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Background To determine the phenotype, molecular characterisation and risk factors of postoperative meningitis induced by Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in China. Methods We performed a multi-centre comparative cohort study of postoperative meningitis patients infected with Enterobacteriaceae in 4 neurosurgical centres in China from January 2014 to December 2019. Phenotype and molecular characteristics of the isolates were reviewed and tested, and independent risk factors of the EPE meningitis were evaluated by binary logistic regression. Results In total, 220 Enterobacteriaceae include 78 EPE were available in this study. 85.6% (67/78) ESBL-related genes were tested, and blaSHV (14.9%) and blaSHV + blaTEM + blaCTX-M-9 (20.9%) were found to be the most frequent mono and combined ESBL-related genes harboured by Enterobacteriaceae. On binary logistic analysis, craniotomy (OR. 2.583, 95% C.I. 1.274–5.235, P = 0.008) and malignancy (OR. 2.406, 95% C.I. 1.299–4.456, P = 0.005) were the associated independent risk factors to meningitis induced by EPE. Conclusions To the best of our knowledge, this is the largest series focusing on risk factors of EPE meningitis which has been conducted in China. Craniotomy and malignancy were independent risk factors for EPE meningitis. The risk factors identified may be further utilized in clinical practice and research to avoid and reduce the mortality in future.

Movement and growth of dendrites are common phenomena during solidification. To numerically investigate these phenomena, two-phase flow model is employed to formulate the FSI (fluid-structure interaction) problem during dendritic solidification. In this model, solid is assumed to have huge viscosity to maintain its own shape and an exponential expression is constructed to describe variable viscosity across s-l (solid-liquid) interface. With an effective preconditioner for saddle point structure, we build a N-S (Navier-Stokes) solver robust to tremendous viscosity ratio (as large as 1010) between solid and liquid. Polycrystalline solidification is computed by vector-valued phase field model, which is computationally convenient to handle contact between dendrites. Locations of dendrites are updated by solving advection equations. Orientation change due to dendrite’s rotation has been considered as well. Calculation is accelerated by two-level time stepping scheme, adaptive mesh refinement, and parallel computation. Settlement and growth of a single dendrite and multiple dendrites in Al-Cu alloy were simulated, showing the availability of the provided model to handle anisotropic growth, motion and impingement of dendrites. This study lays foundation to simulate solidification coupled with deformation in the future.

Introduction: A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in the kidney tissue predicted a worse renal outcome. However, the effect of C1 lesion (crescents in Methods: We investigated 305 biopsy-proven IgAN patients without obvious chronic renal lesions. Clinicopathologic features and treatment modalities were recorded. The patients were divided into several groups according to the presence or absence of a global crescent: no crescent (NC) group, only segmental crescent (SC) group, and global crescent (GC) group. The outcome was the survival from a combined event defined by a ≥15% decline in the estimated glomerular filtration rate (eGFR) after 1 year or ≥30% decline in the eGFR after 2 years. Results: Among all patients, 75.7% were in the NC group, 14.8% were in the SC group, and 9.5% were in the GC group. Compared with the NC group, patients in the SC group and the GC group had more urine protein, lower eGFR, and presented with more severe pathological change. During a median follow-up of 34.8 (26.16–57.95) months, the combined event occurred in 34 individuals (11.1%). In a multivariate model, the GC group (HR = 2.756, 95% CI = 1.068–7.109) was associated with an increased risk of the combined event. Conclusions: In IgAN patients without obvious chronic renal lesions, the GC group had more severe clinical and pathological manifestations than in the NC group. GC is an independent risk factor for the progression of IgAN renal function.

