Identification of lung adenocarcinoma subtypes and a prognostic signature based on activity changes of the hallmark and immunologic gene sets.

Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. Our research attempts to clearness LUAD subtypes and build a reliable prognostic signature according to the activity changes of the hallmark and immunologic gene sets. Methods: According to The Cancer Genome Atlas (TCGA) - LUAD dataset, changes in marker and immune gene activity were analyzed, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the differentially expressed genes (DEGs) between different subtypes were identified, followed by the construction of a prognostic risk score (RS) model and nomogram model. The tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) of different risk groups were compared. Results: Two LUAD subtypes were determined according to the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumor and clinical stages than cluster 1. Moreover, a prognostic RS signature was established using two LUAD subtype-related DEGs, which could stratify patients at different risk levels. Nomogram model incorporated RS and clinical stage exerted good prognostic performance in LUAD patients. A shorter survival time and higher TMB were observed in the high-risk patients. Conclusions: Our findings revealed that our constructed prognostic signature could exactly predict the survival status of LUAD cases, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.

Risk of venous thromboembolism in Chinese pregnant women: Hong Kong venous thromboembolism study

BACKGROUND: Previous Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum period in the Chinese population. We investigated the risk of venous thromboembolism in a “real-world” cohort of pregnant Chinese women with no prior history of venous thromboembolism. METHODS: In this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed. RESULTS: The mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29–36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pulmonary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester. CONCLUSION: Chinese women had a substantially lower risk of venous thromboembolism during pregnancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early pregnancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.

The comparative study of left ventricular diastolic function and disease activity in rheumatoid arthritis / 中华风湿病学杂志

Objective To evaluate the change of left ventricular diastolic function and investigate the relation between left ventricular diastolic function and disease activity in rheumatoid arthritis (RA) without clinical manifestations of heart diseases. Methods Seventy consecutive active RA in-patients without clinical manifestations of heart disease were enrolled, while the control group was recruited from outpatient health physical check-up center and consisted of 60 age- and sex-matched healthy subjects. Cardiac related parame-ters were determined by echocardiography and the correlation between left ventricular diastolic function and the disease activity indexes were evaluated. Chi-square test, t test, Pearson or Spearman′s correlation test and Stepwise backward linear regression analysis were used for statistical analysis. Results RA patients had lower mitral inflow E/A ratio (1.2±0.4, 1.5±0.4, P<0.01), higher E/Em ratio (9.6±3.7, 7.8±2.0, P<0.01), longer isovolumetric relaxation time(IVRT)[(64±16) ms,(58±16) ms, P<0.05] than control group. Whilst, RA patients had higher pulmonary venous inflow A wave velocity-time integral (ArVTI) and A wave duration (DAr)[3.2±0.7,(2.8±0.6) cm; 117±11,(102±9) ms, P<0.05]. Moreover, the E/Em was positively corre-lated with C-reactive protein(CRP)(r=0.581, P<0.01), DAS28(r=0.456, P<0.01). Anti-CCP level was also associated with Em and early diastolic pulmonary venous inflow peak velocity(PVD)(r=-0.359, P<0.05;r=-0.305, P<0.05). In addition, multivariate analysis also revealed that there was linear regression relation-ship between E/Em and CRP, DAS28(t=3.266, P=0.002; t=2.949, P=0.005). Conclusion The study has revealed that left ventricular diastolic function is impaired in RA patients and the left ventricular diastolic function parameters is associated with the disease activity indexes. These results suggest that the decline of left ventricular diastolic function is associated with the inflammation activity in RA patients without clinical manifestations of heart disease.