BackgroundGastrointestinal cancers (GICs) mainly including esophageal, gastric and colorectal cancer, are the most common cause of cancer-related death and lead into high mortality worldwide. We performed this systematic review and meta-analysis to elucidate relationship between multiple microRNAs (miRs) expression and survival of GIC patients.MethodsWe searched a wide range of database. Fixed-effects and random-effects models were used to calculate the pooled hazard ratio values of overall survival and disease free survival. In addition, funnel plots were used to qualitatively analyze the publication bias and verified by Begg's test while it seems asymmetry.Results60 studies involving a total of 6225 patients (1271 with esophageal cancer, 3467 with gastric cancer and 1517 with colorectal cancer) were included in our meta-analysis. The pooled hazard ratio values of overall survival related to different miRs expression in esophageal, gastric, colorectal and gastrointestinal cancer were 2.10 (1.78-2.49), 2.02 (1.83-2.23), 2.54 (2.14-3.02) and 2.15 (1.99-2.31), respectively. We have identified a total of 59 miRs including 23 significantly up-regulated expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, etc.) and 36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p, miR-760, miR-206, miR-26a, miR-200b, miR-185, etc.) correlated with poor prognosis in GIC patients. Moreover, 35 of them revealed mechanisms.ConclusionOverall, specific miRs are significantly associated with the prognosis of GIC patients and potentially eligible for the prediction of patients survival. It also provides a potential value for clinical decision-making development and may serve as a promising miR-based target therapy waiting for further elucidation.

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Survival rates for patients with gastric cancer, especially the advanced form, remain poor and the development of targeted treatments is hampered by a lack of efficient biological targets. Poly( rC ) binding protein 2 ( PCBP 2) is an RNA ‐binding protein that contributes to mRNA stabilization, translational silencing and enhancement and it has been implicated as a promoter of gastric cancer growth. In the present study, we demonstrated that the expression level of PCBP 2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues. A high level of PCBP 2 was correlated with worse postoperative relapse‐free survival and overall survival rates of gastric cancer patients. Small hairpin RNA ‐mediated depletion of PCBP 2 dramatically decreased the viability of gastric cancer cells. Cyclin‐dependent kinase 2 ( CDK 2) was positively regulated by PCBP 2 via a direct 3′ UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. CDK 2 mediated the promoting role of PCBP 2. These results suggest that PCBP 2 acts as an oncogene in human gastric cancer cells and that functionally depleting PCBP 2 could be considered as a potential target for gastric cancer therapy.

Background: There are substantial advances in diagnosis and treatment for idiopathic pulmonary fibrosis (IPF), but without much evidence available on recent mortality and survival trends.Methods: A narrative synthesis approach was used to investigate the mortality trends, then meta-analyses for survival trends were carried out based on various time periods.Results: Six studies reported the mortality data for IPF in 22 countries, and 62 studies (covering 63 307 patients from 20 countries) reported survival data for IPF. Age-standardised mortality for IPF varied from approximately 0.5 to 12 per 100 000 population per year after year 2000. There were increased mortality trends for IPF in Australia, Brazil, Belgium, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Lithuania, Netherlands, Poland, Portugal, Spain, Sweden, and UK, while Austria, Croatia, Denmark, Romania, and US showed decreased mortality trends. The overall 3-year and 5-year cumulative survival rates (CSRs) were 61.8% (95% CI, 58.7–64.9; I2=97.1%) and 45.6% (95% CI, 41.5–49.7; I2=97.7%), respectively. Prior to 2010, the pooled 3-year CSRs was 59.9% (95% CI, 55.8–64.1; I2>95.8%), then not significantly (p=0.067) increased to 66.2% (95% CI, 62.9–69.5; I2=92.6%) in the 2010s decade. After excluding three studies in which no patients received antifibrotics after year 2010, the pooled 3-year CSRs significantly (p=0.039) increased to 67.4% (95% CI, 63.9–70.9; I2=93.1%) in the 2010s decade.Discussion: IPF is a diagnosis associated with high mortality. There was no observed increasing survival trend for patients with IPF before year 2010, with then a switch to an improvement, which is probably multifactorial.

Upregulation of human epididymis protein 4 (HE4) is often observed in different types of cancers, including gastric cancer (GC), but the association of elevated HE4 level with radiation resistance in GC remains unclear. The expression of HE4 and hypoxia-inducible factor 1α subunit (HIF1α) was assessed in GC patient samples and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to reveal the regulation between HE4 and HIF1α. Stable HE4 knockdown and HIF1α overexpression were introduced into GC cell lines to study the role of HE4 in the resistance of GC to radiation therapy. Colony formation assay and the xenograft mouse model were used to investigate the effects of radiation on GC cells. HE4 and HIF1α were upregulated in both GC patient tissues and GC cells. Hypoxia and HIF1α upregulated HE4 by directly targeting the hypoxia response element in its promoter region. Stable HE4 knockdown significantly sensitized GC cells and xenograft tumors to radiation. HIF1α overexpression markedly elevated the radiation resistance of GC cells, which was almost completely abolished by HE4 knockdown. Hypoxia-induced upregulation of HE4 is responsible for resistance to radiation therapy of GC, suggesting that HE4 knockdown or inhibition, combined with radiation therapy, holds great potential in the clinical treatment of GC.

