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Hai-Liang Yuan,1 Xian Zhang,2 Dong-Zhu Peng,1 Guan-Bin Lin,1 Hui-Hui Li,1 Fang-Xian Li,1 Jing-Jing Lu,1 Wei-Wei Chu1 1Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Endocrinology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Wei-Wei Chu, Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, No. 1288, Lushan East Road, Beilun District, Ningbo, Zhejiang Province, People’s Republic of China, Tel +86-134 56123811, Fax +86- 574 86100266, Email chuweiwei920@163.comPurpose: Constipation is a common complication of diabetic patients, which has a negative impact on their own health. This study aims to establish and internally validate the risk nomogram of constipation in patients with type 2 diabetes mellitus (T2DM) and to test its predictive ability.Patients and Methods: This retrospective study included 746 patients with T2DM at two medical centers. Among the 746 patients with T2DM, 382 and 163 patients in the Beilun branch of the First Affiliated Hospital of Zhejiang University were enrolled in the training cohort and the validation cohort, respectively. A total of 201 patients in the First Affiliated Hospital of Nanchang University were enrolled in external validation cohorts. The nomogram was established by optimizing the predictive factors through univariate and multivariable logistic regression analysis. The prediction performance of the nomogram was measured by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and the decision curve analysis (DCA). Furthermore, its applicability was internally and independently validated.Results: Among the 16 clinicopathological features, five variables were selected to develop the prediction nomogram, including age, glycated hemoglobin (HbA1c), calcium, anxiety, and regular exercise. The nomogram revealed good discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.908 (95% CI = 0.865– 0.950) in the training cohort, and 0.867 (95% CI = 0.790– 0.944) and 0.816 (95% CI = 0.751– 0.881) in the internal and external validation cohorts, respectively. The calibration curve presented a good agreement between the prediction by the nomogram and the actual observation. The DCA revealed that the nomogram had a high clinical application value.Conclusion: In this study, the nomogram for pretreatment risk management of constipation in patients with T2DM was developed which could help in making timely personalized clinical decisions for different risk populations.Keywords: constipation, type 2 diabetes mellitus, model, nomogram, prediction

Xing Xiao,1,2,* Wei Chen,3,* Zhe-Wei Wei,4,* Wei-Wei Chu,2 Xiao-Fang Lu,3 Bo Li,1,2 Hong Chen,1 Si-Jun Meng,1 Teng-Fei Hao,1 Ji-Tao Wei,1,2 Yu-Long He,1 Chang-Hua Zhang1 1Center of Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 2Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 3Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 4Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Hua Zhang; Yu-Long He Email zhchangh@mail.sysu.edu.cn; heyulong@mail.sysu.edu.cnBackground: Nab-paclitaxel has been widely used in treating breast cancer and pancreatic patients for its low toxicity and high efficiency. However, its role in gastric cancer (GC) remains ambiguous. The aim of our study was to test the anti-tumor activity of nab-paclitaxel using GC patient-derived organoids.Methods: By using the organoid culture system, we describe the establishment of human gastric cancer organoid lines from surgical samples of three patients with gastric cancer. The consistency of these organoids with original cancer tissues was evaluated by histopathological examination. The characteristics of the cancer organoids were tested using immunofluorescence (IF) staining. Using organoids, the anti-tumor efficiencies of nab-paclitaxel, 5-Fu and epirubicin were compared by CCK8 assay and Annexin V-FITC/PI staining.Results: Three organoids were successfully established and passaged. The morphology of the established GC organoids was consistent with original cancer tissues. The IC50 of nab-paclitaxel was 3.68 μmol/L in hGCO1, 2.41 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3, which was significantly lower than those of 5-FU (72.99 μmol/L in hGCO1, 28.32 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3) and epirubicin (25.85μmol/L in hGCO1, 15.15 μmol/L in hGCO2 and 7.60 μmol/L in hGCO3). When each organoid lines were treated with nab-paclitaxel for increasing period of time, the percentage of the apoptotic cells in each organoid increased accordingly.Conclusion: Nab-paclitaxel showed strong anti-tumor activity and had the potential to become front-line drug for treating GC patients. Gastric cancer organoid may be a good tool to predict in vivo response to drugs.Keywords: nab-paclitaxel, organoid, gastric cancer, anti-tumor

PubAtlas (www.pubatlas.org) is a web service and standalone program providing literature maps for the biomedical research literature. It accepts user-defined sets of terms (PubMed queries) as input, and permits 'BLASTing' of one set against another: for all terms x and y in these sets, deriving the results of the pairwise intersections x AND y. This all vs. all capability extends PubMed with a literature analysis interface. Correspondingly, the basic form of literature map that PubAtlas provides for exploring associations among sets of terms is an interactive tabular display, in heatmap/microarray format.PubAtlas supports development of specialized lexica -- hierarchies of controlled terminology that can represent sets of related concepts or a 'user-defined query language'. PubAtlas also provides historical perspectives on the literature, with temporal query features that highlight historical patterns. Generally, it is a framework for extending the PubMed interface, and an extensible platform for producing interactive literature maps.

Objective: Peritoneal fibrosis (PF) is the main cause of declining efficiency and ultrafiltration failure of the peritoneum, which restricts the long-term application of peritoneal dialysis (PD). This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes (BMSC-Exos) on PF in response to PD., Methods: Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing. C57BL/6J mice were infused with 4.25% glucose-based peritoneal dialysis fluid (PDF) for 6 consecutive weeks to establish a PF model. A total of 36 mice were randomly divided into 6 groups: control group, 1.5% PDF group, 2.5% PDF group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF. HE and Masson staining were performed to evaluate the extent of PF. The therapeutic potential of BMSC-Exos for PF was examined through pathological examination, RT-qPCR, Western blotting, and peritoneal function analyses. Epithelial-mesenchymal transition (EMT) of HMrSV5 was induced with 4.25% PDF. Cells were divided into control group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Cell Counting Kit-8 assay was used to measure cell viability, and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells., Results: Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs. The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos, but decreased in PD mice. We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice. Compared with the control mice, the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-SMA, collagen-I, fibronectin, and ECM1. The mice with PD showed decreased miR-27a-3p. Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment, while PF and mesothelial damage were significantly ameliorated. Additionally, markers of fibrosis (α-SMA, collagen-I, fibronectin, ECM1) and profibrotic cytokines (TGF-β1, PDGF) were downregulated at the mRNA and protein levels after BMSC-Exos treatment. In HMrSV5 cells, BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF. Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin (epithelial marker) and decreased expression of α-SMA, Snail, and vimentin (mesenchymal markers) compared to those of the 4.25% PDF-treated cells. Importantly, a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p. TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos., Conclusion: The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53., (© 2024. Huazhong University of Science and Technology.)

