Comparison of the Efficacy and Safety Between Intravenous Thrombolysis, Direct Endovascular Therapy, and Bridging Therapy for Acute Basilar Artery Occlusion in Cerebral Infarction Patients.

OBJECTIVE: To compare the efficacy and safety of intravenous thrombolysis, direct endovascular therapy (EVT), and bridging therapy (BT = intravenous thrombolysis + EVT) for acute basilar artery occlusion cerebral infarction. METHODS: One hundred and fourteen patients with acute basilar artery occlusion cerebral infarctions admitted between January 2020 and August 2023 were selected. Differences in the reperfusion rate, prognosis, incidence of stroke-associated pneumonia, and mortality rate were compared among the 3 groups. RESULTS: There was no statistically significant difference in the percentage of patients who achieved successful reperfusion (86.8% vs. 84.2%) or complete reperfusion (72.1% vs. 68.4%) between the direct EVT and BT groups (both P > 0.05). There were no statistically significant differences in the rates of symptomatic intracranial hemorrhage (3.7% vs. 10.3% vs. 10.5%, P = 0.763). There were statistically significant differences in the rates of good prognosis (modified ranking scale score 0-2) (59.3% vs. 30.9% vs. 26.3%, P = 0.021), stroke-related pneumonia (29.6% vs. 66.2% vs. 36.8%, P = 0.002), and mortality (14.8% vs. 48.5% vs. 42.1%, P = 0.010) among the 3 treatment groups. According to the binary logistic regression analysis, a good prognosis was independently associated with a baseline National Institutes of Health Stroke Scale score ≤ 10 (odds ratio, 3.714; 95% confidence interval, 1.207-11.430; P = 0.022) and the incidence of stroke-associated pneumonia (odds ratio, 0.640; 95% confidence interval, 0.484-0.845; P = 0.002). CONCLUSIONS: Although there were differences in prognosis, mortality, and incidence of complications among the 3 treatment groups, after adjusting for confounding factors, prognosis was independently correlated only with the baseline NIHSS score and stroke-associated pneumonia but not with treatment methods.

FUNDC1/USP15/Drp1 ameliorated TNF-α-induced pulmonary artery endothelial cell proliferation by regulating mitochondrial dynamics.

Mitochondrial dysfunction in pulmonary artery endothelial cells (PAECs) is related to the pathogenesis of pulmonary hypertension (PH). The mitochondrial receptor protein FUN14 domain containing 1 (FUNDC1) was found to be involved in pulmonary artery smooth muscle cell proliferation in PH. However, its role in PAECs remains unclear. We investigated FUNDC1 expression in the pulmonary artery endothelium in both monocrotaline-induced animal models and TNF-α-stimulated cell models. Additionally, the effect of FUNDC1 on PAECs proliferation and its possible mechanism were also investigated. We observed decreased FUNDC1 protein levels in animals and in vitro in PAECs. FUNDC1 deficiency in PAECs upregulated the expression of the deubiquitination enzyme ubiquitin-specific peptidase 15 (USP15), enhanced dynamin-related protein1 (Drp1)-mediated mitochondrial division, and increased mitochondrial ROS levels via the deubiquitination of Drp1. Additionally, FUNDC1 deficiency increased aerobic glycolysis, the production of ATP and lactic acid, and glucose uptake. FUNDC1 overexpression inhibited PAECs proliferation. Moreover, FUNDC1 overexpression in combination with a mitochondrial division or aerobic glycolysis inhibitor enhanced its inhibitory effect on cell proliferation. Our study findings suggest that FUNDC1 deficiency induced by inflammation can promote PAECs proliferation by regulating mitochondrial dynamics and cell energy metabolism via the USP15/Drp1 pathway.

Effect of cerebral small vessel disease on cognitive impairment in Parkinson's disease.

