Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

Healthy individuals vs patients with bipolar or unipolar depression in gray matter volume.

BACKGROUND: Previous studies using voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) of patients with depression, but the differences between patients with bipolar disorder (BD) and unipolar depression (UD) are less known. AIM: To analyze the whole-brain GMV data of patients with untreated UD and BD compared with healthy controls. METHODS: Fourteen patients with BD and 20 with UD were recruited from the Mental Health Center of Shantou University between August 2014 and July 2015, and 20 non-depressive controls were recruited. After routine three-plane positioning, axial T2WI scanning was performed. The connecting line between the anterior and posterior commissures was used as the scanning baseline. The scanning range extended from the cranial apex to the foramen magnum. Categorical data are presented as frequencies and were analyzed using the Fisher exact test. RESULTS: There were no significant intergroup differences in gender, age, or years of education. Disease course, age at the first episode, and Hamilton depression rating scale scores were similar between patients with UD and those with BD. Compared with the non-depressive controls, patients with BD showed smaller GMVs in the right inferior temporal gyrus, left middle temporal gyrus, right middle occipital gyrus, and right superior parietal gyrus and larger GMVs in the midbrain, left superior frontal gyrus, and right cerebellum. In contrast, UD patients showed smaller GMVs than the controls in the right fusiform gyrus, left inferior occipital gyrus, left paracentral lobule, right superior and inferior temporal gyri, and the right posterior lobe of the cerebellum, and larger GMVs than the controls in the left posterior central gyrus and left middle frontal gyrus. There was no difference in GMV between patients with BD and UD. CONCLUSION: Using VBM, the present study revealed that patients with UD and BD have different patterns of changes in GMV when compared with healthy controls.

The expression of cytoglobin as a prognostic factor in gliomas: a retrospective analysis of 88 patients.

BACKGROUND: Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene. METHODS: We immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors. RESULTS: Low expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFα or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFα and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients' overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis. CONCLUSIONS: Cygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients.

Mechanisms of neuroprotection from hypoxia-ischemia (HI) brain injury by up-regulation of cytoglobin (CYGB) in a neonatal rat model.

This study was designed to investigate the expression profile of CYGB, its potential neuroprotective function, and underlying molecular mechanisms using a model of neonatal hypoxia-ischemia (HI) brain injury. Cygb mRNA and protein expression were evaluated within the first 36 h after the HI model was induced using RT-PCR and Western blotting. Cygb mRNA expression was increased at 18 h in a time-dependent manner, and its level of protein expression increased progressively in 24 h. To verify the neuroprotective effect of CYGB, a gene transfection technique was employed. Cygb cDNA and shRNA delivery adenovirus systems were established (Cygb-cDNA-ADV and Cygb-shRNA-ADV, respectively) and injected into the brains of 3-day-old rats 4 days before they were induced with HI treatment. Rats from different groups were euthanized 24 h post-HI, and brain samples were harvested. 2,3,5-Triphenyltetrazolium chloride, TUNEL, and Nissl staining indicated that an up-regulation of CYGB resulted in reduced acute brain injury. The superoxide dismutase level was found to be dependent on expression of CYGB. The Morris water maze test in 28-day-old rats demonstrated that CYGB expression was associated with improvement of long term cognitive impairment. Studies also demonstrated that CYGB can up-regulate mRNA and protein levels of VEGF and increase both the density and diameter of the microvessels but inhibits activation of caspase-2 and -3. Thus, this is the first in vivo study focusing on the neuroprotective role of CYGB. The reduction of neonatal HI injury by CYGB may be due in part to antioxidant and antiapoptotic mechanisms and by promoting angiogenesis.