[Abstract ] Objective Chronic obstructive pulmonary disease (COPD) is closely related to pulmonary hypertension .This study was to investigate the correlation of the expression of high mobility group protein B 1 ( HMGB1) with its synthesis and secretion of interferon-γ( IFN-γ) in the distal pulmonary arterial smooth muscle cells ( PASMCs ) of COPD rats and its clinical significance . Methods We established COPD models in rats , primarily cultured and identified PASMCs , and detected the synthesis and secretion of cytokine in the PASMCs induced by cigarette smoke extract (CSE) and/or lipopolysaccharide (LPS).The PASMCs in the control, CSE, LPS, and CSE+LPS groups were cultured with anti-HMGB1 antibodies at 0.2 mL 1∶1000.At 12, 24, 48 and 72 hours of inter-vention, the expression of HMGB1 in the PASMCs was detected by Western blot and the concentrations of HMGB 1 and IFN-γin the cell culture supernatant were measured by ELISA , followed by a correlation analysis . Results Light microscopy manifested a peak -valley growth pattern or fusiform shape of the cells , which were identified as PASMCs by α-actin immunohistochemistry and immuno-fluorescence .Western blot and ELISA showed statistically significant differences in the expression of HMGB 1 and concentrations of cell supernatant HMGB1 and IFN-γat 12 hours between any two of the four groups (P<0.05).The HMGB1 expression level was positive-ly correlated with the concentration of IFN-γ(r=0.91), obviously decreased after 12 hours of intervention with anti-HMGB1 antibod-ies as compared with the corresponding experimental groups ( P <0.05).Western blot and ELISA showed no significant differences within the same group at 12, 24, 48 and 72 hours (P>0.05). Conclusion The expression level of HMGB1 was positively correla-ted with the synthesis and secretion of IFN-γin the distal PASMCs of the COPD model rats , and anti-HMGB1 antibodies provide a new in-tervention target for the clinical treatment of COPD and inhibition of its systemic inflammatory response .

OBJECTIVETo assess the impact of natural selection and genetic background on the polymorphisms of HLA-G 3-untranslated regions (UTR) among five ethnic Chinese populations.

METHODSPCR and DNA sequencing were used to determine the polymorphisms among 432 individuals from the five ethnic populations. Their genetic background was determined by genotyping of 10 short tandem repeats (STRs).

RESULTSEight variations were identified among Gelao, Mongolian and Kirgiz populations, while only 7 were found in Shui and Dai people. For all 3 southern populations (Gelao, Shui, and Dai), the observed heterozygosites (Ho) was higher than expected heterozygosities (He). But this was reversed for the 2 northern populations (Mongolian and Kirgiz). The Ho and He of the 10 neutral STRs were in random distribution. Ewens-Watterson testing based on haplotypes of the HLA-G 3'UTR has suggested that a natural selection had occurred in the region where Dai and Shui had inhabited, but not in the northern region where Mongolian and Kirgiz population inhabited. Polygenetic trees based on the HLA and STRs were also different.

CONCLUSIONThe HLA-G 3'UTR of Dai and Shui people who lived in southern China may have subjected to a selection pressure. Based on current knowledge, this pressure may have been driven by a pathogenic selection.

3' Untranslated Regions ; genetics ; China ; ethnology ; Female ; HLA-G Antigens ; genetics ; Humans ; Male ; Microsatellite Repeats ; Polymorphism, Genetic ; Selection, Genetic

Objective The aim of the study is to investigate the therapeutic efficacy of next-generation anaplastic lynphoma kinase-tyrosine kinase inhibitor (ALK-TKI) in advanced non-small cell lung cancer (NSCLC).Methods The clinical data and outcomes of 22 patients with advanced non-small cell lung cancer who received the next generation of ALK-TKI from 2014 to 2017 in our hospital were retrospectively analyzed.Results 22 patients were included for survival analysis with 15 males and 7 females.The median age was 48 and all of them were adenocarcinoma patients.There were 12,2,7 and 1 patients received ceritinib,alectinib,brigatinib and lorlatinib,respectively.A total of 14 patients could be evaluated,including complete response (CR) in 2 cases,partial response (PR) in 3 cases,stable disease (SD) in 6 cases,progressive disease (PD) in 3 cases.The ORR and DCR were 35.7％ and 78.6％,respectively.The median progression free survival (PFS) of the 22 NSCLC patients was 8.7 months.Progression pattern can be analyzed in 17 patients.Among them,10 patients underwent primary progression (lung),occurring at the leading frequency (accounting for 58.8％) and followed by central nerve system (CNS) progression (accounting for 29.4％).Conclusions Next-generation ALK-TKI provide a reasonable choice for crizotinib-resistant patients.Primary progression (lung) is the leading cause for treatment failure.Multi-disciplinary integration may provide a potential choice for prolonging administration of next-generation ALK-TKI.