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  • 简介:AbstractObjective:Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the SLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder.Methods:This prospective pharmacogenetic case-control study that involved genotyping of four SNPs of SLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265).Results:The allele and genotype frequencies of the four candidate SNPs in SCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigated SLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigated SLC17A7 variants (rs1578944) demonstrated a significant association (P=0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted.Conclusion:No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) in SLC17A7 and venlafaxine treatment in the Chinese Han population.

  • 标签: association study major depression pharmacogenomics SLC17A7 gene venlafaxine treatment
  • 简介:AbstractBackground:The Nuclear Dbf2-related (NDR1) kinase is a member of the NDR/LATS family, which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating Yes-associated protein (YAP) remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. This study aimed to investigate the role of NDR1-YAP pathway in GBM.Methods:Bioinformation analysis and immunohistochemistry (IHC) were performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing CCK-8, clone formation, immunofluorescence and flow cytometry, respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-immunoprecipitation and immunofluorescence to observe co-localization.Results:Bioinformation analysis and IHC of our patients’ tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to a lower survival rate. NDR1 could markedly reduce the proliferation and colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-overexpression group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phosphorylate YAP at S127 site. Meanwhile, NDR1 could mediate apoptosis process.Conclusion:In summary, our findings point out that NDR1 functions as a tumor suppressor in GBM. NDR1 is identified as a novel regulator of YAP, which gives us an in-depth comprehension of the Hippo signaling pathway.

  • 标签: Glioblastoma Hippo signaling pathway Nuclear Dbf2-related Yes-associated protein
  • 简介:AbstractBackground:Patients with temporal lobe epilepsy (TLE) originating from different seizure onset zones had distinct electrophysiological characteristics and surgical outcomes. In this study, we aimed to investigate the relationship between the origin and prognosis of TLE, and the stereoelectroencephalography (SEEG) features.Methods:Thirty patients with TLE, who underwent surgical treatment in our functional neurosurgery department from January 2016 to December 2017, were enrolled in this study. All patients underwent anterior temporal lobectomy after an invasive preoperative evaluation with SEEG. Depending on the epileptic focus location, patients were divided into those with medial temporal lobe seizures (MTLS) and those with lateral temporal lobe seizures (LTLS). The Engel classification was used to evaluate operation effectiveness, and the Kaplan-Meier analysis was used to detect seizure-free duration.Results:The mean follow-up time was 25.7 ± 4.8 months. Effectiveness was 63.3% for Engel I (n = 19), 13.3% for Engel II, 3.3% for Engel III, and 20.0% for Engel IV. According to the SEEG, 60.0% (n = 18) had MTLS, and 40.0% (n = 12) had LTLS. Compared with the MTLS group, the operation age of those with LTLS was significantly greater (26.9 ± 6.9 vs. 29.9 ± 12.5 years, t = -0.840, P = 0.009) with longer epilepsy duration (11.9 ± 6.0 vs. 17.9 ± 12.1 years, t = -1.801, P = 0.038). Patients with MTLS had a longer time interval between ictal onset to seizure (67.3 ± 59.1 s vs. 29.3 ± 24.4 s, t = 2.017, P = 0.008). The most common SEEG ictal pattern was a sharp/spike-wave rhythm in the MTLS group (55.6%) and low-voltage fast activity in the LTLS group (58.3%). Compared with the LTLS group, patients with MTLS had a more favorable prognosis (41.7% vs. 77.8%, P = 0.049). Post-operative recurrence was more likely to occur within three months after the operation for both groups, and there appeared to be a stable longterm outcome.Conclusion:Patients with MTLS, who accounted for three-fifths of patients with TLE, showed a more favorable surgical outcome.

  • 标签: Epilepsy Stereoelectroencephalography Surgical outcome Temporal lobe
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