Purpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799– 0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.

Whether long non-coding RNA (lncRNA) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncRNA SNPs and AML outcomes, thirty tagSNPs in five lncRNAs were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T > C) was significantly associated with prognosis of AML (p = 0.018). Patients with rs55829688 CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p = 0.025) and harbored a longer platelets recovery (p = 0.040) than carriers of rs55829688T allele. In vitro study indicated that GAS5 promoter harboring the rs55829688C allele showed marginally increased reporter gene activity (p = 0.019), and the promoter activity was increased by TP63 in a dose-dependent manner (P = 0.001). Moreover, GAS5 higher expression predict shorter AML overall survival (OS), which validated in GEO GSE12417 dataset (p = 0.011). In conclusion, rs55829688 polymorphism could increase GAS5 expression by interacting with TP63, which might aggravate the myelosuppression and in turn lead to poor prognosis in AML. Trail registration number: ChiCTR-PPC-14005297.

Cytarabine arabinoside (Ara-C) has been the core of chemotherapy for adult acute myeloid leukemia (AML). Ara-C undergoes a three-step phosphorylation into the active metabolite Ara-C triphosphosphate (ara-CTP). Several enzymes are involved directly or indirectly in either the formation or detoxification of ara-CTP. A total of 12 eQTL (expression Quantitative Trait Loci) single nucleotide polymorphisms (SNPs) or tag SNPs in 7 genes including CMPK1, NME1, NME2, RRM1, RRM2, SAMHD1 and E2F1 were genotyped in 361 Chinese non-M3 AML patients by using the Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, relapse-free survival (RFS) and overall survival (OS) were analyzed. Three SNPs were observed to be associated increased risk of chemoresistance indicated by CR rate (NME2 rs3744660, E2F1 rs3213150, and RRM2 rs1130609), among which two (rs3744660 and rs1130609) were eQTL. Combined genotypes based on E2F1 rs3213150 and RRM2 rs1130609 polymorphisms further increased the risk of non-CR. The SAMHD1 eQTL polymorphism rs6102991 showed decreased risk of non-CR marginally (P = 0.055). Three SNPs (NME1 rs3760468 and rs2302254, and NME2 rs3744660) were associated with worse RFS, and the RRM2 rs1130609 polymorphism was marginally associated with worse RFS (P = 0.085) and OS (P = 0.080). Three SNPs (NME1 rs3760468, NME2 rs3744660, and RRM1 rs183484) were associated with worse OS in AML patients. Data from our study demonstrated that SNPs in Ara-C and dNTP metabolic pathway predict chemosensitivity and prognosis of AML patients in China.

The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed. DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10−4 and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035). Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients.Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results.Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676–0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model.Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.