Polymorphisms but not mutations of the KCNQ1 gene are associated with lone atrial fibrillation in the Chinese Han population.

BACKGROUND: Recent studies suggest that mutation of the slow delayed rectifier potassium channel (IKs) contributes to familial atrial fibrillation (FAF). In the current study, we identified common genetic variants of KCNQ1 and explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 190 Han Chinese patients with sporadic AF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified six known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 190 LAF patients and 190 healthy controls. RESULTS: One of the SNPs in KCNQ1 was strongly associated with LAF; significant allelic association was detected rs59233444 (P = 0.013, OR = 1.469, 95% confidence interval (CI): 1.083-1.993). A multiple regression analysis indicated that rs59233444 is an independent risk factor for LAF. Twelve new variants were identified in KCNQ1, including one in the 5'-UTR, two in the 3'-UTR, six in introns, two synonymous substitutions, and one missense substitution. Variants c.1009C>T, c.1860C>T, and c.+2285C>T were not present in the 190 controls, and the others were identified in controls at various frequencies. CONCLUSIONS: rs59233444, a common SNP but not mutation in the coding regions of the KCNQ1 gene, is a risk factor for LAF in Chinese Han population.

[KCNQ1 mutation in patients with lone atrial fibrillation].

OBJECTIVE: Recent studies suggest that mutation of the slow delayed rectifier potassium channel [I(Ks)] contributes to familial atrial fibrillation (FAF). In the current study, we explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 95 Han Chinese patients with LAF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified four known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 95 LAF patients and 190 healthy controls. RESULTS: Three new variations were identified in KCNQ1 from 95 sporadic LAF including 1 in 5'UTR(c.-22T > C), 1 in exon9 synonymous mutation (c.1008C > T) and 1 in intron region (c.1590 + 31A > T). These variations were heterozygous and not presented in 190 healthy controls. Highly significant difference was detected between LAF group and control groups in rs760419 polymorphism. Logistic regression revealed that rs760419 was independent risk factor for LAF(OR = 2.056, P = 0.001). CONCLUSIONS: KCNQ1 mutation is associated with LAF and rs760419 polymorphism is a susceptible marker for LAF.

[Binocular clinical comparison study of Tecnis multifocal aspheric and monofocal spherical intraocular lenses].

PURPOSE: To compare visual function in pseudophakic patients with bilateral implantation of Tecnis multifocal aspheric and conventional monofocal spherical intraocular lenses (IOL). METHODS: A prospective study of 100 consecutive cases (200 eyes) was conducted. All cataract patients underwent phacoemulsification were randomized to receive multifocal aspheric IOL (Tecnis ZM900, AMO, multifocal aspheric group) or conventional spherical IOL (Akreos Adapt, Bausch & Lomb, monofocal spherical group). The following investigations were performed to assess the uncorrected and distance-corrected visual acuity of distance, intermediate and near distances, accommodative amplitude, spherical aberrations of total eye, contrast sensitivity, glare sensitivity and near stereoacuity. Patients were surveyed for visual disturbances and lifestyle visual quality. The independent-samples t test was used to compare the measure data which met normal distribution and the Mann-Whitney U test was used to compare the measure data which didn't meet. The chi-square test was applied to compare categorical variables. RESULTS: The uncorrected and distance-corrected bilateral visual acuity of multifocal aspheric group at 30 cm and 40 cm were 0.24 ± 0.12 and 0.22 ± 0.11 (logMAR), better than monofocal spherical group (Z = -8.261, P = 0.000; Z = -5.508, P = 0.000), but the visual acuity at other distances had no statistical difference between two groups. Patients with multifocal aspheric IOL had significantly higher accommodative amplitude than those with monofocal spherical IOL, improved about 2.3 ∼ 2.8 D (Z = -10.655, P = 0.000; Z = -2.709, P = 0.007). Mean spherical aberration of multifocal aspheric group was (0.027 ± 0.160) µm and (0.006 ± 0.083) µm, significantly lower than that of monofocal spherical group (0.269 ± 0.161) µm, (0.037 ± 0.205) µm at 5 mm and 3 mm pupil diameter (Z = -8.815, P = 0.000; Z = -2.791, P = 0.005). The difference of contrast sensitivity was not significant, but glare sensitivity was higher for monofocal spherical group than for multifocal aspheric group. Multifocal aspheric group showed statistically better uncorrected stereoacuity (72.4 ± 29.9)″ than monofocal spherical group (92.8 ± 35.7)″ (Z = -3.089, P = 0.002). CONCLUSIONS: The present clinical results demonstrated that Tecnis multifocal aspheric group had better near visual acuity, accommodative amplitude and near stereoacuity as compared to conventional monofocal spherical group. The aspheric design reduced spherical aberration of total eye and improved contrast sensitivity in some way.