Objectives: To evaluate the molecular epidemiology and mortality risk factors of nosocomial meningitis (NM) induced by multi-drug resistance Enterobacteriaceae (MDRE) in China. Methods: We performed a multi-center study of MDRE NM patients in 2 neurosurgical centers in China from 2014 to 2019. Molecular and phenotype microbiology epidemiology of each MDRE were reviewed and tested, and 21 clinical variables on mortality risk factors were extracted and evaluated by multivariate Cox analysis for NM. Results: In total, 90 MDRE NM patients were included in this study. Klebsiella (K.) pneumoniae occupied the highest proportion (51.11%, 46/90), 44 (44.44%) were meropenem-resistant, ceftriaxone resistance in target MDRE was relatively high (92.22%, 83/90), blaKPC (67.50%, 27/40) was the predominant carbapenem resistance gene, and blaCTX-M-1, blaTEM and blaCTM-M-9 were the three most popular extended spectrum β-lactamases (ESBLs) producing genes of the MDRE. Multivariate Cox analysis showed that external ventricular drainage (EVD, odds ratio (OR) 2.524, 95% confidence interval (CI) 1.101-5.787, P = 0.029) and Glasgow Coma Scale (GCS) ≤8 (OR 4.033, 95% CI 1.526-10.645, P = 0.005) were mortality risk factors of MDRE NM. Conclusions: NM caused by MDRE is an important sign of the failure of neurosurgery, and MDRE has multiple drug resistance genotypes, and EVD and GCS≤8 are independent mortality risk factors of MDRE NM, which deserves the attention of microbiologist and neurosurgical clinicians.

Major depressive disorder (MDD) is a common and complex mental disorder. Recent studies found that genetic variants located in GRIK4, which encoded glutamate ionotropic receptor kainate type subunit 4, was associated with the MDD. In this study, we intended to investigate whether GRIK4 gene was associated with MDD. So five single nucleotide polymorphisms (SNPs) were selected and genotyped (rs79526501, rs11218016, rs4582985, rs6589847, rs56275759) in 568 MDD patients and 846 healthy controls from Chinese Han population. The results showed that rs56275759 demonstrated statistically significant differences between MDD patients and control subjects both in allelic frequencies (p value = 0.011) and genotypic frequencies (p value = 0.029). Rs4582985 was excluded from the further analysis for its deviation from the Hardy-Weinberg equilibrium. Strong linkage disequilibrium (LD) was found among rs11218016, rs6589847 and rs56275759, and this block was significantly associated with MDD. In summary, our results firstly indicated that rs56275759 of GRIK4 gene might be associated with MDD in Chinese Han population.

// Gang Chen 1, * , Yanfei Cao 2, * , Lina Zhang 2 , Hongxing Ma 2 , Chao Shen 2 and Jiang Zhao 3 1 Department of Neurosurgery, Daqing Oilfield General Hospital, Daqing 163001, China 2 Department of Clinical Laboratory, Daqing Oilfield General Hospital, Daqing 163001, China 3 Department of Neurosurgery, Shanghai Fourth People’s Hospital, Shanghai 200081, China * These authors have contributed equally to this work Correspondence to: Jiang Zhao, email: jiangzhaodq@sina.com Keywords: biomarkers, gliomas, glioblastoma multiforme, long non-coding RNAs Received: May 04, 2017 Accepted: June 01, 2017 Published: June 28, 2017 ABSTRACT Long non-coding RNAs have been shown to be associated with cancer development and progression, demonstrating potential applications as novel diagnostic or prognostic molecular markers in clinical management and treatment. However, the functional significance of lncRNAs in the development and malignant progression of gliomas is still unclear and needed to be further explored. we first obtained genome-wide lncRNA expression profiles in a large cohort of patients with gliomas from the Gene Expression Omnibus database using microarray probes repurposing method and investigated the lncRNA expression patterns during the tumorigenesis and malignant progression of gliomas. By using differential expression analysis, we identified a large number of lncRNAs that were associated with the tumorigenesis and malignant progression of gliomas in the training dataset and showed their robustness in the testing dataset. Subsequently, we identified a novel four-lncRNA signature which was closely related to the prognosis of patients with GBM. The prognostic value of this signature was verified in the test set of 80 patients. Functional analysis suggested that the four lncRNAs associated with survival of patients with GBM may be involved in cancer-related biological processes and pathways and their deregulation may lead to GBM tumorigenesis and progression. These novel lncRNA biomarkers will improve our understanding of the molecular mechanisms during the development and progression of glioma and provide novel diagnostic or prognostic markers and therapeutic targets for gliomas.

