Coronary Atherosclerosis Progression Provides Incremental Prognostic Value and Optimizes Risk Reclassification by Computed Tomography Angiography.

PURPOSE: This study investigated the prognostic value and risk reclassification ability of coronary atherosclerosis progression through serial coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study enrolled patients with suspected or confirmed coronary artery disease who underwent serial CCTA. Coronary atherosclerosis progression was represented by coronary artery calcium score (CACS) and segment stenosis score (SSS) progression. The baseline and follow-up CCTA characteristics and coronary atherosclerosis progression were compared. Furthermore, the incremental prognostic value and reclassification ability of three models (model 1, baseline risk factors; model 2, model 1 + SSS; and model 3, model 2 + SSS progression) for major adverse cardiovascular events (MACEs) were compared. RESULTS: In total, 516 patients (aged 56.40 ± 9.56 y, 67.4% men) were enrolled. During a mean follow-up of 65.29 months, 114 MACE occurred. The MACE group exhibited higher CACS and SSS than the non-MACE group at baseline and follow-up CCTA (P < 0.001), and demonstrated higher coronary atherosclerosis progression than the non-MACE group (ΔSSS: 2.63 ± 2.50 vs 1.06 ± 1.78, P < 0.001; ΔCACS: 115.15 ± 186.66 vs 89.91 ± 173.08, P = 0.019). SSS progression provided additional prognostic information (C-index = 0.757 vs 0.715, P < 0.001; integrated discrimination index = 0.066, P < 0.001) and improved the reclassification ability of risk (categorical-net reclassification index = 0.149, P = 0.015) compared with model 2. CONCLUSIONS: Coronary atherosclerosis progression through CCTA significantly increased the prognostic value and risk stratification for MACE compared with baseline risk factor evaluation and CCTA only.

Prognostic value of coronary CT angiography for the prediction of all-cause mortality and non-fatal myocardial infarction: a propensity score analysis.

To explore the relationship between comprehensive assessment of coronary atherosclerosis by coronary CT angiography (CCTA) and all-cause mortality and non-fatal myocardial infarction in the Chinese population. Sixty-three patients from the prospective long-term study who experienced major adverse cardiovascular events (MACE) during the follow-up were included. No-MACE patients were 1:1 propensity-matched. Various qualitative and quantitative CCTA parameters, such as coronary artery calcium score (CACS), high-risk plaque, coronary artery disease (CAD) severity, number of obstructive vessels, segment involvement score (SIS), segment stenosis score (SSS), computed tomography-adapt Leaman score (CT-LeSc), and peri-coronary adipose tissue (PCAT) CT attenuation, were compared between both groups. Cox regression analysis was performed to determine the association between CCTA parameters and MACE. The MACE group had higher CACS, more high-risk plaques, more obstructive CAD, more obstructive vessels, higher PCAT CT attenuation, and higher coronary atherosclerotic burden (SIS: 5.76 ± 3.36 vs. 2.84 ± 3.07; SSS: 11.06 ± 8.41 vs. 3.94 ± 4.78; CT-LeSc: 11.25 ± 6.57 vs. 5.49 ± 5.82) than the control group (all p < 0.05). On multivariable analysis, hazard ratios were 1.058 for the SSS (p = 0.004), and 2.152 for the obstructive CAD. When the burden of coronary atherosclerosis was defined as the CT-LeSc, hazard ratios were 1.057 for the CT-LeSc (p = 0.036), and 2.272 for the obstructive CAD. The SSS, CT-LeSc, and presence of obstructive CAD were independently associated with the all-cause mortality and non-fatal myocardial infarction in the suspected CADs in the Chinese population.

High CBX8 Expression Leads to Poor Prognosis in Laryngeal Squamous Cell Carcinoma by Inducing EMT by Activating the Wnt/ß-Catenin Signaling Pathway.

