Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study.

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.

Carbon dots electrochemically prepared from dopamine and epigallocatechin gallate for hypochlorite detection with high selectivity via a dynamic quenching mechanism.

Monitoring hypochlorite levels in water is of great importance because of its high toxicity and wide applications as water disinfectants. In this manuscript, carbon dot (CD) was electrochemically prepared by using dopamine and epigallocatechin gallate (molar ratio 1:1) as the carbon source for efficient hypochlorite determination. By electrolyzing the solution at 10 V for 12 min with PBS as an electrolyte, dopamine would react with epigallocatechin at the anode, and through polymerization, dehydration, and carbonization, strong blue-fluorescent CDs were obtained. CDs were characterized by UV-Vis spectroscopy, fluorescence spectroscopy, high-resolution transmission electron microscopy, FT-IR, etc. These CDs have an excitation wavelength at 372 nm and an emission wavelength at 462 nm, owing an average particle size of 5.5 nm. The presence of hypochlorites can quench the fluorescence of CDs, and its reduction in intensity is linear with hypochlorite concentration over the range of 0.5-50 µM, ΔF/F0 = 0.0056 + 0.0194CClO-, R2=0.997. The detection limit achieved 0.23 µM (S/N = 3). The mechanism for fluorescence quenching is via a dynamic process. Different from many other fluorescence methods based on the strong oxidizing ability of hypochlorites, our method shows strong selectivity toward hypochlorites over other oxidizing agents such as H2O2. The assay was validated by the detection of hypochlorites in water samples, with recoveries between 98.2% and 104.3%.

Caspofungin Suppresses Brain Cell Necroptosis in Ischemic Stroke Rats via Up-Regulation of Pellino3.

PURPOSE: Pellino3, an ubiquitin E3 ligase, prevents the formation of the death-induced signaling complex in response to TNF-α by targeting receptor-interacting protein kinase 1 (RIPK1), and bioinformatics analysis predicted an interaction between Pellino3 and caspofungin, a common antifungal drug used in clinics. This study aimed to explore the effect of caspofungin on brain injury in ischemic stroke and the underlying mechanisms. METHODS: Ischemic stroke injury was induced in Sprague Dawley rats by occlusion of the middle cerebral artery (MCA) for 2 h, followed by 24 h reperfusion. PC12 cells were deprived of both oxygen and glucose for 8 h and then were cultured for 24 h with oxygen and glucose to mimic an ischemic stroke in vitro. RESULTS: Animal experiments showed brain injury (increase in neurological deficit score and infarct volume) concomitant with a downregulation of Pellino3, a decreased ubiquitination of RIPK1, and an up-regulation of necroptosis-associated proteins [RIPK1, RIPK3, mixed lineage kinase domain-like protein (MLKL), p-RIPK1, p-RIPK3, and p-MLKL]. Administration of caspofungin (6 mg/kg, i.m.) at 1 h and 6 h after ischemia significantly improved neurological function, reduced infarct volume, up-regulated Pellino3 levels, increased RIPK1 ubiquitination, and down-regulated protein levels of RIPK1, p-RIPK1, p-RIPK3, and p-MLKL. PC12 cells deprived of oxygen/glucose developed signs of cellular injury (LDH release and necroptosis) concomitant with downregulation of Pellino3, decreased ubiquitination of RIPK1, and elevated necroptosis-associated proteins. These changes were reversed by overexpression of Pellino3. CONCLUSION: We conclude that Pellino3 has an important role in counteracting necroptosis via ubiquitination of RIPK1 and caspofungin can suppress the brain cell necroptosis in ischemic stroke through upregulation of Pellino3.

The Protective Effect of Vitexin Compound B-1 on Rat Cerebral I/R Injury through a Mechanism Involving Modulation of miR-92b/NOX4 Pathway.

BACKGROUND: Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression. OBJECTIVE: The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression. METHODS: Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b. RESULTS: Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function of miR-92b in suppressing NOX4 expression. CONCLUSION: We conclude the protective effect of VB-1 against rat cerebral I/R injury through a mechanism involving modulation of miR-92b/NOX4 pathway.

