Growth hormone deficiency is common in intracranial tumors, which is usually treated with surgery and radiotherapy. A number of previous studies have investigated the relationship between the growth hormone replacement therapy (GHRT) and risk of tumor recurrence/ progression; however, the evidence remains controversial. We conducted a meta-analysis of published studies to estimate the potential relation between GHRT and intracranial tumors recurrence/progression. Three comprehensive databases, PUBMED, EMBASE, and Cochrane Library, were researched with no limitations, covering all published studies till the end of July, 2014. Reference lists from identified studies were also screened for additional database. The summary relative risks (RR) and 95 % confidence intervals (CI) were calculated by fixed-effects models for estimation. Fifteen eligible studies, involving more than 2232 cases and 3606 controls, were included in our meta-analysis. The results indicated that intracranial tumors recurrence/progression was not associated with GHRT (RR 0.48, 95 % CI 0.39-0.56), and for children, the pooled RR was 0.44 and 95 % CI was 0.34-0.54. In subgroup analysis, risks of recurrence/progression were decreased for craniopharyngioma, medulloblastoma, astrocytoma, glioma, but not for pituitary adenomas, and non-functioning pituitary adenoma (NFPA), ependymoma.Results from our analysis indicate that GHRT decreases the risk of recurrence/progression in children with intracranial tumors, craniopharyngioma, medulloblastoma, astrocytoma, or glioma. However, GHRT for pituitary adenomas, NFPA, and ependymoma was not associated with the recurrence/progression of the tumors. GH replacement seems safe from the aspect of risk of tumor progression.

Background Population-based analysis for the short-term non-bladder cancer related mortality among patients with non-metastatic bladder cancer is currently lacking. The objective of the current study was to assess and quantify cause of death after bladder cancer diagnosis. Methods The custom Surveillance, Epidemiology, and End Results (SEER) dataset for standardized mortality ratios (SMRs) was utilized to identify 24,074 patients who were diagnosed with nonmetastatic (M0) bladder cancer from 2014 to 2015. SMRs for causes of death were calculated. Risk factors for bladder cancer-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were determined using either multivariable Cox or competing risk regression models. Results Among all the 4179 (17.4%) deaths occurred during the follow-up period, almost half of them (44.2%) were attributed to non-bladder cancer cause, including second non-bladder cancer (10%) and other non-cancer causes (34.2%). The most common noncancer causes of death were heart diseases followed by chronic obstructive pulmonary disease. Patients had a higher risk of death from second malignancies (SMR, 1.59; 95% CI, 1.47–1.74) compared with death from first malignancies in the US general population, and also had higher risks of death from heart diseases (SMR, 1.29; 95% CI, 1.18–1.40) and chronic obstructive pulmonary disease (SMR, 1.52; 95% CI, 1.29–1.79) compared with the US general population. Additionally, some risk factors for competing second malignancies or noncancer mortality were determined, such as age, gender, marital status and treatment modalities. Conclusions Death from non-bladder cancer cause contributed to almost half of all deaths in bladder cancer survivors during the short-term follow-up period. These findings can inform medical management and assist clinicians in counseling those survivors regarding their short-term health risks.

Gemcitabine (GEM) is one of the first choice drugs for treating bladder cancer. In this study, we loaded M1 macrophage-derived exosomes (M1-Exo) with GEM by ultrasonication technique to derive an M1-Exo-GEM drug delivery system, and then explored its effects on bladder cancer. After inducing M1 polarization of macrophages in vitro, ultracentrifugation was performed to obtain M1-Exo, followed by construction of M1-Exo-GEM via ultrasonication technique. Mouse bladder cancer MB49 cells were chosen for study. CCK-8, PI staining and flow cytometry (FCM) assays were employed to assess the cell viability and apoptosis level. Inflammatory cytokines were detected by ELISA, while the protein expressions of Bcl-2, Bax and Caspase-3 were examined through Western-Blotting. After injecting M1-Exo-GEM into the tumor-bearing mouse model, the pathological changes were observed by H&E staining, the cancer cell damage was detected by TUNEL staining, and the apoptosis pathway activation was analyzed through immunohistochemical (IHC) staining and protein expression assays for Caspase-3 and Bax. Our results showed that M1-Exo and GEM had cytotoxic effects on MB49 cells, which increased the apoptosis level and the inflammatory cytokine expressions. Compared to M1-Exo and GEM, M1-Exo-GEM was significantly more cytotoxic to MB49 cells while markedly up-regulating the expressions of inflammatory cytokines. In the tumor-bearing mouse model, M1-Exo-GEM significantly inhibited tumor growth and damaged tumor cells, which outperformed GEM. Meanwhile, it also increased the tissue levels of inflammatory cytokines. This study finds that the drug delivery system composed of M1-Exo and GEM can act synergistically with GEM to exert cytotoxicity and induce inflammatory damage of bladder cancer cells.