Purpose: The incidence of gastroparesis is higher in individuals diagnosed with type 2 diabetes mellitus (T2DM) compared to the healthy individuals. Our study aimed to explore the risk factors for gastroparesis in T2DM and to establish a clinical prediction model (nomogram)., Methods: Our study enlisted 694 patients with T2DM from two medical centers over a period of time. From January 2020 to December 2022, 347 and 149 patients were recruited from the Beilun branch of Zhejiang University's First Affiliated Hospital in the training and internal validation cohorts, respectively. The external validation cohort consisted of 198 patients who were enrolled at Nanchang University's First Affiliated Hospital from October 2020 to September 2021. We conducted univariate and multivariate logistic regression analyses to select the risk factors for gastroparesis in patients with T2DM; subsequently,we developed a nomogram model. The performance of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis(DCA)., Results: Four clinical variables, including age, regular exercise, glycated hemoglobin level(HbA1c), and Helicobacter pylori ( H. pylori ) infection, were identified and included in the model. The model demonstrated excellent discrimination, with an AUC of 0.951 (95% CI = 0.925-0.978) in the training group, and 0.910 (95% CI = 0.859-0.961) and 0.875 (95% CI = 0.813-0.937) in the internal and external validation groups, respectively. The calibration curve showed good consistency between prediction of the model and observed gastroparesis. The DCA also demonstrated good clinical efficacy., Conclusion: The nomogram model developed in this study showed good performance in predicting gastroparesis in patients with T2DM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objectives: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit., Research Methodology/design: A prospective and multicentre study., Setting: This study was conducted in 24 intensive care units in Anhui, China., Main Outcome Measures: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay., Results: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition., Conclusion: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales., Implications for Clinical Practice: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

BACKGROUND The aim of this study was to establish and validate an easy-to-use nomogram to predict portal vein thrombosis (PVT) in patients with cirrhosis after splenectomy and to test its predictive ability. MATERIAL AND METHODS This retrospective study included 315 patients with cirrhosis who underwent splenectomy at 2 high-volume medical centers. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the predictors in the training cohort, and multivariable logistic regression analysis was performed to establish the predictive nomogram model. We determined the prediction value of the nomogram by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and decision curve analysis. Finally, the applicability of the nomogram was internally and independently validated. RESULTS The predictors of PVT included portal vein diameter, splenic vein diameter, body mass index, and platelet count. Based on the clinical and radiomic models, the nomogram had good predictive efficiency for predicting PVT in patients with cirrhosis after splenectomy, with an AUROC of 0.887 (0.856 in internal validation and 0.796 in independent validation). The decision curve analysis revealed that the nomogram had good clinical application value. CONCLUSIONS We successfully developed an easy-to-use nomogram to predict the probability of PVT in patients with cirrhosis after splenectomy. The nomogram can help clinicians make timely, individualized clinical decisions for PVT in patients with cirrhosis after splenectomy.

Purpose: The aims of this study were to develop and validate a novel nomogram to predict thromboembolism (TE) in gastric cancer (GC) patients receiving chemotherapy and to test its predictive ability. Methods: This retrospective study included 544 GC patients who received chemotherapy as the initial treatment at two medical centers. Among the 544 GC patients who received chemotherapy, 275 and 137 patients in the First Affiliated Hospital of Nanchang University from January 2014 to March 2019 were enrolled in the training cohort and the validation cohort, respectively. A total of 132 patients in the Beilun branch of the First Affiliated Hospital of Zhejiang University from January 2015 to August 2019 were enrolled in external validation cohorts. The nomogram was based on parameters determined by univariate and multivariate logistic analyses. The prediction performance of the nomogram was measured by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and decision curve analysis (DCA). The applicability of the nomogram was internally and independently validated. Results: The predictors included the Eastern Cooperative Oncology Group Performance Status (ECOG), presence of an active cancer (AC), central venous catheter (CVC), and D-dimer levels. These risk factors are shown on the nomogram and verified. The nomogram demonstrated good discrimination and fine calibration with an AUROC of 0.875 (0.832 in internal validation and 0.807 in independent validation). The DCA revealed that the nomogram had a high clinical application value. Conclusions: We propose the nomogram for predicting TE in patients with GC receiving chemotherapy, which can help in making timely personalized clinical decisions for different risk populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuan, Zhang, Li, Guan, Chu, Yu, Liu, Zheng and Lu.)

Obesity has been steadily rising in the last few decades and to some extent, have been linked to exposure of adverse childhood experiences (ACEs). ACEs are intense stressors or traumatic events experienced or witnessed by children, ranging from all types of abuse (physical, emotional, and sexual), neglect, substance abuse or community violence. These traumatic events deprive the sense of safety and stability of a child, leaving psychological and physiological effects that span into adulthood. The prevalence of ACEs is common across developed and developing countries alike, though the rates differ across ethnicities. Using the United States as an example, the prevalence of ACEs experienced by communities of color is higher than white children. Children around the world could all be exposed to ACEs, hence the original questionnaire capturing the score of ACE has been adapted to different cultural situations. The mechanism linking ACEs to obesity during adulthood include biological, psychological, and environmental factors. Nevertheless, a higher ACE score heightens the risk of poor mental health, attempted suicide and development of obesity and diabetes in adulthood. Prevention of ACEs starts from building positive relationships within families, developing healthy relationship skills, and screening of ACEs during early and routine pediatrician's and primary care visits. Intervention needs to include case management services and psychosocial support programs. When these risk factors are intervened early, it lessens the risk of obesity and diabetes in adulthood., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objective:   To explore whether ischemic postconditioning will lighten hepatic apoptosis caused by hepatic ischemia/reperfusion injury by inhibiting the mitochondria pathway., Materials and Methods: Pathomorphology of hepatic tissues in rats was observed under an optical microscope after hematoxylin-eosin (HE) staining. Hepatic apoptosis was detected using agarose gel electrophoresis (AGE) with DNA fragments and flow cytometry. Changes in morphology structure of mitochondria in hepatocytes of rats were observed under an electron microscope. Changes in mitochondria transmembrane potential of hepatocytes of rats were detected using a laser scanning confocal microscope (LSCM). Western blotting was adopted to detect changes in the expression of caspase-3 and cytochrome C protein in hepatocytes of rats., Results: Compared with that in I/R group, swelling degree of mitochondria in most hepatocytes of rats in ischemic postconditioning (IPOST) group and IPC group was lighter. Changes in expression of caspase-3 and cytochrome C protein in hepatic cells of rats: caspase-3 was lowly expressed and cytochrome C was highly expressed in S group. The expression of caspase-3 was evidently higher in I/R group than that in S group and expression of cytochrome C protein was evidently lower than that in S group (p<0.05). The expression of caspase-3 protein was evidently decreased in IPOST group and IPC group and the expression of cytochrome C protein was evidently increased (p<0.05)., Conclusions: IPOST can reduce hepatic apoptosis caused by hepatic ischemia/reperfusion injury in rats, which may be achieved by inhibiting the mitochondria pathway.