Background: In this study, we detected the expression of chromobox protein homolog 8 (CBX8) in laryngeal squamous cell carcinoma (LSCC) and its influence on the occurrence and progression of LSCC. Methods: Pancancer analysis of CBX8 was analyzed by TCGA database and its expression in LSCC.The expression of CBX8 in 30 pairs of LSCC and adjacent tissues was analyzed by quantitative real-time PCR(qRT-PCR)and immunohistochemical assays, and its association with the prognosis and clinicopathological features of LSCC was further evaluated. A CBX8 knockdown model was constructed in AMC-HN-8 and Hep2 cell lines. The effects of CBX8 on LSCC cell proliferation, migration, invasion and apoptosis were detected by CCK8,EdU,wound healing, Transwell and flow cytometry assays. Levels of apoptosis-related protein, WNT/ß-catenin signaling pathway and epithelial to mesenchymal transition (EMT) proteins, including Bax, Bcl2, ß-catenin, DKK1, GSK3ß, N-cadherin, E-cadherin and Snail1, in LSCC cells were detected by Western blotting. Results: CBX8 was overexpressed in LSCC. High expression of CBX8 in LSCC patients led to shorter overall survival and correlated with tumor stage and lymphatic metastasis. After CBX8 knockdown, the proliferation of AMC-HN-8 and Hep2 cells slowed, and the number of EdU-positive cells decreased. Wound healing slowed down, and the number of Transwell invading cells decreased. The percentage of apoptotic cells increased. The expression levels of Bcl2, ß-catenin, N-cadherin and Snail11 proteins were significantly reduced in the CBX8 knockdown cells, while Bax, DKK1, GSK3ß and E-cadherin significantly increased with their corresponding controls. Conclusion: CBX8 is highly expressed in LSCC and induces the EMT process by activating the Wnt/ß-catenin signaling pathway to promote LSCC cell proliferation and migration and inhibit apoptosis, resulting in poor prognosis.

Evaluation of efficacy and safety of improved transurethral plasma kinetic enucleation of the prostate in high-risk patients with benign prostatic hyperplasia and coronary artery disease.

OBJECTIVE: This prospective study aimed to evaluate the safety of improved transurethral plasma kinetic enucleation of the prostate (iTUPKEP) in the perioperative period in high-risk patients with benign prostatic hyperplasia (BPH) and coronary artery disease. METHODS: Patients with BPH underwent surgical treatment with transurethral vapour resection of the prostate (TUVP) or iTUPKEP. Serum endothelin-1, cardiac troponin-I, and high-sensitivity C-reactive protein concentrations were evaluated in the short term after surgery. The postvoid residual urine volume, maximum urinary flow rate, international prostate symptom score, and quality of life indicators were evaluated in the long term after surgery. RESULTS: Endothelin-1 concentrations were lower in the iTUPKEP group than in the TUVP group at 1 and 2 days postoperatively. The iTUPKEP group had lower cardiac troponin-I and high-sensitivity C-reactive protein concentrations at all time points postoperatively. The postvoid residual urine volume, international prostate symptom score, and quality of life values were lower, but the maximum urinary flow rate was higher, in the iTUPKEP group than in the TUVP group. CONCLUSIONS: The iTUPKEP procedure has a smaller effect on vascular endothelial function compared with TUVP. Therefore, iTUPKEP may reduce the incidence of postoperative cardiovascular adverse events in high-risk patients with BPH and coronary artery disease.

Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase.

