Molecular Characteristics of Salmonella Spp. Responsible for Bloodstream Infections in a Tertiary Hospital in Nanjing, China, 2019-2021.

Objective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital. Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays. Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates. Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke.

The associations among the EH domain-binding protein 1 (EHBP1), tubulin beta class I (TUBB), and WW domain-containing oxidoreductase (WWOX) single nucleotide polymorphisms (SNPs) and coronary artery disease (CAD) and ischemic stroke (IS) are not yet understood. This study aimed to detect the associations of these SNPs, gene-gene and gene-environment interactions and CAD and IS in the Guangxi Han population. A total of 1853 unrelated subjects were recruited into normal control (n = 638), CAD (n = 622), and IS (n = 593) groups. Related genotypes were determined by high-throughput sequencing. The genotypic and minor allelic frequencies of rs2278075 were different between the CAD and control groups, and those of rs2710642, rs3130685, and rs2278075 were also different between the IS and control groups. The rs2278075T allele, rs3130685-rs2222896-rs2278075, rs3130685-rs2222896-diabetes, rs3130685-rs2222896-drinking, and haplotype rs2710642A-rs10496099C-diabetes interactions were associated with increased risk, while G-T-G-C-G-A and G-T-T-T-G-T-drinking were associated with reduced risk of CAD. The rs2278075T and rs2710642G alleles, rs2710642G-rs10496099C haplotype, rs3130685-rs2278075-rs2222896, and rs2710642-rs2278075-hypertension interactions aggravated the association with IS, whereas the rs3130685T allele, rs2710642A-rs10496099C haplotype and the interactions of H1 (s2710642A-rs10496099C)-H2 (rs2710642G-rs10496099C)-drinking and I1 (A-C-G-C-A-A)-I3 (A-C-G-T-A-A)-I4 (A-C-G-T-G-A)-I5 (G-T-G-C-G-A) diminished the association with IS. Carrying WWOX rs2278075T was strongly associated with CAD or IS, while EHBP1 rs2710642 and TUBB rs3130685 might alter the association of IS by modifying the serum lipid profile. This study demonstrates that the EHBP1, TUBB, and WWOX SNPs, gene-gene and gene-environment interactions are associated with the risk of CAD and IS in the Guangxi Han population.

DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke.

Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS. Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders. Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12-1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48-0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (P I < 0.004-0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22-0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04-0.36) decreased the risk of IS (P I < 0.0001). Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.

SYTL3-SLC22A3 Single-Nucleotide Polymorphisms and Gene-Gene/Environment Interactions on the Risk of Hyperlipidemia.

The current study aims to further delineate the associations between the synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single-nucleotide polymorphisms (SNPs) and their haplotypes and gene-gene (G × G)/environment (G × E) interactions on the risk of hyperlipidemia (HLP) in the Maonan and Han ethnic groups. Genotype distribution among the SYTL3-SLC22A3 SNPs in 2,829 individual patients bearing no relationship to each other (Han, 1,436; Maonan, 1,393) was analyzed utilizing next-generation sequencing techniques. The genotype frequencies of the rs6455600, rs2129209, and rs446809 SNPs were varied between the two ethnic groups (P < 0.05-0.001). Various SNPs were correlated with serum levels of triglyceride (TG; rs446809), total cholesterol (TC; rs6455600, rs2129209, and rs539298), and low-density lipoprotein cholesterol (LDL-C; rs446809) among the Han population, whereas various SNPs were also correlated with TC (rs6455600 and rs539298), TG (rs446809), and LDL-C (rs446809) levels in the Maonan ethnic group (P < 0.008-0.001). One part of haplotypes resulted in worsened HLP-related morbidity in the Han (SYTL3 A-C-A-A; SLC22A3 A-A and A-G; and SYTL3-SLC22A3 A-C-A-A-A-A and A-C-A-A-A-G) and Maonan (SYTL3 A-C-A-A; SLC22A3 A-A and A-G; and SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-A-A-A, and G-T-C-A-C-A) ethnic groups, whereas another part of haplotypes lowered HLP-related health risks in the Han (SLC22A3 C-A and C-G and SYTL3-SLC22A3 A-C-A-A-C-A, A-C-A-A-C-G, and G-T-C-A-C-A) and Maonan (SLC22A3 C-G and SYTL3-SLC22A3 A-C-A-A-C-G) ethnic groups. We discovered that the SYTL3-SLC22A3 SNPs and their haplotypes were associated with serum lipid levels and the risk of HLP in our studied populations.

