Association of lactate/albumin ratio with 3-month readmission risk in heart failure patients: a retrospective study.

AIMS: The predictive value of the lactate/albumin ratio (LAR) in mortality is established in various conditions, yet its relevance to 3-month readmission risk in Chinese adults with heart failure (HF) remains unclear. METHOD AND RESULTS: Analysing data from 957 patients with HF at Zigong Fourth People's Hospital, Sichuan, China (December 2016 to June 2019), we assessed baseline characteristics, vital signs, comorbidities, and prescriptions. LAR demonstrated a linear correlation with 3-month readmission risk (HR = 1.60, 95% CI: 1.19-2.16). Tertile 3 (≥-0.48) exhibited higher risk than tertile 1 (<-0.83) and tertile 2 [-0.83, -0.48), with HRs and 95% CI of 1.49 (1.06-2.10), 1.43 (1.01-2.02), 1.48 (1.03-2.12), respectively. Subgroup and sensitivity analyses affirmed consistent influence of LAR on 3-month readmission risk for HF. CONCLUSIONS: Higher LAR significantly correlates with increased 3-month readmission risk in Chinese adult patients with HF, suggesting LAR is a valuable predictor for early readmission.

Generation of KCNH2 heterozygous knockout induced pluripotent stem cell (iPSC) line (Long and Short QT Syndrome).

KCNH2 (Potassium Voltage-Gated Channel Subfamily H Member) encodes a voltage-activated potassium channel role as rapidly activating-delayed rectifier potassium channel that plays an essential role in the final repolarization of the ventricular action potential. Mutations in this gene can cause long QT syndrome and short QT syndrome. Transcript variants encoding distinct isoforms were also identified. In this study, we generated induced pluripotent stem cells (iPSC) from a healthy individual by electroporation of peripheral blood mononuclear cells and generated a KCNH2 heterozygous knockout human iPSC line via CRISPR/Cas9 gene editing. The resulting iPSCs had a normal karyotype, were free of genomically integrated epitomal plasmids, expressed pluripotency markers, and maintained trilineage differentiation potential.

Comparison of outcomes of self-expanding versus balloon-expandable valves for transcatheter aortic valve replacement: a meta-analysis of randomized and propensity-matched studies.

BACKGROUND: The postoperative outcomes of transcatheter aortic valve replacement (TAVR) with the new generation of self-expanding valves (SEV) and balloon-expandable valves (BEV) remain uncertain. METHODS: We conducted a meta-analysis based on randomized controlled trials (RCTs) and propensity score-matched (PSM) studies to evaluate the performance of the new generation TAVR devices, with a focus on Edwards SAPIEN 3/Ultra BEV, Medtronic Evolut R/PRO SEV, and Boston ACURATE neo SEV. Our primary endpoints were mortality and complications at both 30 days and one year post-operation. RESULTS: A total of 4 RCTs and 14 PSM studies were included. Our findings showed no significant difference between SEV and BEV regarding 30-day and 1-year mortality rates. ACURATE SEV required less permanent pacemaker implantation (PPI) at 30-day as compared to SAPIEN BEV, while Evolut SEV required a higher rate of PPI than SAPIEN BEV. The incidence of stroke, major or life-threatening bleeding (MLTB), major vascular complications (MVC), coronary artery obstruction (CAO) and acute kidney injury (AKI) did not differ significantly between the two groups. SEV had a larger effective orifice area (EOA) and lower mean transvalvular gradients (MPG) compared to BEV. However, there was an increased risk of paravalvular leakage (PVL) associated with SEV. CONCLUSIONS: In terms of 30-day mortality, stroke, bleeding, MVC, AKI, CAO, and one-year mortality, there was comparability between the two valve types following TAVR. SEV was associated with better hemodynamic outcomes, except for a higher incidence of PVL. Compared to SAPIEN BEV, ACURATE SEV had a lower risk of PPI at 30 days, while Evolut SEV was associated with a higher risk of PPI. These findings underscore the importance of personalized valve selection.

Bioinformatics Identification of Therapeutic Gene Targets for Gastric Cancer.