The human DNA polymerase gamma (Pol γ) is responsible for DNA replication in mitochondria. Pol γ is particularly susceptible to inhibition by dideoxynucleoside-based inhibitors designed to fight viral infection. Here, we report crystal structures of the replicating Pol γ-DNA complex bound to either substrate or zalcitabine, an inhibitor used for HIV reverse transcriptase. The structures reveal that zalcitabine binds to the Pol γ active site almost identically to the substrate dCTP, providing a structural basis for Pol γ-mediated drug toxicity. When compared to the apo form, Pol γ undergoes intra- and inter-subunit conformational changes upon formation of the ternary complex with primer/template DNA and substrate. We also find that the accessory subunit Pol γB, which lacks intrinsic enzymatic activity and does not contact the primer/template DNA directly, serves as an allosteric regulator of holoenzyme activities. The structures presented here suggest a mechanism for processivity of the holoenzyme and provide a model for understanding the deleterious effects of Pol γ mutations in human disease. Crystal structures of the mitochondrial DNA polymerase, Pol γ, in complex with substrate or antiviral inhibitor zalcitabine provide a basis for understanding Pol γ-mediated drug toxicity.

Marketing to Develop the Premier Medical Brand in the Huaihai Economic Zone.

Based on the practices at Xuzhou Central Hospital, the authors analyzed the improvements in the healthcare quality and economic efficiency after implementing a brand marketing strategy. Using methods including questionnaires and business controlling means, we summarized that the improvements to the healthcare quality and economic efficiency after strategies were implemented in the areas of network, reputation, academic research, and public welfare. After the implementation of a brand marketing campaign, the medical service quality and brand reputation have been greatly improved. Meanwhile, a central hospital group was formed and gradually became the central healthcare provider in the Huaihai Economic Zone. The new marketing facilitated the drastic increase of medical service and brand reputation.

Overexpression of the formaldehyde dehydrogenase gene from Brevibacillus brevis to enhance formaldehyde tolerance and detoxification of tobacco.

The faldh gene coding for a putative Brevibacillus brevis formaldehyde dehydrogenase (FALDH) was isolated and then transformed into tobacco. A total of three lines of transgenic plants were generated, with each showing 2- to 3-fold higher specific formaldehyde dehydrogenase activities than wild-type tobacco, a result that demonstrates the functional activity of the enzyme in formaldehyde (HCHO) oxidation. Overexpression of faldh in tobacco confers a high tolerance to exogenous HCHO and an increased ability to take up HCHO. A (13)C-nuclear magnetic resonance technique revealed that the transgenic plants were able to oxidize more aqueous HCHO to formate than the wild-type (WT) plants. When treated with gaseous HCHO, the transgenic tobacco exhibited an enhanced ability to transform more HCHO into formate, citrate acid, and malate but less glycine than the WT plants. These results indicate that the increased capacity of the transgenic tobacco to take up, tolerate, and metabolize higher concentrations of HCHO was due to the overexpression of B. brevis FALDH, revealing the essential function of this enzyme in HCHO detoxification. Our results provide a potential genetic engineering strategy for improving the phytoremediation of HCHO pollution.

Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions.

Using a combination of techniques we developed, we infected zebrafish embryos using pseudotyped retroviruses and mapped the genomic locations of the proviral integrations in the F(1) offspring of the infected fish. From F(1) fish, we obtained 2,045 sequences representing 933 unique retroviral integrations. A total of 599 were mappable to the current genomic assembly (Zv6), and 233 of the integrations landed within genes. By inbreeding fish carrying proviral integrations in 25 different genes, we were able to demonstrate that in approximately 50% of the gene "hits," the mRNA transcript levels were reduced by >/=70%, with the highest probability for mutation occurring if the integration was in an exon or first intron. Based on these data, the mutagenic frequency for the retrovirus is nearly one in five integrations. In addition, a strong mutagenic effect is seen when murine leukemia virus integrates specifically in the first intron of genes but not in other introns. Three of 19 gene inactivation events had embryonic defects. Using the strategy we outlined, it is possible to identify 1 mutagenic event for every 30 sequencing reactions done on the F(1) fish. This is a 20- to 30-fold increase in efficiency when compared with the current resequencing approach [targeting induced local lesions in genomes (TILLING)] used in zebrafish for identifying mutations in genes. Combining this increase in efficiency with cryopreservation of sperm samples from the F(1) fish, it is now possible to create a stable resource that contains mutations in every known zebrafish gene.