Objective: To explore the effect of ambient fine particulate matters (PM(2.5)) and temperature interaction on schizophrenia admission. Methods: All admission data were retrieved from the Psychiatric Hospital and Municipal Hospital of TongLing from January 1, 2014 to December 31, 2017. Daily air pollution and meteorological data were collected from the Tongling Environmental Protection Agency and Meteorological Bureau, respectively. A distributed lag non-linear model combined with the generalized additive model were applied to explore the effects of PM(2.5), multi-pollutants, and the interaction between temperature and PM(2.5) on schizophrenia admission. The stratification of temperature was divided by three criteria. The low temperature layer was defined as < P (5) or < P (10) or < P (20); P (5)- P (95) or P (10)- P (90) or P (20)- P (80) was defined as the middle temperature layer; > P (95) or > P (90) or > P (80) was defined as the high temperature layer. Results: From 2014 to 2017, 6 642 patients were admitted for schizophrenia in Tongling, and the median of PM(2.5) and temperature were 47.0 μg/m(3) and 17.5 ℃, respectively. The median concentration of PM(2.5) ( P (50)) was taken as a reference. When the exposure concentration of PM(2.5) was P (90), the lagged effect appeared in the first day with RR= 1.03 (95 %CI : 1.00-1.07) and reached the maximum in the fifth day with RR= 1.16 (95 %CI : 1.13-1.19). In the multi-pollutant models, it was found that the simultaneous inclusion of PM(2.5) and NO(2) had higher risk of schizophrenia admission, with the RR= 1.18 (95 %CI : 1.15-1.22), P< 0.001. The risk of schizophrenia admission caused by PM(2.5) exposure at high temperature was greatest under the three temperature stratification standards, which were 12.1% (8.5%-15.7%), 9.7% (6.9%-12.6%) and 17.1% (11.6%-22.8%), all P values <0.001. Conclusion: With the increase of PM(2.5) concentration, the risk of schizophrenia admission is increased, and the risk effect of PM(2.5) is stronger at high temperature.

Lesion location is an important determinant for post-stroke cognitive impairment. Although several 'strategic' brain regions have previously been identified, a comprehensive map of strategic brain regions for post-stroke cognitive impairment is lacking due to limitations in sample size and methodology. We aimed to determine strategic brain regions for post-stroke cognitive impairment by applying multivariate lesion-symptom mapping in a large cohort of 410 acute ischemic stroke patients. Montreal Cognitive Assessment at three to six months after stroke was used to assess global cognitive functioning and cognitive domains (memory, language, attention, executive and visuospatial function). The relation between infarct location and cognition was assessed in multivariate analyses at the voxel-level and the level of regions of interest using support vector regression. These two assumption-free analyses consistently identified the left angular gyrus, left basal ganglia structures and the white matter around the left basal ganglia as strategic structures for global cognitive impairment after stroke. A strategic network involving several overlapping and domain-specific cortical and subcortical structures was identified for each of the cognitive domains. Future studies should aim to develop even more comprehensive infarct location-based models for post-stroke cognitive impairment through multicenter studies including thousands of patients.

Background: Long noncoding RNAs (lncRNAs) are a new class of cancer regulators. Here, we aimed to investigate the diagnostic and therapeutic values of an lncRNA, differentiation antagonizing noncoding RNA (DANCR), in lung cancer., Methods: Real-time polymerase chain reaction was used to compare DANCR levels in normal and cancerous lung tissues as well as lung cancer cells. Lentiviral transduction was used to induce DANCR overexpression or silencing in vitro, followed by monitoring cell proliferation, colony formation, and changes in microRNA-216a (miR-216a) expression. DANCR-specific small hairpin RNA transduction was used to establish cells with stable DANCR knockdown, and silenced cells were used to initiate lung tumor xenografts, followed by monitoring tumor growth., Results: DANCR upregulation was seen in lung cancer, particularly in high-grade lung cancer tissues and aggressive cancer cells. Ectopic DANCR expression induced lung cancer cell proliferation and colony formation, whereas DANCR silencing induced opposing effects. The miR-216a level in cancer cells was negatively correlated with DANCR expression. The DANCR knockdown reduced the growth of tumor xenografts in vivo., Conclusion: DANCR upregulation is a potential indicator of aggressive lung cancer. Silencing of DANCR has great potential as a potent therapeutic strategy in lung cancer.

Oesophageal cancer (OC) is one of the most fatal malignancies in the world, and chemoresistance restricts the therapeutic outcome of OC. Long noncoding RNA (lncRNA) was reported to play roles in multiple cancer types. Yet, the function of lncRNA in chemoresistance of OC has not been reported. A lncRNA gene, PCAT-1, showed higher expression in OC tissues, especially higher in secondary OC compared with normal mucosa tissues. Overexpression of PCAT-1 increased the proliferation rate and growth of OC cells. Inhibition of PCAT-1 decreased proliferation and growth of OC cells, and increased cisplatin chemosensitivity. In a mouse OC xenograft model, PCAT-1 inhibition repressed OC growth in vivo. Therefore, PCAT-1 may potentially serve as a therapeutic target for treating OC. PCAT-1 promotes development of OC and represses the chemoresistance of OC to cisplatin, and silencing of PCAT-1 may be a therapeutic strategy for treating OC., (Copyright © 2018 John Wiley & Sons, Ltd.)

