[Short-term efficacy and safety of cardiac contractility modulation in patients with heart failure].

Objective: To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure. Methods: This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded. Results: CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions: CCM has better short-term safety and efficacy in patients with heart failure.

[Analysis of factors related to systemic embolism in patients≥75 years old with non-valvular atrial fibrillation].

Objective: To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF). Methods: A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE (n=1 127) and SE (n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results: In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio (OR)=2.75, 95% confidence interval (CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L (OR=2.07, 95%CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L (OR=1.91, 95%CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% (OR=2.45, 95%CI 1.63-3.69, P<0.01), left atrial diameter>40 mm (OR=1.54, 95%CI 1.16-2.07, P=0.003), and CHA2DS2-VASc score≥3 (OR=15.14, 95%CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE (OR=0.28, 95%CI 0.15-0.51, P<0.01). Conclusions: History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA2DS2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

[Incidence and risk factors of congenital ventricular septal defect in Qingdao].

Objective: To analyze the incidence and risk factors of ventricular septal defect (VSD) in Qingdao. Methods: A prospective cohort study design was used to include pregnant women who underwent prenatal screening in Qingdao between August 2018 and June 2020 (the whole population coverage). VSD was diagnosed according to the pulse oxygen saturation and heart auscultation, and the final diagnosis was made according to the echocardiography of VSD positive newborns within postnatal day 7. Results: The study included 115 238 live births, among which 388 were diagnosed as VSD, with an incidence of 3.37‰. The results of multivariate logistic regression analysis showed that mother with postgraduate level (OR=1.61, 95%CI: 1.00-2.58, P=0.049) (compared with junior high school and below), preterm birth history (OR=2.90, 95%CI: 1.47-5.70, P=0.002), and pregnancy history of congenital heart disease (OR=5.98, 95%CI: 2.63-14.73, P<0.001) were risk factors for VSD. Compared with female infants, the overall risk of VSD in male infants was relatively low (OR=0.74, 95%CI: 0.60-0.91, P=0.005). Conclusions: The incidence of VSD in Qingdao is 3.37‰. The risk factors of VSD include higher maternal education level, pregnancy history of congenital heart disease and preterm birth history. Moreover, the overall risk of VSD in male infants is low.

Unique motif shared by HLA-B*59:01 and HLA-B*55:02 is associated with methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese.

BACKGROUND: Methazolamide (MTZ) has been occasionally linked to the lethal Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are associated with HLA-B*59:01. However, some MTZ-induced SJS/TEN (MTZ-SJS/TEN) cases are negative for HLA-B*59:01, implying that other genetic factors besides HLA-B*59:01 are contributing to MTZ-SJS/TEN. OBJECTIVES: To comprehensively identify HLA and non-HLA genetic susceptibility to MTZ-SJS/TEN in Han Chinese. METHODS: Eighteen patients with MTZ-SJS/TEN, 806 subjects of the population control and 74 MTZ-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between MTZ and risk HLA proteins. RESULTS: We found a strong signal in the major histocompatibility complex region on chromosome 6 with 22 SNPs reaching exome-wide significance. Compared with MTZ-tolerant controls, a significant association of HLA-B*59:01 with MTZ-SJS/TEN was validated [odds ratio (OR) = 146.00, 95% confidence interval (CI): 16.12-1321.98; P = 6.19 × 10-10 ]. Moreover, 66.7% of MTZ-SJS/TEN patients negative for HLA-B*59:01 were carriers of HLA-B*55:02, whilst 2.7% of the tolerant individuals were observed with HLA-B*55:02 (OR = 71.00, 95% CI: 7.84-643.10; P = 1.43 × 10-4 ). Within HLA-B protein, the E45-L116 motif could completely explain the association of HLA-B*59:01 and HLA-B*55:02 with MTZ-SJS/TEN (OR = 119.33, 95% CI: 29.19-1227.96; P = 4.36 × 10-13 ). Molecular docking analysis indicated that MTZ binds more stably to the pocket of HLA-B*59:01 and HLA-B*55:02 than to that of non-risk alleles of HLA-B*40:01 and HLA-C*01:02. CONCLUSIONS: This study confirmed the association of HLA-B*59:01 with MTZ-SJS/TEN and identified HLA-B*55:02 as a novel risk allele in Han Chinese with the largest sample size to date. Notably, the rs41562914(A)-rs12697944(A) haplotype, encoding E45-L116, is capable of serving as a powerful genetic predictor for MTZ-SJS/TEN with a sensitivity of 89% and specificity of 96%.

