Cross-Talking Pathways of Rapidly Accelerated Fibrosarcoma-1 (RAF-1) in Alzheimer's Disease.

Alzheimer's disease (AD) becomes one of the main global burden diseases with the aging population. This study was to investigate the potential molecular mechanisms of rapidly accelerated fibrosarcoma-1 (RAF-1) in AD through bioinformatics analysis. Differential gene expression analysis was performed in GSE132903 dataset. We used weight gene correlation network analysis (WGCNA) to evaluate the relations among co-expression modules and construct global regulatory network. Cross-talking pathways of RAF-1 in AD were identified by functional enrichment analysis. Totally, 2700 differentially expressed genes (DEGs) were selected between AD versus non-dementia control and RAF-1-high versus low group. Among them, DEGs in turquoise module strongly associated with AD and high expression of RAF-1 were enriched in vascular endothelial growth factor (VEGF), neurotrophin, mitogen-activated protein kinase (MAPK) signaling pathway, oxidative phosphorylation, GABAergic synapse, and axon guidance. Moreover, cross-talking pathways of RAF-1, including MAPK, VEGF, neurotrophin signaling pathways, and axon guidance, were identified by global regulatory network. The performance evaluation of AUC was 84.2%. The gene set enrichment analysis (GSEA) indicated that oxidative phosphorylation and synapse-related biological processes were enriched in RAF-1-high and AD group. Our findings strengthened the potential roles of high RAF-1 level in AD pathogenesis, which were mediated by MAPK, VEGF, neurotrophin signaling pathways, and axon guidance.

Immunotherapy checkpoints in ovarian cancer vasculogenic mimicry: Tumor immune microenvironments, and drugs.

Vasculogenic mimicry (VM), a vessel-like structure independent of endothelial cells, commonly exists in solid tumors which requires blood vessels to grow. As a special source of blood supply for tumor progression to a more aggressive state, VM has been observed in a variety of human malignant tumors and is tightly associated with tumor proliferation, invasion, metastasis, and poor patient prognosis. So far, various factors, including immune cells and cytokines, were reported to regulate ovarian cancer progression by influencing VM formation. Herein, we review the mechanisms that regulate VM formation in ovarian cancer and the effect of cells, cytokines, and signaling molecules in the tumor microenvironment on VM formation, Furthermore, we summarize the current clinical application of drugs targeting VM formation.

The Predicted Key Molecules, Functions, and Pathways That Bridge Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD).

To elucidate the key molecules, functions, and pathways that bridge mild cognitive impairment (MCI) and Alzheimer's disease (AD), we investigated open gene expression data sets. Differential gene expression profiles were analyzed and combined with potential MCI- and AD-related gene expression profiles in public databases. Then, weighted gene co-expression network analysis was performed to identify the gene co-expression modules. One module was significantly negatively associated with MCI samples, in which gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that these genes were related to cytosolic ribosome, ribosomal structure, oxidative phosphorylation, AD, and metabolic pathway. The other two modules correlated significantly with AD samples, in which functional and pathway enrichment analysis revealed strong relationships of these genes with cytoplasmic ribosome, protein binding, AD, cancer, and apoptosis. In addition, we regarded the core genes in the module network closely related to MCI and AD as bridge genes and submitted them to protein interaction network analysis to screen for major pathogenic genes according to the connectivity information. Among them, small nuclear ribonucleoprotein D2 polypeptide (SNRPD2), ribosomal protein S3a (RPS3A), S100 calcium binding protein A8 (S100A8), small nuclear ribonucleoprotein polypeptide G (SNRPG), U6 snRNA-associated Sm-like protein LSm3 (LSM3), ribosomal protein S27a (RPS27A), and ATP synthase F1 subunit gamma (ATP5C1) were not only major pathogenic genes of MCI, but also bridge genes. In addition, SNRPD2, RPS3A, S100A8, SNRPG, LSM3, thioredoxin (TXN), proteasome 20S subunit alpha 4 (PSMA4), annexin A1 (ANXA1), DnaJ heat shock protein family member A1 (DNAJA1), and prefoldin subunit 5 (PFDN5) were not only major pathogenic genes of AD, but also bridge genes. Next, we screened for differentially expressed microRNAs (miRNAs) to predict the miRNAs and transcription factors related the MCI and AD modules, respectively. The significance score of miRNAs in each module was calculated using a hypergeometric test to obtain the miRNApivot-Module interaction pair. Thirty-four bridge regulators were analyzed, among which hsa-miR-519d-3p was recognized as the bridge regulator between MCI and AD. Our study contributed to a better understanding of the pathogenic mechanisms of MCI and AD, and might lead to the development of a new strategy for clinical diagnosis and treatment.

