Genome-Wide Association Analysis of Neonatal White Matter Microstructure.

A better understanding of genetic influences on early white matter development could significantly advance our understanding of neurological and psychiatric conditions characterized by altered integrity of axonal pathways. We conducted a genome-wide association study (GWAS) of diffusion tensor imaging (DTI) phenotypes in 471 neonates. We used a hierarchical functional principal regression model (HFPRM) to perform joint analysis of 44 fiber bundles. HFPRM revealed a latent measure of white matter microstructure that explained approximately 50% of variation in our tractography-based measures and accounted for a large proportion of heritable variation in each individual bundle. An intronic SNP in PSMF1 on chromosome 20 exceeded the conventional GWAS threshold of 5 x 10-8 (p = 4.61 x 10-8). Additional loci nearing genome-wide significance were located near genes with known roles in axon growth and guidance, fasciculation, and myelination.

Improvement of feed intake, digestibility, plasma metabolites, and lactation performance of dairy cows fed mixed silage of sugar beet pulp and rice straw inoculated with lactic acid bacteria.

A study was conducted to investigate the inclusion effects of sugar beet pulp and rice straw mixture silage with inoculation (BRMS), in place of whole-plant corn silage (CS), on the dry matter intake, total-tract nutrient digestibility, plasma metabolites, rumen fermentation, and lactation performance in high-production dairy cows. Sixteen multiparous Holstein cows (body weight, 622 ± 35 kg; days in milk, 90 ± 11 d; mean ± standard deviation) were used in our experiments; the experiments were based on a repeated 4 × 4 Latin square design for 21 d, and each experimental period consisted of 14 d of adaptation, followed by 7 d of data collection. The 4 dietary treatments used were (dry matter basis): (1) 0% BRMS and 28.6% CS (0BRMS); (2) 4.3% BRMS and 24.3% CS (15BRMS); (3) 8.60% BRMS and 20.0% CS (30BRMS); and (4) 12.9% BRMS and 15.7% CS (45BRMS). The increasing inclusion of dietary BRMS was observed to linearly increase the total volatile fatty acids and the propionate concentration. The dry matter intake and digestibility values of neutral detergent fiber and acid detergent fiber increased linearly as the percentage of BRMS increased up to 45%. Milk yield linearly increased with the increase in the content of BRMS (39.0, 39.8, 40.9, and 40.3 kg/d for 0BRMS, 15BRMS, 30BRMS, and 45BRMS, respectively). The increasing inclusion of dietary BRMS induced a decrease in the ammonia nitrogen and milk urea nitrogen concentration, leading to a linear increase in milk protein production (1.15, 1.26, 1.35, and 1.27 kg/d for 0BRMS, 15BRMS, 30BRMS, and 45BRMS, respectively). In conclusion, the diets with the replacement of CS with BRMS up to 45% were beneficial to the production performance of high-production dairy cows, indicating that this method may be an appropriate use of sugar beet pulp and rice straw.

[Detection of drug resistance genes of mycobacterium tuberculosis by rolling circle amplification technique with multicolor fluorescent probes].

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.

Altered Brain Structure in Infants with Turner Syndrome.

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period.

[An analysis of insomnia and its influencing factors in patients with acute coronary syndrome].

Objective: To investigate the current situation of insomnia in patients with acute coronary syndrome (ACS), and analyze the influencing factors of insomnia in the ACS patients, so as to provide information on the development of new strategies for the treatment of insomnia in ACS patients. Methods: This is a multicenter and prospective observational study. A total of 771 ACS patients who met the criteria were selected from March 2013 to June 2015. The baseline social demographic information, sleep quality questionnaire, general anxiety disorder scale-7(GAD-7),patient health questionnaire-9(PHQ-9), short-form 12 health survey questionnaire(SF-12), and enhancing recovery in coronary heart disease patients social inventory(ESSI) were completed within 7 days after admission. Logistic regression analyses were used to analyze the influencing factors of insomnia in ACS patients. Results: A total of 741 subjects with valid questionnaires were collected, including 510 males (68.8%) and 231 females (31.2%). Among them, 487 (65.7%) subjects had at least one insomnia symptom: 308 (41.6%) subjects had difficulty in falling asleep, 369 (49.8%) subjects were easy to wake at night, 116 (15.7%) subjects woke up earlier than they expected, 74 (10.0%) subjects experienced both woke up earlier and difficulty in falling asleep, and 53 (7.2%) subjects woke up earlier, woke up at night and had difficulty in falling asleep at the same time. Logistic regression analyses showed that before admission physical activity (OR =0.636, 95%CI 0.411-0.984), depression (OR=1.908, 95%CI 1.101-3.305) and low social support (OR=0.278, 95%CI 1.198-3.301) were independent factors of insomnia in ACS patients. Conclusions: Nearly 2/3 ACS patients have symptoms of insomnia. Difficulty in falling asleep and easy to wake up at night are the most common manifestations. Physical activity, depression and social support independently are associated with insomnia.