[Effect of RBP2 gene silencing on proliferation, migration and invasion of ovarian epithelial cancer SKOV3/DDP cells and its mechanism].

Objective: To explore the effect of down-regulation of retinol binding protein 2 (RBP2) expression on the biological characteristics of ovarian cancer cells and its mechanism. Methods: Knockdown of RBP2 and cisplatin (DDP)-resistant ovarian cancer cell line SKOV3/DDP-RBP2i was established, the negative control group and blank control group were also set. Cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, flow cytometry was used to detect cell apoptosis, scratch test and Transwell invasion test were used to detect cell migration and invasion ability, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of molecular markers related to epithelial-mesenchymal transition (EMT). The effect of RBP2 on the growth of ovarian cancer was verified through experiment of transplanted tumors in nude mice, and the relationships between RBP2 expression and tumor metastasis and patient prognosis were analyzed using the clinical data of ovarian cancer in TCGA database. Results: After down-regulating the expression of RBP2, the proliferation ability of SKOV3/DDP cell was significantly reduced. On the fifth day, the proliferation activities of SKOV3/DDP-RBP2i group, negative control group and blank control group were (56.67±4.16)%, (84.67±3.51) and (87.00±4.00)% respectively, with statistically significant difference (P<0.001). The apoptosis rate of SKOV3/DDP-RBP2i group was (14.19±1.50)%, higher than (8.77±0.75)% of the negative control group and (7.48±0.52)% of the blank control group (P<0.001). The number of invasive cells of SKOV3/DDP-RBP2i group was (55.20±2.39), lower than (82.60±5.18) and (80.80±7.26) of the negative control group and the blank control group, respectively (P<0.001). The scratch healing rate of SKOV3/DDP-RBP2i group was (28.47±2.72)%, lower than (50.58±4.06)% and (48.92±4.63)% of the negative control group and the blank control group, respectively (P<0.001). The mRNA and protein expressions of E-cadherin in the SKOV3/DDP-RBP2i group were higher than those in the negative control group (P=0.015, P<0.001) and the blank control group (P=0.006, P<0.001). The mRNA and protein expression of N-cadherin in SKOV3/DDP-RBP2i group were lower than those in the negative control group (P=0.012, P<0.001) and the blank control group (P=0.005, P<0.001). The mRNA and protein expressions of vimentin in SKOV3/DDP-RBP2i group were also lower than those in the negative control group (P=0.016, P=0.001) and the blank control group (P=0.011, P=0.001). Five weeks after the cells inoculated into the nude mice, the tumor volume of SKOV3/DDP-RBP2i group, negative control group and blank control group were statistically significant different. The tumor volume of SKOV3/DDP-RBP2i group was smaller than those of negative control group and blank control group (P=0.001). Bioinformatics analysis showed that the expression of RBP2 in patients with metastatic ovarian cancer was higher than that without metastasis (P=0.043), and the median overall survival of ovarian cancer patients with high RBP2 expression was 41 months, shorter than 69 months of low RBP2 expression patients (P<0.001). Conclusion: Downregulation of the expression of RBP2 in SKOV3/DDP cells can inhibit cell migration and invasion, and the mechanism may be related to the inhibition of EMT.

Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China.

