Effectiveness of a community-based peer support service among persons suffering severe mental illness in China.

Background: Community-based peer support service is widely and effectively deployed for persons suffering severe mental illness (SMI) in countries with well-developed outpatient mental health systems. The objective of this study is to evaluate the effectiveness of a 1-year peer service project among persons with SMI implemented in China. Methods: A total of 101 consumers (service recipients) and 66 family caregivers were recruited at baseline from communities located in Beijing and Chengdu. Severity of psychiatric symptoms, personal and social functioning, self-esteem, life satisfaction, and medication adherence were evaluated among consumers. Self-esteem, life satisfaction, anxiety, and depressive symptoms were assessed among family caregivers. Participants were reevaluated at 1 year with the same measures. Changes in outcomes from baseline to 1-year follow-up were examined using paired sample t tests or Stuart-Maxwell tests. Results: Consumers' psychiatric symptoms were decreased at 1 year (p < 0.001). Their personal and social functioning (p = 0.003) and life satisfaction (p < 0.001) were increased. There were no improvements in self-esteem (p = 0.108) and medication adherence (ps ≥ 0.827) among consumers. For caregivers, no increases were presented in outcomes at the 1-year assessment (ps ≥ 0.164). Conclusions: The findings suggest that peer support services could be sustainably implemented across China, with positive impacts on the psychiatric symptoms, social functioning, and life satisfaction of participants suffering SMI.

The Sorting Nexin Genes ChSNX4 and ChSNX41 Are Required for Reproductive Development, Stress Adaption and Virulence in Cochliobolus heterostrophus.

Sorting nexins are a conserved protein family involved in many cellular processes in fungi, and the function of sorting nexin Snx4 (Atg24) and Snx41 (Atg20) in Cochliobolus heterostrophus was not clear. The ΔChsnx4 and ΔChsnx41 mutants were generated by a PCR-based marker method to determine the roles of Snx4 and Snx41 in reproductive development, stress adaption, and virulence in C. heterostrophus. Compared with the wild-type strain, the ΔChsnx4 and ΔChsnx41 mutants exhibited obvious changes in vegetative growth and in morphology of conidia. In addition, the conidiation, appressorium formation, and virulence of snx4 and snx41 mutants were dramatically reduced. Moreover, ΔChsnx4 and ΔChsnx41 mutants were more sensitive to oxidative stress (menadione and H2O2), cell wall integrity stress (Congo red and calcofluor white), fungicides, and isothiocyanates. All the phenotypes mentioned above were restored in complemented strains. In addition, ChSnx4 and ChSnx41 were proven to interact with each other through yeast two-hybrid. Taken together, these findings indicated that ChSNX4 and ChSNX41 were important for fungal growth, asexual development, stress adaption, and virulence in C. heterostrophus.

Differentially expressed miRNAs and potential therapeutic targets for asthenospermia.

Asthenozoospermia is detected in 40% of infertile men, and characterised by low sperm motility. MicroRNAs (miRNAs) play essential roles in spermatogenesis, but little is known regarding the function of seminal plasma miRNAs in asthenozoospermia. In this study, we collected seminal plasma samples from patients with asthenospermia and healthy men and employed high-throughput sequence technology to identify differentially expressed miRNAs. Thirteen altered miRNAs were confirmed by qRT-PCR. Six of these miRNAs were upregulated, and seven were downregulated. Five of the miRNAs (hsa-miR-34c-5p, hsa-miR-34b-5p, hsa-miR-146b-5p, hsa-miR-449a and has-miR-765) had been characterised previously, and eight of the others (miR-5000-3p, miR-4289, miR-6514-3p, miR-6882-5p and miR-6739-5p, miR-135a-5p, miR-509-3p and miR-196b-5p) were identified in asthenospermia for the first time in this study. These miRNAs were significantly associated with PI3K-Akt signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway and FoxO signaling pathway. The identified dysregulated miRNA may be the key to the development of new and enhanced diagnosis and prognosis technologies for asthenospermia, and may also provide new therapeutic possibilities in the field of personalised medicine.

CRISPR/Cas9-Mediated in vivo Genetic Correction in a Mouse Model of Hemophilia A.