Comparison of dabigatran and warfarin used in patients with non-valvular atrial fibrillation: Meta-analysis of random control trial.

BACKGROUND: Dabigatran is a kind of oral anticoagulant and there was little review only about dabigatran and warfarin used in patients with atrial fibrillation. This meta-analysis only assesses the dabigatran and warfarin used in patients with atrial fibrillation. DESIGN: Cochrane Library, PubMed, Clinical Trials.gov, CNKI, and WanFang databases were searched. The primary endpoint was the incidence of stroke and the second endpoints were the incidence of bleeding and embolic events. RESULTS: Six RCTs and 20086 patients were included in our meta-analysis. No significant difference was obtained between 110 mg dabigatran and warfarin on the endpoint of stroke (risk ratio (RR), 0.90; 95% confidence interval [CI], 0.71-1.12; P = .34; I = 0%) and embolic events p (RR, 0.89; 95% CI, 0.71-1.12; P = .32; I = 0%). However, the 110 mg dabigatran associated lower incidence of bleeding (RR, 0.81; 95% CI, 0.69-0.95; P = .01; I = 0%) compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower rate of stroke (RR, 0.96; 95% CI, 0.83-1.12; P = .62; I = 0%) and embolic events (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%) but similar in the incidence of bleeding (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%). CONCLUSION: No significant difference was obtained between 110 mg dabigatran and warfarin in the incidence of stroke and embolic events. However, the 110 mg dabigatran associated lower incidence of bleeding compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower incidence of stroke and embolic events but similar in the incidence of bleeding.

Proteomic analysis of human lens epithelial cells exposed to microwaves.

PURPOSE: To study proteomic changes in human lens epithelial cells (HLECs) exposed to 1800-MHz Global System for Mobile Communication (GSM)-like microwaves. METHODS: In three separate experiments, HLECs were exposed and sham-exposed (six dishes each) to 1800-MHz GSM-like radiation for 2 h. The specific absorption rates were 1.0, 2.0, or 3.5 W/kg. Immediately after radiation, the proteome was extracted from the HLECs. Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis(2-DE; silver staining) and PDQuest 2-DE analysis software were used to separate and analyze the proteome of exposed and sham-exposed HLECs. Four differentially expressed protein spots were selected and identified by using electrospray ionization tandem mass spectrometry (ESI-MS-MS). RESULTS: When the protein profiles of exposed cells were compared with those of sham-exposed cells, four proteins were detected as upregulated. After analysis by ESI-MS-MS and through a database search, heat-shock protein (HSP) 70 and heterogeneous nuclear ribonucleoprotein K (hnRNP K) were determined to be upregulated in the exposed cells. CONCLUSIONS: Two-dimensional polyacrylamide gel electrophoresis combined with mass spectrometry may be a powerful tool for screening potential electromagnetic-reaction protein markers. HSP70 and hnRNP K are involved in the stress reaction of HLECs exposed to microwaves. These cell responses are nonthermal effects of the electromagnetic field.

A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co­expression analysis.

The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co­expression analysis. The microarray dataset associated with HCM (E­GEOD­36961) was obtained from the European Molecular Biology Laboratory­European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co­expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co­expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T­complex protein 1 (CCT)/T­complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co­expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

Attractors of hypertrophic cardiomyopathy using maximal cliques and attract methods.

BACKGROUND: Our study was designed to identify the differential attractor modules related with hypertrophic cardiomyopathy (HCM) by integrating clustering-based on maximal cliques algorithm and Attract method. METHODS: We firstly recruited the HCM-related microarray data from ArrayExpress database. Next, protein-protein interaction (PPI) networks of normal and HCM were constructed and re-weighted using spearman correlation coefficient (SCC). Then, maximal cliques were found from the PPI networks through the clustering-based on maximal cliques approach. Afterwards, highly overlapped cliques were eliminated or merged according to the interconnectivity, and then modules were obtained. Subsequently, we used Attract method to identify differential attractor modules, following by the pathway enrichment analyses for genes in differential attractor modules. RESULTS: After removing the cliques with nodes less than or equal to 4, 926 and 1118 maximal cliques in normal and HCM PPI networks were obtained for module analysis. Then, we obtained 32 and 55 modules from the PPI networks of normal and HCM, respectively. By comparing with normal condition, there were 5 module pairs with the same or similar gene composition. Significantly, based on attract method, we found that these 5 modules were differential attractors. Pathway enrichment analyses indicated that proteasome, ribosome and oxidative phosphorylation were the significant pathways. CONCLUSIONS: Proteasome, ribosome and oxidative phosphorylation might play pathophysiological roles in HCM.

[Clinical observation on effect and safety of combined use of wenxin granule and amiodarone for conversion of auricular fibrillation].