OBJECTIVES: To explore the association between cerebral small vessel disease (cSVD) and cognitive impairment (CI) in Parkinson's disease (PD). METHODS: 81 PD patients were recruited into the study from September 2018 to December 2020. The demographic characteristics and radiologic and laboratory data were collected. Cognitive assessments were carried out using the Montreal Cognitive Assessment. The association between cSVD and cognitive impairment was analyzed using univariate and binary logistic regression analysis. RESULTS: The binary logistic regression analysis showed that, after correcting for age, educational years, hyperhomocysteinemia, hypertension, and diabetes mellitus, total cSVD scores (OR 1.55, 95% CI 1.07-2.27, P = 0.02), the presence of paraventricular white matter hyperintensity (PVH) (OR 11.78, 95% CI 3.08-45.01, P < 0.001), white matter hyperintensity (WMH) (OR 7.95, 95% CI 2.28-27.79, P = 0.001), and perivascular space (PVS) (OR 6.66, 95% CI 2.08-21.40, P = 0.001) were independent risk factors for PD-CI. CONCLUSION: The presence of cSVD was associated with cognitive dysfunction in patients with PD. It may be beneficial to manage cSVD to prevent the progression of cognitive impairment in patients with PD.

Lncrna FGD5-AS1 Aggravates Myocardial Ischemia-Reperfusion Injury by Sponging Mir-129-5p.

Background: LncRNA FGD5-AS1 regulates the pathogenesis of many human diseases. We aimed to elucidate the function of lncRNA FGD5-AS1 and the regulatory mechanism of lncRNA FGD5-AS1/miR-129-5p in myocardial ischemia-reperfusion (I/R) injury. Methods: Myocardial I/R injury mice model and H/R treated H9c2 cells were established. RT-qPCR and Western blot analysis were used to detect the mRNA and protein expression. Cell viability was detected by MTT assay. Dual luciferase reporter assay was applied to confirm the relationship between lncRNA FGD5-AS1 and miR-129-5p. Results: LncRNA FGD5-AS1 was upregulated in myocardial I/R injury mice models and H/R treated H9c2 cells. Functionally, knockdown of lncRNA FGD5-AS1 promoted cell viability and inhibited apoptosis in H/R treated H9c2 cells. In addition, lncRNA FGD5-AS1 directly targets miR-129-5p. Upregulation of lncRNA FGD5-AS1 weakened the protective effect of miR-129-5p on myocardial I/R injury. Conclusion: LncRNA FGD5-AS1 aggravates myocardial I/R injury by downregulating miR-129-5p.

Patients with comorbid coronary artery disease and hypertension: a cross-sectional study with data from the NHANES.

Background: Hypertension (HTN) and coronary artery disease (CAD), two common cardiovascular diseases, are often comorbid and interacted. The patients with comorbid CAD and HTN have worse outcomes and prognosis, however, the prevalence remains unclear. In the cross-sectional study, we aimed to explore the prevalence and influence factors of patients with comorbid CAD and HTN in the USA. Methods: Adult patients with comorbid CAD and HTN derived from the National Health and Nutrition Examination Survey (NHANES) database in the 1999-2000 and 2017-2018 cycles were included. Demographic data, physical examination results, laboratory data, and questionnaire data were collected and compared in the two cycles. Subgroup analyses were performed between the elder (≥65 years of age) and middle-young (18-65 years of age) populations. Results: The age-adjusted prevalence of patients with comorbid CAD and HTN increased from 4.22% [1999-2000] to 5.40% [2017-2018] (P=0.006) and the age decreased from 71 [63-79] to 69 [61-77] years (P=0.008). The HTN control rate, the low-density lipoprotein cholesterol (LDL-C) control rate, systolic blood pressure (SBP), and the levels of blood lipids, as well as the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), ß-blockers and statins improved in the 2017-2018 cycle as compared with the 1999-2000 (all P<0.05). On the other hand, the proportions complicated with diabetes mellitus (DM), obesity and chronic kidney disease (CKD), as well as the levels of serum glucose, glycohemoglobin and creatinine increased from the 1999-2000 to 2017-2018 (all P<0.01). Subgroup analyses revealed that the prevalence of middle-young patients with comorbid CAD and HTN increased more than their elder counterparts, while diastolic blood pressure (DBP), pulse, blood lipids and oral medication rates were inferior to the latter. Conclusions: The recent prevalence of patients with comorbid CAD and HTN increased than 20 years ago, mainly caused by more morbid middle-young population. For another, the control of blood pressure (BP) and lipids were favorably affected by increased use of statins, ACEIs/ARBs and ß-blockers in these patients. Nevertheless, there is still much room for strengthening medication utilization and intervention of risk factors in future.

