Spontaneous spinal epidural hematoma (SSEH) after cesarean section under epidural anesthesia: A case report.

Spontaneous spinal epidural hematoma (SSEH) is an uncommon condition that can lead to severe neurological injuries, often accompanied by back pain. Pregnancy is identified as a risk factor for SSEH. Early diagnosis of SSEH presents challenges due to its atypical manifestations and the use of intraspinal anesthesia and analgesic techniques. In this case, we present the instance of a 29-year-old woman who initially received epidural labor analgesia during the first stage of labor but subsequently required a cesarean section under epidural anesthesia according to amniotic fluid turbidity. Unfortunately, the anomalous recovery of neurological function in her left lower extremity was not given sufficient attention at an early stage, and paralysis in the non-puncture segment occurred 45.5 hours after the initial puncture. Interestingly, she did not experience any back pain during these procedures. MRI examination and consultation with neurosurgeons confirmed the diagnosis of SSEH, prompting the patient to undergo emergency decompression surgery. She made an incomplete recovery 17 months after the operation. This case emphasizes the importance of considering the possibility of SSEH in pregnant women undergoing epidural analgesia, highlighting the need for spinal imaging and early neurosurgical interventions to facilitate treatment.

Anesthetic management of fetal pulmonary valvuloplasty: A case report.

Anesthesia management of fetal pulmonary valvuloplasty (FPV) is difficult, requiring careful consideration of both the mother and the fetus. Few reports have been published on specific anesthesia implementation and intraoperative management. We report the case of a pregnant woman who was treated with FPV under combined spinal epidural anesthesia (CSEA) with dexmedetomidine in the second trimester of pregnancy. Meanwhile, the application of fetal anesthesia through the umbilical vein was optimal. During the operation, the vital signs of the pregnant woman were stable with no complications and the fetal bradycardia was corrected by intracardiac injection of epinephrine. Four months postoperatively, a boy was born alive by full-term transvaginal delivery. CSEA may be a suitable anesthesia method for FPV surgery. Nevertheless, maternal hemodynamic stability maintenance, effective fetal anesthesia, and timely fetal resuscitation were necessary.

Protective mechanism of the EZH2/microRNA-15a-5p/CXCL10 axis in rats with depressive-like behaviors.

OBJECTIVE: Enhancer of zeste homolog 2 (EZH2), microRNA-15a-5p (miR-15a-5p), and chemokine C-X-C ligand 10 (CXCL10) have been studied in many diseases. However, the investigation of the EZH2/miR-15a-5p/CXCL10 axis in depression is not sufficient. Our study aimed to investigate the regulatory functions of the EZH2/miR-15a-5p/CXCL10 axis in rats with depressive-like behaviors. METHODS: The rat model of depression-like behaviors was established by chronic unpredictable mild stress (CUMS), and EZH2, miR-15a-5p, and CXCL10 expression levels in rats with depression-like behaviors were detected. The silenced EZH2 or enhanced miR-15a-5p recombinant lentivirus was injected into the rats with depression-like behaviors to assess the changes in behavioral tests, hippocampal pathological structure, levels of inflammatory cytokines in the hippocampus, and hippocampal neuron apoptosis. The regulatory relationships among EZH2, miR-15a-5p, and CXCL10 were measured. RESULTS: miR-15a-5p expression was reduced, and EZH2 and CXCL10 expression levels were elevated in rats with depressive-like behaviors. Downregulation of EZH2 or elevation of miR-15a-5p improved depressive behavior, and inhibited hippocampal inflammatory response and hippocampal neuron apoptosis. EZH2 promoted histone methylation at the promoter of miR-15a-5p, and miR-15a-5p bound to CXCL10 to inhibit its expression. CONCLUSION: Our study summarizes that EZH2 promotes the hypermethylation of the miR-15a-5p promoter, thereby promoting CXCL10 expression. Upregulation of miR-15a-5p or inhibition of EZH2 can improve the symptoms in rats with depressive-like behaviors.

Histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit exacerbates inflammation in depression rats by modulating microglia polarization.

