Benefits of and barriers to telehealth for the informal caregivers of elderly individuals in rural areas: A scoping review.

INTRODUCTION: Maintaining care for elderly individuals in rural areas is heavily dependent on support from informal caregivers. Many informal caregivers of the elderly in rural areas feel burdened and urgently require professional support. Interests in telehealth that can provide support irrespective of geographical location have been increasing. OBJECTIVE: To identify the benefits of and barriers in telehealth engagement for rural caregivers to provide evidence for service improvement. DESIGN: A scoping review method was used following PRISMA-ScR guidelines and Arksey and O'Malley's five-stage framework. Five databases were searched. The search terms were chosen based on the target intervention (i.e. telehealth), target population (caregivers of elderly individuals) and target context (rural areas). Two authors independently assessed the eligibility of studies and extracted data from eligible studies. FINDINGS: Of 4220 retrieved studies, 19 articles met the inclusion criteria. This study identified four benefits of and two barriers to telehealth for rural caregivers. Four subthemes were identified as the key benefits in using telehealth for caregivers: decrease in psychological distress, increase in care efficiency, increase in social support and increase in access to resources, while inadequate telehealth infrastructures and caregivers' own reasons were the primary barriers in using telehealth for those populations. CONCLUSIONS: Telehealth was shown to significantly benefit rural caregivers. Future research can be designed and conducted for overcoming the barriers to telehealth. Additionally, the benefits identified by this review need to be translated from research into practice for rural caregivers' care.

Tanshinone I restrains osteosarcoma progression by regulating circ_0000376/miR-432-5p/BCL2 axis.

Circular RNAs (circRNAs) have been identified as important regulators in cancer progression. Nevertheless, little is known about the biological function of circ_0000376 in the progression of osteosarcoma (OS). Cell viability, colony formation ability, apoptosis, and motility were analyzed by Cell Counting Kit-8 assay, colony formation assay, flow cytometry, and transwell assays. Cellular glycolytic metabolism was analyzed using commercial kits. RT-qPCR and Western blot assay were performed to analyze RNA and protein expression in OS tissues and cells. Starbase software was used to establish circRNA-microRNA (miRNA)-messenger RNA linkage, and intermolecular interaction was verified by dual-luciferase reporter assay. Xenograft tumor assay was conducted to analyze the effects of Tanshinone I (Tan I) and circ_0000376 on xenograft tumor growth in vivo. Tan I treatment suppressed the viability, migration, invasion, and glycolysis and triggered the apoptosis of OS cells. Tan I treatment markedly down-regulated circ_0000376 expression in OS cells. The addition of circ_0000376 plasmid largely rescued the malignant behaviors of OS cells upon Tan I exposure. Circ_0000376 interacted with miR-432-5p in OS cells. Circ_0000376 overexpression-mediated protective effects in Tan I-induced OS cells were partly attenuated by the accumulation of miR-432-5p. miR-432-5p bound to the 3' untranslated region (3'UTR) of B-cell leukemia/lymphoma 2 (BCL2) in OS cells. miR-432-5p interference-induced effects in Tan I-treated OS cells were partly overturned by the silence of BCL2. Circ_0000376 can act as miR-432-5p sponge to up-regulate BCL2 expression in OS cells. Circ_0000376 silencing contributed to the anti-tumor effect of Tan I on the growth of xenograft tumors in vivo. Tan I exerted an anti-tumor role in OS progression by targeting circ_0000376/miR-432-5p/BCL2 axis.

The Cost-Effectiveness of Pulmonary Rehabilitation for COPD in Different Settings: A Systematic Review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality rates. COPD impairs body functioning, reduces quality of life, and creates a great economic burden for society. Pulmonary rehabilitation (PR) has become an important nonpharmacological treatment for COPD. This paper systematically reviews economic evaluations of PR in COPD patients in different settings. OBJECTIVES: We aimed to understand the cost-effectiveness of PR in different settings for COPD to provide economic evidence for decision-makers. METHODS: We searched eight databases from their inception to 23 November 2019. The results were presented in terms of an incremental cost-effectiveness ratio (ICER), and the decision uncertainty was expressed by cost-effectiveness acceptability curves (CEACs). We used the Consensus on Health Economic Criteria to assess study quality. RESULTS: This review included ten studies that matched the selection criteria. Five studies compared PR with usual care in primary healthcare or outpatient departments. Two studies compared community-based PR with hospital PR or usual care. In the other studies, PR was mainly carried out at home. Compared with usual care, PR was cost-effective in primary healthcare institutions or outpatient departments. According to CEACs, community-based PR had a 50% probability of cost-effectiveness at £30,000/quality-adjusted life year (QALY) compared with hospital PR in the UK. Based on the ICER, community-based PR was "moderately" cost-effective, with a ratio of €32,425/QALY compared with usual care in the Netherlands. Home-based PR was dominant compared with usual care, and tele-rehabilitation was dominant compared with traditional home PR. CONCLUSIONS: PR conducted in different settings can potentially be cost-effective, as measured using QALY or the Chronic Respiratory Questionnaire (CRQ).