Systemic immune inflammation index and system inflammation response index are potential biomarkers of atrial fibrillation among the patients presenting with ischemic stroke.

BACKGROUND: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. METHODS: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. RESULTS: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). CONCLUSIONS: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke.

Correlation Between Intracranial Carotid Artery Calcification and Prognosis of Acute Ischemic Stroke After Intravenous Thrombolysis.

Objective: To investigate the correlation between prognosis and intracranial carotid artery calcification (ICAC) in patients with acute ischemic stroke (AIS) who receive intravenous thrombolysis (IVT). Methods: A total of 156 AIS patients who received IVT from March 2019 to March 2020 were enrolled. The modified Woodcock visual score was used to evaluate ICAC in nonenhanced head CT scans. Patients were divided into high calcification burden (HCB; score ≥3) and low calcification burden (LCB; score <3) groups. Demographic, laboratory, imaging and clinical data were compared between the two groups, and whether HCB was a prognostic factor was evaluated. Results: Compared with the LCB group, the HCB group had a higher incidence of atrial fibrillation (49.2 vs.22.1%, P < 0.001) and coronary heart disease (24.6 vs. 10.0%, P = 0.019) and higher serum homocysteine [15.31 (12.15, 17.50) vs. 14.40 (11.20, 16.20), P = 0.036] and hemoglobin A1c (6.93 ± 1.77 vs. 6.37 ± 0.74, P = 0.023) levels. Binary logistic regression analysis showed that atrial fibrillation (OR = 3.031, 95% CI: 1.312-7.006, P = 0.009) and HbA1c (OR = 1.488, 95% CI: 1.050-2.109, P = 0.026) were independent risk factors for ICAC. After adjusting for other risk factors, symptomatic-side and bilateral ICACs were independent risk factors for poor prognosis (OR = 1.969, 95% CI: 1.220-3.178, P = 0.006), (OR = 1.354, 95% CI: 1.065-1.722, P = 0.013) and mortality (OR = 4.245, 95% CI: 1.114-16.171, P = 0.034), (OR = 2.414, 95% CI = 1.152-5.060, P = 0.020) in patients with AIS who received IVT. Conclusion: ICAC is closely related to the prognosis of acute ischemic stroke after intravenous thrombolysis.

The Correlation Between MDR1 Gene Polymorphism and Clopidogrel Resistance in People of the Hui and Han Nationalities.

To investigate the differences in the correlation between multidrug resistance protein 1 (MDR1) (ABCB1) gene polymorphism and clopidogrel resistance in patients of the Hui and Han nationalities with percutaneous coronary intervention (PCI). A total of 377 subjects (154 people of Hui nationality, 223 people of Han nationality) with PCI were enrolled in the study. Each patient's platelet aggregation rate was induced by adenosine diphosphate and measured using light turbidimetry. Based on the results, the patients were divided into two groups: a clopidogrel resistance (CR) group and a non-clopidogrel resistance (NCR) group. Restrictive fragment-length polymorphism polymerase chain reaction technology was then used to determine the genotype and alleles at two loci (C3435 T[rs1045642] and C1236 T[rs1128503]), calculate the frequencies of the genotype and alleles at these two loci, and conduct correlation analysis. The incidence rate of clopidogrel resistance was 23.4%, and the frequencies of the TT genotype and T allele at C3435 T for patients of both nationalities were significantly higher in the CR group than in the NCR group (P < 0.05). There were no significant differences between the two groups in genotype or allele frequency at C1236 T. There was a significant difference in the distribution of C1236 T polymorphism between the two nationalities (P < 0.05), but there was no significant difference between the two nationalities in C3435 T polymorphism. Patients with a T allele at MDR1 C3435 T are more likely to show clopidogrel resistance, and no significant differences were identified in C3435 T gene polymorphism between the two nationalities.

Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment.

Stem cell-derived exosomes (SC-EXO) was an emerging therapeutic agent in regenerative medicine. Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction (ED) treatment. However, high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection. In this study, a Polydopamine nanoparticles (PDNPs) incorporated poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PDNPs-PELA) thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes (EXO). The hydrogels exhibited sol-gel transition at body temperature. Moreover, the in-situ polymerization of PDNPs using poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PELA) block copolymer as a template was found to be more stable dispersion in the gel system. After being encapsulated into the hydrogel, EXO shows sustained release behavior within two weeks. In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons, increase of the cavity's pressure, thereby restoring the erectile function. In particular, since the PDNPs in thermosensitive gels have excellent photoacoustic performance, the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging. These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.

