious issue that requires more attention.

Effects of common polymorphisms in miR-146a and miR-196a2 on lung cancer susceptibility: a meta-analysis.

BACKGROUND: MicroRNAs (miRNAs) may play an important role in organ development, cell differentiation, apoptosis, proliferation, cell growth regulation and act as tumor suppressor genes or proto-oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs are considered to be genetic factors to influence the susceptibility to lung cancer (LC). Rs2910164 in miR-146a and rs11614913 in miR-196a2 are shown to be associated with increased/decreased LC risk. The aim of this meta-analysis was to systematically summarize the possible association. METHODS: The relevant articles were retrieved from several important databases. Studies were selected using specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between miRNA polymorphism and susceptibility to LC. All analyses were performed using the Stata software. RESULTS: Seven studies were included in this meta-analysis. There were 3,225 cases and 3,268 controls for SNP rs2910164 and 2,794 cases and 2,840 controls for SNP rs11614913. The significant associations between SNP rs2910164 and LC risk were observed (CC vs. GG: OR =1.30, 95% CI: 1.13-1.50; CC + GC vs. GG: OR =1.15, 95% CI: 1.02-1.29; CC vs. GC + GG: OR =1.27, 95% CI: 1.13-1.42; C vs. G: OR =1.15, 95% CI: 1.08-1.24). SNP rs11614913 was found to be associated with LC risk in most genetic models (TC vs. TT: OR =1.16, 95% CI: 1.02-1.32; CC vs. TT: OR =1.24, 95% CI: 1.06-1.44; CC + TC vs. TT: OR =1.19, 95% CI: 1.06-1.34; C vs. T: OR =1.11, 95% CI: 1.03-1.20). In the subgroup analysis by ethnicity, genotyping method and control characteristics, significantly affected LC risks were also suggested. CONCLUSIONS: The rs2910164 in miR-146a and the rs11614913 in miR-196a2 are likely to be associated with LC risks.

Multilocus sequence typing analysis of Cronobacter spp. isolated from China.

Multilocus sequence typing (MLST) has proven to be an effective approach for the subtyping isolates of the Cronobacter genus and to exhibit a high level of discrimination between isolates. In this study, 151 Cronobacter strains were isolated from different sources and provinces across China from 2010 to 2012 and analyzed by MLST. Their sequence type profiles were compared with strains from other countries which were widely geographically and temporally distributed. Out of 151 strains in this study, the majority of strains were Cronobacter sakazakii (70.9 %), C. malonaticus (15.9 %), C. dublinensis (10.6 %), C. turicensis (2.0 %), and C. muytjensii (0.7 %). The strains were divided into 85 sequence types (STs), among which only 17 had previously been reported in other countries. The 85 identified STs for the Cronobacter genus were grouped into 14 clonal complexes and 47 singletons according to eBURST algorithm. The Cronobacter isolated from China showed a high diversity when they were subtyped using the MLST method. When compared to the Cronobacter PubMLST database, some sequence types of strains cultured from food and/or water in this study were also the same with strains isolated from patients in other countries as reported previously. This result showed the potential hazard of strains contaminating water and weaning food from China.

TP63 gene polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in Chinese non-smoking females.

BACKGROUND: Genetic polymorphisms of TP63 have been suggested to influence susceptibility to lung adenocarcinoma development in East Asian populations. This study aimed to investigate the relationship between common polymorphisms in the TP63 gene and the risk of lung adenocarcinoma, as well as interactions of the polymorphisms with environmental risk factors in Chinese non-smoking females. METHODS: A case-control study of 260 cases and 318 controls was conducted. Data concerning demographic and risk factors were obtained for each subject. The genetic polymorphisms were determined by Taqman real-time PCR and statistical analyses were performed using SPSS software. RESULTS: For 10937405, carriers of the CT genotype or at least one T allele (CT/TT) had lower risks of lung adenocarcinoma compared with the homozygous wild CC genotype in Chinese nonsmoking females (adjusted ORs were 0.68 and 0.69, 95%CIs were 0.48-0.97 and 0.50-0.97, P values were 0.033 and 0.030, respectively). Allele comparison showed that the T allele of rs10937405 was associated with a decreased risk of lung adenocarcinoma with an OR of 0.78 (95%CI=0.60-1.01, P=0.059). Our results showed that exposure to cooking oil fumes was associated with increased risk of lung adenocarcinoma in Chinese nonsmoking females (adjusted OR=1.58, 95%CI=1.11-2.25, P=0.011). However, we did not observe a significant interaction of cooking oil fumes and TP63 polymorphisms. CONCLUSION: TP63 polymorphism might be a genetic susceptibility factor for lung adenocarcinoma in Chinese non-smoking females, but no significant interaction was found with cooking oil fume exposure.

Lack of influence of an XRCC3 gene polymorphism on oral cancer susceptibility: meta-analysis.

BACKGROUND: To systematically summarize the association between the X-ray repair cross complementing 3 (XRCC3) gene polymorphism and oral cancer susceptibility by meta-analysis. MATERIALS AND METHODS: Databases including PubMed, EMbase, CNKI, VIP and WanFang Data were searched to identify case-control studies concerning the association between an XRCC3 gene polymorphism and the risk of oral cancer from the inception to June 2014. Two reviewers independently screened the literature according to the criteria, extracted the data and assessed the quality. Then meta-analysis was performed using Stata 11.0 software. RESULTS: Seven published case-control studies including 775 patients with oral cancer and 1922 controls were selected. Associations between the rs861539 polymorphism and overall oral cancer risk were not statistically significant in all kinds of comparison models (CT vs CC: OR=0.94, 95%CI=0.74-1.18; TT vs CC: OR=0.94, 95%CI=0.64- 1.38; dominant model: OR=0.95, 95%CI=0.76-1.18; recessive model: OR=0.94, 95%CI=0.69-1.29; allele T vs C: OR=0.97, 95%CI=0.84-1.11). In the stratified analysis by ethnicity, no significant associations were found among Asians and Caucasians. On stratification by tumor type, no significant associations were found for cancer and oral premalignant lesions. CONCLUSIONS: The XRCC3 gene polymorphism was not found to be associated with the risk of oral cancer. Considering the limited quality of the included case-control studies, more high quality studies with large sample size are needed to verify the above conclusion.