INTRODUCTION: The global prevalence of gastric cancer (GC) is increasing, and novel chemotherapeutic targets are needed. METHODS: We searched for potential biomarkers for GC in three microarray data sets within the Gene Expression Omnibus (GEO) database. FunRich (v3.1.3) was used to perform Gene Ontology (GO) analyses and STRUN and Cytoscape (v3.6.0) were employed to construct a protein-protein interaction (PPI) network. To explore hub gene expression and survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier (KM) plotter. Drugs that were closely related to key genes were screened by the Gene Set Cancer Analysis (GSCA), and relevant correlations were verified experimentally. We validated that the sensitivity of a GC cell line to these drugs was correlated with fibrillin 1 (FBN1) mRNA expression levels. RESULTS: We identified 83 upregulated and 133 downregulated differentially expressed genes (DEGs) and these were enriched with regards to their cellular component (extracellular and exosomes), molecular function (extracellular matrix structural constituent and catalytic activity), and biological process (cell growth and/or maintenance and metabolism). The biological pathways most prominently involved were epithelial-to-mesenchymal transition (EMT) and ß3 integrin cell surface interactions. For the PPI network, we selected 10 hub genes, and 70% of these were significantly connected to poor overall survival (OS) in patients with GC. We found a significant link between the expression of FBN1 and two small molecule drugs (PAC-1 and PHA-793887). CONCLUSIONS: Overall, we suggest that these hub genes can be used as biomarkers and novel targets for GC. FBN1 may be associated with drug resistance in gastric cancer.

Overexpression of ECRG4 enhances chemosensitivity to 5-fluorouracil in the human gastric cancer SGC-7901 cell line.

The aim of this study was to examine the effects of esophageal cancer-related gene 4 (ECRG4) expression levels on chemotherapeutic sensitivity of gastric cancer cells. A SGC-7901 cell system with tetracycline-inducible ECRG4 expression (SGC-7901/ECRG4) was successfully established. ECRG4 mRNA and protein expression levels were detected using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Chemosensitivity to 5-fluorouracil (5-FU) was examined by cell proliferation assay and cell apoptosis assay. ECRG4 mRNA and protein expression levels were significantly upregulated in SGC-7901/ECRG4 cells induced with tetracycline. Compared with control cells, the growth inhibition rate of cells with ECRG4 overexpression was significantly increased when treated with 5-FU. Treatment with 5 µmol/l 5-FU resulted in 15.2 % apoptotic cells, whereas such treatment after overexpression of ECRG4 resulted in 44.5 % apoptotic cells. In conclusion, overexpression of ECRG4 enhanced the chemosensitivity of gastric cancer SGC-7901 cells to 5-FU through induction of apoptosis.

High COL4A3 expression correlates with poor prognosis after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer.

In this study, we investigated whether COL4A3 mRNA expression levels were associated with clinical outcomes after treatment with a combination of gemcitabine (Gem)/cis-diamminedichloroplatinum(II) (CDDP) regimen for patients with advanced stage non-small cell lung cancer (NSCLC). Response and survival were correlated with the level of COL4A3 expression in 58 patients with advanced (stage IIIb or IV) NSCLC treated as part of a multicenter randomized trial with Gem 1,250 mg/m(2) on days 1 and 8 plus CDDP 100 mg/m(2) on day 1 every 3 weeks. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens, and relative expression levels of COL4A3/ß-actin were measured using a quantitative reverse transcription-PCR (Taqman) system. COL4A3 expression was detectable in all tumors. There were no significant differences in COL4A3 levels by gender, age, performance status, weight loss, or tumor stage. The overall response rate was 45.8 %. There were no significant associations between COL4A3 expression and response. Median overall survival was significantly longer in patients with low COL4A3 expression tumors compared to patients with high expression tumors. COL4A3 expression, Eastern Cooperative Oncology Group performance status, and presence of weight loss were significant prognostic factors for survival in a Cox proportional hazards multivariable analysis. These data suggest that COL4A3 expression is a predictive factor for survival after CDDP/Gem therapy in advanced NSCLC. Although there was a trend toward decreased response with high COL4A3 mRNA levels, this difference failed to reach statistical significance. This result may reflect the impact of Gem and the requirement for COL4A3 expression for CDDP/Gem synergism or may be attributable to the relatively small patient sample size in this study. Prospective studies of COL4A3 as a predictive marker for activity of CDDP-based regimens in NSCLC are warranted.