Background: To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. Methods: Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. Results: A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16-1.39, P < 0.001, I 2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15-1.40, P < 0.001, I 2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer. Conclusions: Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

Multiple systematic reviews on greenspace and health outcomes exist, but the overall evidence base remains unclear. Therefore, we performed an umbrella review to collect and appraise all relevant systematic reviews of epidemiological studies on greenness exposure and health. We searched PubMed, Embase, and Web of Science from inception to June 28, 2021, and screened references of relevant articles. Systematic reviews with or without meta-analyses of epidemiological studies that examined the associations of greenness with any health outcome were included. Two independent investigators performed study selection and data extraction. We also evaluated the methodological quality of the included systematic reviews using the “Assessing the Methodological Quality of Systematic Reviews 2” checklist. A total of 40 systematic reviews and meta-analyses were included, of which most were cross-sectional studies conducted in high-income countries. Greenspace exposure was estimated with various objective and subjective parameters. Beneficial associations of greenspace with all-cause and stroke-specific mortality, CVD morbidity, cardiometabolic factors, mental health, low birth weight, physical activity, sleep quality, and urban crime were observed. No consistent associations between greenspace and other health outcomes (e.g., cancers) were observed. Most of the included systematic reviews and meta-analyses had one or more limitations in methodology. Our findings provide supportive evidence regarding the beneficial effects of greenspace exposure on some aspects of human health. However, the credibility of such evidence was compromised by methodological limitations. Better performed systematic reviews and meta-analyses as well as longitudinal designed primary studies are needed to validate this conclusion.

Several reviews have been conducted to assess the association between greenspace and overweight or obesity, but the conclusions were inconsistent. However, an updated comprehensive review and meta-analysis is warranted, because several high-quality papers have been published more recently. The objectives of this study are to systematically and quantitatively assess the evidence for a link between greenspace with overweight/obesity and to make specific recommendations for further research. We searched three English language databases, four Chinese language databases and the reference lists of previously published reviews for epidemiological studies on greenspace and overweight/obesity published before January 2020. We developed inclusion criteria, screened the literature and extracted key data from selected papers. We assessed methodological quality and risk of bias, and we graded the credibility of the pooled evidence. We also performed sensitivity analyses. Fifty-seven records met our inclusion criteria and were included in the study. Most studies were cross-sectional designs (81%) and were from developed nations (88%). More than half (55%) of the included studies found beneficial associations between greenspace and overweight/obesity in overall or subpopulations. Our meta-analytical results showed that greater normalized difference vegetation index was associated with lower odds of overweight/obesity in a statistically significant fashion (odds ratio [OR]: 0.88; 95% CI: 0.84, 0.91) but not residential proximity to greenspace (OR: 0.99; 95% CI: 0.99, 1.00), proportion of greenspace (OR: 0.96; 95% CI: 0.85, 1.08) or number of parks in an area (OR: 0.99; 95% CI: 0.97, 1.01). However, we detected high between-study heterogeneity in two of the four meta-analyses, which reduced the credibility of the pooled evidence. Current evidence indicates that there might be an association between greater access to greenspace and lower odds of overweight/obesity. However, additional high-quality studies are needed to more definitively assess the evidence for a causal association.

BackgroundVimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC.MethodsDatabases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) ‘vimentin’ OR ‘vim’ OR ‘vmt’ OR ‘vm’ OR ‘hel113’ OR ‘ctrct30’ and (2) ‘pulmon*’ OR ‘lung’ OR ‘alveolar’ and (3) ‘cancer’ OR ‘carcinoma’ OR ‘tumor’ OR ‘adenocarcinoma’ OR ‘squamous’ OR ‘neoplas*’ OR ‘malignan*’. The data were combined by random effect model and the H value and I2 were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0.ResultsThirty-two qualified studies (4118 cases) were included in the current meta-analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315–2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906–1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921–1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985–1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098–1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664–2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987–5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063–11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857–3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052–2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397–3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05).ConclusionAn overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC.