Hemophilia A (HA), a common bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII), has long been considered an attractive target for gene therapy studies. However, full-length F8 cDNA cannot be packaged efficiently by adeno-associated virus (AAV) vectors. As the second most prevalent mutation causing severe HA, F8 intron 1 inversion (Inv1) is caused by an intrachromosomal recombination, leaving the majority of F8 (exons 2-26) untranscribed. In theory, the truncated gene could be rescued by integrating a promoter and the coding sequence of exon 1. To test this strategy in vivo, we generated an HA mouse model by deleting the promoter region and exon 1 of F8. Donor DNA and CRISPR/SaCas9 were packaged into AAV vectors and injected into HA mice intravenously. After treatment, F8 expression was restored and activated partial thromboplastin time (aPTT) was shortened. We also compared two liver-specific promoters and two types of integrating donor vectors. When an active promoter was used, all of the treated mice survived the tail-clip challenge. This is the first report of an in vivo gene repair strategy with the potential to treat a recurrent mutation in HA patients.

Decoding m6A mRNA methylation by reader proteins in cancer.

N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNAs, regulates gene expression at the post-transcriptional level. The reader proteins of m6A, mainly YTH domain-containing proteins, specifically recognize m6A-modified mRNAs and regulate their metabolism. Recent studies have highlighted essential roles of m6A readers in the initiation and development of human cancers. In this review, we summarize recent findings about the biological functions of YTH domain proteins in cancers, the underlying mechanisms, and clinical implications. Gene expression reprogramming by dysregulated m6A reader proteins offers potential targets for cancer treatment, while targeted m6A editors and readers provide tools to manipulate m6A metabolism in cancers.

Novel small molecular inhibitor of Pit-Oct-Unc transcription factor 1 suppresses hepatocellular carcinoma cell proliferation.

Hepatocellular carcinoma (HCC) is one of the most prevalent fatal malignancies in the Chinese population, due to high rates of hepatitis virus infection. Molecular targeted drugs such as sorafenib are the anti-tumor agents of choice for HCC treatment, but their results are generally unsatisfactory. In the present study the use of Pit-Oct-Unc transcription factor 1 (OCT1/POU2F1) as a potential therapeutic target for HCC was investigated, and a novel small molecular inhibitor of OCT1 (SMIO-1) was designed and its therapeutic efficacy against HCC was assessed. OCT1 expression was higher in HCC specimens than in corresponding non-tumor tissues, and higher OCT1 was associated with poorer prognosis in advanced HCC patients undergoing sorafenib treatment. For the first time, the novel SMIO-1 was investigated in conjunction with OCT1 via molecular docking. Interaction between SMIO-1 and OCT1 was confirmed via OCT1 point mutation. Treatment with SMIO-1 repressed OCT1 transcription factor activation by disrupting the interaction between OCT1 and its cofactors. It also repressed the proliferation and metastasis of HCC cells, and inhibited proliferation-related and metastasis-related genes downstream of OCT1. Therefore, SMIO-1 is a promising strategy for HCC treatment.

The prevalence and independent influencing factors of obesity and underweight in patients with schizophrenia: a multicentre cross-sectional study.

BACKGROUND: Few studies have investigated the weight of patients with schizophrenia in China. OBJECTIVE: The aim of this study was to analyse the prevalence, clinical characteristics and influencing factors of obesity and underweight in patients with chronic schizophrenia in China. METHODS: A total of 325 patients with schizophrenia and 172 sex- and age-matched healthy controls from the community were recruited. Socio-demographic data and laboratory measurements were collected for all subjects. Using the Positive and Negative Syndrome Scale (PANSS), we evaluated the psychiatric symptoms of patients with schizophrenia. According to the body mass index (BMI) criteria in China, BMI ≥ 28 kg/m2 indicates obesity, and BMI < 18.5 kg/m2 indicates underweight. RESULTS: Of the patients with schizophrenia, 16.3% were obese, and 6.8% were underweight; 11.0% of the healthy controls were obese, and 3.5% were underweight. There was no difference between the two groups in the prevalence of obesity and underweight. After controlling for relevant variables, the obesity rate remained non significant, but the underweight rate appeared to be different. The multinomial regression analysis revealed that among the patients with schizophrenia, female sex, triglyceride level and LDL level were independent risk factors for obesity and that HDL level was an independent protective factor against obesity. In contrast, male sex and HDL level were independent risk factors for underweight. CONCLUSION: We found that the patients with schizophrenia had an increased rate of underweight and some factors related to weight. LEVEL OF EVIDENCE: Level V, descriptive study.