This study assessed the effect of myostatin on adipogenesis by porcine intramuscular preadipocytes. Intramuscular preadipocytes were isolated from the longissimus dorsi muscle of newborn pigs. Myostatin inhibited intramuscular preadipocyte differentiation in a dose-dependent manner. Myostatin treatment during preadipocyte differentiation significantly (P < 0.05) inhibited the expression of the adipogenic marker genes CCAAT/enhancer-binding protein β, CCAAT/enhancer-binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, fatty acid-binding protein, and adiponectin. Myostatin also significantly (P < 0.05) reduced the release of glycerol and decreased both adipose triglyceride lipase and hormone-sensitive lipase expression in intramuscular adipocytes. Our study suggests that myostatin acts as an extrinsic regulatory factor in regulating intramuscular adipogenesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Mutations in epidermal growth factor receptor (EGFR) rendering it constitutively active is one of the major causes for metastatic non-small-cell lung cancer (NSCLC), and EGFR-targeted therapies utilizing tyrosine kinase inhibitors (TKIs) are often used clinically as the first-line treatment. But approximately half of NSCLC patients develop resistance to these therapies, where the MET proto-oncogene is amplified by EGFR through the hypoxia-inducible factor (HIF)-1α. Here we report that endothelial PAS domain-containing protein 1 (EPAS1), with 48% sequence identity to HIF-1α, specifically binds to TKI-resistant T790M EGFR, but not to wild-type EGFR, in NSCLC cell lines. Expression of EPAS1 enhances amplification of MET when simultaneously expressed with T790M EGFR but not with wild-type EGFR, and this enhancement is independent of ligand binding domain of EGFR. MET amplification requires EPAS1, since EPAS1 knock-down reduced MET levels. When NSCLC cells expressing T790M EGFR were treated with TKIs, reduced EPAS1 levels significantly enhanced the drug effect, whereas over-expression of EPAS1 increased the drug resistant effect. This EPAS1-dependent TKI-resistance was abolished by knocking-down MET, suggesting that EPAS1 does not cause TKI-resistance itself but functions to bridge EGFR and MET interactions. Our findings suggest that EPAS1 is a key factor in the EGFR-MET crosstalk in conferring TKI-resistance in NSCLC cases, and could be used as a potential therapeutic target in TKI-resistant NSCLC patients.

Background: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA)., Methods: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia., Results: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively., Conclusions: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Studies in stroke patients suggest that lacunar stroke and intracerebral hemorrhage might be more common in Chinese than Whites. We hypothesized that other manifestations of subclinical cerebral small vessel disease, namely white matter hyperintensities (WMH), lacunes, and microbleeds, are also more common in Chinese than Whites. We compared the community prevalence of these lesions between Han Chinese and White Australians., Methods: Magnetic resonance imaging (1·5-Tesla) was performed on participants of the Shanghai Aging Study (n = 321, mean age 69 ± 6 years) and Tasmanian Study of Cognition and Gait (n = 397, mean age 72 ± 7 years). A single-rater recorded measures of WMH, lacunes, and microbleeds. We compared lesion prevalence between age- and gender-matched subgroups from the two cohorts. Among all subjects (n = 718), we performed multivariable logistic regression to examine if race-ethnicity was independently associated with these lesions., Results: Among age- and gender-matched subjects, confluent WMH were significantly more prevalent in Chinese (38·5%) than Whites (28·4%; P = 0·01). There was no difference in the prevalence of lacunes (Chinese 29·1% vs. Whites 29·5%, P = 0·93) and microbleeds (Chinese 10·1% vs. 9·0%, P = 0·67) between Chinese and Whites. In multivariable logistic regression, Chinese ethnicity was associated with confluent WMH (odds ratio 1·7, 95% confidence interval 1·1-2·6, P = 0·01), but no differences were seen for lacunes and microbleeds. The association between Chinese ethnicity with confluent WMH became insignificant when subjects with history of stroke were excluded., Conclusions: In this population-based cross-national comparison, Han Chinese had a higher prevalence of confluent WMH than White Australians, but had a similar prevalence of lacunes and microbleeds., (© 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.)

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52 cm(3) vs 5.01 ± 6.00 cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Background and Purpose: Vascular cognitive impairment (VCI) affects up to half of stroke survivors and predicts poor outcomes. Valid and reliable assessement for VCI is lacking, especially for the Chinese population. In 2005, the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) Harmonisation workshop proposed a set of three neuropsychology protocols for VCI evaluation. This paper is to introduce the protocol design and to report the psychometric properties of the Chinese NINDS-CSN VCI protocols., Methods: Fifty patients with mild stroke (mean National Institute of Health Stroke Scale 2.2 (SD=3.2)) and 50 controls were recruited. The NINDS-CSN VCI protocols were adapted into Chinese. We assessed protocols' (1) external validity, defined by how well the protocol summary scores differentiated patients from controls using receiver operating characteristics (ROC) curve analysis; (2) concurrent validity, by correlations with functional measures including Stroke Impact Scale memory score and Chinese Disability Assessment for Dementia; (3) internal consistency; and (4) ease of administration., Results: All three protocols differentiated patients from controls (area under ROC for the three protocols between 0.77 to 0.79, p<0.001), and significantly correlated with the functional measures (Pearson r ranged from 0.37 to 0.51). A cut-off of 19/20 on MMSE identified only one-tenth of patients classified as impaired on the 5-min protocol. Cronbach's α across the four cognitive domains of the 60-min protocol was 0.78 for all subjects and 0.76 for stroke patients., Conclusions: The Chinese NINDS-CSN VCI protocols are valid and reliable for cognitive assessment in Chinese patients with mild stroke.

Background: Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH., Methods: We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini-Mental State Examination, Mattis dementia rating scale--initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters., Results: Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale--initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer's disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline., Conclusions: Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer's pathology., (Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Renal dysfunction can be evaluated by increased intra-renal arterial resistance index (RI). We evaluated 113 Chinese men with type 2 diabetes on their RI. Results suggest that RI is associated with chronic kidney disease and subclinical arteriosclerosis. RI may help monitoring the deterioration of intra-renal hemodynamics., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The present study aimed to investigate the change of cytochrome c in postconditioning-attenuated ischemia-reperfusion (I/R)-induced mucosal apoptosis in rat intestine compared with ischemic preconditioning (IPC). Using rat model of intestine I/R injury, male Sprague-Dawley rats weighing 220-250 g were divided into 4 groups which were Sham operation group, I/R group, IPC group and ischemic postconditioning (IPOST) group. In these groups, I/R procedure was performed by the occlusion of the superior mesenteric artery (SMA) for 45 min followed by reperfusion for 1 h. In Sham group, there was no intervention. In IPC group, SMA was occluded for 5 min and reperfused for 5 min, for two cycles, before the prolonged occlusion. In IPOST group, three cycles of 30-s reperfusion and 30-s reocclusion were preceded at the start of reperfusion. After the reperfusion, the small intestines were sampled for experimental detection. Intestinal mucosal mitochondrial membrane potential was detected by confocal laser scanning microscopy. Expressions of cytochrome c and caspase-3 proteins were detected using Western-blot method. The apoptosis of intestinal mucosal cells was determined with agarose gel electrophoresis and deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) technique. Compared with I/R group, the mitochondrial membrane potentials and the expressions of cytochrome c protein were significantly increased, while the expressions of caspase-3 and the apoptotic rates were decreased in IPOST and IPC groups (P<0.05). There were no significant differences between IPOST and IPC groups (P>0.05). These data provide substantial evidence that IPOST attenuates I/R-induced mucosal apoptosis by reducing the release of cytochrome c from mitochondria in the rat small intestine.