Polymyxin B Reduces Brain Injury in Ischemic Stroke Rat Through a Mechanism Involving Targeting ESCRT-III Machinery and RIPK1/RIPK3/MLKL Pathway.

Endosomal sorting complex required for transport III (ESCRT-III) machinery is a key component to counteract the mixed lineage kinase domain-like pseudokinase (MLKL)-induced plasma membrane broken in cells undergoing necroptosis. Based on the bioinformatics analysis, polymyxin B, a polypeptide antibiotic, is predicted to simultaneously interact with ESCRT-III subunits and necroptosis-relevant proteins. This study aims to explore whether polymyxin B could reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and/or suppressing the RIPK1/RIPK3/MLKL pathway. The stroke rats showed evident brain injury, concomitant with the downregulation of ESCRT-III subunits and the upregulation of necroptosis-relevant proteins. Post-ischemic administration of polymyxin B could alleviate the brain injury, accompanied by restoration of the levels of ESCRT-III subunits and suppression of necroptosis-relevant proteins. And, polymyxin B exerted similar effects in hypoxia-treated HT22 cells. We conclude that polymyxin B can reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and suppressing the RIPK1/RIPK3/MLKL pathway simultaneously.

Dipsacoside B Exerts a Beneficial Effect on Brain Injury in the Ischemic Stroke Rat through Inhibition of Mitochondrial E3 Ubiquitin Ligase 1.

BACKGROUND: Upregulation of mitochondrial E3 ubiquitin ligase 1 (Mul1) contributes to brain injury in ischemic stroke due to disturbance of mitochondrial dynamics, and bioinformatics analysis predicts that Mul1 is a potential target of Dipsacoside B. OBJECTIVE: The aim of the study was to explore whether Dipsacoside B can exert a beneficial effect on brain injury in the ischemic stroke rat via targeting Mul1. METHODS: The SD rat brains or PC12 cells were subjected to 2 h-ischemia or 8 h-hypoxia plus 24 h-reperfusion or 24 h-reoxygenation to establish the ischemic stroke rat model in vivo or in vitro, which were treated with Dipsacoside B at different dosages. The brain or PC12 cell injury, relevant protein levels and mitochondrial functions were measured by methods of biochemistry, flow cytometry or Western blot. RESULTS: The neurological dysfunction and brain injury (such as infarction and apoptosis) observed in the ischemic stroke rats were accompanied by increases in Mul1 and Dynamin-related protein 1 (Drp1) levels along with decreases in mitofusin 2 (Mfn2) level and ATP production. These effects were attenuated by Dipsacoside B. Consistently, cell injury (necroptosis and apoptosis) occurred in the PC12 cells exposed to hypoxia concomitant with the upregulation of Mul1 and Drp1 along with downregulation of Mfn2 and mitochondrial functions (such as increases in reactive oxygen species production and mitochondrial fission and decreases in mitochondrial membrane potential and ATP production).These phenomena were reversed in the presence of Dipsacoside B. CONCLUSION: Dipsacoside B can protect the rat brain against ischemic injury via inhibition of Mul1 due to the improvement of mitochondrial function.

Development and validation of a new scoring system for the early diagnosis of tuberculous meningitis in adults.

We developed and validated a new diagnostic scoring system by simultaneously comparing 28 factors (including clinical, laboratory, and imaging) of HIV uninfected adult tuberculous meningitis (TBM) with viral meningitis (VM), bacterial meningitis (BM), and cryptococcal meningitis (CM). Predictors of TBM diagnosis obtained by logistic regression. A total of 382 patients with intracranial infection participated, and eight factors were independently associated with TBM diagnosis: symptom duration, evidence of extracranial tuberculosis, cerebrospinal fluid (CSF) leukocyte, CSF neutrophil, CSF protein, low serum sodium, meningeal enhancement, and tuberculomas. Factors are assigned according to weight, a score of ≥ 5 was suggestive of TBM with a sensitivity of 85.8% and a specificity of 87.7%, and the area under the receiver operating characteristic curve was 0.923. When applied to a prospective validation cohort, this scoring model showed robust performance. Our study suggests that the application of this score can help diagnose TBM more efficiently.