Comparison of Survival and Risk Factors of Differentiated Thyroid Cancer in the Geriatric Population.

Purpose: The incidence rate of differentiated thyroid cancer (DTC), the most common type of thyroid cancer, has increased in the past two decades. The present study analyzed the clinical and pathological characteristics of DTC, and discussed the risk factors for survival in elderly age-risk DTC patients. Methods: Elderly patients who were diagnosed with DTC, and subsequently underwent surgery for DTC, were identified from the SEER database (1988-2008). Based on histology, these patients were divided into C-PTC, FV-PTC, and FTC. The clinical characteristics, pathological features, and treatments undertaken were compared among these patients. Cox proportional hazards analysis was performed to evaluate the risk factors to disease-specific survival (DSS). Results: In elderly DTC patients, FV-PTC shows intermediate tumor features compared to C-PTC and FTC, but presented a better outcome. Being male, African-American, tumors sized bigger than 4 cm, extrathyroidal extension, lymph node metastasis, and distant metastasis, were all strong risk factors for DSS in elderly DTC patients (all p < 0.05). No difference was found between lobectomy and total thyroidectomy with respect to DSS, and radiation therapy conferred no apparent advantage with respect to DSS (both p > 0.05). Discussion: Patients with FV-PTC needed more specific histology cataloging and risk assessment, suggesting conservative therapy. Risk stratification should be paid attention to, and treatment should be individualized for elderly patients.

In utero and postnatal exposure to environmental tobacco smoke, blood pressure, and hypertension in children: the Seven Northeastern Cities study.

To evaluate the association of environmental tobacco smoke (ETS) exposure with hypertension and blood pressure (BP) in children, a sample of 9,354 children, aged 5-17 years, was studied from seven northeastern cities of China in 2012-2013. The results showesd that significant associations were observed for hypertension with ETS exposure in utero [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.18-1.57], with current major ETS exposure from fathers (1.38, 1.21-1.57) or anyone (1.26, 1.12-1.42), and with intensity of ETS exposure greater than 1 cigarette per day (ORs ranged from 1.20 to 1.35). For SBP, significant associations were only observed in children with major ETS exposure from father and with cigarettes smoking >10/day. When stratified by sex, more significant associations were found in girls than in boys. In conclusion, prenatal and postnatal ETS exposure was significantly associated with increased odds of hypertension in children, especially in girls.

Clinic-pathologic Features and Prognostic Analysis of Thyroid Cancer in the Older Adult: A SEER Based Study.

Purpose: Age at diagnosis has been identified as a major determinant of thyroid cancer-specific survival. But the cut-off value for age was controversial. The interaction among gender, age and histologic subtypes needed to be answered. Methods: We identified 59,892 thyroid cancer (TC) patients from the Surveillance, Epidemiology, and End Results (SEER) database. We divided the patients into the following three groups according to age: 20-44 years (young), 45-64 years (middle-aged), and ≥ 65 years (elderly). Logistic regression model was used to identify factors relating to prognosis in elderly patients. Multivariable Cox regression model identified potential prognostic factors. All statistical tests were two-sided. Results: Elderly patients had significantly worse prognosis than the other two groups, P=0.001. Elderly patients had higher proportion of male gender, advanced tumor grade, follicular subtype and advanced tumor stage. There was no survival difference for elderly patients to receive lobectomy and total thyroidectomy, P=0.852. Cox proportional hazards regression model showed that gender, marital status, histology, tumor grade, tumor size, TNM stage, surgery and radiotherapy were all independent prognostic factors in the multivariable analysis. Male patients with TC had worse prognosis than their female counterparts in differentiated tumor but not in undifferentiated tumor. There were more patients of larger tumor, advanced TNM stage and histologic subtypes in male patients. Conclusions: In conclusion, there were a series of factors contributing to the poor prognosis in elderly patients including clinic-pathologic factors and therapy selection. There was no survival difference for elderly patients to receive lobectomy and total thyroidectomy.