CENPE, PRC1, TTK, and PLK4 May Play Crucial Roles in the Osteosarcoma Progression.

Osteosarcoma (OS) is a cancerous tumor in a bone. We aimed to identify the critical genes involved in OS progression, and then try to elucidate the molecular mechanisms of this disease. The microarray data of GSE32395 was used for the present study. We analyzed differentially expressed genes (DEGs) in OS cells compared with control group by Student's t-test. The significant enriched gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways were analyzed for upregulated genes and downregulated genes, respectively. In addition, a protein-protein interaction (PPI) network was constructed. GO and KEGG enrichment analyses were conducted for genes in the PPI network. In total, 183 DEGs, including 100 upregulated DEGs and 83 downregulated DEGs were screened. The upregulated DEGs were significantly enriched in 2 KEGG pathways, such as "Glycosaminoglycan biosynthesis-chondroitin sulfate" and the downregulated DEGs were significantly enriched in 12 pathways, including "cell adhesion molecules," "pentose phosphate pathway" and "allograft rejection." GO enrichment analysis indicated that the upregulated DEGs were significantly involved in biological process, such as "multicellular organismal metabolic process" and "limb morphogenesis," while the downregulated DEGs were significantly enriched in biological process, such as "Positive regulation of pathway-restricted SMAD protein phosphorylation." The PPI network included 84 interactions and 51 nodes. The "glycosaminoglycan biosynthesis-chondroitin sulfate pathway," "microtubule motor activityfunction," and "regulation of mitosis process" were significantly enriched by genes in PPI network. In particular, CENPE, PRC1, TTK, and PLK4 had higher degrees in the PPI network. The interactions between TTK and PLK4 as well as CENPE and PRC1 may involve in the OS development. These 4 genes might be possible biomarkers for the treatment and diagnosis of OS.

Symptom Clusters and Health-related Quality of Life in Chinese patients with Chronic Obstructive Pulmonary Disease.

This study aimed to identify symptom clusters of chronic obstructive pulmonary disease (COPD) and to examine the relationship between symptom clusters and health-related quality of life (HRQoL). It included 154 hospitalized patients with COPD. The majority of the participants (88.6%) were aged 60 years and above, and the numbers of men and women were approximately equal (men: 55.2%). The Charlson Comorbidity Index (CCI), the Memorial Symptom Assessment Scale (MSAS), and the Chinese version of the Clinical COPD Questionnaire (CCQ) were used to evaluate comorbidity, participant's symptoms, and HRQoL, respectively. Five symptom clusters were identified using exploratory factor analysis, and symptom clusters, especially the Psychological, Pain and Fatigue, GI, and Dyspnea-Sweat symptom clusters, had negative effects on HRQoL in patients with COPD. Understanding the patterns and occurrences of symptom clusters could be essential for developing effective interventions to manage COPD symptoms and improve the patients' HRQoL.

Association of cardiovascular risk factor clustering and prehypertension among adults：Results from the China health and retirement longitudinal study baseline.

Background: Prehypertension is common in China, but its causes and associated factors have not been well studied. This study aimed to examine the age and gender-specific associations between CVD risk factor clustering and prehypertension among adults in China.Methods: This cross-sectional study used data from participants (n = 8735) aged over 45 in the China Health and Retirement Longitudinal Study (CHARLS) Baseline conducted from 2011-2012. The participants' data were collected using standard questionnaires, anthropometric, and biochemical tests. Logistic regression analyses were used to examine the associations between cardiovascular risk factors, their clustering and prehypertension.Results: Overall, 21.1%, 39.5%, 27.6% and 11.8% participants had 0, 1, 2, ≥ 3 CVD risk factors in prehypertension group, respectively. Diabetes and overweight/obesity were significantly associated with prehypertension (OR, 1.24; 95% confidence interval [CI], 1.06-1.44; OR, 1.55; 95% CI, 1.38-1.75) in the overall population, and diabetes was associated with prehypertension only in men (OR, 1.26; 95% CI, 1.00-1.58) and older adults (OR, 1.32; 95% CI, 1.03-1.69). Moreover, participants with 1, 2 and ≥3 risk factors had increased odds of having prehypertension (OR, 1.29; 95% CI, 1.12-1.49; OR, 1.59; 95% CI, 1.31-1.78; OR, 2.05; 95% CI, 1.66-2.53, respectively) and existed dose-response relationship, regardless of age and gender.Conclusions: This study indicated that CVD risk factor clustering was significantly associated with prehypertension and hypertension. These results provide valuable information for health professionals to better understand the impact of CVD risk factor clustering on prehypertension and hypertension.