Effect of SYTL3-SLC22A3 Variants, Their Haplotypes, and G × E Interactions on Serum Lipid Levels and the Risk of Coronary Artery Disease and Ischaemic Stroke.

Background: The current study aimed to investigate the effects of synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single nucleotide polymorphisms (SNPs) and gene-environment (G × E) interactions on blood lipid levels as well as the risk of coronary artery disease (CAD) and ischaemic stroke (IS) in the Southern Chinese Han population. Methods: The genetic makeup of 6 SYTL3-SLC22A3 SNPs in 2269 unrelated participants (controls, 755; CAD, 758 and IS, 756) of Chinese Han ethnicity was detected by the next-generation sequencing techniques. Results: The allele and genotype frequencies of the SYTL3 rs2129209 and SLC22A3 rs539298 SNPs were significantly different between the case and control groups. The SLC22A3 rs539298 SNP was correlated with total cholesterol (TC) levels in controls, the rs539298G allele carriers maintained lower TC levels than the rs539298G allele non-carriers. At the same time, the SLC22A3 rs539298 SNP interacted with alcohol consumption reduced the risk of CAD and IS. The SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-G-C-A and A-T-A-A-C-A haplotypes increased and the A-C-A-A-C-G haplotype reduced the risk of CAD, whereas the SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-G-A-G and A-T-A-A-C-A haplotypes increased and the A-C-A-A-A-G and A-C-A-A-C-G haplotypes reduced the risk of IS. In addition, several SNPs interacted with alcohol consumption, body mass index ≥ 24 kg/m2 and cigarette smoking to affect serum lipid parameters such as triglyceride, high-density lipoprotein cholesterol, TC, and apolipoprotein A1 levels. Conclusions: Several SYTL3-SLC22A3 variants, especially the rs539298 SNP, several haplotypes, and G × E interactions, were related to blood lipid parameters and the risk of CAD and IS in the Southern Chinese Han population.

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation.

PURPOSE: To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). METHODS: The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß and c-Jun N-terminal kinase (JNK) were assessed. RESULTS: Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1ß, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. CONCLUSION: HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

XKR6 rs7014968 SNP Increases Serum Total Cholesterol Levels and the Risk of Coronary Heart Disease and Ischemic Stroke.

The X Kell blood group complex subunit-related family member 6 (XKR6) gene single-nucleotide polymorphisms (SNPs) have been associated with serum lipid profiles and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in several previous studies, but the association between the XKR6 rs7014968 SNP and serum lipid levels and the risk of CHD and IS has not been detected previously. This study aims to explore the association between the XKR6 rs7014968 SNP and serum lipid traits and the susceptibility to CHD and IS in the Guangxi Han Chinese population. Snapshot technology was used to determine the genotypes of the XKR6 rs7014968 SNP in 624 controls, 588 patients with CHD, and 544 patients with IS. The XKR6 rs7014968C allele carriers in the control group had higher serum total cholesterol (TC) levels than the C allele noncarriers (P = .025). The XKR6 rs7014968C allele carriers also had an increased risk of CHD and IS (P < .05-.01). Stratified analysis showed that the patients with the rs7014968C allele in the female, age >60 years, body mass index (BMI) >24 kg/m2, and hypertension subgroups had a higher risk of CHD than those in the subgroup counterparts. The patients with the rs7014968C allele in the male, BMI > 24 kg/m2, smoker, and hypertension subgroups also had a higher risk of IS than those in the subgroup counterparts. These results suggest that the XKR6 rs7014968 SNP is likely to increase the risk of CHD and IS by increasing serum TC levels in our study populations.

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

Psychological effects of advanced care on patients received endoscopic gastric cancer resection.