Worsening CSF parameters after the start of anti-tuberculosis treatment predicts intracerebral tuberculoma development.

OBJECTIVES: We investigated whether early worsening of cerebrospinal fluid (CSF) predicts the later paradoxical tuberculomas and is a potential predictive biomarker. METHODS: Patients of HIV-negative tuberculous meningitis fulfilling the inclusion criteria(n = 98) underwent clinical and CSF evaluation, together with repeated neuroimaging. We compared the baseline clinical data and continuous CSF of patients who did (n = 36) and did not (n = 62) develop paradoxical tuberculomas, and reported the changes associated with symptomatic tuberculomas. A logistic regression analysis was developed to reveal predictors for paradoxical tuberculomas. RESULTS: The proportion of worsening CSF parameters (WBC count and percent neutrophils) in the paradoxical tuberculomas group (27/36, 75.0%) was significantly higher than the non-paradoxical tuberculomas group (15/62, 24.2%). The logistic regression analysis revealed that worsening CSF parameters was the highest risk predictor for paradoxical tuberculomas. Most worsening CSF parameters (81.0%) occurred within two weeks after treatment (2-24 days, median 7 days), and paradoxical tuberculomas commonly happened two weeks later (12 days to 13 months, median 22 days). The period between worsening CSF parameters and paradoxical tuberculomas ranged from 6 to 383 days (median 21days). There were no significant differences in mortality and prognosis between the two groups. CONCLUSIONS: Early worsening of CSF parameters predicts subsequent development or progression of tuberculomas.

Paradoxical reaction in HIV-negative tuberculous meningitis patients with spinal involvement.

OBJECTIVE: The aim of this study was to investigate the occurrence of paradoxical reaction (PR) in HIV-negative tuberculous meningitis (TBM) patients with spinal involvement, as well as its possible risk factors. METHODS: Fifty TBM patients with spinal involvement were studied retrospectively and divided into a PR group and a non-PR group according to the presence of PR. Their demographic, clinical, radiological, and laboratory data, and status at follow-up were collected and compared. RESULTS: PR developed in 26 patients (52%), with the median time to the development of PR being 30days (range 15-330 days) after the initiation of tuberculosis therapy. At initial diagnosis, age, documented acid-fast bacilli (AFB), and the cerebrospinal fluid protein level were found to differ significantly between the two groups. After multivariate analysis, age, documented AFB, and vertebral involvement were significantly associated with the development of PR. CONCLUSIONS: PR was common in TBM patients with spinal involvement. Age, documented AFB, and musculoskeletal involvement may be predictors of PR development.

[Correlation between cerebrovascular hemodynamic index accumulative score and subclinical arteriosclerosis indicators].

OBJECTIVE: To explore the correlation between cerebrovascular hemodynamic index (CVHI)accumulative score and subclinical arteriosclerosis indicators.
 Methods: A total of 27 184 cases were collected from the Health Management Center, the Third Xiangya Hospital, Central South University. Linear regression analysis was carried out to confirm the correlations between CVHI accumulative score and the modified Framingham stroke profile (FSP), as well as between CVHI accumulative score and cerebrovascular diseases (ICVD) scale. The correlation between CVHI accumulative score and brachial-ankle pulse wave velocity (baPWV), carotid plaque orcarotid intima-media thickness (CIMT) was analyzed by multifactor logistic regression model in 11 580 cases. Moreover, the correlation between CVHI accumulative score and microalbuminuria or serum cystatin C was performed by multifactor logistic regression model in 9 860 cases.
 Results: In this study, the people whose CVHI accumulative score was less than 75 accounted for 12.98%. The CVHI accumulative score was negatively related with the modified FSP score (r=-0.484, P<0.01) or ICVD score (r=-0.455, P<0.01). The multifactor logistic regression model found that the baPWV, carotid plaque, microalbuminuria and serum cystatin C were independent predictors for CVHI accumulative score.
 Conclusion: The CVHI accumulative score is correlated with the modified FSP score, ICVD score and indexes of subclinical arteriosclerosis (baPWV, carotid plaque, microalbuminuria and serum cystatin C). The CVHI accumulative score could be used as a tool for zero-level and primary prevention of cerebral stroke.