We performed MRI assessment in 37 adult Chinese patients with thalassemia intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*, only 5% of patients had cardiac hemosiderosis. The two patients with reduced ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI values. Prospective data with serial functional and imaging monitoring is needed to verify the utility for chelation to improve cardiac and endocrine function in this group of patients.

Objective: To investigate the effect of perindopril, amlodipine and telmisartan on improving the artery stiffness in patients with hypertension., Methods: Patients with primary hypertension were randomly assigned to perindopril (4 mg/day), Amlodipine (5 mg/day) and telmisartan (80 mg/day) regimen for 3 months (n = 34 each). Brachial-ankle pulse wave velocity (baPWV) was measured by an automatic brachial ankle pulse wave velocity device before the treatment, one-month and three-month after the treatment., Results: (1) SBP, DBP and PP were significantly decreased in all three groups (P < 0.001). There were no significant changes in HR in all three groups (P > 0.05). (2) BaPWV was significantly decreased in all three groups. In the perindopril, Amlodipine, telmisartan group, baPWV was (1859 +/- 492) cm/s, (1780 +/- 335) cm/s, (1859 +/- 337) cm/s before the treatment; was (1757 +/- 508) cm/s, (1647 +/- 285) cm/s, (1632 +/- 261) cm/s one-month after the treatment; was (1702 +/- 538) cm/s, (1559 +/- 288) cm/s, (1566 +/- 326) cm/s three-month after the treatment. Compare the baPWV one-month after the treatment to before the treatment P < 0.001; Compare the baPWV three-month after the treatment to before the treatment P < 0.001; Compare the baPWV three-month to one-month after the treatment perindopril group and telmisartan group P < 0.01, amlodipine group P < 0.001. (3) The changes of baPWV in one or three months were significantly more in the telmisartan group than in the perindopril and amlodipine groups (1 months P < 0.01, 3 months P < 0.05). The change of baPWV was significantly greater in three months than in one montin in all three grops (P < 0.01)., Conclusion: Arterial stiffness of hypertensive patients was improved post Telmisartan, amlodipine and perindopril therapy in proportion to therapy duration. Telmisartan is superior to amlodipine and perindopril on improving arterial stiffness of hypertensive patients. Continuous anti-hypertensive treatment with telmisartan, amlodipine and perindopril will have a persistent improvement of the artery flexibility.

PubAtlas (www.pubatlas.org) is a web service and standalone program providing literature maps for the biomedical research literature. It accepts user-defined sets of terms (PubMed queries) as input, and permits 'BLASTing' of one set against another: for all terms x and y in these sets, deriving the results of the pairwise intersections x AND y. This all vs. all capability extends PubMed with a literature analysis interface. Correspondingly, the basic form of literature map that PubAtlas provides for exploring associations among sets of terms is an interactive tabular display, in heatmap/microarray format.PubAtlas supports development of specialized lexica -- hierarchies of controlled terminology that can represent sets of related concepts or a 'user-defined query language'. PubAtlas also provides historical perspectives on the literature, with temporal query features that highlight historical patterns. Generally, it is a framework for extending the PubMed interface, and an extensible platform for producing interactive literature maps.

Now that genome-wide association studies (GWAS) are dominating the landscape of genetic research on neuropsychiatric syndromes, investigators are being faced with complexity on an unprecedented scale. It is now clear that phenomics, the systematic study of phenotypes on a genome-wide scale, comprises a rate-limiting step on the road to genomic discovery. To gain traction on the myriad paths leading from genomic variation to syndromal manifestations, informatics strategies must be deployed to navigate increasingly broad domains of knowledge and help researchers find the most important signals. The success of the Gene Ontology project suggests the potential benefits of developing schemata to represent higher levels of phenotypic expression. Challenges in cognitive ontology development include the lack of formal definitions of key concepts and relations among entities, the inconsistent use of terminology across investigators and time, and the fact that relations among cognitive concepts are not likely to be well represented by simple hierarchical "tree" structures. Because cognitive concept labels are labile, there is a need to represent empirical findings at the cognitive test indicator level. This level of description has greater consistency, and benefits from operational definitions of its concepts and relations to quantitative data. Considering cognitive test indicators as the foundation of cognitive ontologies carries several implications, including the likely utility of cognitive task taxonomies. The concept of cognitive "test speciation" is introduced to mark the evolution of paradigms sufficiently unique that their results cannot be "mated" productively with others in meta-analysis. Several projects have been initiated to develop cognitive ontologies at the Consortium for Neuropsychiatric Phenomics (www.phenomics.ucla.edu), in the hope that these ultimately will enable more effective collaboration, and facilitate connections of information about cognitive phenotypes to other levels of biological knowledge. Several free web applications are available already to support examination and visualisation of cognitive concepts in the literature (PubGraph, PubAtlas, PubBrain) and to aid collaborative development of cognitive ontologies (Phenowiki and the Cognitive Atlas). It is hoped that these tools will help formalise inference about cognitive concepts in behavioural and neuroimaging studies, and facilitate discovery of the genetic bases of both healthy cognition and cognitive disorders.