One-Step Preparation of an AgNP-nHA@RGO Three-Dimensional Porous Scaffold and Its Application in Infected Bone Defect Treatment.

BACKGROUND: Bactericidal capacity, durable inhibition of biofilm formation, and a three-dimensional (3D) porous structure are the emphases of infected bone defect (IBD) treatment via local scaffold implantation strategy. PURPOSE: In this study, silver nanoparticle (AgNP)-loaded nano-hydroxyapatite (nHA)@ reduced graphene oxide (RGO) 3D scaffolds (AHRG scaffolds) were designed to alleviate bone infection, inhibit biofilm formation, and promote bone repair through the synergistic effects of AgNPs, RGO, and nHA. MATERIALS AND METHODS: AHRGs were prepared using a one-step preparation method, to create a 3D porous scaffold to facilitate a uniform distribution of AgNPs and nHA. Methicillin-resistant Staphylococcus aureus (MRSA) was used as a model-resistant bacterium, and the effects of different silver loadings on the antimicrobial activity and cytocompatibility of materials were evaluated. Finally, a rabbit IBD model was used to evaluate the therapeutic effect of the AHRG scaffold in vivo. RESULTS: The results showed successful synthesis of the AHRG scaffold. The ideal 3D porous structure was verified using scanning electron microscopy and transmission electron microscopy, and X-ray photoelectron spectroscopy and selected area electron diffraction measurements revealed uniform distributions of AgNP and nHA. In vitro antibacterial and cytocompatibility indicated that the 4% AHRG scaffolds possessed the most favorable balance of bactericidal properties and cytocompatibility. In vivo evaluation of the IBD model showed promising treatment efficacy of AHRG scaffolds. CONCLUSION: The as-fabricated AHRG scaffolds effectively eliminated infection and inhibited biofilm formation. IBD repair was facilitated by the bactericidal properties and 3D porous structure of the AHRG scaffold, suggesting its potential in the treatment of IBDs.

Impact of anatomical variations of the left ventricular outflow tract on stroke volume calculation by Doppler echocardiography in aortic stenosis.

BACKGROUND: Accurate calculation of stroke volume (SV) by Doppler echocardiography is important for the assessment of aortic stenosis (AS), which may be impacted by anatomical variations of left ventricular outflow tract (LVOT). METHODS: Patients with AS (n = 64) were studied using computed tomography (CT) and transthoracic echocardiography (TTE). Anatomical variations of LVOT areas were measured at (a) the aortic annulus (Aa ); (b) 5 mm (A5 ); and (c) 10 mm below the annulus (A10 ) by CT. LVOT diameters were also measured by 2D TTE at these three levels for calculation of LVOT areas. Stroke volumes (SV) were calculated using continuity equation. The impacts of anatomical variations of LVOT on SV calculation were evaluated. RESULTS: Anatomical LVOT area increased from Aa to A10 (5.0 ± 0.9 cm2 vs 5.8 ± 1.9 cm2 , P < .01). Differences between TTE-calculated LVOT areas and anatomical areas were most significant at A10 due to elongation of mediolateral diameters with variable changes in anteroposterior diameters (5.8 ± 1.9 cm2 vs 3.4 ± 1.1 cm2 , P < .001). Although mean calculated SV by TTE was not significant at different LVOT levels (Aa 69 ± 22 mL, vs A5 66 ± 21 mL, vs A10 66 ± 28 ± 22 mL, P > .05), the most significant variations in individuals were at A10 levels (ΔSV: 8.2 ± 6.4 mL, 12 ± 9%). CONCLUSION: Variations of LVOT anatomy in individuals with AS significantly impact the SV calculated by Doppler echocardiography. These features should be taken into account for AS diagnosis and a clinical decision-making for intervention.

Obstructive sleep apnea in Parkinson's disease: a study in 239 Chinese patients.