Screen time and sleep disorder in preschool children: identifying the safe threshold in a digital world.

OBJECTIVES: Sleep disorder is a common problem in children that can jeopardize their health and well-being. With the popularity of electronic devices such as portable tablets and smartphones in the 21st century, children are spending much more time on screen, but the impact of such change on children's sleep disorder has been less investigated so far. This study aims to examine the dose-response association between time spent on different electronic devices and children's sleep disorder. STUDY DESIGN: The design of this study is a cross-sectional study. METHODS: We randomly selected 2278 children aged 3-6 years from 15 kindergartens in Tongling, China. The potentially non-linear association between screen-viewing time (i.e. television [TV], computer, iPad, Phone) and the risk of sleep disorder was examined using a logistic generalized additive model. RESULTS: We observed a J-shaped association between TV viewing time and the risk of sleep disorder, with a threshold of 1 h/day. For each 1 h/day increment in TV viewing time over the threshold, the risk of sleep disorder increased by 12.35% (95% confidence interval: 1.87-23.92%). This association seemed to be greater for girls than boys and for TV viewing at weekend than on weekdays, but the difference was not statistically significant (P-value>0.05). We did not find adequate evidence of an adverse effect of more time spent on computer, iPad and Phone. CONCLUSIONS: This study suggests a positive but non-linear relationship between time spent on watching TV and sleep disorder in Chinese preschool children. Setting the TV viewing time limit less than 1 h/day may help reduce the risk of developing sleep disorder. Further investigation is also needed to examine and compare the effects of heavy use of other electronic devices on sleep disorder.

[Efficacy comparison of primary percutaneous coronary intervention by drug-coated balloon angioplasty or drug-eluting stenting in acute myocardial infarction patients with de novo coronary lesions].

Objective: To compare the safety profile, angiographic and clinical outcomes between drug-coated balloon(DCB) only strategy versus drug eluting stent(DES) implantation in primary percutaneous coronary intervention(PCI) for acute myocardial infarction(AMI) patients. Methods: A total of 380 AMI patients who underwent primary PCI in Beijing Chaoyang Hospital from January 2016 to May 2019 were enrolled. They were allocated into DEB group(n=180) or DES group(n=200). The Primary endpoint was the major adverse cardiac events(MACE) in hospital and within 3 months after discharge, the composite event of cardiac death, non-fatal myocardial infarction(MI), target vessel revascularization(TVR) and in stent thrombosis. The secondary endpoints included: (1)TIMI blood flow grade and myocardial perfusion grade (TMP grade) of infarct-related vessels before and after PCI. (2)The degree of ST segment resolution(STR) between half hour and two hours after PCI, and STR was represented by percentage of summed ST-segment reduction between baseline and post-PCI. Using the most significant lead of ST segment elevation, calculating the rate of decline in the ST segment after treatment; or the most significant lead of the ST segment depression, to calculate the rate of recovery in the ST segment after treatment. STR<50% was defined as incomplete STR. (3)The occurrence of coronary artery dissection during operation. (4)The peak value of myocardial enzymes. (5)The incidence of bleeding in hospital and within 3 months after discharge. The inverse probability weighting method based on propensity score (IPTW) was used to compare the effects of the two treatments on MACE occurrence in the logistic regression model. Results: There was no significant difference in sex, age, risk factors of coronary heart disease, type and site of AMI, interventional therapy data(P>0.05) between the two groups. The ratio of bifurcation lesions in DCB group was significantly higher than that in DES group, and the diameter of the DCB was smaller while the length was longer than that of DES (all P<0.05). One death occurred in each group during hospitalization. Compared with the DES group, the incidence of MI ï¼»2.8%(5/180) vs. 0.5% (1/200), P=0.10ï¼½ and TVR ï¼»2.8%(5/180) vs. 0.5%(1/200), P=0.10ï¼½ in the DCB group during hospitalization showed an increasing trend, and were mostly associated with delayed coronary dissection. The incidence of MACE was similar between the two groups (3.3%(6/180) and 1.0%(2/200), P=0.15) during hospitalization. There was no MACE occurred in the two groups within 3 months after discharge. There was no significant difference between the two groups in TIMI grade, TMP grade, incomplete STR rate and peak value of myocardial enzyme (all P>0.05). The incidence of coronary artery dissection was significantly higher in DCB group than in DES group (8.3%(15/180) and 3.0%(6/200), P=0.02), but most of them were type B or A dissection and did not need special treatment. There was no significant difference in bleeding event between the two groups(P=0.91). Logistic regression analysis showed that there was no difference in the risk of MACE during hospitalization between DES and DCB groups for AMI patients receiving PCI (compared with DCB, OR=0.35, 95%CI 0.08-1.43, P=0.13). Conclusions: The initial safety and efficacy profiles of DCB are similar with those of DES for the AMI patients during PCI. The study highlights that the incidence of coronary dissection (type A or B) is higher post DCB treatment than post DES, but it does not affect blood flow. However, the incidence of in-hospital MI due to delayed coronary dissection trends to be higher post DCB. So we should pay close attention to the risk of delayed coronary dissection after DCB in AMI patients with de novo lesion.

