Search

Joubert syndrome is a neurologic disorder with a pathognomonic “molar tooth sign” on brain imaging. The purpose of this study was to identify potential mutations in a Chinese patient with Joubert syndrome by targeted massively parallel sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18 Joubert-causing genes of a Chinese patient with classic Joubert syndrome were sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323_7327delAGAAG and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2 variants were inherited from each parents, respectively. Both variants are located in the C-terminal region of the CEP290 protein and are predicted to be deleterious. The results support that the combination of targeted genes enrichment and next-generation sequencing is valuable molecular diagnostic tool and suitable for clinical application. [ABSTRACT FROM PUBLISHER]

To investigate the potential of diffusion tensor imaging (DTI) in quantitatively monitoring chronic constriction injuri (CCI) of sciatic nerves and to analyse the association of DTI parameters with nerve histology and limb function. CCI was created on sciatic nerves in the right hind legs of 20 rabbits with the left as control. DTI parameters—fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD) and radial diffusivity (RD)—and limb function were longitudinally evaluated. Pathology analysis was performed on day 3 (d3), week 1 (w1), 2, 4, 6, 8 and 10. FA of the constricted nerves decreased on d3 (0.316 ± 0.044) and increased from w1 to w10 (0.331 ± 0.018, 0.354 ± 0.044, 0.375 ± 0.015, 0.394 ± 0.020, 0.42 ± 0.03 and 0.464 ± 0.039). ADC increased on d3 until w2 (1.502 ± 0.126, 1.462 ± 0.058 and 1.473 ± 0.124 × 10−3 mm2 s−1) and decreased to normal from w4 to w10 (1.356 ± 0.129, 1.375 ± 0.107, 1.290 ± 0.064 and 1.298 ± 0.026 × 10−3 mm2 s−1). AD decreased and stayed low from d3 to w10 (2.042 ± 0.160, 2.005 ± 0.095, 2.057 ± 0.124, 1.952 ± 0.213, 1.988 ± 0.180, 1.947 ± 0.106 and 2.097 ± 0.114). RD increased on d3 (1.233 ± 0.152) and declined from w1 to w10 (1.19 ± 0.06, 1.181 ± 0.14, 1.071 ± 0.102, 1.068 ± 0.084, 0.961 ± 0.063 and 0.923 ± 0.058). FA, ADC and RD correlated significantly with limb functional scores (all Ps < 0.0001) and their changes were associated with histological changes. FA, ADC and RD are promising to monitor CCI. AD may be a stable indicator for injury. Histological changes, oedema, axon loss and demyelination, and fibrosis, accompanied the changes of these parameters. DTI parameters can detect and monitor acute and chronic changes after nerve compression. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells, which have been revealed to inhibit T-cell responses in tumor-bearing mice. In addition, a number of immune suppressive mechanisms have linked MDSCs and the development of human cancer. However, the role of MDSCs in human gastric cancer tissue remains to be elucidated as specific markers are lacking. Therefore, the aim of the present study was to investigate the frequency and immune suppressive function of MDSCs denoted in the present study as cluster of differentiation 14 (CD14)+human leukocyte antigen (HLA)-DR-/low in gastric cancer patients. In the present study, MDSCs were directly isolated and characterized from the tumor and adjacent normal tissue of gastric cancer patients. Functional analysis of the CD14+HLA-DR-/low MDSCs co-cultured with allogeneic CD4+ T cells were performed and compared with controls. In addition, the interferon-γ (IFN-γ) and interleukin (IL)-2 production was compared in order to investigate the capacity of vasoactive intestinal peptide (VIP) to induce CD14+HLA-DR(-/low) MDSC-mediated CD4+ T-cell dysfunction and whether IL-10 secretion is involved in this mechanism. As a result, the quantity of CD14+HLA-DR(-/low) cells in tumor tissue from gastric cancer patients was significantly higher than that in the adjacent normal tissue. In addition, CD14+HLA-DR-/low MDSCs isolated from tumor tissue were observed to inhibit the CD4+ T-cells' immune responses in comparison with those from the adjacent normal tissue. Furthermore, VIP was able to induce the differentiation of CD14+ mononuclear cells isolated from healthy donor peripheral blood mononuclear cells into activated MDSC cells. Of note, the immunosuppressive effect of VIP-induced CD14+HLA-DR(-/low) MDSCs on CD4+ T cells was mediated by IL-10 secretion, which was demonstrated in the subsequent decrease of IFN-γ and IL-2 production. In conclusion, CD14+HLA-DR(-/low) cells were significantly increased in gastric cancer tissue and were shown to have a critical role in CD4+T-cell immunosuppression. In addition, VIP as a novel cytokine may induce the differentiation of CD14+ mononuclear cells towards CD14+HLA-DR(-/low) MDSCs. An improved understanding of phenotypic heterogeneity and the mechanism of generation of MDSCs in gastric cancer patients is important in the design of effective immunotherapeutic strategies.

Objective: To assess the effect of laparoscopic colectomy on the exfoliated cancer cells in peritoneal cavity, recurrence and metastasis of patients with colonic carcinoma., Methods: One hundred and fifty-nine patients with colonic cancer proven by colonoscopy and pathology were divided into two groups based on patient's preference: laparoscopic group (n=74) and open group (n=85). The positive rate of exfoliated cancer cells in peritoneal cavity was compared by cytological detection before and after cancer resection. Recurrence, metastasis rate and 3-year survival were compared between the two groups., Results: The positive rates of exfoliated cancer cells in peritoneal cavity were 12.2% (9/74) in the laparoscopic group and 15.3% (13/85) in the open group before cancer resection without significant difference (P=0.718); 20.3% (15/74) and 30.6% (26/85) after cancer resection without significant difference (P=0.138). The follow-up ranged from 4 to 45 months. The 3-year local recurrence rates were 13.6% (8/59) and 8.8% (6/68) (P=0.455), the 3-year distal metastasis rates were 11.9% (7/59) and 17.6% (12/68) (P=0.416) and the 3-year survival rates were 79.7% and 80.0% (P=0.998), and the differences were not statistically significant., Conclusion: The laparoscopic operation does not increase the recurrence and metastasis rate and results in similar survival in patients with colonic cancer as compared to open procedure.