Identification of human lactate dehydrogenase A inhibitors with anti-osteosarcoma activity through cell-based phenotypic screening.

Human lactate dehydrogenase A plays a key role in the glycolytic process, the inhibition of the enzyme is therefore considered of interest in developing anticancer therapeutics. However, due to the highly polar nature of hLDHA binding pocket, it is very challenge to discover potent cellular active hLDHA inhibitor. Combined a cell-based phenotypic screening assay with a primary enzymatic assay, we discovered three cellular active hLDHA inhibitors, namely 38, 63, and 374, which reduced MG-63 cell proliferation with IC50 values of 6.47, 2.93, and 6.10 µM, respectively, and inhibited hLDHA with EC50 values of 3.03, 0.63, and 3.26 µM, respectively.

Identification of crucial miRNAs and lncRNAs for ossification of ligamentum flavum.

The present study aimed to screen crucial micro (mi)RNAs and long non­coding (lnc)RNAs involved in the development of ossification of ligamentum flavum (OLF) based on the miRNA­mRNA and lncRNA­miRNA­mRNA competing endogenous (ce)RNA regulatory network analyses, which are rarely reported. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMs) between 4 OLF and 4 healthy controls were identified using two microarray datasets GSE106253 and GSE106256 collected from the Gene Expression Omnibus database. A protein­protein interaction (PPI) network was constructed, followed by calculation of topological characteristics and sub­module analysis in order to obtain hub DEGs. The miRNA­mRNA and lncRNA­miRNA networks that were established based on their interaction pairs, obtained from miRwalk and starBase databases, respectively, were integrated to form the ceRNA network. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The present study screened 828 DEGs, 119 DELs and 81 DEMs between OLF and controls. PPI network and module analyses identified interleukin (IL)10, adenylate cyclase (ADCY)5, suppressor of cytokine signaling (SOCS)3, G protein subunit gamma (GNG) 4, collagen type II α 1 chain (COL2A1) and collagen type XIII α 1 chain (COL13A1) as hub genes. The miRNA­mRNA network analysis demonstrated IL10 could be regulated by miR­210­3p, while COL13A1 and COL2A1 could be modulated by miR­329­3p and miR­222­5p, respectively. lncRNA­miRNA­mRNA ceRNA network analysis identified that small nucleolar RNA host gene 16­hsa­miR­196a­5p­SOCS3, ankyrin repeat and SOCS box containing 16­AS1­hsa­miR­379­5p­GNG4, nuclear enriched abundant transcript 1­has­miR­181b­5p­ADCY5, rhophilin 1­AS1­hsa­miR­299­3p­WNT7B interaction axes may be crucial. DAVID analysis predicted IL10, ADCY5, GNG4 and SOCS3 were involved in 'adaptive immune response', 'Chemokine signaling pathway' and 'regulation of apoptosis' processes, while COL2A1, COL13A1 and WNT7B may be ossification related. In conclusion, the identification of these crucial miRNAs and lncRNAs may be conducive for explaining the pathogenesis of OLF and provide certain natural, endogenous and nontoxic drug targets for the treatment of OLF.

Down-regulation of microRNA-98 promoted apoptosis of TNF-α stimulated human fibroblast-like synoviocytes via up-regulating IL-10.