Depression is a major cause of emotional agony and degraded living quality. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is involved in histone methylation in human diseases. This experiment was designed to investigate the mechanism of EZH2 on depression. Depression rat model was established via the treatment of chronic unpredictable mild stress (CUMS) to identify rat depression-like behaviors. EZH2 expression was determined and then silenced to assess its effect on depression-like behaviors and neuroinflammation. Microglia were isolated, cultured, identified and activated to assess EZH2 expression. Effect of EZH2 on microglia polarization was evaluated. Next, the binding relation between microRNA (miR)-29b-3p and EZH2 or matrix metallopeptidase 2 (MMP2) was analyzed. Levels of miR-29b-3p expression and MMP2 transcription were examined. Additionally, the role of miR-29b-3p in microglia polarization was tested. Depression-like behaviors were exhibited after CUMS induction. EZH2 was overexpressed in CUMS-treated rats and lipopolysaccharide (LPS)-induced microglia. EZH2 silencing reversed depression-like behaviors. EZH2 silencing mitigated inflammation in depression by manipulating microglia M2-type polarization. EZH2 targeted miR-29b-3p expression to promote MMP2 transcription. Inhibition of miR-29b-3p reversed the role of EZH2 silencing in microglia M2-type polarization and promoted inflammation. EZH2 inhibited miR-29b-3p expression by combining with miR-29b-3p promoter and trimethylation of histone H3-lysine 27-trimethylated upregulation, and then elevated MMP2 transcription and triggered microglia M1-type polarization, thus exacerbating depression-like behaviors and neuroinflammation of depression.

Nrf2 Alleviates Cognitive Dysfunction and Brain Inflammatory Injury via Mediating Wfs1 in Rats with Depression-Like Behaviors.

Depression is a major threat to global mental health and demands targeted therapeutic regimens. The current study set out to evaluate the regulatory mechanism of nuclear factor erythroid-2 related factor 2 (Nrf2) in depression-induced cognitive dysfunction and inflammatory injury. First, depressive rat models were established via chronic unpredicted mild stress (CUMS) treatment. Cognitive function of rats was assessed by a series of behavioral tests. Rats were further stereotactically injected with Nrf2 overexpression vector, with expression patterns of Nrf2, miR-17-5p, and wolfram syndrome 1 (Wfs1) detected using qRT-PCR and Western blot assay. In addition, pathological changes of murine hippocampus were analyzed using hematoxylin-eosin staining. In vitro cell models were additionally established using lipopolysaccharide. Cell viability was detected via the CCK-8 method. Moreover, levels of TNF-α, IL-1ß, and IL-10 were detected via ELISA. Furthermore, the binding relationships between Nrf2 and the miR-17-5p promoter, miR-17-5p, and Wfs1 were verified. It was found that Nrf2 was weakly expressed in CUMS-treated rats, whereas Nrf2 upregulation alleviated cognitive dysfunction and brain inflammatory injury. Meanwhile, Nrf2 inhibited miR-17-5p expression via binding to the miR-17-5p promoter. miR-17-5p was also found to limit Wfs1 transcription. miR-17-5p overexpression or Wfs1 downregulation partly reversed the role of Nrf2 in reliving inflammatory injury of murine hippocampal neurons. Overall, our findings indicated that Nrf2 inhibited miR-17-5p expression and promoted Wfs1 transcription, thereby alleviating cognitive dysfunction and inflammatory injury in rats with depression-like behaviors.

Regulation of glial cell-derived neurotrophic factor in sevoflurane-induced neuronal apoptosis by long non-coding RNA CDKN2B-AS1 as a ceRNA to adsorb miR-133.