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at -15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (-15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

[Study on the prevalence of Beijing genotype Mycobacterium tuberculosis and its relationship with second-line anti-tuberculosis drug resistance].

Objective: To explore the prevalence risk factors of Beijing genotype Mycobacterium tuberculosis (MTB) in Beijing and its correlation with second-line anti tuberculosis drug resistance. Methods: A total of 1 140 clinical MTB positive strains were collected from various districts in Beijing, and the drug sensitivity was detected by proportion method. Beijing genotype and non Beijing genotype MTB were identified by the method of Spoligotyping. Using SPSS 22.0 statistical software, chi square test or Fisher exact probability test was used to analyze the experimental data. Results: Among 1 140 MTB clinical isolates, 941 (82.5%) were Beijing genotype MTB, 199 were non Beijing genotype MTB. There were 663 males (70.5%) in Beijing genotype and 124 males (62.3%) in non Beijing genotype strains. There were significant differences in the proportion of males between the two genotypes [P=0.021, OR (95% CI):1.442 (1.048-1.985)]. There were 441 floating population (46.9%) in Beijing genotype MTB and 78 floating population (39.2%) in non Beijing genotype MTB. There was a significant difference in the proportion of floating population between the two genotypes [P=0.048,OR (95%CI):1.368(1.001-1.869)]. There were 129 patients (13.7%) aged 65 or older in Beijing genotype MTB, 40 patients (20.1%) aged 65 or older in non Beijing genotype MTB. The difference was statistically significant [P=0.021, or (95% CI): 0.631 (0.426-0.936)]. The resistance drug rates of Levofloxacin (Lfx), Amikacin (Am), Capreomycin (Cm), Para-aminosalicylic (PAS) in Beijing genotypes were 5.5% (52/941), 1.3% (12/941), 3.2% (30/941) and 3.0% (28/941), respectively, and those of non Beijing genotypes were 10.6% (21/199), 8.5% (17/199, 12.6% (25/199) and 11.6% (23/199), the difference was statistically significant (all P<0.05). There were 58 (6.2%) multidrug-resistant (MDR) strains in Beijing genotype MTB and 19 (9.5%) multidrug-resistant strains in non Beijing genotype. There was no significant difference in the proportion of MDR strains between Beijing genotype and non Beijing genotype (P>0.05). Conclusions: Beijing genotype MTB is widespread in Beijing and has a higher proportion in male population and floating population. Compared with non Beijing genotype, Beijing genotype MTB has a lower resistance rate to Lfx, Am, Cm and PAS, and there is no significant difference in the proportion of MDR-TB patients between the two genotypes.

[Analysis of the KCNQ1 gene mutation in 2 families with congenital long QT syndrome type 1 in Xinjiang Uygur Autonomous Region].

Objective: Present study analyzed the association betwen the postassium voltage-gated channel KQT-like subfamily member 1 gene (KCNQ1) mutation and the clinical and the electrocardiographic features in 2 pedigrees with congenital long QT syndrome type 1 (LQT1) in Xinjiang Uygur Autonomous Region. Methods: Three family members were diagnosed as LQT1 patients in 2 Uygur congenital LQT1 families, these 3 LQT1 patients served as long QT group, 24 Uygur healthy volunteers served as control group. Electrocardiogram (ECG) and the gene detection were applied to compare the ECG and molecular genetic features between the long QT group and control group, and to explore the relationship between the KCNQ1 gene mutation and the clinical and the electrocardiographic features in these 2 families with congenital long QT syndrome type 1. Results: The LQT1 was diagnosed in 3 cases of the 2 pedigrees. The common features of ECG were QTc>480 ms, prolonged ST segment, and delayed T wave. The gene test evidenced a polymorphism of KCNQ1 gene exon 13:47G➝A(R16R). The mutation of 133G➝A9(G45S) of exon 16 resulted in the change of the original glycine (G) to serine (s). The ECG of the control group were normal, and there were no KCNQ1 gene mutations in control group. Conclusion: The exon sequencing results of KCNQ1 gene in 2 Xinjiang Uygur congenital long LQT1 families showed that exon16 missense changes (133G to A (G45S)) can lead to amino acid mutation, this mutation may be a pathogenic mutation. Subsequent validation of the expanded sample will provide a reference for revealing the relationship between the KCNQ1 gene and the pathogenesis of LQT1.