In this study, we constructed a tumor necrosis factor α (TNF-α)-induced synovial cell inflammatory model using human synoviocytes (HS) cell line to explore the function of miR-98 in rheumatoid arthritis (RA). miR-98 mimics or miR-98 inhibitor were transfected into HS cells to up-regulate or down-regulate the expression of miR-98. The proliferation and apoptosis of HS cells were determined using CCK8 assay and flow cytometry, respectively. TargetScan website was utilized to predict the targets of miR-98. Luciferase assay was carried out to verify that IL-10 is a target of miR-98. Western blot was performed to analyze the expression of IL-10, apoptosis-related and NF-κB signaling pathway-related proteins. Our results demonstrated that the expression of miR-98 was up-regulated in HS cells stimulated by TNF-α. Down-regulation of miR-98 by inhibitor in TNF-α-stimulated HS cells dramatically inhibited cell proliferation and promoted cell apoptosis compared with the miR-98 inhibitor NC group. The protein expression of Bcl-2 was declined while the levels of Bax and Bim were increased by miR-98 inhibitor in TNF-α-stimulated HS cells. IL-10 was predicted and verified as a target of miR-98. qRT-PCR and western blot results revealed that the level of IL-10 was negatively regulated by miR-98. Finally, we identified that down-regulation of miR-98 reduced the expression level of p-p65 and p-IκBα in TNF-α-stimulated HS cells. In summary, our present study demonstrated that down-regulation of miR-98 inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated HS partly by targeting IL-10 and regulating NF-κB signaling pathway, insinuating miR-98 as a candidate biomarker in RA.

Computational Exploration of Natural Compounds to Target Cytosolic Phospholipase A 2 Protein: A Novel Therapeutic Target for Spinal Cord Injury.

BACKGROUND: Cytosolic Phospholipase A2 (cPLA2), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of Spinal Cord Injury (SCI). The expression and activation of Cpla2 are significantly higher in SCI, leading to neuronal death in spinal cord tissue. Novel strategies are needed to substantially reverse the effect of cPLA2 activation; one such strategy is inhibiting cPLA2 by jamming its lipid binding C2 domain. OBJECTIVE: To develop a much needed strategy to treat SCI, we used a Computer Aided Drug Design (CADD) method to discover novel cPLA2 inhibitors. METHODS: we used a natural chemiome database for virtual screening, from which we selected the compounds exhibiting the greatest drug-likeliness properties for molecular docking simulation analysis. RESULTS: We studied the interaction of lead compounds at the atomic level; the results yielded a cPLA2 inhibitor of natural origin with the potential for ameliorating secondary tissue damage and promoting recovery of function after SCI. The top compound, lead 4exibited a binding energy of -10.02 Kcal/mol and formed three hydrogen bonds with the lipid binding C2 domain of the cPLA2 protein. An evaluation of cell cytotoxicity revealed an IC50 for lead4 of 134.2 ± 6.8 µM. An in-vitro analysis of lead4 is indicated anti-apoptotic activity via a decrease in caspase-3 expression. CONCLUSION: We used the CADD method to make a novel lead discovery for the treatment of SCI using compounds of natural origin. The selected natural compounds are non-toxic promising drugs against cPLA2 protein, allowing us to limits our focus on single compound for future in-vitro and invivo testing.

Translation and evaluation of Chinese version of the symptom experience index.

Symptom assessment is crucial for patient care through the entire disease trajectory. Patients often experience multiple symptoms concurrently. The symptom experience index is reliable and valid as an instrument developed in the USA for assessing multiple symptoms and distress. The aim of the study was to translate and evaluate the Chinese version of the instrument in healthy adults and oncology patients. This is a psychometric study with a cross-sectional design. To ensure the semantic equivalence and content validity, an integrative translation method was employed to translate the English version into Chinese language. The participants were recruited during 2014 from a large university, two university-affiliated hospitals and a community in Changchun, China. The Chinese version demonstrated high internal consistency, test-retest reliability and content validity. Construct validity was supported by factor analysis and significant differences of symptom experience scores between healthy and oncology groups. Participants' acceptance of the Chinese version and its ability to collect adequate data among Chinese population provided evidence for using this version among Chinese population. This study provided initial evidence to support the psychometric properties of the Chinese version. The Chinese version demonstrated adequate reliability and validity to assess multiple symptom experience by Chinese populations.

Effects of cytokines and chemokines on migration of mesenchymal stem cells following spinal cord injury.

We investigated the effects of cytokines and chemokines and their associated signaling pathways on mesenchymal stem cell migration after spinal cord injury, to determine their roles in the curative effects of mesenchymal stem cells. This study reviewed the effects of tumor necrosis factor-α, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin like growth factor-1, stromal cell-derived factor and monocyte chemoattractant protein-1, 3 during mesenchymal stem cell migration to damaged sites, and analyzed the signal transduction pathways involved in their effects on mesenchymal stem cell migration. The results confirmed that phosphatidylinositol 3-kinase/serine/threonine protein kinases and nuclear factor-κB play crucial roles in the migration of mesenchymal stem cells induced by cytokines and chemokines.