OBJECTIVE: To investigate the regulatory mechanism of sevoflurane-induced neuronal apoptosis through analyzing the expression of glial cell-derived neurotrophic factor (GDNF) mediated by miR-133, sponged by long non-coding RNA (lncRNA) CDKN2B-AS1. METHODS: An in vitro cell injury model was established by using different concentrations of sevoflurane and primary hippocampal neurons. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8); caspase-3 and caspase-9 activities were detected by colorimetry, and apoptotic cells were determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Fluorescence in situ hybridization (FISH) analysis was used to detect localized expression of CDKN2B antisense RNA 1 (CDKN2B-AS1), and dual-luciferase reporter assay was employed to verify the correlation of CDKN2B-AS1 and miR-133, and of miR-133 and GDNF. The expression of CDKN2B-AS1, miR-133, and GDNF mRNA in the cell injury model were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was utilized to detect the expression of GDNF protein in the cell injury model. RESULTS: In the cell injury model, CDKN2B-AS1 was highly expressed in the cytoplasm, and CDKN2B-AS1 and GDNF were downregulated and miR-133 was upregulated as detected by qRT-PCR (all P<0.05). The connections between CDKN2B-AS1 and miR-133, and between miR-133 and GDNF were confirmed. That is, CDKN2B-AS1 regulated the expression of GDNF by adsorbing miR-133 (all P<0.05). In cells treated with sevoflurane, overexpression of CDKN2B-AS1 could inhibit caspase-3 and caspase-9 activities and the degree of apoptosis. miR-133 could partially alleviate the effect of overexpressing CDKN2B-AS1 on cells, and si-GDNF the effect of miR-133 inhibitor (all P<0.05). CONCLUSION: lncRNA CDKN2B-AS1 can up-regulate the expression of GDNF, inhibit neuronal apoptosis, and ease the toxic effect of sevoflurane on neural cells by acting as a sponge to adsorb miR-133.

Overexpression of Ubiquitin-Specific Protease15 (USP15) Promotes Tumor Growth and Inhibits Apoptosis and Correlated With Poor Disease-Free Survival in Hepatocellular Carcinoma.

USP15 is a member of ubiquitin-specific proteases (USPs, the largest subfamily of deubiquitinases) and functions as a stabilize factor of target proteins in reversible ubiquitiantion progression. Dysregulated expression of USP15 has been observed in various cancers. However the expression profile and regulatory mechanism of USP15 in hepatocellular carcinoma (HCC) remains largely elusive. To exam the USP15 expression changes in the progression of HCC, we performed IHC analysis to test USP15 expression in a series of cancer-prone diseases including 2 normal liver tissues, 6 liver cirrhosis, 16 primary liver lesions and 15 metastases of hepatocellular carcinoma. The expression of USP15 was upregulated in various liver diseases in compared with normal tissue significantly (p < 0.05). Although no significant different of USP15 expression were discovered between cirrhotic tissue and primary tissue, its expression in HCC metastatic tissue was upregulated. Subsequently, we test the USP15 expression profile in a cohort of 66 HCC patients. USP15 expression was positively correlated with the recurrence of HCC significantly (p = 0.004). HCC patients with high USP15 expression had shorter disease free survival time in compare with those with low USP15 expression (56.9% VS 26.7%, P = 0.012). Subsequently, Cox multivariate analyses of clinical factors associated with disease free survival were performed and USP15 expression (p = 0.008) together with tumor size (p = 0.034) were proved to be independent predict factors in HCC. Then, we silenced USP15 expression in HCC cells and the results showed that downregulated USP15 expression resulting proliferation inhibition and apoptosis induction. In conclusion, our results suppose USP15 to be a potential target in HCC.

Inonotus obliquus Polysaccharide Ameliorates Azoxymethane/Dextran Sulfate Sodium-Induced Colitis-Associated Cancer in Mice via Activation of the NLRP3 Inflammasome.