Novel mutations in mevalonate kinase cause disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is located at 12q23·2-q24·1. Subsequently, the mevalonate kinase gene (MVK) was shown to be pathogenic in DSAP. OBJECTIVES: To elucidate the mechanism by which MVK mutations lead to keratinocyte apoptosis and DSAP, and to report a new missense mutation, c.566 C>T (p.A189V), in MVK in a Chinese DSAP pedigree. METHODS: The half-life of wild-type (WT) MVK protein and mutants was assessed using cycloheximide treatment of cells. Dimerization of MVK was analysed by coimmunoprecipitation and glutathione S transferase pull-down assay. MVK kinase activity, production of cell cholesterol, mitochondrial complex activity and apoptosis were detected, using the corresponding commercial kits, in cells overexpressing MVK WT and mutants. RESULTS: Mechanically, we demonstrated that both the pathogenic p.A189V mutant and a sporadic mutation p.H312R (c.935A>G), which we reported previously, have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Also, we found the p.H312R mutation confers on the MVK protein an inability to dimerize. Further, we demonstrated that the mutants are impaired in mitochondrial function and lead to increased apoptosis. CONCLUSIONS: Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.

(CAG)n loci as genetic modifiers of age at onset in patients with spinocerebellar ataxia type 1 from mainland China.

BACKGROUND AND PURPOSE: The expanded repeat length in ATXN1 negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non-causative CAG repeats on the AAO of SCA patients. However, studies on Chinese SCA1 patients regarding candidate modifier factors involved in the variability in AAO are rare. METHODS: In all, 152 Chinese SCA1 patients who were genotyped for ATXN1 and nine other (CAG)n -containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of ATXN1 (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)n -containing genes. RESULTS: Our results verified the negative effect of the expanded allele in ATXN1 by regression analysis. Some (CAG)n -containing genes including TBP, ATN1 and HTT modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ATXN2, ATXN3, CACNA1A, ATXN7, KCNN3, RAI1 and normal ATXN1 alleles in trans were detected. CONCLUSION: By using interaction analyses, TBP, ATN1 and HTT were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.

Superresolution Microscopy of Single Rare-Earth Emitters in YAG and H3 Centers in Diamond.

We demonstrate superresolution imaging of single rare-earth emitting centers, namely, trivalent cerium, in yttrium aluminum garnet crystals by means of stimulated emission depletion (STED) microscopy. The achieved all-optical resolution is ≈50 nm. Similar results were obtained on H3 color centers in diamond. In both cases, STED resolution is improving slower than the conventional inverse square-root dependence on the depletion beam intensity. In the proposed model of this effect, the anomalous behavior is caused by excited state absorption and the interaction of the emitter with nonfluorescing crystal defects in its local surrounding.