Background Nicotinic acetylcholine receptors (nAChRs) are among the oldest and most conserved transmembrane receptors involved in signal transduction. Despite the prevalence and significance of cholinergic signaling, the diversity and evolution of nAChRs are not fully understood. Result By comparative genomic analysis, we found massive expansions of nAChR genes in molluscs and some other lophotrochozoans. The expansion is particularly pronounced in stationary bivalve molluscs with simple nervous systems, with the number of nAChR genes ranging from 99 to 217 in five bivalves, compared with 10 to 29 in five ecdysozoans and vertebrates. The expanded molluscan nAChR genes tend to be intronless and in tandem arrays due to retroposition followed by tandem duplication. Phylogenetic analysis revealed diverse nAChR families in the common ancestor of bilaterians, which subsequently experienced lineage-specific expansions or contractions. The expanded molluscan nAChR genes are highly diverse in sequence, domain structure, temporal and spatial expression profiles, implying diversified functions. Some molluscan nAChR genes are expressed in early development before the development of the nervous system, while others are involved in immune and stress responses. Conclusion The massive expansion and diversification of nAChR genes in bivalve molluscs may be a compensation for reduced nervous systems as part of adaptation to stationary life under dynamic environments, while in vertebrates a subset of specialized nAChRs are retained to work with advanced nervous systems. The unprecedented diversity identified in molluscs broadens our view on the evolution and function of nAChRs that are critical to animal physiology and human health.

Major depressive disorder (MDD) is a common mental disorder. Venlafaxine (VEN) is used to treat patients with MDD as an antidepressant of serotonin-norepinephrine reuptake inhibitor. In addition, current reports reveal that CYP enzymes mediate its metabolism, thereby affecting the treatment efficacy. The aim of this study was to test whether the genetic polymorphisms of CYP1A2 are associated with remission after VEN treatment for MDD. A total of 175 Han Chinese depressed patients have been recruited to accept a 6-week treatment with VEN. Three single-nucleotide polymorphisms of CYP1A2 were selected from dbSNP and previous literature to compare the allele and genotype frequencies between remitters and nonremitters. The A 17-item Hamilton Depression Scale was used to access the improvement of patients' depressive symptoms from the baseline to endpoint. A logistic regression analysis for remission was conducted. Between remitters and nonremitters, the allele and genotype frequencies of single-nucleotide polymorphism rs2470890 demonstrated significant differences. They still had significant differences between remitters and nonremitters after controlling baseline Hamilton Depression Scale scores, sex, and age in logistic regression. Our results suggest that the single-nucleotide polymorphism rs2470890 of CYP1A2 gene might be associated with treatment remission after VEN treatment in patients with MDD.

Schizophrenia is a highly heritable psychiatric disorder often associated with dopamine-related genetic variations. Thus, we performed a case-control study in 1504 Han Chinese population to evaluate the association of DRD1, DRD2 and DRD3 polymorphisms with schizophrenia. No statistically significant difference in allelic or genotypic frequency was found between schizophrenia and control subjects. Strong positive linkage disequilibrium was detected among the SNPs within DRD1 and DRD2. However, no positive haplotype distribution was found to be associated with schizophrenia. Our results indicated that DRD1, DRD2 and DRD3 may not be the susceptibility genes for schizophrenia in the Chinese Han population.