Inonotus obliquus polysaccharide (IOP), the primary constituent of the parasitic fungus Inonotus obliquus, has anti-tumor, anti-inflammatory, anti-oxidation effects. However, the roles of IOP on colitis-associated cancer (CAC) are still unclear. Herein, we tested the efficacy of IOP using a mouse model of CAC induced by azoxymethane and dextran sulfate sodium (AOM/DSS). We confirmed that intragastric administration of IOP decreased CAC-induced body weight loss, colon tissue damage, colon shortening, and expression of proinflammatory mediators. Meanwhile, IOP treatment increased in expression of the NLRP3 inflammasome, IL-1ß, and IL-18 in the colon of CAC mice. Moreover, in vitro, IOP inhibited the proliferation of SW620 colorectal cancer cells. Finally, overexpression of NLRP3 with plasmid transfection could further enhance the activation of NLRP3 inflammasome by IOP. Taken together, these results suggest that IOP suppresses the development of CAC, possibly by activation of the NLRP3 inflammasome, and reveal that IOP may be a therapeutic drug candidate for CAC.

[The effect on the pro-inflammatory role of N9 microglia exposured to hyperoxia after preconditioning with lipopolysaccharide in vitro].

AIM: To observe the time-dapendcrt expression of TLR4 and TNF-α of N9 microglia exposured to normobaric hyperoxia after preconditioning with lipopolysaccharide in vitro and to explore the role of hyperoxia on the pro-flammation response of microglia and mechanism. METHODS: N9 microglia cell line cultured in vitro was randomly divided into six groups(n=3): normoxia group, sLPS group(100 ng/mL), hLPS group(1 mg/L), hyperoxia group, hyperoxia+sLPS group(100 ng/mL), hyperoxia+hLPS group(1 mg/L). Each of the last two groups, 30 min after pretreatment with different level of LPS, was subjected to 900 mL/L hyperoxia for various times (2 h, 6 h, 12 h, 24 h and 48 h). The remanent groups was cultured in ambient O(2); in which sLPS group and hLPS group respectively was treated with 100 ng/mL and 1 mg/mL LPS in the cell supernatant. After treatment, at each time point, the cells of each group was harvested and TLR4 gene expression were observed by RT-PCR. TLR4 protein expression at 12 h was observed by Western blotting. TNF-α concentrations in the supernatant of cultured microglia N9 cells at different time points were tested with ELISA. RESULTS: After 6 h in hLPS group and 16 h in sLPS group, the expression of TLR4 mRNA was gradually increased(P<0.05), following with increasing time and concentration of LPS, which reached to the maximum at 24 h in hLPS group. Compared with hLPS group, hyperoxia+hLPS group showed downregulation of TLR4 mRNA at each time point after 6 h(P<0.05), especially at 16 h and 24 h. At 12 h, the level of TLR4 protein of hyperoxia+sLPS group and hyperoxia+hLPS group respectively was lower than the corresponding concentration of LPS group. The result of ELISA show that at each time point, compared with the corresponding concentration of LPS group respectively, the expression of TNF-α of hyperoxia+sLPS group and hyperoxia+hLPS significantly increased(P<0.05). CONCLUSION: Hyperoxia enhance the pro-flammation response of N9 microglia triggered by LPS and TLR4 may be the important negative-control target molecule.

Phenotype-specific down-regulation of nicotinic acetylcholine receptors in the pelvic ganglia of castrated rats: implications for neurogenic erectile dysfunction.

Pelvic ganglia (PG) play critical roles in relaying sympathetic and parasympathetic information from the spinal cord to the penile vasculature and, controlling the penile reflex. Animal studies have shown that androgen deprivation by castration causes erectile dysfunction (ED). Until now, however, neural mechanisms underlying castration-induced ED remain unclear. Therefore, we examined whether androgen deprivation down-regulates nicotinic acetylcholine receptors (nAchRs), which mediate fast excitatory synaptic transmission in the PG. Toward this end, neurogenic ED was demonstrated by measuring the intracavernous pressure in castrated rats. Real-time PCR analysis revealed that the transcripts encoding nAchR α3/α5/ß4 subunits were significantly down-regulated in the PG neurons. In addition, down-regulation of the nAchR subunits was reversed by replacement of testosterone. Patch-clamp experiments showed that the nAchR currents were selectively attenuated in the parasympathetic PG neurons innervating the penile vasculature, activation of which elicits penile erection. Taken together, our data suggest that phenotype-specific down-regulation of nAchRs in the PG neurons may contribute to the neurogenic ED in castrated rats.

Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia.