Evaluation of the oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population.

AIM: Type 2 diabetes mellitus is a polygenic metabolic disorder resulting from oxidative stress, the root cause of insulin resistance, ß-cell dysfunction and impaired glucose tolerance. The aim of this study was to investigate the role of oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO in type 2 diabetes mellitus susceptibility in the Chinese Han population. METHODS: A total of 396 type 2 diabetes mellitus patients and 678 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222, GPX1 rs1050450, GPX3 rs3828599 and MPO rs2107545 gene polymorphisms were genotyped. RESULTS: We found one single-nucleotide polymorphism in the MPO gene was associated with type 2 diabetes mellitus susceptibility [rs2107545: odds ratio = 1.563 (1.166-2.096); p = 0.003], after adjusting for covariates. Furthermore, we also considered the likely complexity of effects of genetic and conventional risk factors in type 2 diabetes mellitus-related vascular complications, such as carotid plaques. Our analysis revealed that the GPX1 rs1050450 and MPO rs2107545 were significantly associated with increased risk of carotid plaques in type 2 diabetes mellitus patients. CONCLUSION: Our study presents novel evidence for main effects of MPO gene on type 2 diabetes mellitus susceptibility. Furthermore, our study supported the association between variants of oxidative stress-related genes ( GPX1 and MPO) and carotid plaques in type 2 diabetes mellitus patients, which indicated a modulation of type 2 diabetes mellitus-related vascular complication susceptibility by genetic predisposition.

Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic Interactions in a Chinese Population.

BACKGROUND/AIMS: To investigate the roles of the oxidative stress related-genes ALOX5, ALOX5AP and MPO in ischemic stroke susceptibility in the Han Chinese population. METHODS: A total of 351 ischemic stroke patients and 417 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 gene polymorphisms were genotyped. RESULTS: We identified that rs2107545 of MPO gene was significantly associated with ischemic stroke susceptibility after adjusting for covariates. Furthermore, we also considered the likely complexity of oxidative stress and inflammatory process in stroke by assessing the combined effects of multiple genes. Generalized multifactor dimensionality reduction (GMDR) analysis revealed that the combination of ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 was significantly associated with increased risk of ischemic stroke (P=0.0040, OR (95% CI) =1.991 (1.241 to 3.195)). Additionally, the MPO rs2107545 genotype was significantly associated with clinical outcomes at 6 months after discharge from the hospital. CONCLUSION: Our study revealed that epistatic interaction among the ALOX5, ALOX5AP and MPO genes played a significant role in vulnerability to ischemic stroke. Furthermore, these results also suggest that the rs2107545 of MPO gene can be used as a biomarker for the susceptibility and prognosis of ischemic stroke patients.

[Meta-analysis for the relationship between lipoprotein-associated phospholipase A2 and ischemic stroke].

OBJECTIVE: To analyze the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and ischemic stroke.
 Methods: Corresponding data, with case-control studies or cohorts regarding Lp-PLA2 and ischemic stroke, were retrieved from PubMed, Web of Science, Embase, the Cochrane Library, Chinese Biomedical Literature (CMB), VIP, China National Knowledge Infrastructure (CNKI), and Wanfang Database. Meta-analysis was performed by using Stata12.0.
 Results: Eight studies including 46 034 participants met the inclusion criteria. Meta-analysis showed that the combined effect of relative risk (RR) between Lp-PLA2 mass and ischemic stroke was [1.04 (0.98 to 1.11)] and that the combined effect of RR between Lp-PLA2 activity and ischemic stroke was [1.03 (0.96 to 1.10)], suggesting that Lp-PLA2 mass and activity were not associated with ischemic stroke.
 Conclusion: It cannot be considered that Lp-PLA2 mass and Lp-PLA2 activity was the risk factor for ischemic stroke.

Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population.

BACKGROUND: Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. METHODS: 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. RESULTS: No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95% CI) = 1.55 (1.07-2.23)) in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313), hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p < 0.0001, OR (95% CI) = 6.57 (4.79-9.01)). CONCLUSION: Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke.

Variants in the Atherogenic ALOX5AP, THBD, and KNG1 Genes Potentiate the Risk of Ischemic Stroke via a Genetic Main Effect and Epistatic Interactions in a Chinese Population.

BACKGROUND: Ischemic stroke (IS) is a multifactorial disease that displays a strong genetic predisposition. However, the genetic architecture of IS has yet to be fully elucidated. It was hypothesized that epistasis between genes in multiple atherothrombotic pathways may play a vital role in determining the susceptibility to IS. The aim of the present study was to investigate the contributions of the hypothesized genetic factors to IS and the interactions between these genetic factors in a Chinese population. METHODS: In this study, 351 cases with IS and 417 control subjects from a Chinese population were genotyped for single-nucleotide polymorphisms (SNPs) in 12 genes hypothesized to be involved in atherosclerosis, coagulation, and related pathways. We examined SNP main effects and epistatic interactions between these polymorphic loci. RESULTS: rs710446 of the KNG1 gene was associated with IS susceptibility based on an additive genetic model (rs710446: P = .012; odds ratio [OR], 1.247; 95% confidence interval [CI], 1.050-1.481) after adjusting for covariates. Furthermore, an epistatic interaction between the ALOX5AP, THBD, and KNG1 gene was also identified in association with stroke susceptibility (P < .001 after 1000 permutations). Based on the chi-squared test, the OR of the high-risk combination of the three-locus model increased the risk of IS by 2.53-fold (95% CI, 1.60-4.01; P < .0001). CONCLUSIONS: Our findings support the association of the epistatic interactions of ALOX5AP, THBD, and KNG1 and present novel evidence for the main effect of KNG1 gene on IS susceptibility, suggesting a modulation of stroke risk by a genetic main effect and gene-gene interactions.

Gene polymorphism of rs556621 but Not rs11984041 is associated with the risk of large artery atherosclerotic stroke in a Xinjiang Uyghur population.

BACKGROUND: Stroke is one of the main causes of death and adult chronic disability. Recently, 2 independent genome-wide association studies reported that the genetic variants (rs556621 and rs11984041) are significantly associated with large artery atherosclerosis (LAA). METHODS: To determine whether these 2 variants are associated with the pathogenesis of LAA in stroke patients from the Xinjiang Uyghur autonomous region of China, both variants were evaluated in a series of 733 LAA stroke patients (434 Han and 299 Uyghur) and 725 age-, gender-, smoking-, alcohol habits- and ethnicity-matched controls (401 Han and 324 Uyghur). RESULTS: For rs556621, significant differences in genotypic and allelic distributions were observed between Uyghur patients and controls (P = .045 for genotypic distribution, P = .042 for allelic distribution) but not in the Chinese Han cohort (P > .05). No significant differences were found in genotypic and allele distributions between patients and controls for rs11984041 in either the Chinese Han or Uyghur cohort (P > .05). CONCLUSIONS: The variant rs556621 but not rs11984041 may increase susceptibility of LAA stroke in the Xinjiang Uyghur population.

Hygroscopicity and optical properties of alkylaminium sulfates.

The hygroscopicity and optical properties of alkylaminium sulfates (AASs) were investigated using a hygroscopicity tandem differential mobility analyzer coupled to a cavity ring-down spectrometer and a nephelometer. AAS particles do not exhibit a deliquescence phenomenon and show a monotonic increase in diameter as the relative humidity (RH) ascends. Hygroscopic growth factors (GFs) for 40, 100 and 150 nm alkylaminium sulfate particles do not show an apparent Kelvin effect when RH is less than 45%, whereas GFs of the salt aerosols increase with initial particle size when RH is higher than 45%. Calculation using the Zdanovskii-Stokes-Robinson mixing rule suggests that hygroscopic growth of triethylaminium sulfate-ammonium sulfate mixtures is non-deliquescent, occurring at very low RH, implying that the displacement of ammonia by amine will significantly enhance the hygroscopicity of (NH4)2SO4 aerosols. In addition, light extinction of AAS particles is a combined effect of both scattering and absorption under dry conditions, but is dominated by scattering under wet conditions.