Gastrointestinal cancers (GICs) are a huge threat to human health, which mainly include esophageal, gastric, and colorectal cancers. The purpose of this study was to clarify the prognostic value of long noncoding RNAs (lncRNAs) in GICs. A total of 111 articles were included, and 13103 patients (3123 with esophageal cancer, 4972 with gastric cancer, and 5008 with colorectal cancer) were enrolled in this study. The pooled hazard ratio (HR) values and corresponding 95% confidence interval (95% CI) of overall survival (OS) related to different lncRNA expressions in esophageal, gastric, colorectal, and gastrointestinal cancer patients were 1.92 (1.70–2.16), 1.96 (1.77–2.16), 2.10 (1.87–2.36), and 2.00 (1.87–2.13), respectively. We have identified 74 lncRNAs which were associated closely with poor prognosis of GIC patients, including 58 significantly upregulated lncRNA expression and 16 significantly downregulated lncRNA expression. In addition, 47 of the included studies revealed relative mechanisms and 12 of them investigated the correlation between lncRNAs and microRNAs. Taken together, this meta-analysis supports that specific lncRNAs are significantly related to the prognosis of GIC patients and may serve as novel markers for predicting the prognosis of GIC patients. Furthermore, lncRNAs may have a promising contribution to lncRNA-based targeted therapy and clinical decision-making in the future.

Background and ObjectiveLittle is known about the association between ambient air pollution and idiopathic pulmonary fibrosis (IPF) in areas with lower levels of exposure. We aimed to investigate the impact of air pollution on lung function and rapid progression of IPF in Australia.MethodsParticipants were recruited from the Australian IPF Registry (n = 570). The impact of air pollution on changes in lung function was assessed using linear mixed models and Cox regression was used to investigate the association with rapid progression.ResultsMedian (25th–75th percentiles) annual fine particulate matter (<2.5 μm, PM2.5) and nitrogen dioxide (NO2) were 6.8 (5.7, 7.9) μg/m3 and 6.7 (4.9, 8.2) ppb, respectively. Compared to living more than 100 m from a major road, living within 100 m was associated with a 1.3% predicted/year (95% confidence interval [CI] −2.4 to −0.3) faster annual decline in diffusing capacity of the lungs for carbon monoxide (DLco). Each interquartile range (IQR) of 2.2 μg/m3 increase in PM2.5 was associated with a 0.9% predicted/year (95% CI −1.6 to −0.3) faster annual decline in DLco, while there was no association observed with NO2. There was also no association between air pollution and rapid progression of IPF.ConclusionLiving near a major road and increased PM2.5 were both associated with an increased rate of annual decline in DLco. This study adds to the evidence supporting the negative effects of air pollution on lung function decline in people with IPF living at low‐level concentrations of exposure.

Objectives Several studies have compared outcomes of peritoneal dialysis (PD) between elderly and non-elderly patients but with variable results. We hereby designed this review to compare mortality, peritonitis, and technique survival between elderly and non-elderly patients on PD. Methods PubMed, Embase, and Google Scholar were searched for studies comparing outcomes of PD between elderly and non-elderly patients. The last search date was 14th July 2021. Results Fourteen studies were included. 12 studies defined the elderly as ≥65 years of age and these were included in the meta-analysis. Pooled analysis of crude (RR: 2.45 95% CI: 1.36, 4.40 I2 = 97% p = 0.003) and adjusted data (HR: 2.80 95% CI: 2.45, 3.09 I2 = 0% p<0.00001) indicated a statistically significant increased risk of mortality amongst elderly patients as compared to non-elderly patients. Meta-analysis of four studies demonstrated a statistically significant increased risk of peritonitis in the elderly (RR: 1.56 95% CI: 1.18, 2.07 I2 = 76% p = 0.002). Pooled analysis demonstrated no statistically significant difference in technique survival between the two groups (RR: 0.95 95% CI: 0.86, 1.05 I2 = 86% p = 0.32). Conclusion Elderly patients on PD have a significantly increased risk of mortality as compared to non-elderly patients. The risk of peritonitis is also significantly increased in older adults but the increased age has no impact on technique survival. Further studies are needed to strengthen our conclusions.