OBJECTIVE: To observe the clinical effect of the combined use of amiodarone and Wenxin Granule (WXG) in auricular fibrillation (AF) conversion and its safety. METHODS: Two hundred and twenty-four patients, in whom AF lasted for less than 1 year, were enrolled and randomly assigned into two groups, 112 in each group. Patients in the treated group were treated with WXG and amiodorane and the others in the control group were orally administered with amiodarone alone. The accumulative conversion rate of AF and adverse reaction were monitored during the 6-month observation period. RESULTS: Six-month observation was completed in 109 cases in the treated group and 107 in the control group, while 3 cases and 5 cases in the two groups were dropped out respectively. The difference of accumulative AF conversion rates between the two groups become significant early after one month medication (P < 0.05), and was 65.1% and 47.7% respectively after 6-month of treatment (P < 0.05). Inter-group significant difference was also shown in the aspects of average conversion time, dosage of amiodarone required and the occurrence of adverse reaction (P < 0.05). CONCLUSION: Combined use of WXG and amiodarone has a better effect in improving conversion rate of AF, shortening conversion time and decreasing the required dosage of amiodarone in treating AF as compared with the treatment with amiodarone alone, and by which the adverse reaction of long-term using amiodarone could be avoided.

[The autonomic pupillary dysfunction in type II diabetes mellitus].

OBJECTIVE: To evaluate the pupillary disorder associated with autonomic neuropathy of type II diabetes mellitus by investigating pupil diameters under mesopic, photopic and pharmacologically dilated conditions. METHODS: Forty of type II diabetic patients were divided into two groups based on the results of fundus fluorescein angiography, one group was the subclinic diabetic retinopathy and another was the NPDR (nonproliferative diabetic retinopathy), 20 age-matched healthy subjects were selected as control. High-resolution images of the pupil in 60 subjects were taken using an infrared-sensitive camera under mesopic, photopic and pharmacologically dilated conditions, respectively. From the images, the pupil diameters, constriction ratio and dilatation ratio were analyzed using Photoshop, Acdsee, and Imagetools software. RESULTS: The mean pupil diameter of tested subjects in mesopic control, subclinic and the NPDR were (6.02 +/- 0.48), (5.87 +/- 0.99), (4.95 +/- 1.12)mm, respectively. The mean photopic pupil diameter in three groups were (3.40 +/- 0.33), (3.37 +/- 0.31), (3.25 +/- 0.47) mm, respectively, where the mean pharmacologically dilated pupil diameter in three groups were (7.37 +/- 0.59), (6.91 +/- 1.00), (5.49 +/- 1.24) mm, respectively. The mean constriction ratio of these three groups were (43 +/- 7)%, (41 +/- 10)%, (32 +/- 14)%, respectively. The mean dilatation ratio of these three groups were (23 +/- 8)%, (19 +/- 13)%, (11 +/- 5)%, respectively. There were statistically significant differences among three groups in dark adapted pupil diameter, dilated pupil diameter, constriction ratio and dilatation ratio (P < 0.05). CONCLUSIONS: Autonomic pupillary dysfunction occurs early in type II diabetic patients. Pupillary diameters under mesopic and pharmacologically dilated conditions, and other pupil changes such as constriction ratio and dilatation ratio can be the reliable sign to evaluate autonomic neuropathy of type II diabetes mellitus.

A comparable study of clinical and optical outcomes after 1.8, 2.0 mm microcoaxial and 3.0 mm coaxial cataract surgery.

AIM: To evaluate the clinical and optical outcomes after clear corneal incision cataract surgery (CICS) with three different incision sizes (1.8, 2.0 and 3.0 mm). METHODS: Eyes of 150 patients with age-related cataract scheduled for coaxial cataract surgery were randomized to three groups: 1.8, 2.0, or 3.0 mm CICS. Intraoperative data and postoperative outcomes including surgically induced astigmatism (SIA), the corneal incision thickness, wavefront aberrations and modulation transfer function (MTF) of cornea were obtained. RESULTS: There were no significant differences among the three groups in demographic characteristics and intraoperative outcome. The 1.8 and 2.0 mm microincisions showed more satisfactory clinical outcomes than the 3.0 mm incision. The 1.8 mm incision showed significantly less SIA than the 2.0 mm incision until postoperative 1mo (P<0.05), but the difference was only 0.14-0.18 D. Combined with less increased incision thickness only at postoperative 1d (P=0.013), the 1.8 mm incision presented better uncorrected distance visual acuity (UCDVA) than the 2.0 mm incision only at 1d postoperatively (P=0.008). For higher-order aberrations and other Zernike coefficients, there were no significant differences between the 1.8 mm group and 2.0 mm group (P>0.05). CONCLUSION: Converting from 3.0 mm CICS to 1.8 or 2.0 mm CICS result in better clinical and optical outcomes. However, when incision is 1.8 mm, the benefits from further reduction in size compared with 2.0 mm are limited. The necessity to reduce the incision size is to be deliberated.