The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00-0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC.

BackgroundGrowing evidence has demonstrated that Ki-67/MIB-1 has an effect on the clinical progression and prognosis in cancers. However, the diagnostic and prognostic values of Ki-67/MIB-1 in thyroid cancer remain unclear.Materials and methodsThe meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were retrieved from PubMed, EBSCO, EMBASE, ISI Web of Science, China National Knowledge Infrastructure, WanFang and Chinese VIP databases. MetaDiSc and STATA12.0 were used to analyze the meta-analysis. Fixed-effect analysis and random-effect analysis were applied to pool the relative ratio based on heterogeneity in this meta-analysis.ResultsIn the meta-analysis, 51 eligible studies were included. The pooled sensitivity of Ki-67/MIB-1 was 0.61 (95% confidence interval [CI]: 0.59–0.63) and specificity was 0.75 (95% CI: 0.74–0.77) in thyroid cancer. The pooled positive likelihood ratio was 3.19 (95% CI: 2.30–4.42) and negative likelihood ratio was 0.43 (95% CI: 0.35–0.54). In the diagnosis of thyroid cancer, the pooled diagnostic odds ratio of Ki-67/MIB-1 was 8.54 (95% CI: 5.03–14.49). The area under the symmetric receiver operating characteristic curve was 0.804 (standard error =0.031). Our results showed that there were statistical associations between Ki-67/MIB-1 and age (odds ratio [OR] =1.71, 95% CI: 1.14–2.57, P=0.010), tumor size (OR =1.86, 95% CI: 1.17–2.96, P=0.008), lymph node metastasis (OR =2.49, 95% CI: 1.42–4.39, P=0.002), metastasis status (OR =6.96, 95% CI: 2.46–19.69, P<0.001), tumor node metastasis stage (OR =6.56, 95% CI: 3.80–11.34, P<0.001) and extrathyroid extension (OR =1.91, 95% CI: 1.27–2.87, P=0.002). Furthermore, thyroid cancer patients with a high level of Ki-67/MIB-1 had a worse disease-free survival as compared to patients with a low level of Ki-67/MIB-1 (hazard ratio =5.19, 95% CI: 3.18–8.46, P<0.001). Also, Ki-67/MIB-1 was found to be associated with increased risk of mortality (hazard ratio =3.56, 95% CI: 1.17–10.83, P=0.025).ConclusionOur results demonstrated that Ki-67/MIB-1 might act as a potential factor in diagnosing thyroid cancer in Chinese. Also, the meta-analysis indicated that Ki-67/MIB-1 might have an effect on prognosis in non-Chinese thyroid cancer patients.

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Scholars are striving to apply molecular biology involving long non-coding RNA (lncRNA) in the prognostication of papillary thyroid cancer (PTC). However, the clinical role of lncRNAs in the prognostic setting of PTC is still unclear. Herein, a comprehensive inquiry was performed to screen lncRNA expression profiling with 507 PTC patients from The Cancer Genome Atlas RNA-sequencing datasets. A total of 734 lncRNAs were detected to be aberrantly expressed, among which three novel lncRNAs including AC079630.2, CRNDE and CTD-2171N6.1 were markedly related to the progression and survival of PTC. Furthermore, the aberrant expression of these lncRNAs could be verified by other cohorts from gene expression omnibus (GEO) as detected by microarrays. Next, we established a three-lncRNA signature and divided the PTC patients into two subgroups of high- and low-risk. Interestingly, patients with high-risk tended to gain obviously poorer outcome. Most importantly, this three-lncRNA signature was an independent biomarker to predict the patient survival of PTC. The accurate molecular roles of these three lncRNAs remains unclarified and warrants further characterization, but our current data propose that they might play pivotal roles in PTC tumorigenesis and more importantly, these novel lncRNAs are closely related to patients’ survival. These discoveries will have far-reaching consequences with respect to molecular prediction of PTC.