HLA-B*51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions.

Clindamycin causes cutaneous adverse drug reactions (cADRs), sometimes with the mechanisms of pathogenicity or risk factors unknown. This study aims to assess whether HLA alleles are associated with clindamycin-related cADRs in the Han Chinese population. We performed an association study of 12 subjects with clindamycin-related cADRs, 279 controls and 26 clindamycin-tolerant subjects. Subjects who received clindamycin through intravenous drip were analyzed separately. Unbiased, in silico docking was conducted. We found 6 out of 12 clindamycin-induced cADR patients carried HLA-B*51:01, and all of them received clindamycin via intravenous drip (6/9). The carrier frequency of HLA-B*51:01 is significantly higher compared with the control group (P=0.0006; OR=9.731, 95% CI: 2.927-32.353) and the clindamycin-tolerant group (OR=24.000, 95% CI: 3.247-177.405). In silico docking showed clindamycin is potentially more stable inside HLA-B*51:01 protein. Our results suggested, for the first time, that HLA-B*51:01 is a risk allele for clindamycin-related cADRs in Han Chinese, especially when clindamycin is administered via intravenous drip.

Coniella vitis sp. nov. Is the Common Pathogen of White Rot in Chinese Vineyards.

Grape white rot is a common disease and causes considerable yield losses in many grape-growing regions when environmental conditions are favorable. We surveyed grape white rot in five provinces in China and collected 27 isolates from diseased grape tissues. Multigene phylogenetic analyses of the internal transcribed spacer region (ITS1-5.8S-ITS2), the 28S large subunit of nuclear ribosomal RNA (LSU), partial translation elongation factor 1-alpha gene (TEF 1-α), and partial histone 3 gene (HIS), coupled with genealogical concordance phylogenetic species recognition and morphological observations, revealed that Coniella vitis sp. nov. and C. diplodiella are the causal agents of grape white rot in China. Koch's postulates were performed on Vitis vinifera cv. Summer Black in a greenhouse. These results confirmed the pathogenicity on grapes, as symptoms were reproduced, and also indicated significant variations in the virulence among C. vitis isolates. This work provides evidence that C. vitis is the main pathogen of grape white rot in China and also provides an optimized multigene backbone for resolving Coniella species.

[The relationship between LDL-C and ischemic stroke in 2 470 patients with nonvalvular atrial fibrillation in Xinjiang region].

Objective: To evaluate the association between LDL-C and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Method: A total of 2 470 patients with nonvalvular AF were included in the present study. The clinical data and laboratory examination results of the patients in the hospital were collected. The subjects were either divided into the ischemic stroke history (n=560), and non- ischemic stroke history groups (n=1 910), or divided into the low-middle risk (n=566) and high risk groups (n=1 904) based on CHA(2)DS(2) - VASc score. Results: There were significant differences in the proportion of Han, the ratio of gender, age, hemoglobin, hematocrit, ALT, serum uric acid, HDL-C and LDL-C between the patients with ischemic stroke history and without (all P<0.05). Similarly, there were significant differences in the proportion of Han, the ratio of gender, age, white blood cell count, hemoglobin, hematocrit, platelet count, ALT, albumin, TG and LDL-C between subjects in the low-middle risk group and those in the high risk group (all P<0.05). A logistical regression analysis showed that LDL-C was an independent risk factor for both the ischemic stroke history (OR 2.089, 95% CI 1.860-2.347, P<0.05), and future ischemic stroke risk (OR 1.270, 95% CI 1.079-1.494, P<0.05) in patients with nonvalvular AF. Conclusion: LDL-C is associated with ischemic stroke in patients with nonvalvular AF, and it is also an independent risk factor for future ischemic stroke in these patients.

