Influence of HLA Class II Alleles and DRB1-DQB1 Haplotypes on Rheumatoid Arthritis Susceptibility and Autoantibody Status in the Chinese Han Population.

Human leukocyte antigen (HLA) class II alleles are considered to play a key role in the progress of rheumatoid arthritis (RA). This study was carried out to investigate the presence of HLA class II alleles and their influence on disease risk and autoantibody status in Chinese Han patients with RA. Here, HLA-DRB1, DQB1 and DPB1 genotyping was performed in 125 RA patients and 120 healthy controls by using the next-generation sequencing (NGS). Strong positive associations were shown between high-resolution typed HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01, DPB1*02:01:02 and RA patients. Moreover, the haplotypes HLA-DRB1*04:05:01~ DQB1*04:01:01 and HLA-DRB1*10:01:01~ DQB1*05:01:01 were found to be more frequent in RA populations than in healthy controls. These possible susceptible HLA alleles (HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01 and DPB1*02:01:02) also showed higher frequencies in seropositive RA patients as compared to normal controls. The present study provided evidence that alleles HLA-DRB1*04:05:01, DRB1*10:01:01, DQB1*04:01:01 and DPB1*02:01:02 constituted RA risk alleles, and haplotypes HLA-DRB1*04:05:01~ DQB1*04:01:01, HLA-DRB1*10:01:01~ DQB1*05:01:01 also showed prevalence in Chinese Han patients with RA. Serological results preliminary demonstrated patients carrying RA-risk HLA alleles might elevate the serum level of anti-citrullinated protein antibodies and rheumatoid factor and affect RA progression.

High Platelet Levels Attenuate the Efficacy of Platinum-Based Treatment in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: The correlation between platelet levels and clinical outcomes has received increasing attention, but it is not yet clear whether and how platelet levels affect the therapeutic response in non-small cell lung cancer (NSCLC). In the current study, we aimed to explore the role of platelet levels in responsive to platinum-based chemotherapy and investigated the underlying mechanism. METHODS: We evaluated the possibility of platelet level as a biomarker for response to platinum-based therapy in NSCLC by retrospective analysis of NSCLC patients. Cell proliferation was evaluated using cell counter and flow cytometry. Cell capillary-like structures of HPMEC were estimated with ECMatrix. The effect of platelets on A549, H1299, and HPMEC apoptosis was measured by flow cytometry. A A549-bearing NOD/ SCID mice model was employed to determine whether platelets could counteract cisplatin-induced apoptosis in vivo. In vivo cell proliferation and apoptosis were evaluated with Ki-67 antibody and TUNEL staining respectively. The angiogenesis of tumor was estimated by CD31 microvessel density. The protein levels of Akt, Bad and Bcl-2 were assessed by western blot. To further examine platelet-driven effects of the chemotherapeutic response, we used platelet depletion and platelet transfusion in A549-bearing NOD/SCID mice. RESULTS: Thrombocytosis at NSCLC diagnosis was associated with lower progression-free survival and median overall survival. Platelet levels before chemotherapy in the no response group were markedly higher than in the responsive group. Platelets rescued the inhibition of cell proliferation and angiogenesis and protected against cell apoptosis induced by cisplatin, platelets rescued cisplatin-induced apoptosis via the Akt/Bad/Bcl-2 signaling pathway under endoplasmic reticulum stress. Platelet transfusion decreased the therapeutic effect of cisplatin, while it was increased by platelet depletion. CONCLUSION: We confirmed an important anti-apoptosis mechanism mediated by platelets and found that platelets could counteract cisplatin-induced apoptosis. Reducing platelet levels or blocking platelet-based cytoprotection may represent new methods for improving the chemotherapeutic effect.

Comprehensive Analysis of Connectivity and Permeability of a Pore-Fracture Structure in Low Permeability Seam of Huainan-Huaibei Coalfield.

The connectivity and permeability of the coal seam pore structures control the occurrence and migration of coalbed methane. Coal samples were used from Huainan-Huaibei to reconstruct three-dimensional models of the pores and an equivalent pore network model, Statistical pore structure characteristic parameters. The pore structure of the coal reservoir was analyzed from the direction of multidimensional and multiangle. It shows that based on quantitative analysis, the representative Elementary volume of 500 × 500 × 500 was the most suitable experimental volume. The Y-axis direction of the Renlou sample had poor pore connectivity compared to that of other samples. Large volume connected pores dominated their pore systems. In terms of coal sample pore connectivity, the coal samples from the Liuzhuang and Qidong regions had pore connectivity better than those from the other regions. The pore connectivity of the Liuzhuang coal samples was the best. In terms of coal permeability, the Liuzhuang sample had better permeability than the other three samples, and the permeability was the best in the Y-axis direction. For all the combinations of the different types of throats, the shorter the throat, the greater the equivalent radius and the better the permeability. Conversely, the worse the permeability. During gas injection production, the closer the gas injection area was to the gas injection well, the poorer the connectivity and the lower the permeability over time. Near the production area, where the CO2 did not reach the production area, the fracture porosity and effective connected porosity of the coal reservoir increased over time. When CO2 reached the production area, the change in its connected pore structure was consistent with the change in the connected pores in the gas injection area. With this study, the coal seam pore structure on a microscale was characterized. A comprehensive analysis of the coal reservoir pore connectivity and permeability was completed. The study results are significant for the exploration and development of coalbed methane in the Huainan-Huaibei coalfield.

Correlation Evaluation and Schematic Analysis of Influencing Factors Affecting Pore and Fracture Connectivity on the Microscale and Their Application Discussion in Coal Reservoir Based on X-ray CT Data.

The connectivity of the pore/fracture system is the key to CO2 injection and CH4 production, which is of great significance in analyzing the correlation and weight of the influencing factors affecting the connectivity on the microscale. First, the 3D reconstruction of the coal reservoir is realized. Second, the characteristic parameters of pore/fracture structures are analyzed. Next, the characteristics of absolute permeability are analyzed, and then the correlation and weight analysis of the influencing factors are realized. Finally, the schematic analysis and application discussion of the influencing factors are carried out. The results show that porosity is the key factor restricting fluid migration. The heterogeneity of the reservoir can be characterized by the volume changes of the pore/fracture, organic matter, and mineral. The interconnected pores/fractures are mainly distributed in sheets and bands. The coordination number ranges from 1 to 15. The Ferret diameter is 0-10 µm. The tortuosity is 2.27111, 1.9034, 3.98522, and 3.51516, respectively, and the Euler characteristic number is 0.931868, 0.974719, 0.921144, and 0.897697, respectively. The permeability of the SH and YW samples is higher than that of the RL and PY samples. The single weight of the influencing factor is as follows: coordination number > Ferret diameter > Euler characteristic number > porosity > tortuosity. The analysis area of the comprehensive evaluation score of the influencing factors and the permeability value can be divided into three grades. There is a positive correlation among the coordination number, the quantity equilibrium of pores and throats, and the connectivity. The shape factor gradually increases with the increase of the Ferret diameter. The reservoir permeability is indirectly characterized by the coordination number, Ferret diameter, tortuosity, Euler characteristic number, and shape factor. This study can provide new ideas for clarifying the correlation degree and weight value of the characteristic parameters and can enrich the development of 3D digital core and CO2-ECBM technology.