Schizophrenia is a severe and complex mental disorder with high heritability. There is evidence that mutations in the gene of Nmethyl-d-aspartate-type glutamate receptors (NMDAR) are associated with schizophrenia. GRIN2B encodes a subunit of NMDARs, and has been identified as a candidate gene for many psychiatric disorders, especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRIN2B were associated with schizophrenia. Four SNPs (rs890, rs1806191, rs219872, rs172677) were genotyped in 752 schizophrenic patients and 846 healthy controls of the Chinese Han population. Our results indicate differences in allele and genotype frequencies of rs890 between case and control. These results were assessed by adapting different genetic models (codominant, dominant, recessive, overdominant, log-additive models). After controlling for confounding factors including sex and age, rs890 remained associated with schizophrenia. In addition, rs890 and rs1806191 were found to form a haplotype associated with schizophrenia. In summary, our results indicate that the GRIN2B SNP rs890 might be associated with schizophrenia in the Chinese Han population.

This study was intended to ascertain whether SNPs in dopaminergic and serotoninergic pathway genes SLC6A2, SLC6A3 and DRD2 are associated with schizophrenia in Han Chinese people. We conducted a case-control study by genotyping 7 SNPs of the three genes in 1034 schizophrenia patients and 1034 controls. No significant difference in the allelic or genotypic frequency was detected between cases and controls despite one positive haplotype (rs1362621-rs2242446-rs5564). Stratified analysis of gender and gene-gene interaction analysis showed no positive results. In summary, our study denies the major role of these SNPs within the three genes for schizophrenia in Han Chinese.

Schizophrenia is a severe and complex mental disorder with high heritability. There is an evidence that metabotropic glutamate receptors (GRM) are associated with schizophrenia. GRM7 has been identified as a candidate gene for many psychiatric disorders especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRM7 were associated with schizophrenia. Four SNPs (rs9814881, rs13353402, rs9870680 and rs1531939) were genotyped in 1034 schizophrenic patients and 1034 healthy controls of Chinese Han origin. The results showed that the two SNPs rs13353402 and rs1531939 demonstrated significant difference between schizophrenic patients and control subjects in allele frequencies (rs13353402: P value=0.0307, rs1531939: P value=0.0328, respectively). Nevertheless, there was no significant discrepancies in genotype distribution. In summary, our results indicate that the GRM7 SNPs rs13353402 and rs1531939 might be associated with schizophrenia in Chinese Han population.

Background Congenital cataract is the most frequent cause of blindness during infancy or early childhood. To date, more than 40 loci associated with congenital cataract have been identified, including at least 26 genes on different chromosomes associated with inherited cataract. This present study aimed to identify the genetic mutation in a six-generation Chinese family affected with congenital cataract. Methods A detailed six-generation Chinese cataract family history and clinical data of the family members were recorded. A total of 27 family members, including 14 affected and 13 unaffected individuals were recruited. Whole exome sequencing was performed to determine the disease-causing mutation. Sanger sequencing was used to confirm the results. Results A known missense mutation, c. 139G > A (p. D47N), in Cx50 was identified. This mutation co-segregated with all affected individuals and was not observed in the unaffected family members or in 100 unrelated controls. The homology modeling showed that the structure of the mutant protein was different with that wild-type Cx50. Conclusions The missense mutation c.139G > A in GJA8 gene is associated with autosomal dominant congenital cataract in a six-generation Chinese family. The result of this present study provides further evidence that the p. D47N mutation in CX50 is a hot-spot mutation.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major depressive disorder (MDD), although the treatment outcomes vary in different people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been reported associated with MDD. According to its role in glutamate transmission, it is reasonable to consider it as a potential pharmacogenetic candidate in SSRI treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were recruited. Their genotypes were assessed for the presence of 4 single-nucleotide polymorphisms, which were selected from either the HapMap Chinese ethnic group or the literature report. Treatment effects were evaluated by the change rate of Hamilton Rating Scale for Depression. After the adjustment for the false discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery rate; P = 0.032) demonstrated significant association with SSRI treatment response at week 6. Our results suggest that genetic variants in the SLC17A7 gene may be indicators of treatment response in MDD patients treated by SSRIs.