The dopamine D3 receptor has been implicated in the pathophysiology of schizophrenia (SZ). A glycine-to-serine polymorphism at codon 9 of the dopamine D3 receptor gene (DRD3), rs6280, has been widely studied for its association with SZ, but with conflicting results. Altered levels of DRD3 mRNA have also been reported in SZ compared with normal controls. Moreover, it has been suggested that DRD3 is subject to recent positive selection in European populations. To explore the potential role of DRD3 in SZ from these various aspects, we conducted a threefold study. First, we tested the genetic association of rs6280 with SZ in 685 SZ patients and 768 normal controls. Second, we examined DRD3 mRNA levels in peripheral leukocytes in a subset of 37 patients and 37 controls. Finally, we investigated the possible recent positive selection on DRD3 in an East Asian population. Consequently, we observed that the genotypic distribution of rs6280 was nominally associated with SZ (P = 0.045), with the ancestral CC genotype being significantly over-represented in SZ patients. DRD3 mRNA levels were significantly lower in patients than in controls (P = 5.91E-5). The derived C-allele of rs6280 might have been subject to recent positive selection (P < 0.001) in the East Asian population. Taken together, our results suggest that DRD3, a gene possibly under natural selection, might be involved in vulnerability to SZ in the Han Chinese population. These findings may further add to the body of data implicating DRD3 as a schizophrenia risk gene.

MicroRNAs and target site screening reveals a pre-microRNA-30e variant associated with schizophrenia.

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the stability and translation of mRNA targets. Increasing evidence suggests that miRNAs could be involved in the initiation and progression of neuropsychiatric disorders. Prior to this study, six miRNAs had been reported to show a significantly abnormal expression level in schizophrenic brains. Also, common single nucleotide polymorphisms within two miRNA transcripts have shown genetic associations with schizophrenia. However, it remains largely unknown whether variants in these miRNA genes and/or in their target sites are associated with schizophrenia. Here, we selected the above eight miRNAs, plus 15 of their experimentally validated target sites, as candidate susceptibility factors for schizophrenia, for mutation screening and further association studies in Chinese case-control samples. We identified a new potentially functional variant ss178077483 located in the pre-mir-30e, which was strongly associated with schizophrenia (allelic P=0.00017; genotypic P=0.00015), with an odds ratio of 4.952 (95% confidence interval: 1.887-12.998). We also demonstrated that this new variant ss178077483, combined with mir-30e rs7556088 and mir-24-MAPK14 rs3804452, showed a weak gene-gene interaction for schizophrenia risk (P=0.001). In addition, analysis of gene expression demonstrated that expression of the mature mir-30e in the peripheral leukocytes was significantly higher in patients' group than in the control group (P=6.79e-7).This is the first study to indicate that mir-30e ss178077483 plays a role in schizophrenia susceptibility. It suggests that the contribution of mir-30e to the processes that lead to schizophrenia should be further investigated.

An association study of DRD2 gene polymorphisms with schizophrenia in a Chinese Han population.

Dopamine signaling is strongly implicated in the etiology of schizophrenia (SZ). Because of the essential role dopamine D2 receptor (DRD2) in dopamine signaling, DRD2 gene has been regarded as one of the top candidate genes for SZ. However, the findings from linkage and association analyses on this gene are mixed and largely inconsistent across various studies. The aim of this study is to investigate the correlation of DRD2 gene variation and the risk for SZ in a Chinese Han population. Three SNPs (rs1801028, rs6275 and rs6277) of DRD2 gene were genotyped in a patient-control sample involving 421 SZ patients and 404 healthy controls. Our data indicated a nominally significant association of rs6277 with SZ, with T-allele being the risk allele (OR=1.58, 95%CI=1.03-2.43, P=0.034). This study suggests that rs6277 T-allele may play a role in the genetic vulnerability for SZ, supporting the involvement of DRD2 gene in SZ pathogenesis.

The norepinephrine transporter gene modulates the relationship between urban/rural residency and major depressive disorder in a Chinese population.

