Inherited Genetic Susceptibility to Nonimmunosuppressed Epstein-Barr Virus-associated T/NK-cell Lymphoproliferative Diseases in Chinese Patients.

Epstein-Barr virus (EBV) T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells, including chronic active EBV infection of T/NK-cell type (CAEBV+T/NK), EBV-associated hemophagocytic lymphohistiocytosis (EBV+HLH), extranodal NK/T-cell lymphoma of nasal type (ENKTL), and aggressive NK-cell leukemia (ANKL). However, the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown. A total of 171 nonimmunosuppressed patients with EBV+T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed. The 94 gene variants, mostly located in UNC13D, LYST, ITK, and PRF1 genes were detected, and mutations covered 28/50 (56.00%) of CAEBV-T/NK, 31/51 (60.78%) of EBV+HLH, 13/28 (46.42%) of ENKTL, and 13/48 (27.09%) of ANKL. Most mutations represented monoallelic and missense. Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations (P=0.0284, P=0.0137). Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV+T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.

Novel bioinformatic classification system for genetic signatures identification in diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a spectrum of disease comprising more than 30% of non-Hodgkin lymphomas. Although studies have identified several molecular subgroups, the heterogeneous genetic background of DLBCL remains ambiguous. In this study we aimed to develop a novel approach and to provide a distinctive classification system to unravel its molecular features. METHOD: A cohort of 342 patient samples diagnosed with DLBCL in our hospital were retrospectively enrolled in this study. A total of 46 genes were included in next-generation sequencing panel. Non-mutually exclusive genetic signatures for the factorization of complex genomic patterns were generated by random forest algorithm. RESULTS: A total of four non-mutually exclusive signatures were generated, including those with MYC-translocation (MYC-trans) (n = 62), with BCL2-translocation (BCL2-trans) (n = 69), with BCL6-translocation (BCL6-trans) (n = 108), and those with MYD88 and/or CD79B mutations (MC) signatures (n = 115). Comparison analysis between our model and traditional mutually exclusive Schmitz's model demonstrated consistent classification pattern. And prognostic heterogeneity existed within EZB subgroup of de novo DLBCL patients. As for prognostic impact, MYC-trans signature was an independent unfavorable prognostic factor. Furthermore, tumors carrying three different signature markers exhibited significantly inferior prognoses compared with their counterparts with no genetic signature. CONCLUSION: Compared with traditional mutually exclusive molecular sub-classification, non-mutually exclusive genetic fingerprint model generated from our study provided novel insight into not only the complex genetic features, but also the prognostic heterogeneity of DLBCL patients.

[Threshold Flux and Membrane Fouling Analysis of the Hybrid Pre-ozonation and CNTs Membrane Modification Process].

Polyvinylidene fluoride (PVDF) hollow fiber ultrafiltration membranes were modified with carbon nanotubes (CNT). Hybrid pre-ozonation and CNT modification were investigated by experimentally manipulating the ozonation process, threshold flux, and membrane fouling. The results showed that the threshold fluxes of the unmodified membrane and hybrid process were 45 L·(m2·h)-1 and 81 L·(m2·h)-1, respectively. Additionally, the fouling rate of the hybrid process was about 0.00137 kPa·min-1·L-1·m2·h, which was notably lower compared to other process. The results showed that the filtration volume under threshold flux was higher than that under critical flux with the same CNT loading mass and ozone dosage. This comparison indicated that membrane fouling was alleviated under threshold flux and that the corresponding operation period was extended. Through the carbon balance experiment, the fouling capacity and recoverability improved remarkably after CNT modification. Additionally, ozonation could enhance the recoverability of membranes. The hybrid process examined in this study could dramatically improve the permeability and extend the operation time of the ultrafiltration membrane.

[Effect of Hybrid Process of Pre-ozonation and CNT Modification on Hollow Fiber Membrane Fouling Control].

Polyvinylidene fluoride (PVDF) hollow fiber ultrafiltration membranes were modified with carbon nanotube (CNT). Combined with the ozonation process, the effect of the hybrid pre-ozonation and CNT modification on fouling alleviation was investigated. The impacts of CNT loading mass and ozone dosage on the variation of flux and antifouling ability of the membrane modules were evaluated. Under a critical flux of 144 L·(m2·h)-1, CNT loading mass of 3 g·m-2, and ozone dosage(O3/DOC) of 0.22 mg·mg-1, the results revealed that the filtration volume of the hybrid process was promoted to 850 L·m-2, which was about 4.5 times higher than that of the original unmodified membrane. With a flux of 18 L·(m2·h)-1 and 15 day operation, the filtration volume was promoted to 3000 L·m-2, which was 10 times that of the unmodified membrane. The fouling membrane surface was observed using confocal laser scanning electron microscopy (CLSM). The results demonstrated that more living bacteria were present on the membrane surface of the unmodified membrane, which showed a rapid transmembrane pressure (TMP) increase. Both pre-ozonation and CNT modification decreased the total amount of microorganisms and the amount of the living bacteria as well, which mitigated the increase in TMP. After pre-ozonation, the presence of a CNT layer on the membrane surface further decreased the number of living bacteria. Although the CNT layer captured some dead bacteria, it had no obvious relationship with the increase in TMP.

[Effect of PVDF Hollow Fiber Ultrafiltration Membranes Modification with Carbonnanotube on Membrane Fouling Control During Ultrafiltration of Sewage Effluent].

The modification of hollow fiber ultrafiltration membranes with carbon nanotube (CNTs) on fouling control was investigated.Considering the antifouling ability of the CNT-modified membranes and the stability of CNTs layer,several factors were analyzed and evaluated,including the concentration of ethanol-dispersion,the diameter of CNTs,and the loading mass of CNTs.Besides,DOC,UV254,and fluorescence characteristics of the permeate from the CNT-modified membrane were analyzed.The results revealed that the optimal modification method included a 50%(volume fraction) ethanol-dispersion,a 30-50 nm diameter-CNTs,and 3 g·m-2 CNTs' loading.Compared with the virgin membrane,the removal rates of DOC and UV254 by the CNT-modified membrane were increased by 37% and 56%,respectively.Meanwhile,it was proved that the humic-like and protein-like materials were more easily removed by the CNT-modified membrane.