BACKGROUND: This study will systematically evaluate the psychological effects of advanced care (AC) on patients who received endoscopic gastric cancer resection (EGCR). METHODS: This study will search the following databases of Cochrane Library, Pubmed, EMBASE, Web of Science, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to the present with no language limitation. All randomized controlled trials on assessing the psychological effects of AC for patients with EGCR will be included. RESULTS: This study will explore the psychological effects of AC on EGCR by assessing depression, anxiety, health-related quality of life, and adverse events. CONCLUSION: This study will summarize recent evidence for the psychological effects of AC on EGCR. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019139868.

TIMD4 rs6882076 SNP Is Associated with Decreased Levels of Triglycerides and the Risk of Coronary Heart Disease and Ischemic Stroke.

Background: The T-cell immunoglobulin and mucin domain 4 gene (TIMD4) rs6882076 single nucleotide polymorphism (SNP) has been associated with serum total cholesterol, low-density lipoprotein cholesterol and triglycerides (TG) levels, but the results are inconsistent. Moreover, little is known about such association in Chinese populations. The aim of this study was to detect the association of the TIMD4 rs6882076 SNP and serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Southern Chinese Han population. Methods: Genotypes of the TIMD4 rs6882076 SNP in 1765 unrelated subjects (CHD, 581; IS, 559 and healthy controls, 625) were determined by the Snapshot Technology. Results: The genotypic and allelic frequencies of the TIMD4 rs6882076 SNP were different between the CHD/IS patients and controls (P < 0.05 for all). The subjects with CT/TT genotypes were associated with decreased risk of CHD (P = 0.014 for CT/TT vs. CC genotypes, P = 0.010 for T vs. C alleles) and IS (P = 0.003 for CT/TT vs. CC genotypes; P = 0.016 for T vs. C alleles). The T allele carriers in healthy controls were also associated with decreased levels of serum TG. Conclusions: The results of the present study suggest that the TIMD4 rs6882076 SNP is associated with decreased risk of CHD and IS in our study population. It is likely to decrease the CHD and IS risk by reducing serum TG levels.

A novel lncRNA-miRNA-mRNA triple network identifies lncRNA TWF1 as an important regulator of miRNA and gene expression in coronary artery disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in numerous physiological functions. Yet, their mechanisms in coronary artery disease (CAD) are not well understood. METHODS: The expression profile of genes associated to CAD was reannotated into the lncRNA-mRNA biphasic profile. The target microRNA data were used to design a global CAD triple network. Thereafter, we conducted a functional enrichment analysis and clustering using the triple network from the level of topology analyses. The expression of four non-coding RNAs (ncRNAs) was measured by qRT-PCR and the risk of CAD was calculated by nomogram. The prognostic value of three ncRNAs was evaluated using receiver operating characteristic (ROC) curve. RESULTS: A CAD lncRNA-miRNA-mRNA network was constructed which included 15 mRNAs, 3 miRNAs, 19 edges and one lncRNA. Nomogram showed that four ncRNAs were the risk of CAD. After RT-PCR validation in four ncRNAs between CAD and non-CAD samples, only three ncRNAs had significant meaning for further analysis. ROC curve showed that TWF1 presented an area under curve (AUC) of 0.862, the AUC of hsa -miR-142-3p was 0.856 and hsa -miR126-5p was 0.822. After the pairwise comparison, we found that TWF1 had significant statistical significance (P TWF1-142 < 0.05 and P TWF1-126 < 0.01). The results of functional enrichment analysis of interacting gene and microRNA showed that the shared lncRNA TWF1 may be a new factor for CAD. CONCLUSIONS: This investigation on the regulatory networks of lncRNA-miRNA-mRNA in CAD suggests that a novel lncRNA, lncRNA TWF1 is a risk factor for CAD, and expands our understanding into the mechanisms involved in the pathogenesis of CAD.

Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease.