Objective: To study the protective effect of ischemic preconditioning (I-pre) and ischemic postconditioning (I-post) against ischemia/reperfusion (I/R) injury in rat's liver., Methods: Using rat model of hepatic segmental I/R injury, rats were divided into 5 groups: Group A (sham group), Group B (I/R injury), Group C (I-pre group), Group D (I-post group) and Group E (combined treatment of I-pre and I-post). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) in hepatic tissues were determined, respectively. In addition, 7 days'survival of Groups B, C, D and E were evaluated., Results: Compared with Group B, Groups C, D and E exhibited significantly decreased ALT and AST release, minimized tissue injury, suppressed values of MDA and MPO, increased activities of SOD, GSH-Px and GSH (P less than 0.05), as well as improved animal survival. The differences among Groups C, D and E were not statistically significant., Conclusions: I-pre, I-post and combined therapy of I-pre and I-post have protective effect against hepatic I/R injury, which is correlated with its function of reducing the production of reactive oxygen species, maintaining the activities of antioxidant systems and suppressing neutrophils recruitment. No additive effect can be obtained in Group E.

Sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) significantly decrease the need for repeat interventions compared with bare metal stents. Comparative outcome data from randomized, controlled, head-to-head trials using these systems in a selected group of patients and lesions are conflicting; therefore, we compared clinical outcomes of unselected patients who underwent contemporary percutaneous coronary intervention with SES or PES implantation. In the REWARDS registry, 1-year clinical outcomes of 1,925 patients who received SESs were compared with 844 patients who received PESs. Outcomes at 30 days and 6 months were similar between groups, with a trend toward higher rates of stent thrombosis in the SES group compared with the PES group. Stent thrombosis rate at 12 months was significantly higher in the SES than in the PES group, with cumulative stent thrombosis rates of 1.9% in the SES group and 0.8% in the PES group (p = 0.034). However, overall rates of major adverse cardiac events (MACEs) were similar in the 2 groups at 12 months. After adjusting for significant multivariate predictors of MACEs, the hazard ratio at 1 year was 1.06 (95% confidence interval 0.85 to 1.33, p = 0.607) and the major predictors for MACEs were a history of renal failure, diabetes, previous myocardial infarction, cardiogenic shock, class III or IV heart failure, type C lesions, and saphenous vein grafts. In conclusion, use of SESs and PESs in unrestricted, contemporary practice had comparable outcomes in terms of low rates of revascularization and clinical events. Stent thrombosis continues to be a major concern for SESs and PESs.

Sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) implantation for the treatment of single coronary lesions has proved to be effective and durable. However, the safety and efficacy of overlapping drug-eluting stents for the treatment of long lesions have not been well established. In total, 114 patients who received overlapping drug-eluting stents were identified, 55 of whom received overlapping SESs and 59 received overlapping PESs. Baseline clinical and angiographic characteristics were balanced. In-hospital complications were similar between the 2 groups. At 30-day and 6-month follow-ups, all clinical outcomes were also similar. In addition, the event-free survival rate was comparable (p = 0.71). Implantation of overlapping drug-eluting stents for the treatment of long, native coronary lesions is feasible and effective. In conclusion, in this observational study, clinical outcomes appeared similar in patients treated with overlapping SES implantation compared with those treated with overlapping PES implantation.

This study examined the outcomes of patients who underwent sirolimus-eluting stent (SES) implantation for the treatment of heavily calcified coronary lesions (HCCL) with and without the use of rotational atherectomy (rotablator). We investigated 150 consecutive patients with angiographic evidence of HCCL who underwent SES implantation. Sixty-nine patients underwent SES implantation without the need of rotablator (SES), and 81 patients required rotational atherectomy to modify the plaque and facilitate the delivery of the stent (SES + rotational atherectomy). Clinical success was equivalent in both groups (>98%) and there were no in-hospital outcome differences. At 6 months, the target lesion revascularization rate was 4.9% in SES vs. 4.2% in SES + rotational atherectomy groups, respectively (P = NS). Mortality at 6 months was 7.9% in the SES group vs. 6.8% in the SES + rotational atherectomy group (P = NS). SES performs well in patients with complex HCCL, with a relative low event rate. Lesions requiring rotational atherectomy to facilitate dilation and stenting had similar outcomes after SES implantation to those that could be stented without the need for rotablator.

Drug-eluting stents (DESs), although promising technology, still are associated with restenosis; therefore, we evaluated the safety and efficacy of intravascular radiation therapy for the treatment of DES in-stent restenosis (ISR). Treatment of DES ISR has not been established, although intravascular radiation therapy is an effective treatment for patients with ISR of bare metal stents. Other modalities are conventional percutaneous coronary intervention (PCI), including restenting with DES. Radiation for Eluting Stents in Coronary FailUrE (RESCUE) is an international, Internet-based registry of 61 patients who presented with ISR of a DES and were assigned to intravascular radiation therapy with commercially available systems after PCI. Outcomes of these patients were compared with those of a consecutive series of 50 patients who presented with ISR of a DES and were assigned to repeat DES (r-DES) treatment. Baseline clinical and angiographic characteristics were similar between groups, except for more Cypher stents as the initial DES that restenosed in the r-DES group than in the intravascular radiation therapy group (88.5% vs 69%, p = 0.01). At 8 months there were fewer overall major adverse cardiac events in the intravascular radiation therapy group compared with the r-DES group (9.8% vs 24%, p = 0.044). The need for target vessel and target lesion revascularizations was similar in the 2 groups at 8 months. There has been no report of subacute thrombosis in either group. In conclusion, intravascular radiation therapy as adjunct therapy to PCI for patients presenting with ISR of a DES is safe and should be considered an alternative therapeutic option for this difficult subset of patients.

We used intravascular ultrasound to evaluate the incidence, characteristics, and clinical sequel of plaque prolapse within drug-eluting stents. The influence of stent design on plaque prolapse has not been studied. Drug-eluting stents were serially expanded, first at 14 atm and then at 20 atm, with intravascular ultrasound imaging after each inflation. The stent, lumen, and maximum plaque prolapse areas were measured. The residual lumen area and percentage of plaque prolapse burden (maximum plaque prolapse area/stent area) were calculated. Plaque prolapse was divided into grades 1 (<5%), 2 (5% to 10%), and 3 (10% to 20%). Eighty patients (83 lesions, 41 Cypher and 42 Taxus Express stents) were studied. The incidence of plaque prolapse was 41% (17 of 41 lesions) with the Cypher stents versus 24% (10 of 41 lesions) with the Taxus stents after 14 atm (p = 0.096) and 35% (14 of 40) in Cypher stents versus 17.8% (5 of 28) in Taxus stents after 20 atm (p = 0.17). However, the maximum plaque prolapse area was never >20% of the stent area. The frequency and amount of plaque prolapse neither increased nor decreased at higher (20 atm) inflation pressures. Lesions with prolapse were longer (p = 0.004), with a larger external elastic membrane area and greater plaque burden (each p <0.0001) and a larger remodeling index (p = 0.013). Conversely, nonprolapsed plaques had a higher incidence of superficial calcium (p = 0.001). Creatinine kinase-MB elevation was higher with plaque prolapse, and the magnitude of creatinine kinase-MB elevation correlated with the extent of plaque prolapse (r = 0.664, p = 0.002). Multiple logistic regression analysis indicated that a longer lesion length (p = 0.012), and smaller minimal luminal area (p = 0.031) had higher risks of plaque prolapse. In conclusion, plaque prolapse was frequently observed in Cypher and Taxus stents. However, sequential intravascular ultrasound imaging showed that the frequency and amount of plaque prolapse were neither increased nor decreased by additional higher pressure inflations.