Background Glioma is a type of malignant tumor that occurs in the central nervous system of adults. Long non-coding RNAs (lncRNAs) that potentially participate in the initiation and progression of glioma have been widely reported. As a now-found lncRNA, HLA complex group 11 (HCG11) has not yet been studied in glioma. The present study aimed to determine the role of HCG11 in the tumorigenesis of glioma. Methods A quantitative real-time polymerase chain reaction assay was performed to examine the expression pattern of HCG11 in 84 glioma tissues and cell lines. The overall survival rate of glioma patients with a high or low level of HCG11 or metastasis-associated 1 family member 3 (MTA3) was analyzed by Kaplan-Meier analysis. The effect of HCG11 on glioma cell growth was determined by in vitro and in vivo experiments. MicroRNAs (miRNAs) that potentially interact with HCG11 were searched and determined by bioinformatics analysis and a luciferase reporter assay. Similarly, the target of miRNA-4425 was identified. Finally, rescue assays were conducted to determine the bio-function of the competing endogenous RNA pathway. Results HCG11 was downregulated in 84 pairs of glioma tissues and cell lines. Moreover, a low level of HCG11 indicted the lower overall survival rate of glioma patients. Regarding the mechanism, HCG11 was abundant in the cytoplasm of glioma cells and interacted with miR-4425 to release the expression of MTA3. miR-4425 and MTA3 participated in HCG11-mediated glioma growth. Conclusions LncRNA HCG11 suppresses the growth of glioma by cooperating with the miR-4425/MTA3 axis.

Evidence has indicated that the incidence of colorectal cancer (CRC) among schizophrenia is lower than normal. To explore this potential protective effect, we employed an innovative strategy combining association study with allele-specific expression (ASE) analysis in MCC gene. We first genotyped four polymorphisms within MCC in 312 CRC patients, 270 schizophrenia patients and 270 controls. Using the MassArray technique, we performed ASE measurements in a second sample series consisting of 50 sporadic CRC patients, 50 schizophrenia patients and 52 controls. Rs2227947 showed significant differences between schizophrenia cases and controls, and haplotype analysis reported some significant discrepancies among these three subject groups. ASE values of rs2227948 and rs2227947 presented consistently differences between CRC (or schizophrenia) patients and controls. Of the three groups, highest frequencies of ASE in MCC were concordantly found in CRC group, whereas lowest frequencies of ASE were observed in schizophrenia group. Similar trends were confirmed in both haplotype frequencies and ASE frequencies (i.e. CRC > control > schizophrenia). We provide a first indication that MCC might confer alterative genetic susceptibility to CRC in individuals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression.

Schizophrenia (SZ) and major depressive disorder (MDD) are two common severe mental disorders that have arisen to public awareness in recent years. Serotonin (5-HT) receptors have been implicated in the pathophysiology of psychiatric disorders especially in MDD and SZ. The aim of this study is to explore whether the variants in the 5-HT1A and 5-HT2A gene are susceptible to SZ or MDD in the Chinese Han population. Five SNPs (Single Nucleotide Polymorphisms) (rs1364043, rs10042486, rs6313, rs6311, rs17289304) in these genes were genotyped from 752 SZ patients, 568 MDD patients, and 846 normal controls of Chinese Han origin. The results showed that the 5-HT1A rs10042486 was significantly associated with SZ ( P allele = 0.0369, P genotype = 0.0098). Moreover, the haplotype (C-T) composed of rs10042486 and rs1364043 showed significant difference between SZ cases and healthy controls ( P = 0.0302) while another haplotype (T-G) was significant for MDD ( P = 0.0247). Our study is the first to suggest a positive association of the 5-HT1A gene with SZ in the Han Chinese population.

The SLC6A3 and SLC6A4 genes are members of a class of neurotransmitter transporters for the release, re-uptake and recycling of neurotransmitters in synapses. SLC6A3 and SLC6A4 encode a dopamine transporter and serotonin transporter, respectively. Abnormal expression and genetic polymorphism of SLC6A3 and SLC6A4 genes may increase the risk of developing mental illness, such as schizophrenia, bipolar disorder, ADHD, and aggressive behavior in Alzheimer disease, etc. Nevertheless, association between SLC6A3, SLC6A4 genes polymorphism and schizophrenia patients have not been well studied in Han Chinese people. In this study, we examined whether single nucleotide polymorphisms (SNPs) in SLC6A3, SLC6A4 were associated with schizophrenia in Han Chinese people (893 schizophrenia patients and 611 healthy controls). No significant difference in allelic or genotypic frequency was found between schizophrenia patients and healthy controls. No positive linkage disequilibrium (LD) was detected either. No haplotypic distributions were positive. Accordingly, our study suggests that the 10 SNPs within both genes we examined do not play a major role in schizophrenia in the Han Chinese population.