[Recombinant human bone morphogenetic protein 7 inhibits the proliferation and extracellular matrix secretion of fibroblast of urethral scars].

Objective: To study the effect and its mechanism of recombinant human bone morphogenetic protein 7 (rhBMP-7) on urethral keloid fibroblast. Methods: Urethral fibroblasts were extracted and cultured, and the fourth-generation fibroblasts were used for experiment. Urethral fibroblasts were treated with rhBMP-7. Proliferation rate was detected by CCK-8 method. RT-PCR was applied to test changes of mRNA in α smooth muscle actin (α-SMA) and type Ⅰ collagen protein (COL-1) of each group. Western blot was used to measure α-SMA protein expression and the effect of rhBMP-7 on signaling pathway of urethral keloid fibroblasts. Results: With the increase of rhBMP-7 concentrations, the proliferation rate of urethral keloid fibroblast was generally decreased. Cells kept proliferating with time at the same concentration of rhBMP-7. mRNA level of COL-1 and α-SMA in rhBMP-7-treated (>20 ng/ml) urethral keloid fibroblasts was greatly reduced with statistical significance (P<0.05) and dose dependency. It was found rhBMP-7 inhibited the overexpression of p-smad2/3 and α-SMA mediated by transforming growth factor beta 1 (TGF-ß(1)) signaling pathway. Conclusion: rhBMP-7 could adjust TGF-ß(1) signaling pathway to inhibit gene expression of COL-1 and a-SMA in urethral keloid fibroblast, which provided evidences for further animal experiments or clinical trials.

Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats.

This study evaluated whether dietary resistant starch (RS) and green tea extract (GTE), which have anti-inflammatory and anticancer properties, protect against colitis-associated colorectal cancer (CAC) using a rat model, also investigated potential mechanisms of action of these agents including their effects on the gut microbiota. Rats were fed a control diet or diets containing 10% RS, 0.5% GTE or a combination of the two (RS + GTE). CAC was initiated with 2 weekly azoxymethane (AOM) injections (10mg/kg) followed by 2% dextran sodium sulphate in drinking water for 7 days after 2 weeks on diets. Rats were killed 20 weeks after the first AOM. Colon tissues and tumours were examined for histopathology by H&E, gene/protein expression by PCR and immunohistochemistry and digesta for analyses of fermentation products and microbiota populations. RS and RS + GTE (but not GTE) diets significantly (P< 0.05) decreased tumour multiplicity and adenocarcinoma formation, relative to the control diet. Effects of RS + GTE were not different from RS alone. RS diet caused significant shifts in microbial composition/diversity, with increases in Parabacteroides, Barnesiella, Ruminococcus, Marvinbryantia and Bifidobacterium as primary contributors to the shift. RS-containing diets increased short chain fatty acids (SCFA) and expression of the SCFA receptor GPR43 mRNA, and reduced inflammation (COX-2, NF-kB, TNF-α and IL-1ß mRNA) and cell proliferation P< 0.05. GTE had no effect. This is the first study that demonstrates chemopreventive effects of RS (but not GTE) in a rodent CAC model, suggesting RS might have benefit to patients with ulcerative colitis who are at an increased risk of developing CRC.

Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population.

Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61.

HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese.