To evaluate DNA methylation sites and gene expression associated with coronary artery disease (CAD) and the possible pathological mechanism involved, we performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood datasets from the Gene Expression Omnibus repository of CAD samples and controls; (2) functional enrichment analysis and differential methylation gene regulatory network construction; (3) validation tests of 11 differential methylation positions of interest and the corresponding gene expression; and (4) correlation analysis for DNA methylation and mRNA expression data. A total of 669 differentially expressed mRNAs were matched to differentially methylated genes. After disease ontology, Kyoto Encyclopedia of Genes and Genomes pathway, gene ontology, protein-protein interaction and network construction and module analyses, 11 differentially methylated positions (DMPs) corresponding to 11 unique genes were observed: BDNF - cg26949694, BTRC - cg24381155, CDH5 - cg02223351, CXCL12 - cg11267527, EGFR - cg27637738, IL-6 - cg13104385, ITGB1 - cg20545410, PDGFRB - cg25613180, PIK3R1- cg00559992, PLCB1 - cg27178677 and PTPRC - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that CXCL12 was less hypomethylated in the CAD group, whereas the relative expression of ITGB1, PDGFRB and PIK3R1 was lower in CAD samples, and CXCL12 and ITGB1 methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of CXCL12 in CAD pathogenesis.

TRIB1 and TRPS1 variants, G × G and G × E interactions on serum lipid levels, the risk of coronary heart disease and ischemic stroke.

This study aimed to assess the association of the tribbles pseudokinase 1 (TRIB1) and transcriptional repressor GATA binding 1 (TRPS1) single nucleotide polymorphisms (SNPs) and the gene-gene (G × G) and gene-environment (G × E) interactions with serum lipid levels, the risk of coronary heart disease (CHD) and ischemic stroke (IS) in the Guangxi Han population. Genotyping of the rs2954029, rs2980880, rs10808546, rs231150, rs2737229 and rs10505248 SNPs was performed in 625 controls and 1146 unrelated patients (CHD, 593 and IS, 553). The genotypic and allelic frequencies of some SNPs were different between controls and patients (CHD, rs2954029 and rs231150; IS, rs2954029 and rs2980880; P < 0.05-0.01). Two SNPs were associated with increased risk of CHD (rs2954029 and rs231150) and IS (rs2954029) in different genetic models. Several SNPs in controls were associated with total cholesterol (rs2954029, rs2980880 and rs2737229), triglyceride (rs2954029 and rs10808546), low-density lipoprotein cholesterol (rs2954029), high-density lipoprotein cholesterol (rs2980880 and rs231150) and apolipoprotein A1 (rs2737229) levels. The rs2954029TA/AA-age (>60 year) interaction increased the risk of CHD, whereas the rs10808546CT/TT-drinking interaction decreased the risk of IS. The rs2954029A-rs2980880C-rs10808546C haplotype was associated with increased risk of CHD and IS. The rs2954029A-rs2980880T-rs10808546C haplotype was associated with increased risk of CHD. The rs2954029-rs231150 interactions had an increased risk of both CHD and IS. These results suggest that several TRIB1 and TRPS1 SNPs were associated with dyslipidemia and increased risk of CHD and IS in our study population. The G × G and G × E interactions on serum lipid levels, and the risk of CHD and IS were also observed.

Sonographic diagnosis of colorectal polyps in children: Diagnostic accuracy and multi-factor combination evaluation.

This study was established to evaluate the diagnostic value of ultrasonography in screening colorectal polyps in children and to discuss the necessity of colonic preparation before an ultrasonic examination.In this study, 288 children with colorectal polyps managed at our hospital between January 2007 and December 2016 were retrospectively reviewed. All patients were examined before and after basic colon preparation. The colorectal polyps were confirmed by colonoscopy/laparotomy and histopathology. Among all 288 patients, solitary polyps were identified in 278 patients (96.52%), and multiple polyps were identified in 10 patients (43 polyps) (3.48%) by colonoscopy/laparotomy and histopathology.By ultrasonic examination, 264 cases (264/278) were detected as solitary polyp and 9 cases (9/10) as multiple polyps (31 polyps). In 278 solitary polyps, 180 (64.74%) were detected by ultrasonic examination without a colon preparation. Following glycerine enema (10-20 mL) treatment, 264 (94.96%) cases were detected by ultrasonic examination. The sensitivity and specificity of ultrasonography with glycerine enema for the detection of colorectal polyps were 94.96% and 100%, respectively. Colon preparation significantly increased the proportion of polyps identified by ultrasonography (P < .0001), as well as the diagnostic rate of polyps in rectum, sigmoid colon and descending colon (P < .05).Ultrasonography can be the primary diagnostic method for screening colorectal polyps in children on the strength of its safety, validity, and accuracy. Basic colon preparation with glycerine enema is recommended for children, which enable the detection of intraluminal lesions before ultrasonic examination.