Objective Bipolar disorder (BPD) is a serious and common mental disorder with high heritability. The serotonergic system is known to be implicated in the etiology of the disorder. Tryptophan hydroxylase isoform-2 (TPH2), which controls the synthesis of serotonin in the brain, has been suggested as a candidate gene for BDP. The aim of this study was to examine the association between the polymorphisms in TPH2 and BPD. Methods We conducted a case–control study by genotyping six SNPs (rs10784941, rs1386494, rs2171363, rs4760816, rs1386486, and rs1872824) in 506 bipolar patients and 507 controls of Chinese Han origin. Results rs10784941 was not in the Hardy–Weinberg equilibrium and therefore excluded from further analysis. rs1386486 and rs1872824 showed statistically significant differences between cases and controls in genotype frequencies (rs1386486: p = 0.043351; rs1872824: p = 0.016563), but no association in allele frequencies. Strong LD was found among rs1386494, rs2171363 and rs4760816, but no positive association with BPD was found for haplotypes. Conclusion Our results indicate that in the Han Chinese population TPH2 may be a potential susceptibility gene for bipolar disorder. Further studies are needed to validate this association.

Aim: Major depressive disorder is a common psychiatric disorder with worldwide prevalence. The most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs). ATP-binding cassette proteins are responsible for the membrane transport of various molecules including antidepressive drugs. We investigated whether SNPs in ABCB6, ABCB1 and ABCG1 were associated with the treatment response of SSRIs. Materials & methods: A pharmacogenetic study genotyping nine SNPs was conducted in 290 major depressive disorder patients in the Chinese Han population. Allele and genotype frequencies were compared between responders and nonresponders. Results: The allele frequencies of rs28401781 and rs4148739 in ABCB1 showed significant difference between responders and nonresponders before correction (p = 0.0297 and p = 0.0359, respectively). No significant associations were detected for the ABCB6 or ABCG1 gene. Conclusion: Our results suggest that ABCB1 polymorphisms might be associated with SSRIs treatment response in the Chinese Han population. Original submitted 29 April 2013; Revision submitted 29 July 2013

Purpose This study aims to explore gene expression signatures and serum biomarkers to predict intrinsic chemoresistance in epithelial ovarian cancer (EOC). Patients and Methods Gene expression profiling data of 322 high-grade EOC cases between 2009 and 2010 in The Cancer Genome Atlas project (TCGA) were used to develop and validate gene expression signatures that could discriminate different responses to first-line platinum/paclitaxel-based treatments. A gene regulation network was then built to further identify hub genes responsible for differential gene expression between the complete response (CR) group and the progressive disease (PD) group. Further, to find more robust serum biomarkers for clinical application, we integrated our gene signatures and gene signatures reported previously to identify secretory protein-encoding genes by searching the DAVID database. In the end, gene-drug interaction network was constructed by searching Comparative Toxicogenomics Database (CTD) and literature. Results A 349-gene predictive model and an 18-gene model independent of key clinical features with high accuracy were developed for prediction of chemoresistance in EOC. Among them, ten important hub genes and six critical signaling pathways were identified to have important implications in chemotherapeutic response. Further, ten potential serum biomarkers were identified for predicting chemoresistance in EOC. Finally, we suggested some drugs for individualized treatment. Conclusion We have developed the predictive models and serum biomarkers for platinum/paclitaxel response and established the new approach to discover potential serum biomarkers from gene expression profiles. The potential drugs that target hub genes are also suggested.