Objectives: We sought to compare the adequacy of paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) expansion based on intravascular ultrasound (IVUS) imaging criteria at conventional delivery pressures., Methods: Forty-six patients underwent SES implantation and 42 patients underwent PES implantation for de novo native coronary lesions<33 mm in length with reference lumen diameters of 2.5-3.5 mm. Stents were serially expanded with gradual balloon inflations at 14 and 20 atm. IVUS imaging was performed prior to intervention and after each balloon inflation. Stent expansion (minimal stent cross-sectional area/reference lumen cross-sectional area) was measured. Inadequate stent expansion was defined using the MUSIC criteria (all struts apposed, no tissue protrusion, and final lumen cross-sectional area>80% of the reference or >90% if minimal lumen cross-sectional area was <9 mm2)., Results: The baseline characteristics of the two groups were similar except for shorter lesion length, larger mean lumen cross-sectional area, larger lumen diameter, and lower plaque burden in the PES group. Stent expansion was inadequate in 80% of patients with SES versus 63% of patients with PES at 14 atm, although this was not statistically significant. After 20 atm, 48% of patients with SES remained underexpanded as compared with 35% of patients with PES., Conclusion: Drug-eluting stents showed significant underexpansion by MUSIC criteria at conventionally used inflation pressures. Higher balloon inflations are required especially during deployment of a SES. IVUS guidance is recommended to ensure optimal results and outcomes with both stents.

Intra-aortic balloon pump (IABP) has been shown to support patients who are at high risk for percutaneous coronary interventions (PCIs) or becoming hemodynamically unstable during PCI, but the longer term outcomes of these strategies are unknown. This study investigated the outcomes of high-risk patients who received a prophylactic IABP (P-IABP) versus patients who required rescue IABP (R-IABP) because of intraprocedural complications. Clinical outcomes of 68 consecutive patients (69 procedures) who underwent high-risk PCI with P-IABP support were compared with those of 46 patients who required R-IABP. Patients who presented with cardiogenic shock or acute ST-segment elevation myocardial infarction, and those who were on mechanical ventilators were excluded. Clinical baseline characteristics were similar between groups except for more diabetics and patients with hypercholesterolemia in the P-IABP group. The procedural success was higher in the P-IABP group, with lower in-hospital mortality and major complications, than in the R-IABP group. At 6 months, the mortality and major adverse cardiac event rates were lower in the P-IABP group (8% vs 29%, p < 0.01, and 12% vs 32%, p = 0.02, respectively). Multivariate analysis showed that prophylactic insertion of an IABP is the only independent predictor of survival at 6 months. The incidence of vascular complications was low and comparable except for more major bleeding (15% vs 3%, p = 0.03) in the R-IABP group. In conclusion, patients who undergo high-risk PCI and then receive P-IABP support have favorable outcomes compared with those who require R-IABP for intraprocedural complications. Therefore, in high-risk patients undergoing PCI, liberal use of a P-IABP should be considered.

Longer stent length has remained associated with the incidence of major adverse cardiac events (MACEs) in the drug-eluting stent (DES) era; therefore, we aimed to determine clinical outcomes after extensive stent coverage with DES implantations in single coronary lesions. We evaluated the data from 99 consecutive patients treated with extensive DES coverage, defined as > or = 50 mm (mean 63.3 +/- 13.2, range 50 to 115), and a concurrent series of 466 patients with < or = 24-mm DES length (mean 18.4 +/- 3.8, range 8 to 24). The periprocedural, 1-, and 6-month outcomes were compared between the 2 groups. The baseline characteristics were mostly comparable between the 2 groups, and procedural and in-hospital outcomes were similar. Although the incidence of death and myocardial infarction at follow-up were comparable, the combined end points of target lesion revascularization plus MACEs at 6 months occurred more often with extensive stent coverage. Multivariate analysis revealed stent length to be the only independent predictor of target lesion revascularization plus MACEs. Patients treated with extensive DES coverage had similar procedural success, major in-hospital complications, and death and myocardial infarction at follow-up, but had more combined adverse events because of an overall higher target lesion revascularization rate.

This study was performed to compare the safety and efficacy of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) on the outcomes of diabetic patients. Recent data with drug-eluting stents have shown improved clinical outcomes in diabetic patients. This study compared outcomes between the 2 available drug-eluting stents, SESs and PESs. From the prospective drug-eluting stent registries at the investigators' institution, 1,320 consecutive diabetic patients treated with SESs (n=873, 1,293 lesions) and PESs (n=447, 733 lesions) were identified and their in-hospital and 1- and 6-month clinical outcomes compared. Baseline characteristics showed more men, more patients with previous coronary bypass surgery, and smaller ejection fractions in the PES group and more obese patients in the SES group. Procedural characteristics were similar except for more left anterior descending artery and proximal lesions and the greater use of glycoprotein IIb/IIIa inhibitors in the SES group and more type C lesions, direct stenting, and stents per patient in the PES group. In-hospital complications were similar. Clinical follow-up at 1 month was also similar between the 2 groups, including subacute stent thrombosis. At 6 months, the 2 groups had similar mortality (7% vs 7%), myocardial infarctions (18% vs 21%), target lesion revascularization, target vessel revascularization, major adverse cardiac events (11% vs 12%), and late thrombosis (0.3% vs 0%). Subanalysis of insulin-treated diabetic patients showed no significant differences in outcomes in the 2 groups. No significant differences were found between SESs and PESs on Cox regression analysis for hazard ratios. In conclusion, SESs and PESs are associated with similar efficacy and safety with regard to repeat revascularization rates, major adverse cardiac events, and stent thrombosis up to 6 months for the treatment of coronary artery disease in patients with diabetes mellitus regardless of insulin therapy.