The norepinephrine transporter (NET), which is involved in the neurotransmission of norepinephrine (NE), may play an important role in the development of major depressive disorder (MDD). Recent studies have suggested that a gene-environment interaction may confer susceptibility to depression. The aims of this study were to test modifying effects of the NET gene on the association between residency and MDD, as well as to reveal the relationship between gender and this gene-environment interaction in MDD. This study recruited a total of 442 patients with MDD and 393 controls. Residence was defined as reported in the data of the 5th Chinese census. Logistic regression models were used to analyze gene-environment interactions. A gene-environment interaction between the G1287A polymorphism and residency was found in the female sample. In addition, and odds ratio analysis showed that only rural women carrying the G/G genotype of the G1287A polymorphism were susceptible to MDD, but others were not. To our knowledge, this is the first report showing that the G1287A polymorphism modifies rural residency as a risk factor for MDD. These findings support the possibility that the NET gene is an important factor in susceptibility to MDD in a Han Chinese population.

Essential involvement of cross-talk between IFN-gamma and TNF-alpha in CXCL10 production in human THP-1 monocytes.

Interferon (IFN)-gamma-induced protein 10 (IP-10/CXCL10), a CXC chemokine, has been documented in several inflammatory and autoimmune disorders including atopic dermatitis and bronchial asthma. Although CXCL10 could be induced by IFN-gamma depending on cell type, the mechanisms regulating CXCL10 production following treatment with combination of IFN-gamma and TNF-alpha have not been adequately elucidated in human monocytes. In this study, we showed that TNF-alpha had more potential than IFN-gamma to induce CXCL10 production in THP-1 monocytes. Furthermore, IFN-gamma synergistically enhanced the production of CXCL10 in parallel with the activation of NF-kappaB in TNF-alpha-stimulated THP-1 cells. Blockage of STAT1 or NF-kappaB suppressed CXCL10 production. JAKs inhibitors suppressed IFN-gamma plus TNF-alpha-induced production of CXCL10 in parallel with activation of STAT1 and NF-kappaB, while ERK inhibitor suppressed production of CXCL10 as well as activation of NF-kappaB, but not that of STAT1. IFN-gamma-induced phosphorylation of JAK1 and JAK2, whereas TNF-alpha induced phosphorylation of ERK1/2. Interestingly, IFN-gamma alone had no effect on phosphorylation and degradation of IkappaB-alpha, whereas it significantly promoted TNF-alpha-induced phosphorylation and degradation of IkappaB-alpha. These results suggest that TNF-alpha induces CXCL10 production by activating NF-kappaB through ERK and that IFN-gamma induces CXCL10 production by increasing the activation of STAT1 through JAKs pathways. Of note, TNF-alpha-induced NF-kappaB may be the primary pathway contributing to CXCL10 production in THP-1 cells. IFN-gamma potentiates TNF-alpha-induced CXCL10 production in THP-1 cells by increasing the activation of STAT1 and NF-kappaB through JAK1 and JAK2.

The adenylyl cyclase-cAMP system suppresses TARC/CCL17 and MDC/CCL22 production through p38 MAPK and NF-kappaB in HaCaT keratinocytes.

Patients with atopic dermatitis (AD) have significantly reduced plasma cAMP levels, and the cAMP level is correlated with the immunopathogenesis of AD. The production of thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) in keratinocytes is significantly enhanced in patients with AD. In the present study, we investigated the in vitro effects of the adenylyl cyclase-cAMP system on IFN-gamma and TNF-alpha-stimulated production of TARC and MDC in human HaCaT keratinocytes. Both forskolin (a direct activator of adenylyl cyclase) and dibutyryl-cAMP (DBcAMP, a permeable analog of cAMP) suppressed production of TARC and MDC in parallel with the activation of NF-kappaB in IFN-gamma and TNF-alpha-stimulated HaCaT cells. Moreover, inhibition of NF-kappaB suppressed TARC and MDC production induced by IFN-gamma plus TNF-alpha. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the secretion of these chemokines. An inhibitor of p38 MAPK suppressed the production of TARC and MDC in parallel to the activation of NF-kappaB in HaCaT cells. Of note, the IFN-gamma plus TNF-alpha-stimulated activation of p38 MAPK was suppressed following incubation with forskolin or DBcAMP alone. These results indicate that the adenylyl cyclase-cAMP system has an inhibitory role in IFN-gamma plus TNF-alpha-stimulated production of TARC and MDC in HaCaT keratinocytes by inhibiting NF-kappaB activation through p38 MAPK pathway, implying that the adenylyl cyclase-cAMP system could be a candidate therapeutic target of Th2-skewed skin inflammation such as AD.