TIMP-1 polymorphisms in a Chinese Han population with intracerebral hemorrhage.

Remodeling of extracellular matrix (ECM) and breakdown of blood-brain barrier (BBB) are crucial events in the pathogenesis of intracerebral hemorrhage (ICH). Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, are the most important degrading enzymes in the ECM and BBB. These proteolytic effects are controlled predominantly by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is the main endogenous inhibitor of MMP-9. Two polymorphisms in the TIMP-1 gene (rs4898 and rs2070584) were selected through a literature review and successfully genotyped in a study sample of 410 ICH patients and 305 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined. Furthermore, the serum levels of TIMP-1 were measured in a subgroup of 96 ICH patients on days 1 after ICH onset and 76 controls. Analyses showed that C allele of rs2070584 was significantly associated with the development of ICH in male subjects (p = 0.037, OR = 1.535, 95%CI 1.025-2.300). Multiple logistic regression analysis under three genetic models demonstrated both rs4898 and rs2070584 were not risk factors for ICH in female subjects. Furthermore, serum levels of TIMP-1 were significantly higher in ICH patients than those in normal controls. However, the serum levels of TIMP-1 showed a nonsignificant decrease, depending on the alleles and genotypes of rs2070584 both in male and female cases. In conclusion, this is the first association study of the TIMP-1 gene variants with ICH. Our data suggest that C allele of rs2070584 is a risk factor for ICH development in the Chinese male population. However, the precise function of this variant needs further investigation.

[Association of ApoAI gene rs12721026 polymorphism with cerebral hemorrhage in Changsha Han population and its effect on plasma lipid levels].

OBJECTIVE: To explore the association between apolipoprotein AI (ApoAI) gene rs12721026 polymorphism and cerebral hemorrhage (CH) in Changsha Han population, and to evaluate the effect of rs12721026 polymorphism on plasma lipid levels. METHODS: A total of 273 patients with CH and 140 healthy controls were collected. The rs12721026 polymorphism of ApoAI was analyzed by SNaPshot genotyping analysis and DNA sequencing. The total cholesterol (TG), triglyceride (TC), HDL-C and LDL-C were examined by oxidase method. RESULTS: There was no significant difference in the genotype and allele frequencies of rs12721026 polymorphism between the CH group and the control group (P>0.05). Both in the CH group and in the control group, the level of HDL-C of the TT gene type of rs12721026 was significantly higher than that of the GT/GG gene type (P<0.05). There was no significant difference in the levels of TG, TC and LDL-C among different subgroups of gene types. CONCLUSION: There may be no association between apoAI gene rs12721026 polymorphism with CH in Changsha Han population, which may still influence the HDL-C levels.

[Determination of trace chloride in sodium sulfate of analytical reagent-grade by valve-switching ion chromatography].

A valve-switching ion chromatography system was developed for the determination of trace chloride in sodium sulfate using a single pump, a suppressor, two valves and three columns. Using this technique, the trace chloride was eluted from the concentrator column (IonPac TAC-ULP1, 23 mm x 5 mm) to the analytical column (IonPac AS18, 250 mm x 4 mm), and the sulfate flowed to the waste. Under the optimized separation conditions, the method showed good linearity (r2 > 0.999) in the range of 0.03 - 1 mg/L and the average recoveries of chloride were 98.0% - 103.0% with the relative standard deviation less than 2%. The limit of detection was 0.01 mg/L (S/N = 3). The results demonstrated that this system has the advantages of high sensitivity, facile automation and simple sample pretreatment, which might be a promising approach for the determination of trace chloride in high-purity reagents.