ANGPTL4 variants and their haplotypes are associated with serum lipid levels, the risk of coronary artery disease and ischemic stroke and atorvastatin cholesterol-lowering responses.

BACKGROUND: This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population. METHODS: Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks. RESULTS: The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR = 0.68, 95% CI = 0.47-0.99, P = 0.043 for CT/TT vs. CC) and IS (adjusted OR = 0.55, 95% CI = 0.38-0.80, P = 0.020 for CT/TT vs. CC). There was no significant association between the four SNPs and angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001; a P < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment (P < 0.001). CONCLUSIONS: The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the ANGPTL4 rs4076317 and rs2967605 SNPs.

[Establishment and Identification of MDS Mouse Model with Irom Overload].

OBJECTIVE: To establish a MDS mouse model with iron overload and to study the effect of iron overload on MDS. METHODS: The exogenous mutant gene RUNX1-S291fs was inserted into the mice bone marrow mononuclear cell's genome in mice by retrovirus and transplanted into C57BL/6 mice irradiated by 60 Co γ-ray. After 8 weeks,intraperitoneal injection of iron was performed to establish an MDS mouse model with iron overload. After 24 weeks of transplantation, the peripheral blood, bone marrow, femur, liver and spleen of mice were taken, then the morphological characteristics of peripheral blood and bone marrow cells were observed by Wright's staining; the liver, spleen and bone marrow were stained with Prussian blue to observe the iron deposition. The surface antigens of bone marrow cells were detected by flow cytometry. Bone marrow mononuclear cells and spleen tissue proteins were detected by Western blot to confirm the transfection of RUNX1-S291fs gene and expression of protein. The blood routine and transplanted cell chimeric rate of mice were monitored periodically. RESULTS: Compared with the empty plasmid control mice, levels of leukocyte and hemoglobin as well as platelet were decreased in RUNX1-S291fs mutant mice; the peripheral blood cells and bone marrow cells showed pathological hematopoiesis; the liver and spleen enlarged significantly; the tissue structure of femur, liver and spleen was abnormal; the expression of bone marrow cell surface antigens was abnormal. Bone marrow cells and spleen tissue expressed the RUNX1-S291fs protein. Compared with the controlled mice injected with normal saline, iron deposition occurred in the bone marrow, liver and spleen stained with Prussian blue in the mice injected with iron agent. CONCLUSION: Mice engineered to carry exogenous mutant gene RUNX1-S291fs and injected with iron showed pathologic features of MDS and iron overload, resulting in establishing MDS iron overloaded mouse model successfully, which lays a foundation for studying the effect of iron overload on MDS.

Association between the PPP1R3B polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke in a southern Chinese Han population.

BACKGROUND: Little is known about the association of the protein phosphatase 1 regulatory subunit 3B gene (PPP1R3B) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study detected such association in a Southern Chinese Han population. METHODS: Genotypes of 4 novel PPP1R3B SNPs (rs12785, rs330910, rs330915 and rs9949) in 1704 Han Chinese (CAD, 556; IS, 531 and control, 617) were determined by the Snapshot technology. RESULTS: The rs12785A and rs9949A allele frequency was higher in both CAD/IS patients than in controls. The rs330910T and rs330915T allele frequency was also higher in CAD patients than in controls. The rs330910T allele carriers in controls had lower serum low-density lipoprotein cholesterol (LDL-C) levels than the rs330910T allele non-carriers (P < 0.0014). The rs12785A, rs9949A and rs330910T allele carriers were associated with an increased risk of CAD (P = 0.008-0.004). There was strong linkage disequilibrium among the 4 SNPs in the controls and CAD/IS patients. The T-A-A-G haplotype was associated with a decreased risk of CAD and IS, whereas the A-A-T-A haplotype was associated with an increased risk for IS. Haplotype-environment interactions on the risk of CAD and IS were also observed. CONCLUSIONS: Several PPP1R3B polymorphisms were associated with serum LDL-C levels, the risk of CAD and IS in the Southern Chinese Han population. But these findings still need to be confirmed in the other populations with larger sample sizes.