An association study of ADSS gene polymorphisms with schizophrenia.

BACKGROUND: Adenylosuccinate synthase (ADSS) catalyzes the first committed step of AMP synthesis. It was suggested that the blood-derived RNA of ADSS was down-regulated in schizophrenia (SZ) and one of the eight putative biomarker genes to discriminate SZ from normal controls. However, it remains unclear whether the reduction of ADSS RNA is due to the polymorphisms of the gene or not. METHODS: We attempted to examine the association of ADSS gene with schizophrenia in a Chinese population of 480 schizophrenics and 502 normal controls. Genotyping was performed by the Sequenom platform. RESULTS: The 6 marker SNPs (rs3102460, rs3127459, rs3127460, rs3127465, rs3006001, and rs3003211) were genotyped. The frequencies of alleles, genotypes, and haplotypes were tested between cases and controls. There was no significant difference of genotypic, allelic, or haplotypic distributions of the 6 SNPs between the two groups. CONCLUSION: Our data did not support ADSS gene as a susceptibility gene for SZ in Chinese Han population. Large sample size study is needed to validate or replicate our association study, especially from other ethnic populations.

[Analysis on neuropsychological characteristics of subtypes of attention deficit hyperactivity disorder].

OBJECTIVE: To explore the neuropsychological characteristics of children with attention deficit hyperactivity disorder (ADHD). METHODS: Neuropsychological tests, including visual working memory, Stroop test, digits inverse reciting, vocabulary fluency, Wisconsin card sort test (WCST), and Temporal discounting were used to evaluate the capacity of response inhibition, phonological working memory, visual working memory executive function and delayed satisfying capacity of subjects. RESULTS: 1. The ADHD children spent longer time [ADHD-I (84(20), ADHD-C: 98 (31), normal: 70 (28)] to accomplish color naming and made more errors [ADHD-I: 3 (3), ADHD-C: 6 (19), normal: 2 (5)] than the normal control when the color was inconsistent with the word meaning in Stroop test (P < 0.01). 2. The scores of digits reciting [ADHD-I: 3 (3), ADHD-C: 3 (4), normal 4 (4)] inverse was lower in ADHD than in normal control (P < 0.01). 3. The representation of ADHD was poorer than normal control in visual working memory [ADHD-I: 21 (3), ADHD-C: 20 (5), Normal: 20 (3)], and in delayed visual memory [ADHD-I: 19 (5), ADHD-C: 19 (5), Normal: 20 (5)] (P < 0.01). 4. The scores of vocabulary fluency [ADHD-I: 1 (1), ADHD-C: 2 (1), normal: 0 (0)] was lower in ADHD than in normal control (P < 0.01). 5. In WCST, the ADHD children made more errors [ADHD-I :15 (17), ADHD-C: 15 (15), normal: 13 (13)] and less classification [ADHD-I: 5 (4), ADHD-C: 5 (4), normal: 5 (3)] than normal control (P < 0.01). 6. In Temporal discounting, the ADHD children showed significantly more impairments than normal control did (P < 0.01). 7. There was significant difference between the two subtype groups on some tests (P < 0.01). CONCLUSIONS: Obvious cognitive impairments were found in children with ADHD, involving poor response inhibition, impaired working memory, dysfunction of planning and set-shifting, and there was no significant difference between the two subtype groups.

Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population.

BACKGROUND: The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes. METHODS: Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform. RESULTS: There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10. CONCLUSION: These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population.