Background: Bivalirudin is replacing heparin as the anticoagulant agent of choice for elective percutaneous coronary intervention (PCI). This study aimed to assess the safety and clinical outcomes of bivalirudin versus unfractionated heparin (UFH) in patients undergoing PCI for acute myocardial infarction (AMI)., Methods: A cohort of 672 consecutive patients presenting with AMI without prior thrombolytic therapy were treated with either bivalirudin (216 patients) or UFH (456 patients). Platelet glycoprotein IIb/IIIa inhibitors were administered at the operator's discretion. The in-hospital, 30-day, and 6-month outcomes of the two groups were compared., Results: Baseline clinical and angiographic characteristics were similar between the groups. In-hospital complications were similar, although there was a trend of a less major hematocrit drop in the bivalirudin group (0.9% vs. 3.1%, P=.09). All clinical outcomes were similar between the groups at 30-day and 6-month follow-ups. There was no statistical significance for acute thrombosis and subacute thrombosis between the groups, and there was no late thrombosis from either group. The event-free survival rate was similar between the groups (P=.41)., Conclusion: The use of bivalirudin in patients undergoing PCI after AMI is safe and feasible. Bivalirudin should be considered as an alternative anticoagulant agent during PCI to treat patients presenting with AMI.

Objectives: The purpose of this study was to examine the clinical outcomes of patients who underwent stenting with > or =3 sirolimus-eluting stents (SES) when compared with those treated with > or =3 paclitaxel-eluting stents (PES)., Background: Drug-eluting stent (DES) implantation for single coronary lesions is proven to be effective and durable., Methods: A total of 126 patients who received DES were identified, of which 66 patients received > or =3 SES (SES group) and 60 patients received > or =3 PES (PES group)., Results: The baseline clinical and angiographic characteristics were compatible between the two study groups. During the index hospitalization, all clinical outcomes were similar between the two groups. There were no deaths or Q-wave myocardial infarctions (MIs) in either group. At 30 days' and 6 months' follow-up, all clinical outcomes, including death, Q-wave MI, non-Q-wave MI, target lesion revascularization, target vascular revascularization, and major adverse cardiac events, were compatible between both groups. There were 2 patients (3.0%) with subacute thrombosis in the SES group and 1 patient (1.7%) in the PES group, but there was no statistical significance. There was no late thrombosis from either group. In addition, patients in the SES group had similar event-free survival rates as compared with those in the PES group (P = 0.56)., Conclusions: Patients who require > or =3 DES implantations experienced increased adverse clinical events as compared with historical single stent implantation. However, there were no differences in safety and efficacy among the patients treated with SES as compared with those treated with PES., (Copyright 2006 Wiley-Liss, Inc.)

Objectives: We aimed to compare the clinical outcomes of dialysis versus nondialysis patients after coronary drug-eluting stent (DES) implantation., Background: The revascularization of ischemic heart disease in dialysis patients has remained controversial due to consistent exclusion of this population from major trials, especially in the context of percutaneous coronary interventions (PCI) with DES., Methods: We analyzed the data on 3,442 consecutive patients who underwent PCI and DES implantation since March 2003. Periprocedural events, 1- and 6-month clinical outcomes were then compared between dialysis (n = 72) and nondialysis patients (n = 3,370)., Results: Baseline characteristics revealed a higher prevalence of female gender (p = 0.03), African Americans (p < 0.001), hypertension (p < 0.001), diabetes mellitus (p < 0.001), number of diseased vessels (p = 0.04), lower ejection fraction (p < 0.001), and a higher prevalence of acute myocardial infarction (MI) (p = 0.04) in dialysis patients. Nondialysis patients showed more history of smoking (p < 0.001) and obesity (p = 0.02). Procedural success was higher (p = 0.05), while there was a trend toward a lower mortality rate, in the nondialysis group during hospitalization. At 6 months, the restenosis rate was low and comparable, but mortality occurred more often (16% vs. 3.8%; p < 0.001) in dialysis patients. Multivariate analysis revealed cardiogenic shock (p = 0.04) to be an independent predictor of mortality., Conclusions: PCI with DES in dialysis patients is safe and feasible, with a similar reduction of repeat revascularization when compared with nondialysis patients. There was, however, a higher incidence of mortality in dialysis patients at 6 months, mostly influenced by contributing comorbidities and more severe conditions at presentation.

We investigated the safety and efficacy of drug-eluting stents (DESs) for the treatment of patients who presented with in-stent restenosis (ISR) of saphenous vein grafts (SVGs) and compared the in-hospital and 6-month clinical outcomes of DESs with those of intravascular brachytherapy and balloon angioplasty alone. Records of 187 patients who presented with ISR of SVGs were analyzed. Of these, 34 consecutive patients were treated with DES implantation, 93 were treated with intravascular brachytherapy (n = 60 with gamma-radiation, n = 33 with beta-radiation), and 60 patients underwent conventional treatment with balloon angioplasty alone. Clinical and angiographic characteristics at baseline were comparable between groups. The DES group had less non-Q-wave myocardial infarction than did the intravascular brachytherapy and balloon angioplasty groups (0%, 20%, and 26%, p = 0.003 and <0.001, respectively). At 6 months, death occurred in 0% of the DES group, 2% of the intravascular brachytherapy group, and 5% of the balloon angioplasty group (p = 0.36 and <0.18, respectively). Target lesion revascularization/major adverse cardiac events were similar in the intravascular brachytherapy and DES groups (12% and 3%, p = 0.13) and significantly decreased compared with patients who were treated with balloon angioplasty alone (55%, p <0.001 for the 2 comparisons). The results of this retrospective analysis suggest that DES implantation is at least as effective and safe as intravascular brachytherapy for the treatment of SVG ISR and that these treatment modalities are superior to balloon angioplasty alone.

Contrast-induced nephropathy (CIN) is a common complication of coronary angiography that is associated with significant morbidity and mortality. Preexisting renal dysfunction is the most important risk factor for the development of CIN. A novel strategy of infusing 1 L of 5% dextrose immediately before catheterization is associated with a lower rate of CIN in those at high risk (creatinine clearance < or = 60 ml/min). CIN occurred in 47 patients (5.7%) in the control group and 2 patients (1.4%) in the group treated with 5% dextrose. The relative risk decrease was 73% (p = 0.03). This is an effective, quick, and inexpensive method of improving outcomes in patients who undergo percutaneous coronary interventions.