Synchronization Theory-Based Analysis of Coupled Vibrations of Dual-Tube Coriolis Mass Flowmeters.

Certain nonlinear influences are found in dual-tube Coriolis mass flowmeters (CMFs). According to experimentation, a nonlinearity dominated by frequency-doubling signals can be observed in the measuring signal. In general, such nonlinear effects are simplified as linear systems or neglected through processing. In this paper, a simplified model has been constructed for dual-beam CMFs based on the theory of nonlinear dynamics, with the spring-damper system as the medium for the dual-beam coupled vibrations. Next, the dynamics differential equation of the coupled vibrations is set up on the basis of the Lagrangian equation. Furthermore, numerical solutions are obtained using the Runge-Kutta fourth-order method. The study then fits discrete points of the numerical solutions, which are converted into the frequency domain to observe the existence of frequency-doubling signal components. Our findings show that frequency-doubling components exist in the spectrogram, proving that these nonlinear influences are a result of the motions of coupled vibrations. In this study, non-linear frequency-doubling signal sources are qualitatively analyzed to formulate a theoretical basis for CMFs design.

Critical roles of mRNA m6A modification and YTHDC2 expression for meiotic initiation and progression in female germ cells.

Meiotic entry and progression require dynamic regulation of germline gene expression. m6A on mRNAs and recognition by YTHDC2 has been known as post-transcriptional regulatory complex, but the roles of this regulator remain unclear for meiotic initiation and progression in female germ cells (FGCs). This study showed that m6A modification occurred mainly in FGCs rather than ovarian somatic cells (SOMAs), and m6A levels in FGCs increased significantly with meiotic initiation. m6A inhibition suppressed expression of the meiotic markers and affected the percent of FGCs at zygotene, pachytene and diplotene stage respectively. YTHDC2 expression also increased in the same pattern with m6A. Ythdc2 knockdown decreased the percent of STRA8-positive FGCs and altered the percent of FGCs at zygotene and pachytene stage respectively. Taken together, these results suggest that mRNA m6A modification and YTHDC2 expression are essential for meiotic initiation and progression in FGCs.

Inhibition of RNA polymerase III transcription by Triptolide attenuates colorectal tumorigenesis.

BACKGROUND: Upregulation of RNA polymerase (Pol) III products, including tRNAs and 5S rRNA, in tumor cells leads to enhanced protein synthesis and tumor formation, making it a potential target for cancer treatment. In this study, we evaluated the inhibition of Pol III transcription by triptolide and the anti-cancer effect of this drug in colorectal tumorigenesis. METHODS: The effect of triptolide on colorectal cancer development was assessed in colorectal cancer mouse models, 3D organoids, and cultured cells. Colorectal cancer cells were treated with triptolide. Pol III transcription was measured by real-time quantitative polymerase chain reaction (PCR). The formation of TFIIIB, a multi-subunit transcription factor for Pol III, was determined by chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), and fluorescence resonance energy transfer (FRET). RESULTS: Triptolide reduced both tumor number and tumor size in adenomatous polyposis coli (Apc) mutated (ApcMin/+) mice as well as AOM/DSS-induced mice. Moreover, triptolide effectively inhibited colorectal cancer cell proliferation, colony formation, and organoid growth in vitro, which was associated with decreased Pol III target genes. Mechanistically, triptolide treatment blocked TBP/Brf1interaction, leading to the reduced formation of TFIIIB at the promoters of tRNAs and 5S rRNA. CONCLUSIONS: Together, our data suggest that inhibition of Pol III transcription with existing drugs such as triptolide provides a new avenue for developing novel therapies for colorectal cancer.

Heavy Metal and Metalloid Contamination Assessments of Soil around an Abandoned Uranium Tailings Pond and the Contaminations' Spatial Distribution and Variability.