Clinical analysis of antithrombotic treatment and occurrence of stroke in elderly patients with nonvalvular persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in elderly patients and is associated with ischemic stroke. We sought to explore the current status of antithrombotic therapy in elderly patients with nonvalvular persistent AF. METHODS: This is a retrospective study and data were collected from the First Hospital of China Medical University. A total of 300 patients were enrolled from January 2015 to June 2017. Patients were divided into two groups: Group 1 (from 65-74) and Group 2 (older than 75). The status of antithrombotic treatment was recorded. Follow-ups were done at 7, 90 , 180, and 360 days after discharge. The occurrence of stroke was recorded. RESULTS: For 287 patients with a CHA2 DS2 -VASc score ≥2, 41.10% received oral anticoagulants (OAC), 27.20% received new oral anticoagulants (NOAC), 42.20% received antiplatelet agents, 16.70% received no antithrombotic treatment. From 2015 to the first half 2017, the ratio of OAC was 25.90%, 51.89%, and 49.30%, respectively; ratio of NOAC were 16.90%, 30.19%, and 39.10%, respectively. During the four times follow-up, percentage of patients who had good treatment compliance was 65%, 49.2%, 38.5%, and 25% stroke rate was 6.7% in total 300 patients. Logistic regression analysis showed age older than 75 (odds ratio [OR] 4.812), prior stroke (OR 4.109) were risk factors of stroke, and OAC treatment (OR 0.021) could prevent stroke. CONCLUSION: Ratio of antithrombotic therapy in elderly patients with nonvalvular persistent AF was low and drug compliance was poor. Age, prior history of stroke, and OAC treatment are the important predictive factors of stoke in elderly patients.

Clinical-pathological Characteristics and Prognostic Factors for Papillary Thyroid Microcarcinoma in the Elderly.

Background: The incidence of papillary thyroid microcarcinoma (PTMC) has increased dramatically over the past three decades worldwide. The annual rate of increase in the elderly (≥65) PTMC patients is 1.4 times higher than that in the adult (<65) PTMC patients. The aim of the present study is to identify the clinical-pathological characteristics and prognostic factors in the elderly PTMC patients. Methods: The source population is PTMC patients whose information is available in the Surveillance, Epidemiology and End Results (SEER) database (2004-2013). We analyzed specific selected clinical-pathological parameters and prognostic factors for the PTMC patients who were aged 65 or above (N=4812). Results: Within the elderly group, the male patients, in comparison to the females, had a higher percentage of lymph-node metastases (5.29% vs. 12.27%, P < 0.001), distant metastasis (0.27% vs. 1.07%, P < 0.001), and stage III-IV tumors (9.19% vs. 15.85%, P < 0.001). Moreover, the elderly patients had a lower median cause-specific survival (CSS) compared with the adult patients (P < 0.001). Stage III-IV disease (hazard ratio (HR): 8.064, P < 0.001) was a strong risk factor for PTMC CSS. Being female (HR: 0.440, P = 0.011), total thyroidectomy (HR: 0.057, P = 0.001), and lobectomy (HR: 0.058, P < 0.001) were all strong protectors of PTMC CSS. Conclusion: Thyroidectomy improved CSS of the elderly PTMC patients. Compared with thyroid lobectomy, total thyroidectomy did not increase CSS for the elderly PTMC patients. The elderly PTMC patients who received radio therapy did not experience an increase in CSS.

Availability and characteristics of cardiac rehabilitation programmes in China.

OBJECTIVE: Cardiac rehabilitation (CR) improves patient outcomes in cardiovascular disease (CVD), but little is known about its current practice in China. Since China has a high CVD burden, the potential impact of CR is large. We surveyed large hospitals in China to assess the prevalence and characteristics of CR. METHODS: We carried out a cross-sectional survey of 454 large medical centres in China to ascertain the prevalence of CR, perceived barriers to CR and various other characteristics of centres with and without CR programmes. RESULTS: Responses were received from 124 (27%) of the 454 centres surveyed. Of these, only 30 (24%) reported having an operating CR programme. This was true, despite the near universal availability of advanced imaging, coronary stenting and other technologies. Overall, the estimated availability of CR programmes was about 2 programmes per 100 million inhabitants. Centres with CR were more likely than centres without CR to be university or government hospitals, have more inpatient cardiovascular beds and provide secondary CVD prevention services. Perceived barriers to CR included a lack of awareness, training and experience in CR, as well as limited resources for a CR programme. Respondents suggested that educational and training activities could help promote greater implementation of CR in China. CONCLUSIONS: The availability of CR is low (24%) in the large medical centres in China we surveyed, highlighting the importance of efforts to raise awareness of the benefits of CR, to provide CR training to healthcare professionals and to improve CR availability throughout China.