DOCK7-ANGPTL3 SNPs and their haplotypes with serum lipid levels and the risk of coronary artery disease and ischemic stroke.

BACKGROUND: Little is known about the association of the dedicator of cytokinesis 7 (DOCK7 rs1748195) and angiopoietin like 3 (ANGPTL3 rs12563308) single nucleotide polymorphisms (SNPs) and their haplotypes with serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study aimed to detect such association in a Southern Chinese Han population. METHODS: This study included 1728 subjects (CAD, 568; IS, 539; and controls, 621). Genotypes of the two SNPs were determined by the Snapshot technology. RESULTS: The genotypic and allelic frequencies of the rs1748195 SNP were different between CAD patients and controls (P < 0.05 for each), the rs1748195G allele frequency was higher in CAD patients than in controls (27.6% vs. 23.6%, P = 0.024). The genotypic frequencies of the rs12563308 SNP were also different between CAD patients and controls (P = 0.021). The rs1748195 SNP was associated with an increased risk of CAD after controlling for potential confounders and Bonferroni correction (P < 0.025 considered statistically significant; Recessive: OR = 1.79, 95% CI = 1.04-3.06, P = 0.017; Log-additive: OR = 1.27, 95% CI = 1.02-1.57, P = 0.014), whereas the rs12563308 SNP was associated with a decreased risk of CAD (Dominant: OR = 0.69, 95% CI = 0.45-0.94, P = 0.011; Log-additive: OR = 0.73, 95% CI = 0.49-0.89, P = 0.009). The rs1748195 SNP was also associated with an increased risk of severity to coronary artery atherosclerosis (Dominant: OR = 1.45, 95% CI = 1.07-2.11, P = 0.017; Log-additive: OR = 1.35, 95% CI = 1.09-1.82, P = 0.013). The interactions of SNP-environment on serum lipid levels and the risk of severity to coronary artery atherosclerosis, CAD and IS were noted. The rs1748195G-rs12563308T haplotype was associated with an increased angiographic severity to coronary artery atherosclerosis (OR = 1.46, 95% CI = 1.05-2.03), and the risk of CAD (OR = 1.37, 95% CI = 1.08-1.74). The interactions of haplotype-hypertension on the risk of CAD and haplotype-drinking on the risk of CAD/IS were observed. CONCLUSIONS: These results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of CAD and IS in the Southern Chinese Han population.

Plasma Exosomal miRNA-122-5p and miR-300-3p as Potential Markers for Transient Ischaemic Attack in Rats.

Background: Differentiation of transient ischaemic attack (TIA) from ischaemic stroke within the thrombolysis time window is difficult. Although TIA may be diagnosed within this window, the latest imaging technologies are complex and costly. Serum markers, which are non-invasive, rapid and economic, are used for diagnosis and prognosis of various diseases. Exosome-derived miRNA markers for TIA are unknown. Methods: We examined focal brain ischaemia produced by occlusion of the middle cerebral artery (MCAo) for 5 min, 10 min, and 2 h in rats. Exosomal miRNAs with consistent trends in cerebrospinal fluid (CSF) and plasma were identified by deep sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic accuracy of these miRNAs for TIA in rats. Results: Rno-miR-122-5p and rno-miR-300-3p were selected. Plasma exosomal rno-miR-122-5p was significantly downregulated in 10 min ischaemic rats compared with control and 5 min plasma. Plasma exosomal rno-miR-300-3p was significantly upregulated in 5 min ischaemic rats compared with control, 10 min and 2 h rats. Plasma and CSF levels of these miRNAs were correlated. ROC analysis showed high AUC values for rno-miR-122-5p (0.960) and rno-miR-300-3p (0.970) in the 10 and 5 min rats, respectively, compared with controls. Conclusions: Plasma exosomal rno-miR-122-5p and rno-miR-300-3p may be blood-based TIA biomarkers.

Erratum: The association between the DNAH11 rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

[This corrects the article on p. 4585 in vol. 11, PMID: 31949857.].