OBJECTIVE: Our objective was to explore the clinical characteristics of Parkinson's disease (PD) comorbidity with obstructive sleep apnea (OSA), explore the correlation between OSA and PD features and identify factors that are independent predictors of OSA in PD patients. METHODS: In sum, 239 PD patients were divided into two groups according to the presence of OSA (apnea-hypopnea index (AHI) score ≥5) (PD-OSA vs PD-non-OSA). Blinded to sleep apnea status, participants underwent an extensive assessment to determine demographic features, concomitant disease, disease severity, polysomnography (PSG) characteristics and non-motor symptoms (NMSs). RESULTS: Of the 239 patients, 66 (27.62%) had an AHI score ≥5, including 14.2% (34/239) with mild, 6.7% (16/239) with moderate, and 6.7% (16/239) with severe sleep apnea. The binary logistic regression analyses indicated that age and male gender were risk factors for OSA, while rapid eye movement (REM) sleep disorder (RBD) and higher Levodopa equivalent dose (LED) were protective factors for OSA. PD-OSA patients had higher Epworth Sleepiness Scale (ESS) scores than those of PD-non-OSA patients. No differences were found for other NMSs between groups. CONCLUSION: Our data suggest that OSA in PD was lower in patients with RBD and higher LED. RBD and higher LDEs were significant protective factors for OSA in PD. OSA in PD was increased with age and male gender. Age and male gender were risk factors for OSA in PD. OSA can aggravate excessive daytime somnolence in PD patients but is not associated with other NMSs.

Identification and characterization of biomarkers and their functions for docetaxel-resistant prostate cancer cells.

Docetaxel treatment is a standard chemotherapy strategy for castration-resistant prostate cancer (CRPC), and patients with CRPC eventually develop resistance to treatment. However, little is understood regarding the underlying mechanism of resistance. The present study aimed to identify the underlying crucial genes and regulatory networks associated with docetaxel resistance in prostate cancer using bioinformatics analyses. For this purpose, one expression profile dataset (GSE33455), which included two docetaxel-sensitive and two docetaxel-resistant cell lines, was downloaded from the Gene Expression Omnibus database, and analyses of differential gene expression and function enrichment were performed. A protein-protein interaction (PPI) network was constructed, and the associated hub genes were investigated using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. A total of 756 differentially expression genes (DEGs) were identified, including 509 downregulated and 247 upregulated genes. Enrichment analysis revealed that the DEGs were associated with the interferon-γ-mediated signaling pathway, protein binding, bicellular tight junctions and cancer pathways. Two modules were screened from the PPI network, and the corresponding genes were identified to be largely enriched in the interferon-γ-mediated signaling pathway and the negative regulators of the DExD/H-Box helicase 58/interferon induced with helicase C domain 1 signaling pathway, and enriched in cell-cell adhesion and the Rap1 signaling pathway. Among the ten hub genes, epidermal growth factor receptor, spleen tyrosine kinase (SYK), intracellular adhesion molecule 1 (ICAM1), interleukin (IL)6, CXC motif chemokine ligand 8 (CXCL8), cyclin dependent kinase 1 and CD44 molecule (CD44) were significantly differentially expressed in prostate cancer tissues compared with healthy tissues based on The Cancer Genome Atlas data. The Gene Expression Profiling Interactive Analysis database revealed that ICAM1 was positively associated with IL6 and CXCL8, and epidermal growth factor receptor was positively associated with CD44 and SYK. Additionally, ten hub genes, which were identified to be associated with the drug resistance of docetaxel in prostatic carcinoma in the present study, were predominantly associated with tumor progression and metastasis. Reverse transcription-quantitative PCR analysis performed on docetaxel-sensitive and docetaxel-resistant prostate cancer cell lines demonstrated that certain hub genes, including CDK1, 2'-5'-oligoadenylate synthetase 3, CXCL8 and CDH1, were highly expressed in the docetaxel-resistant cell lines, which confirmed the bioinformatics results. In conclusion, the present study identified a number of important genes that are associated with the molecular mechanism of docetaxel resistance by integrated bioinformatical analysis, and these genes and regulatory networks may assist with identifying potential gene therapy targets for CRPC. Further functional analyses are required to validate the current findings.

Association of homocysteine, folate, and white matter hyperintensities in Parkinson's patients with different motor phenotypes.

