The platelet-to-albumin ratio (PAR) was developed to evaluate inflammatory and nutritional status among patients. The primary goal of the current study was to gain insight into the prognostic role of PAR in critically ill patients with colorectal cancer (CRC). The secondary aim was to develop and verify a clinical model including PAR for the prediction of 28-day mortality. This observational, multicenter study used data from the Medical Information Mart for Intensive Care (MIMIC) IV, e-ICU databases, and Union cohort. Data from 776 critically ill patients with CRC were from the e-ICU database, 219 from the MIMC-IV database, and 135 from the Wuhan Union Hospital. Propensity score matching (PSM) analysis, along with inverse probability treatment weighting, was used to control the influence of confounding factors. Support vector machine (SVM) and LASSO Cox models were then applied to identify significant metrics associated with 28-day mortality in the test cohort. Receiver operating curve (ROC) analysis, along with sensitivity and specificity, was measured to assess the predictive performances of PAR and the survival nomogram. The threshold value for PAR was 8.6, and patients with high PAR (≥8.6) experienced higher 28-day mortality compared to those with low PAR (<8.6). ROC curve analyses revealed that the discriminative ability of PAR was better than platelet count and albumin alone. LASSO Cox regression along with SVM identified six significant metrics associated with 28-day mortality in critically ill patients with CRC, including PAR. The C-index of the critically ill CRC nomogram was 0.802 (0.744–0.859) in the e-ICU training cohort, 0.839 (0.779–0.899) in the e-ICU validation cohort, 0.787 (0.695–0.879) in the MIMIC-IV cohort, and 0.767 (0.703–0.831) in the Union cohort. PAR is a simple score that combines inflammatory and nutritional status. PAR was a reliable index to predict short-term survival outcome of critically ill patients with CRC. Moreover, a clinical nomogram incorporating PAR exhibited satisfactory performance for predicting 28-day mortality of critically ill patients with CRC.
Objective
We investigated a custom congenital heart disease (CHD) geneset to assess the diagnostic value of whole‐exome sequencing (WES) in karyotype‐ and copy number variation (CNV)‐negative aborted fetuses with conotruncal defects (CTDs), and to explore the impact of postnatal phenotyping on genetic diagnosis.
Methods
We sequentially analyzed CNV‐seq and WES data from 47 CTD fetuses detected by prenatal ultrasonography. Fetuses with either a confirmed aneuploidy or pathogenic CNV were excluded from the WES analyses, which were performed following the American College of Medical Genetics and Genomics recommendations and a custom CHD‐geneset. Imaging and autopsy were applied to obtain postnatal phenotypic information about aborted fetuses.
Results
CNV‐seq identified aneuploidy in 7/47 cases while 13/47 fetuses were CNV‐positive. Eighty‐five rare deleterious variants in 61 genes (from custom geneset) were identified by WES in the remaining 27 fetuses. Of these, five pathogenic or likely pathogenic variants (PV/LPV) were identified in five fetuses, revealing a 10.6% (5/47) incremental diagnostic yield. Furthermore, RERE:c.2461_2472delGGGATGTGGCGA was reclassified as LPV based on postnatal phenotypic data.
Conclusion
We have developed and defined a CHD gene panel that can be utilized in a subset of fetuses with CTDs. We demonstrate the utility of incorporating both prenatal and postnatal phenotypic information may facilitate WES diagnostics.
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMDmediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.
Indoor visible light communication, as an emerging broadband wireless access technology, is currently in the stage of scientific research. This paper focuses on researching fractionally spaced equalizer for indoor visible light communication system, and studies have shown that equalization of indoor visible light communication "multipath interference" to the quality of the communication interference had good inhibitory effect. This paper also proved that the phase conjugate light and transmission light which generated by four wave mixing effect of LiNbO3 thin film materials have bright quantum entanglement properties. Using visible light communication system with nonlinear film material external modulator, it will be expected to realize indoor quantum communication.
Background: Metabolic reprogramming is a hallmark of cancer, alteration of nucleotide metabolism of hepatocellular carcinoma (HCC) is not well-understood. MYBL2 regulates cell cycle progression and hepatocarcinogenesis, its role in metabolic regulation remains elusive. Patients and methods: Copy number, mRNA and protein level of MYBL2 and IMPDH1 were analyzed in HCC, and correlated with patient survival. Chromatin Immunoprecipitation sequence (Chip-seq) and Chromatin Immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) were used to explore the relationship between MYBL2 and IMPDH1. Metabolomics were used to analyze how MYBL2 affected purine metabolism. The regulating effect of MYBL2 in HCC was further validated in vivo using xenograft models. Results: The Results showed that copy-number alterations of MYBL2 occur in about 10% of human HCC. Expression of MYBL2, IMPDH1, or combination of both were significantly upregulated and associated with poor prognosis in HCC. Correlation, ChIP-seq and ChIP-qPCR analysis revealed that MYBL2 activates transcription of IMPDH1, while knock-out of MYBL2 retarded IMPDH1 expression and inhibited proliferation of HCC cells. Metabolomic analysis post knocking-out of MYBL2 demonstrated that it was essential in de novo purine synthesis, especially guanine nucleotides. In vivo analysis using xenograft tumors also revealed MYBL2 regulated purine synthesis by regulating IMPDH1, and thus, influencing tumor progression. Conclusion: MYBL2 is a key regulator of purine synthesis and promotes HCC progression by transcriptionally activating IMPDH1, it could be a potential candidate for targeted therapy for HCC.
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