To investigate the heavy metal and metalloid contamination of soil around a Huanan uranium tailings pond, abandoned in 1998, we defined a study area of 41.25 km² by a natural boundary and targeted 5 elements' (U, Mn, As, Pb, Cr) single contamination and comprehensive pollution as the assessment contents. First, we collected 205 samples and evaluated them with the contamination factor (CF) method aiming at judging whether the single target element concentration exceeded the local background value and environmental quality standard. We obtained CF1 (the background value of a certain target element as the baseline value) and CF2 (the environmental quality standard for soils as the baseline value). Second, we evaluated the ecological risk of the key pollutant U with the risk assessment code (RAC) method, taking the 27 samples whose CF2 > 1 as examples and concluded that the environmental risk of U was relatively high and should arouse concern. Third, we selected comprehensive pollution index (CPI) to assess the compound pollution degree of five target elements. Fourth, we constructed the U contamination and CPI's continuous distribution maps with spatial interpolation, from which we worked out the sizes and positions of slightly, moderately and strongly polluted zones. Finally, we analyzed the spatial variability of U and CPI with the aid of a geostatistical variogram. We deduced that the spatial variation of uranium was in close relationship with local topography, and probably precipitation was the driving force of U contamination diffusion, whereas CPI exhibited weak spatial dependence with random characteristics. The above work showed that 3.14 km² soil near the pond was fairly seriously polluted, and the other 4 elements' single contaminations were less serious, but the 5 target elements' cumulative pollution could not be ignored; there were other potential pollution sources besides the uranium tailings pond. Some emergency measures should be taken to treat U pollution, and bioremediation is recommended, taking account into U's high bioavailability. Further, special alerts should be implemented to identify the other pollution sources.

Long-Term Diabetes Mellitus Is Associated with an Increased Risk of Pancreatic Cancer: A Meta-Analysis.

PURPOSE: Previous studies have shown a bidirectional relationship between diabetes and pancreatic cancer (PC). In particular, new-onset diabetes might be induced by PC, and people with long-term diabetes might be at increased risk for the development of PC. The purpose of our study was to examine whether long-term diabetes represented an independent risk factor for PC development. METHODOLOGY: A literature search was performed by searching electronic databases for studies published before July 1, 2014, and relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. Data pertaining to diabetes were recorded at both individual and study levels, with RRs calculated separately to analyze the relationship between the duration of diabetes and the development of PC. RESULTS: Forty-four studies were included in this meta-analysis, including 18 studies with a case-control design, 5 with a nested case-control design and 21 with a cohort design. The overall summary estimate for the relationship between the population with a duration of diabetes ≥2 years and PC was 1.64 (1.52-1.78). The pooled RR (95% CI) of PC for the population with a duration of diabetes ≥5 years was 1.58 (1.42-1.75). For the population with a duration of diabetes ≥10 years, the RR (95% CI) of PC was 1.50 (1.28-1.75). CONCLUSIONS: Our study suggests that long-term diabetes mellitus is associated with an increased risk of PC. However, the level of risk is negatively correlated with increasing diabetes mellitus duration.

rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia.

OBJECTIVE: To investigate the relationship between a functional variant rs189037(G>A) in ATM promoter and idiopathic nonobstructive azoospermia (INOA) in a Chinese population. DESIGN: Case-control study. SETTING: Medical academy and hospital. PATIENT(S): Two hundred twenty-nine INOA patients and 236 fertile male controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genotyping was performed by polymerase chain reaction-based restriction fragment length polymorphism and subsequently confirmed by DNA sequencing. Odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotype and allele. Bioinformatic analysis was also performed to predict the biological function of rs189037(G>A). RESULT(S): The AA genotype and A allele at rs189037(G>A) locus were both associated with an increased risk of INOA, with OR 1.90 (95% CI 1.214-3.007) for AA and 1.41 (95% CI 1.112-1.775) for A allele. The heterozygous GA and GA+AA had no relationship with INOA risk, with OR 1.06 (95% CI 0.761-1.472) and 1.28 (95% CI 0.954-1.708), respectively. Meanwhile, stratification by genotype showed that INOA patients with AA had higher FSH level, lower total T level, and smaller testicular size than those patients with GG. Furthermore, bioinformatic analysis predicted that the rs189037(G>A) variant was located in a well-conserved region in ATM promoter and that the transition of allele G to allele A might lead to differential allelic expression of ATM gene via modifying of the DNA-binding ability of transcription factor E2F1. CONCLUSION(S): The genetic variant rs189037(G>A) in ATM gene promoter contributes to an increased risk of INOA in a Chinese population, possibly through affecting the DNA-binding ability of E2F1 and subsequent ATM expression.