BackgroundAcute kidney injury (AKI) is the most common major complication of cardiac surgery field. The purpose of this study is to investigate the association between acute kidney injury and the prognoses of cardiac surgery patients in the Medical Information Mart for Intensive Care III (MIMIC-III) database.MethodsClinical data were extracted from the MIMIC-III database. Adult (≥18 years) cardiac surgery patients in the database were enrolled. Multivariable logistic regression analyses were employed to assess the associations between acute kidney injury (AKI) comorbidity and 30-day mortality, 90-day mortality and hospital mortality. Different adjusting models were used to adjust for potential confounders.ResultsA total of 6,002 patients were involved, among which 485 patients (8.08%) had comorbid AKI. Patients with AKI were at higher risks of prolonged ICU stay, hospital mortality, 90-day mortality (all P < 0.001), and 30-day mortality (P = 0.008). AKI was a risk factor for hospital mortality [Model 1, OR (95% CI) = 2.50 (1.45–4.33); Model 2, OR (95% CI) = 2.44 (1.48–4.02)], 30-day mortality [Model 1, OR (95% CI) = 1.84 (1.05–3.24); Model 2, OR (95% CI) = 1.96 (1.13–3.22)] and 90-day mortality [Model 1, OR (95% CI) = 2.05 (1.37–3.01); Model 2, OR (95% CI) = 2.76 (1.93–3.94)]. Higher hospital mortality, 30-day mortality and 90-day mortality was observed in higher KDIGO grade for cardiac surgery patients with AKI (all P < 0.05).ConclusionComorbid AKI increased the risk of hospital mortality, 30-day mortality, and 90-day mortality of cardiac surgery patients in the MIMIC-III database.

Long noncoding RNAs play an important regulatory role in the development and progression of tumors. Our study found that LINC00478 was upregulated in clear cell renal cell carcinoma (ccRCC), so we made an in-depth exploration into its mechanism. In Caki-2 cells, we established the oe-LINC00478 cell line overexpressing LINC00478, and established underexpressing sh-LINC00478 cell line by short hairpin RNA silencing. The abilities of oe-LINC00478 cell invasion and metastasis were significantly enhanced, and the cell proliferative potential was also improved. The cellular expressions of PBX3, CDCA8, and CDK2 were upregulated, while in the sh-LINC00478 cells, the proliferative potential and metastatic and invasive abilities were weakened. Similarly, we established the PBX3-overexpressing oe-PBX3 cell line and the PBX3-underexpressing sh-PBX3 cell line, finding that the PBX3 overexpression enhanced the metastatic and invasive abilities of Caki-2 cells.When we overexpressed LINC00478 in PBX3-knockout Caki-2-PBX3 −/− cells, no significant changes were noted in the metastatic or invasive ability. Through RNA pull-down and RNA-binding protein immunoprecipitation assays, we found that LINC00478 could facilitate the transcription-translation processes of PBX3 by binding to it, thus further promoting the expression of downstream cyclins to exert its action. In animal experimentation, the oe-LINC00478 and sh-LINC00478 Caki-2 cells were separately seeded, revealing that the tumor volume was significantly larger in the oe-LINC00478 group than in the sh-LINC00478 group. This study finds that by promoting the PBX3 transcription, LINC00478 can further regulate the expressions of downstream cyclins, thereby facilitating the metastasis and invasion of ccRCC.