OBJECTIVE: To investigate the association of homocysteine (Hcy), folate, and white matter hyperintensities in Parkinson's disease (PD) with different motor phenotypes. METHODS: Of the PD patients, 176 were included. Based on the Unified Parkinson's Disease Rating Scale, the PD patients were classified into postural instability gait disorder (PIGD) and non-PIGD phenotypes. According to the Fazekas score, patients were divided into the none/mild white matter hyperintensity (WMH) group and the moderate/severe WMH group. The relationship of Hcy, folate, and white matter hyperintensities (WMHs), and the motor phenotype of PD were analyzed. RESULTS: PD-PIGD patients had higher proportion of moderate/severe WMHs, Hcy levels, and lower folate levels than PD-non-PIGD patients (p all ≤ 0.001). In the subgroup analysis, patients with both PD-PIGD and moderate/severe WMHs had the highest Hcy and lowest folate levels compared with others. Binary logistic regression analysis showed that age, folate, and Hcy were independent risk factors for WMHs. In an a priori-determined stratified analysis, after adjustment for confounding factors, the odds ratio of WMHs was 8.01 (95% CI 2.700-23.767, p trend = 0.001) in the patients with Hcy levels in the highest quintile compared with the lowest quintile and 16.81 (95% CI 4.74-59.65, p trend < 0.001) in the patients with folate levels in the lowest quintile compared with the highest quintile. CONCLUSIONS: Our data showed a close association between WMHs and Hcy, folate especially in PD-PIGD patients. It can be speculated that higher Hcy and lower folate probably played important roles in the development of WMHs and motor heterogeneity in PD.

RAB14 activates MAPK signaling to promote bladder tumorigenesis.

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential and its abundance was significantly associated with lymph node metastasis (P = 0.001), a high-grade tumor stage (P = 0.009), poor differentiation (P < 0.001) and unfavorable prognoses of BC patients (P = 0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein and inhibited cell migration and invasion (P < 0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling through upregulation of MAPK1/MAPK8 and downregulation of dual-specificity protein phosphatase 6/Src homology 2 domain containing transforming protein/Fos proto-oncogene, AP-1 transcription factor subunit (FOS). We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

Risk Factors for Mild Cognitive Impairment in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Endovascular Coiling.

OBJECTIVE: To assess the potential early risk factors of mild cognitive impairment after aneurysmal subarachnoid hemorrhage. METHODS: We prospectively enrolled patients with aneurysmal subarachnoid hemorrhage treated with endovascular coiling during a 5-year period. The demographic characteristics and radiologic and laboratory data were collected. Cognitive assessments were carried out using the Montreal Cognitive Assessment at 6 months after ictus. Multivariate logistic regression was used to determine the risk factors associated with the development of mild cognitive impairment. RESULTS: Of 152 patients, 59 patients (39%) developed cognitive impairment 6 months later. Univariate analysis showed that the patients with anterior communicating artery or anterior cerebral artery aneurysms (P < 0.001) with Glasgow Outcome Scale score of 7 or less at ictus (P = 0.002), Hunt and Hess grade of 3 or higher (P = 0.002), and Fisher grade of 3 or higher (P = 0.032) were more likely to develop mild cognitive impairment. The risk of mild cognitive impairment was increased for patients who had delayed cerebral ischemia (P = 0.040) and hydrocephalus (P = 0.002). In multivariate logistic regression analysis, mild cognitive impairment was independently associated with anterior communicating artery or anterior cerebral aneurysms (odds ratio [OR], 11.046; 95% confidence interval [CI], 3.371-36.198; P < 0.001), delayed cerebral ischemia (OR, 6.153; 95% CI, 1.587-23.855; P = 0.009), and hydrocephalus (OR, 8.768; 95% CI, 2.115-36.345; P = 0.003). CONCLUSIONS: The location of the aneurysm, delayed cerebral ischemia, and hydrocephalus were independently associated with the occurrence of mild cognitive impairment after aneurysmal subarachnoid hemorrhage and can contribute to improved identification of patients at high risk for mild cognitive impairment.

Diastolic dysfunction predicts the risk of contrast-induced nephropathy and outcome post-emergency percutaneous coronary intervention in AMI patients with preserved ejection fraction.