Methazolamide is an intraocular pressure-lowering drug that is used in the treatment of glaucoma and other ophthalmologic abnormalities. The use of methazolamide has been shown to cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients of Asian ancestry. Methazolamide-induced SJS/TEN is associated with the presence of HLA-B59 serotype/HLA-B*59:01 in Korean and Japanese populations. To better understand the genetic risk factors for these adverse reactions in the Han Chinese population, we characterized the HLA class I genotypes of eight Chinese patients with methazolamide-induced SJS/TEN from 2008 to 2014. The frequency of HLA-B*59:01 was 87.5% (7/8) in the case patients, which was significantly different from 0% (0/30) in the methazolamide-tolerant patients (odds ratio (OR)=305.0; P=6.3 × 10(-7)) and 0.35% (1/283) in healthy subjects from the human major histocompatibility complex database (OR=1974.0; P=2.0 × 10(-12)). HLA-C*01:02, which is closely linked to HLA-B*59:01, had a weaker but notable association with methazolamide-induced SJS/TEN compared with the tolerant controls (OR=12.1; P=0.016) and general population (OR=15.5; P=2.0 × 10(-3)). The distribution of the HLA-B*59:01-C*01:02 haplotype was also significantly different in cases and controls. This study demonstrated a strong association between HLA-B*59:01 and methazolamide-induced SJS/TEN in the Han Chinese population for the first time. Pretherapy screening for HLA-B*59:01 would be useful to reduce the risk of methazolamide-induced SJS/TEN.

Association of COL4A1 gene polymorphisms with cerebral palsy in a Chinese Han population.

The basement membrane (BM) is an extracellular matrix associated with overlying cells and is important for proper tissue development, stability, and physiology. COL4A1 is the most abundant component of type IV collagen in the BM, and COL4A1 variants can present with variable phenotypes that might be related to cerebral palsy (CP). We postulated, therefore, that variations in the COL4A1 gene might play an important role in the etiology of CP. In this study, six single nucleotide polymorphisms (SNPs) in the COL4A1 gene were genotyped among 351 CP patients and 220 healthy controls from the Chinese Han population. Significant association was found for an association between CP and rs1961495 (allele: p = 0.008, odds ratio (OR) = 1.387, 95% confidence interval (CI) = 1.088-1.767) and rs1411040 (allele: p = 0.009, OR = 1.746, 95% CI = 1.148-2.656) SNPs of the COL4A1 gene. Multifactor dimensionality reduction analysis suggested that these SNPs had interactive effects on the risk of CP. This study is the first attempt to investigate the contribution of polymorphisms in the COL4A1 gene to the susceptibility of CP in a Chinese Han population. This study shows an association of the COL4A1 gene with CP and suggests a potential role of COL4A1 in the pathogenesis of CP.

Supplementation with Brazil nuts and green tea extract regulates targeted biomarkers related to colorectal cancer risk in humans.

Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers. In total, thirty-two volunteers (>50 years of age) with plasma Se≤1·36 µmol/l were randomised to one of three treatment groups: nine to Se (approximately 48 µg/d) as six Brazil nuts, eleven to four GTE capsules (800 mg (-)-epigallocatechin-3-gallate) and twelve to a combination of Brazil nuts and GTE. Blood and rectal biopsies were obtained before and after each intervention. Plasma Se levels, rectal selenoprotein P (SePP) and ß-catenin mRNA increased significantly in subjects consuming Brazil nuts alone or in combination, whereas rectal DNA methyltransferase (DNMT1) and NF-κB mRNA were reduced significantly in subjects consuming GTE alone or in combination. None of the interventions significantly affected rectal acetylated histone H3 or Ki-67 expression at the protein level or plasma C-reactive protein. Effects of the combination of Brazil nuts and GTE did not differ from what would be expected from either agent alone. In conclusion, supplementation of Brazil nuts and/or GTE regulates targeted biomarkers related to CRC oncogenesis, specifically genes associated with selenoproteins (SePP), WNT signalling (ß-catenin), inflammation (NF-κB) and methylation (DNMT1). Their combination does not appear to provide additional effects compared with either agent alone.

DNA methylation levels of imprinted and nonimprinted genes DMRs associated with defective human spermatozoa.