Effect of magnetization boundary condition on cavity magnon polariton of YIG thin film.

Motivated by recent studies of cavity magnon polariton (CMP), we extended a previous theoretical work to generalize microwave transmission calculation with various magnetization boundary condition of YIG thin film embedded in cavity. It is found that numerical implementation given in this paper can be easily applied to other magnetization boundary condition and extended to magnetic multilayers. Numerical results show that ferromagnetic resonance mode of microwave transmission spectrum, which is absent in previous calculation, can be recovered by altering the pinning condition of surface spins. The demonstrated reliability of our theory opens attractive perspectives for studying CMP of thin film with complicated surface magnetization distribution and magnetic multilayers.

Experimental study on TGF-ß1-mediated CD147 expression in oral submucous fibrosis.

OBJECTIVE: Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remains largely unknown. METHODS: In this study, we investigated the expression of CD147 and transforming growth factor ß1 (TGF-ß1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-ß1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-ß1 or LY2157299, an inhibitor of TGF-ß1 receptor and arecoline stimulation. RESULTS: We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-ß1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-ß1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-ß1 down-regulated CD147 expression. CONCLUSION: Our findings suggest arecoline promotes CD147 expression via the TGF-ß1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

Phenotypes and cellular effects of GJB1 mutations causing CMT1X in a cohort of 226 Chinese CMT families.

The aim of this study is to explore the phenotypic and genotypic features of X-linked Charcot-Marie-Tooth (CMT) disease in the mainland of China and to study the cellular effects of six novel Gap junction protein beta-1 variants. We identified 25 missense and 1 non-sense mutations of GJB1 in 31 unrelated families out of 226 CMT families. The frequency of GJB1 mutations was 13.7% of the total and 65% of intermediate CMT. Six novel GJB1 variants (c.5A>G, c.8G>A, c.242T>C, c.269T>C, c.317T>C and c.434T>G) were detected in six unrelated intermediate CMT families. Fluorescence revealed that HeLa cells transfected with EGFP-GJB1-V74M, EGFP-GJB1-L81P or EGFP-GJB1-L90P had diffuse endoplasmic reticulum staining, HeLa cells transfected with EGFP-GJB1-L106P had diffuse intracellular staining, and HeLa cells transfected with EGFP-GJB1-N2S had cytoplasmic and nuclear staining. The distribution of Cx32 in HeLa cells transfected with EGFP-GJB1-F145C was similar to that of those transfected with wild-type (WT). These six variants resulted in a higher percentage of apoptosis than did WT as detected by flow cytometry and Hoechst staining. In conclusion, mutation screening should be first performed in intermediate CMT patients, especially those with additional features. The novel GJB1 variants c.5A>G, c.8G>A, c.242T>C and c.269T>C are considered pathogenic, and c.317T>C and c.434T>G are classified as probably pathogenic.

Gene expression in major depressive disorder.

The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD.

[Social support status and related influential factors of patients with acute coronary syndrome].

Objectives: To investigate the social support status, related influential factors and the impact on one year outcome in patients with acute coronary syndrome (ACS), our data might be helpful to provide basis for making new treatment strategy aimed at improving social support for patients with ACS. Methods: From January 2013 to June 2014, a total of 778 hospitalized patients with ACS were enrolled in the study. All patients completed enhancing recovery in coronary heart disease patients social support inventory(ESSI), general anxiety disorder scale(GAD-7), patient health questionnaire(PHQ-9), short-form 12 health survey questionnaire(SF-12), sleep questionnaire and demographic questionnaire within 7 days after admission and at 6 months and one year post discharge. Multiple linear regressions were performed to analyze factors that influenced the social support. Results: The total score of social support was 17.08±3.61, 17.72±3.04, and 17.76±3.05 respectively in patients with ACS at baseline, 6 months and 12 months after discharge. Patients had a higher point of social support at 6 months (t=-2.69, P<0.01) and 12 months (t=-2.86, P<0.01) after discharge than at baseline. Multiple regression analysis for baseline data identified five significant predictors of low social support status: workers or farmers (t=2.82, P<0.01), low family monthly income (t=2.42, P<0.05), anxiety (t=-3.66, P<0.01), depression (t=-3.22, P<0.01) and low quality of life (t=4.38, P<0.01). Conclusions: Social support of patients with ACS is lower in China, and there are significant relationships between low social support and occupation, economic status, anxiety, depression, quality of life of ACS patients.

Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.

Spinocerebellar ataxia type 36 (SCA36) is a new SCA subtype recently reported in Japanese and Spanish pedigrees. To assess the frequency and clinical characteristics of SCA36 in patients from Mainland China, we combined the repeat-primed polymerase chain reaction method and Southern blot analysis to detect the GGCCTG hexanucleotide repeats of NOP56 in 364 probands with SCA, 126 probands with hereditary spastic paraplegia and 99 probands with amyotrophic lateral sclerosis (ALS). Systematic and targeted clinical evaluations and investigations were conducted in the SCA36 patients. As a result, eight autosomal dominant spinocerebellar ataxia (ADCA) pedigrees (a total of 13 patients) and one sporadic SCA (S-SCA) patient were identified as SCA36 in the SCA cohort, accounting for approximately 1.60% of the cases in the ADCA group and 0.32% of those in the S-SCA group in Mainland China. The characteristics include late onset and slow progression accompanied by acoustic impairments and 'possible' ALS phenotype in patients from Mainland China.

[The effect and safety of tirofiban on acute ST segment elevation myocardial infarction patients receiving no early reperfusion therapy].

OBJECTIVE: To study the efficacy and safety of tirofiban on acute ST segment elevation myocardial infarction (STEMI) in patients who do not receive early reperfusion therapy. METHODS: A total of 153 STEMI patients without early reperfusion therapy were randomly distributed into tirofiban group (therapeutic group, n=78) and non-tirofiban group (control group, n=75). Coronary angiography was performed on the 5(th) and 10(th) day after treatment, and percutaneous coronary intervention (PCI) was conducted when necessary. The differences of initial patency of the infarct related artery (IRA), bleeding complication and clinic events within 30 days between these two groups were compared. RESULTS: Tirofiban did not increase the percentage of patients with initial patency of IRA (60.3% vs 64.0%, P=0.63). The percentage of patients with thrombolysis in myocardial infarction (TIMI) 3 after PCI was 100.0% in tirofiban group and 97.1% in the control group (P=0.09). However, application of tirofiban significantly decreased poor myocardial perfusion rate after PCI (1.4% vs 8.8%, P=0.04). No significant differences were observed in major adverse cardiovascular events (MACE) (3.8% vs 2.7%, P=0.68) between therapeutic and control group. The same is true for mild (5/78 vs 4/75 cases, P=0.78) and severe hemorrhage (2/78 vs 1/75 cases, P=0.58), and severe thrombocytopenia (2/78 vs 0/75 cases, P=0.10) between these two groups within 30 days. CONCLUSIONS: Tirofiban did not increase initial patency in STEMI patients without early reperfusion therapy. However, it can improve myocardial perfusion after PCI.

SPG35 contributes to the second common subtype of AR-HSP in China: frequency analysis and functional characterization of FA2H gene mutations.

Hereditary spastic paraplegias (HSPs) encompass a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, mutations in fatty acid 2-hydroxylase gene (FA2H) have been identified responsible for HSPs type 35 (SPG35). This study aims to define the contribution of FA2H to Chinese autosomal recessive HSP (AR-HSP) patients and provide insights into the enzymatic functions of the novel mutations. Direct sequencing of FA2H was conducted in 31 AR-HSP families and 55 sporadic cases without SPG11, SPG15, SPG5 and SPG7 gene mutations. Enzymatic activity of the mutated proteins was further examined. Three novel mutations were found in two Chinese families, including two compound heterozygous mutations (c.388C>T/p.L130F and c.506+6C>G) and one homozygous mutation (c.230T>G/p.L77R). The c.506+6C>G splice-site mutation led to the deletion of exon 3. Measurement of enzymatic functions revealed a significant reduction in the enzymatic activity of FA2H associated with p.L130F and p.L77R. Overall, our data widens the spectrum of the mutations on FA2H, and functional analyses indicate that these mutations severely impair the enzymatic activity of FA2H. Furthermore, frequency analysis shows that SPG35 is the second most common subtype of AR-HSP in China.

Common genetic variants on 1p13.2 associate with risk of autism.

Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.