Association of the CAG repeat polymorphisms in androgen receptor gene with polycystic ovary syndrome: a systemic review and meta-analysis.

BACKGROUND: Many studies have reported the associations of polymorphic CAG repeats in androgen receptor (AR) gene with PCOS risk, but with inconsistent results. So, the aim of present meta-analysis was to clarify such inconsistence, so as to provide more conclusive results. METHODS: PubMed was searched for the eligible reports published until February 2012 without language limitation. The studies reporting the relationship between CAG repeat length and PCOS were selected for the meta-analysis according to the inclusion criteria. Two reviewers independently extracted the data and evaluated the study quality. PRINCIPAL FINDINGS: As for the relationship between CAG repeat length and PCOS risk, the pooled results showed that the biallelic mean was not significantly different between PCOS and controls (SMD -0.03, 95% CI -0.16-0.10, P=0.603), and that the ORs of PCOS were not demonstrated for the individuals with the biallelic mean less than median (OR 0.96, 95% CI 0.68-1.35, P=0.794), with the short CAG allele (OR 0.94, 95% CI 0.80-1.10, P=0.424), or with the X-weighted biallelic mean (OR 0.81, 95% CI 0.46-1.41, P=0.447). Further, as for the relationship between CAG repeat length and T levels in PCOS patients, the biallelic mean was not significantly different between PCOS patients with high T and those with low T (SMD 0.79, 95% CI -0.12-1.70, P=0.088), while the summary correlation r indicated that the CAG biallelic mean appeared to be positively associated with T levels in PCOS (r 0.20, 95% CI 0.11-0.30, p=0.000). CONCLUSIONS: This meta-analysis demonstrates no evident association between the CAG length variations in AR gene and PCOS risk, while the CAG length appears to be positively associated with T levels in PCOS patients.

A panel of five circulating microRNAs as potential biomarkers for prostate cancer.

BACKGROUND: Circulating microRNA (miRNAs) have been shown to have the potential as noninvasive diagnosis markers in several types of cancers. In this study, we investigated whether circulating miRNAs could be used in the diagnosis of prostate cancer (CaP) in a Chinese patient population. METHODS: Illumina's Human v2 miRNA microarray was used to analyze miRNAs levels in a small set of patients [25 CaP, 17 benign prostatic hyperplasia (BPH)] in an effort to identify CaP-specific miRNAs. The identified miRNAs were further examined by quantitative real-time PCR (qRT-PCR) in the same small set of patients. After the training phase of screening and selecting, the candidate miRNAs were validated in a larger independent cohort (80 CaP, 44 BPH, and 54 healthy controls) with qRT-PCR in the verification phase. RESULTS: Five miRNAs were confirmed by qRT-PCR analysis in validation sets. Receiver operating characteristic (ROC) curve analysis showed all 5 miRNAs had diagnostic value. More importantly, further principal component analysis indicated component 1 extracted from expression data of the 5 miRNAs could differentiate CaP from BPH and healthy controls with high diagnosis performance, with an AUC of 0.924 and 0.860, respectively. CONCLUSIONS: Our data suggested that circulating miRNAs could serve as biomarkers for CaP, and compared to single miRNA, the 5 miRNAs panel can accurately discriminate CaP from BPH and healthy controls with high sensitivity and specificity, and therefore, combined with routine PSA test, these 5 CaP-specific miRNAs may help improve CaP diagnosis in clinical application.

CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis.