Asthenozoospermia (AS) is a common cause of human male infertility. Recent studies have shown significant associations of aberrant DNA methylation in spermatozoa with male infertility. The aims of the this investigation were to assess the changes in DNA methylation of known imprinted genes (MEST, GNAS and H19), novel imprinted gene (FAM50B) and nonimprinted genes (LINE-1 and P16) DMRs in the spermatozoa of infertile men with single-factor AS. Semen samples were obtained from 46 AS patients and 49 age-matched normal controls. DNA methylation levels of detected genes DMR were determined by MassARRAY quantitative methylation analysis. The average methylation level at the P16 and MEST DMRs was significantly lower in AS patients than in controls (patients 6.51 ± 0.32%, controls 7.66 ± 0.40%, P < 0.01). The methylation level of 6 CpG sites of P16 DMR, and 1 CpG site of MEST, GNAS, FAM50B and LINE-1 DMRs, was lower in AS group than in control group. For the first time, the data presented here suggest that increased methylation defects of P16 DMR may be associated with low sperm motility. This study provides the potential association between low sperm motility infertile men and the aberrant DNA methylation of MEST, LINE-1, GNAS and FAM50B DMRs.

[A study on the evaluation of anticoagulation status comparing of CHADS2 versus CHA2DS2-VASc scores in patients with non valvular atrial fibrillation in Xinjiang area].

OBJECTIVE: To evaluate the current status of anticoagulation therapy in patients with atrial fibrillation(AF)in Xinjiang, and compare the two scoring systems(CHADS2 and CHA2DS2-VASc scores) in determining the risk of strokes in AF patients in Xinjiang. METHODS: Subjects with AF were collected by searching the electronic and paper medical records from 35 hospitals in Xinjiang area during October 2013 to October 2014, and followed up for the incident strokes after 10 to 12 months. RESULTS: Totally, 5 953 AF patients were enrolled in the study with the age of (67.9±12.0) years old, and men to women ratio of 1.44. Most patients were in age groups of 60-69 (23.92%) and 70-79 years (37.81%). Among patients with a CHADS2 score of 1 or less, the CHA2DS2-VASc scores of these subjects ranged from 0 to 3. After 10 to 12 months of follow-up, 22 patients developed new strokes. Only 30.79% patients ( n=1 460) received the anticoagulation treatment among those (n=4 742) who need to be treated with anticoagulation drugs. In patients receiving anticoagulant therapy, 1 162 patients were treated with warfarin, and 298 patients with new oral anticoagulant drugs.Totally 1 110 patients treated with warfarin were monitored with international normalized ratio (INR). The median INR was 1.14 with only 97 cases meeting the recommended INR ranging of 2.0-3.0 in the guidelines. The compliance rate was 8.74%. CONCLUSIONS: The current status of anticoagulation for AF in Xinjiang area is characterized by "low anticoagulation rate" and "low compliance rate". The CHA2DS2-VASc score is more suitable for predicting the risk of strokes in patients with non valvular atrial fibrillation in Xinjiang area.

[Clinical research of second resection on early stage primary bladder adenocarcinoma and literature review].

OBJECTIVE: To investigate the clinical and pathological characteristics, as well as the diagnosis and treatment of primary bladder adenocarcinoma in the early stage. METHODS: The clinical features, pathological results, diagnosis and treatment profiles of 7 cases of primary bladder adenocarcinoma admitted in Affiliated Hospital of Nantong University from January 2010 to July 2015 were analyzed ret rospectively. RESULTS: All seven cases were diagnosed pathologically as primary bladder adenocarinoma.Histological staging T1 was revealed in six cases, while T2 in one case after the first resection.After four weeks, all patients received the second resection while one patient underwent immediately radical cystectomy. Multimodality therapy such as radiotherapy or chemotherapy was performed for longer postoperative survival.only one man died while another patient had been healthy for 6 years till January 2016. CONCLUSION: Primary bladder adenocarcinoma is a highly malignant disease in bladder cancer.According to the results of the second resection, multimodality therapy for patients in early stage with no lymph node or other organs metastasis can improve the quality of life without affectiong their lives.