Patients with acute myocardial infarction (AMI) and reduced left ventricular ejection fraction (LVEF) are at high risk of contrast-induced nephropathy (CIN). However, the risk factors of CIN in AMI patients with preserved LVEF remain largely unknown now. The present study explored the relationship between LV diastolic function and CIN in this patient cohort. The present prospective cohort study enrolled 379 AMI patients with preserved LVEF (≥ 50%) who underwent emergency percutaneous coronary interventions (PCI). Transthoracic echocardiography was performed before PCI using a portable echocardiography system. Diastolic function was graded as normal, indeterminate and diastolic dysfunction according to the current recommendation of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. A total of 88 patients (23.2%) developed CIN. Multivariate logistic regression analysis showed that both diastolic dysfunction (DD) and the mitral E velocity to mitral annular tissue Doppler E' velocity ratio (E/E') were independent predictors of CIN (P < 0.001). Other independent risk factors of CIN included increased Mehran score, ST-segment-elevation myocardial infarction, higher HbA1c and left anterior descending lesion, as well as the use of diuretics. Multivariate Cox regression analysis found that CIN, DD, higher N-terminal pro-B-type natriuretic peptide and HbA1c were independent predictors of MACE 2 years after AMI. Diastolic dysfunction determined before emergency PCI is linked with increased risk of CIN in AMI patients with preserved LVEF. CIN and diastolic dysfunction are independent predictors of MACE at 2 years in this patient cohort.

Cardiac-Specific Overexpression of Silent Information Regulator 1 Protects Against Heart and Kidney Deterioration in Cardiorenal Syndrome via Inhibition of Endoplasmic Reticulum Stress.

BACKGROUND/AIMS: Increased endoplasmic reticulum (ER) stress contributes to development of cardiorenal syndrome (CRS), and Silent Information Regulator 1 (SIRT1), a class III histone deacetylase, may have protective effects on heart and renal disease, by reducing ER stress. We aimed to determine if SIRT1 alleviates CRS through ER stress reduction. METHODS: Wild type mice (n=37), mice with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and corresponding controls, were randomized into four groups: sham MI (myocardial infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx) and myocardial infarction (MI) (induced by ligation of the left anterior descending (LAD) coronary artery) were performed successively to establish CRS model. At week 8, the mice were sacrificed after sequential echocardiographic and hemodynamic studies, and then pathology and Western-blot analysis were performed. RESULTS: Neither MI nor STNx alone significantly influenced the other healthy organ. However, in MI groups, STNx led to more severe cardiac structural and functional deterioration, with increased remodeling, increased BNP levels, and decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups. Conversely, in STNx groups, MI led to renal structural and functional deterioration, with more severe morphologic changes, augmented desmin and decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx groups, SIRT1 knockout led to more severe cardiac structural and functional deterioration, with higher Masson-staining score and BNP levels, and lower EF, FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater structural and functional deterioration, as evidenced by more severe morphologic changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-ß expression, while SIRT1 overexpression resulted in less severe morphologic changes and increased nephrin expression without significant influence on BUN or SCr levels. The SIRT1 knockout but not overexpression resulted in increased myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or overexpression resulted in increased or decreased renal expression of CHOP, Bax, and p53 respectively. CONCLUSIONS: Myocardial SIRT1 activation appears protective to both heart and kidney in CRS models, probably through modulation of ER stress.

Insulin upregulates GRIM-19 and protects cardiac mitochondrial morphology in type 1 diabetic rats partly through PI3K/AKT signaling pathway.

Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction. Furthermore, the effects of insulin on mitochondrial complex I were detected in HeLa cells and H9C2 cardiac myocytes. During the development of diabetic heart disease, the cardiac function did not change within the 8 weeks, but the mitochondrial morphology was altered. The hearts from the rats with STZ-induced diabetes exhibited reduced expression of GRIM-19. Prior to the overt cardiac dilatation, mitochondrial alterations were already present. Following subcutaneous insulin injection, it was demonstrated that GRIM-19 protein was altered, as well as the mitochondrial morphology. The phosphoinositide 3-kinase inhibitor LY294002 had an effect on insulin signaling in H9C2 cardiacmyocytes, and decreased the level of GRIM-19 by half compared with that in the insulin group. The results indicate that insulin is essential for the control of cardiac mitochondrial morphology and the GRIM-19 expression partly via PI3K/AKT signaling pathways.