BACKGROUND: Numerous studies have reported CFTR mutations in CBAVD (congenital bilateral absence of the vas deferens) patients, but their results are not completely consistent. Here, we present a systemic review and meta-analysis with emphasis on clarifying further the genetic association of CFTR mutations with CBAVD. METHODS: We searched the MEDLINE database until March, 2011 for eligible articles reporting CFTR mutations in CBAVD. Relevant data from each included study were abstracted by two independent reviewers. The overall frequency of CFTR mutations in CBAVD and the odds ratio (OR) for common specific alleles were pooled under random-effect or fixed-effect model as appropriate. Subgroup analysis was performed by ethnicity, and potential heterogeneity and bias were both assessed. RESULTS: Among CBAVD patients, 78% had at least one CFTR mutation, 46% having two and 28% only one. Moreover, the common heterozygous F508del/5T and F508del/R117H were observed in 17 and 4% of CBAVD cases respectively, and the allele frequency in CBAVD was 17% for F508del, 25% for 5T and 3% for R117H. Subgroup analysis indicated an increased frequency of cases with two mutations in Caucasian patients than in Non-Caucasian (68 versus 50%, P= 0.012), but no differences for cases with at least one mutation (88 versus 77%, P= 0.163) or with only one mutation (17 versus 25%, P= 0.115). Caucasian patients had higher F508del frequency, but lower 5T frequency, than Non-Caucasian (22 versus 8%, P= 0.001; 20 versus 31%, P= 0.009). Summary OR was 9.25 for 5T [95% confidence interval (CI) 7.07-12.11, P= 0.000], with moderate heterogeneity (I(2)= 49.20%, P= 0.019) and evident bias (Egger's test, P= 0.005), and it was 19.43 for 5T/(TG)12_13 (95% CI 10.48-30.03, P= 0.000) without any evidence of heterogeneity (I(2)= 0.1%, P= 0.391) and bias (Egger's test, P= 0.160). The OR for 5T/(TG)12_13 was significantly higher than that for 5T allele (P= 0.000). CONCLUSIONS: In summary, our results demonstrate a high frequency of CFTR mutations in CBAVD patients, and these exhibit evident ethnic differences. In addition, 5T allele and 5T/(TG)12_13 may contribute to the increased risk for CBAVD, with the 5T penetrance probably being modulated by adjacent (TG)12_13.

Association of genetic variants in CFTR gene, IVS8 c.1210-12T[5_9] and c.1210-35_1210-12GT[8_12], with spermatogenetic failure: case-control study and meta-analysis.

It has been proposed that the genetic variants of IVS8 c.1210-12T[5_9] and adjacent c.1210-35_1210-12GT[8_12] in cystic fibrosis transmembrane conductance regulator gene might contribute to the spermatogenetic failure, but numerous genetic association studies that aimed to test this hypothesis reported conflicting results. So, in order to clarify such inconsistencies, we first conducted an original case-control study in Chinese Han population that consisted of 126 non-obstructive azoospermia, 169 severe oligospermia and 213 fertile male controls, and subsequently performed a meta-analysis of the available data, including our results. Our case-control study revealed that the frequencies of the T[5] allele and the T[5]+GT[12] combination in patients with non-obstructive azoospermia were both significantly higher than those in the fertile controls (13.1 versus 2.8%, P<0.01; 97.0 versus 41.7%, P<0.01, respectively), thus indicating a high risk susceptibility to non-obstructive azoospermia for males with T[5] allele or T[5]+GT[12]. However, as for the patients with severe oligospermia, both the T[5] allele frequency and T[5]+GT[12] did not differ from that for the control subjects (4.4 versus 2.8%, P>0.01; 53.3 versus 41.7%, P>0.01, respectively). In addition, our meta-analysis showed a significant increased risk of non-obstructive azoospermia for males with T[5] allele [odds ratio (OR) 3.45, 95% confidence intervals (CI) 2.29-5.20, P=0.000] and T[5]+GT[12] (OR 7.57, 95% CI 2.53-22.65, P=0.000) compared with males carrying other alleles. By contrast, neither T[5] allele itself nor T[5]+GT[12] combination had any effects on the risk of severe oligospermia (OR 0.96, 95% CI 0.42-2.21, P=0.002; OR 1.33, 95% CI 0.64-2.76, P=0.447). On the basis of these results, it can be concluded that the T[5] allele itself, or in combination with GT[12] repeat, may increase the susceptibility risk of non-obstructive azoospermia, but not that of severe oligospermia.

LQTS gene LOVD database.

The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians.