LINC00858 facilitates formation of hepatic metastases from colorectal cancer via regulating the miR-132-3p/IGF2BP1 axis.

Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.

Comparison of hexaminolevulinate (HAL) -guided versus white light transurethral resection for NMIBC: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We systematically reviewed the effectiveness of hexaminolevulinic acid (HAL) after traditional light cystoscopy vs. only white light cystoscopy (WLC) on nonmuscle-invasive bladder cancer (NMIBC) clinical outcomes. METHODS: Systematic literature searches of PubMed, Embase, Web of Science, and the Cochrane database and reference lists were performed. A total of 12 randomized controlled trials (RCTs) of HAL fluorescent cystoscopy (FC) and WLC vs. white light cystoscopy alone for the diagnosis of initial or recurrent bladder cancer that reported bladder cancer recurrence, progression, recurrence-free survival (RFS), and other effects were selected for review. RESULTS: Our results included 2,775 patients identified for analysis and showed that the HAL group had a lower recurrence rate than the white light cystoscopy group with a statistically significant difference (RR=0.77, 95% CI 0.69-0.85. P < 0.05), and this advantage still existed for patients receiving intravesical chemotherapy. There was also a statistically significant difference in favour of fluorescent cystoscopy in recurrence-free survival and progression rate (HR=0.79, 95% CI 0.67-0.92. P < 0.05, RR = 0.63, 95% CI 0.43-0.94. P < 0.05, respectively). The time to first recurrence was not significantly different from that in the WLC group (SMD=0.73, 95% CI, -0.39-1.85. P = 0.2). And the HAL group did not have a significantly reduced residual tumor rate (RR=0.59, 95% CI 0.23-1.51. P = 0.27). CONCLUSIONS: Fluorescent cystoscopy was associated with a reduced risk of bladder cancer recurrence and reduced progression rate; it also has advantages for RFS. However, there was no significant difference in the rate of residual tumor and the time of first recurrence. More studies are needed to better understand the effects of the photosensitizer used on NMIBC patients.

Passenger lymphocyte syndrome in renal transplantation: A systematic review of published case reports.

BACKGROUND: Passenger lymphocyte syndrome (PLS) is an immune-mediated hemolysis that occurs after ABO-mismatched kidney transplantation. PLS is caused by donor lymphocytes producing antibodies to recipient red blood cells, resulting in hemolysis. The incidence of PLS has been reported to be approximately 20% in patients with ABO-mismatched groups. Nevertheless, there is no comprehensive review of PLS following renal transplantation. In this review, we systematically summarized the data of patients with PLS after renal transplantation to help clinicians diagnose and treat more effectively. METHODS: A systematic review was conducted using PubMed, Embase, and Web of Science. All relevant data were collected, including age, sex, and clinical and immune parameters. RESULTS: A total of 91 published cases were identified. The age ranged from 9 to 70 years old and 58.2% were male. Eighty-six cases were only kidney transplantations, one was liver-kidney transplantation, three were pancreas-kidney transplantations, and one was intestinal-kidney transplantation. Of these cases, 27 received kidneys from deceased donors, whereas 40 received kidneys from living donors. Most patients showed immune hemolysis dominated by anaemia, which was significantly improved after symptomatic support treatment, such as blood transfusion and erythropoietin injection. CONCLUSION: PLS is an immune-mediated disease that can occur in patients with ABO-mismatched renal transplantation, which commonly causes hemolysis, although death or deformities of the graft can also occur in patients with the disorder. Symptomatic supportive treatment is an effective treatment scheme at present, but more effective treatment and prevention schemes still need to be explored.

Prognostic Factors in Stage IV Colorectal Cancer Patients With Resection of Liver and/or Pulmonary Metastases: A Population-Based Cohort Study.

Importance: Currently, surgical resection of distant metastatic lesions has become the preferred treatment for select colorectal cancer (CRC) patients with liver metastasis (LM) and/or pulmonary metastasis (PM). Metastasectomy is the most common curative method. However, evidence of the factors affecting the prognosis of CRC patients after resection of LM and/or PM is still insufficient. Objective: To explore the prognostic factors of CRC patients with LM and/or PM who have undergone resection of metastatic tumors and to provide reliable selection factors for surgical treatment in patients affected by LM and/or PM from CRC. Methods: The SEER database was used to identify eligible CRC LM and/or PM patients who underwent resection of the primary tumor and distant metastases from January 1, 2010, to December 31, 2018. The Kaplan-Meier method was used to calculate survival, and comparisons were performed using the log-rank test for univariate analysis. A Cox proportional hazards regression model was used to identify prognostic factors for the multivariate analysis. The outcomes included overall survival (OS) and cancer-specific survival (CSS). Results: A total of 3,003 eligible colorectal cancer patients with LM and/or PM were included in this study. The 3-year and 5-year OS rates were 53% and 33.6%, respectively, and the 3-year and 5-year CSS rates were 54.2% and 35.3%, respectively. In the adjusted multivariate analysis, age < 65 years (OS: p=0.002, CSS: p=0.002) was associated with better long-term outcomes, and primary tumors located on the left side of the colon (OS: p=0.004, CSS: p=0.006) or rectum (OS: p=0.004, CSS: p=0.006), T3 stage (OS: p<0.001, CSS: p<0.001), number of regional lymph nodes examined ≥ 12 (OS: p<0.001, CSS: p=0.001), and CRC LM (OS: p<0.001, CSS: p<0.001) were positive prognostic factors for survival after resection of metastatic tumors. Conclusion: Age < 65 years is associated with better long-term outcomes in colorectal cancer patients with LM and/or PM, analogously to the left sided primary tumor, T3 stage, number of regional lymph nodes examined ≥ 12 and liver metastases.

Contrast between traditional and machine learning algorithms based on a urine culture predictive model: a multicenter retrospective study in patients with urinary calculi.

Background: Quick and accurate identification of urinary calculi patients with positive urinary cultures is critical to the choice of the treatment strategy. Predictive models based on machine learning algorithms provide a new way to solve this problem. This study aims to determine the predictive value of machine learning algorithms using a urine culture predictive model based on patients with urinary calculi. Methods: Data were collected from four clinical centers in the period of June 2016, to May 2019. 2,054 cases were included in the study. The dataset was randomly split into ratios of 5:5, 6:4, and 7:3 for model construction and validation. Predictive models of urine culture outcomes were constructed and validated by logistic regression, random forest, adaboost, and gradient boosting decision tree (GBDT) models. Each ratio's construction and verification were repeated five times independently for cross-validation. The Matthews correlation coefficient (MMC), F1-score, receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate the performance of each prediction model. The additive net reclassification index (NRI) and absolute NRI were used to assess the predictive capabilities of the models. Results: Four prediction models of urinary culture results in patients with urinary calculi were constructed. The mean AUCs of the logistic regression, random forest, adaboost, and GBDT models were 0.761 (95% CI: 0.753-0.770), 0.790 (95% CI: 0.782-0.798), 0.779 (95% CI: 0.766-0.791), and 0.831 (95% CI: 0.823-0.840), respectively. Moreover, the average MMC and F1-score of GBDT model was 0.460 and 0.588, which was improved compared to logistic regression model of 0.335 and 0.501. The additive NRI and absolute NRI of the GBDT and logistic regression models were 0.124 (95% CI: 0.106-0.142) and 0.065 (95% CI: 0.060-0.069), respectively. Conclusions: Our results indicate that machine learning algorithms may be useful tools for urine culture outcome prediction in patients with urinary calculi because they exhibit superior performance compared with the logistic regression model.

DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden.

Background: Immune checkpoint inhibitor (ICI) therapy has proven to be a promising treatment for colorectal cancer (CRC). We aim to investigate the relationship between DNA methylation and tumor mutation burden (TMB) by integrating genomic and epigenetic profiles to precisely identify clinical benefit populations and to evaluate the effect of ICI therapy. Methods: A total of 536 CRC tissues from the Cancer Genome Atlas (TCGA) with mutation data were collected and subjected to calculate TMB. 80 CRC patients with high TMB and paired normal tissues were selected as training sets and developed the diagnostic and prognostic methylation models, respectively. In the validation set, the diagnostic model was validated in our in-house 47 CRC tissues and 122 CRC tissues from the Gene Expression Omnibus (GEO) datasets, respectively. And a total of 38 CRC tissues with high TMB from the COLONOMICS dataset verified the prognostic model. Results: A positive correlation between differential methylation positions and TMB level was observed in TCGA CRC cohort (r=0.45). The diagnostic score that consisted of methylation levels of four genes (ADHFE1, DOK6, GPR75, and MAP3K14-AS1) showed high diagnostic performance in the discovery (AUC=1.000) and two independent validation (AUC=0.946, AUC=0.857) datasets. Additionally, these four genes showed significant positive correlations with NK cells. The prognostic score containing three genes (POU3F3, SYN2, and TMEM178A) had significantly poorer survival in the high-risk TMB samples than those in the low-risk TMB samples (P=0.016). CRC patients with low-risk scores combined with TMB levels represent a favorable survival. Conclusions: By integrating analyses of methylation and mutation data, it is suggested that DNA methylation patterns combined with TMB serve as a novel potential biomarker for early screening in more high-TMB populations and for evaluating the prognostic effect of CRC patients with ICI therapy.

Balloon versus Amplatz for tract dilation in fluoroscopically guided percutaneous nephrolithotomy: a systematic review and meta-analysis.

OBJECTIVE: To compare the safety and efficacy of balloon and Amplatz for tract dilation in fluoroscopically guided percutaneous nephrolithotomy (PCNL). METHOD: EMBASE, PUBMED, MEDLINE and the Cochrane Central Register of Controlled Trials were searched for pertinent studies up until 30 October 2019. Pooled effects were calculated as ORs with 95% CIs or mean differences (MD) with 95% CIs. Endpoints included postoperative decrease in haemoglobin, transfusion rate, complication rate, successful dilation rate, stone-free rate, fluoroscopy time, access time, total operation time and length of postoperative hospitalisation (LPH). Bonferroni's correction was intercalated to reduce the likelihood of making a meta-analytical false positive. RESULTS: One randomised controlled trial and five controlled clinical trials were included, which involved 1317 patients in total. We found a lower drop in postoperative haemoglobin for patients receiving balloon dilation compared with those in the Amplatz group (MD=-0.21, 95% CI -0.33 to 0.09, p=0.0005; Bonferroni correction a=0.005). Access time in the balloon group was also, on average, 2.61 min shorter than the Amplatz group (MD=-2.61, 95% CI -4.20 to 1.01, p=0.001; Bonferroni correction a=0.005). No significant differences were identified between the two dilation methods in terms of transfusion rate, complication rate, successful dilation rate, stone-free rate, fluoroscopy time, total operation time and LPH. CONCLUSION: Balloon dilation is a safe and effective tract dilation technique for access creation during fluoroscopically guided PCNL. Both of methods have similar success rates although balloon dilation is associated with significantly less postoperative haemoglobin decline and shorter access time. Therefore, balloon dilation appears to be the superior tract dilation technique, but further confirmatory research is required to confirm these findings.

MicroRNA-34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression.

MicroRNA-34a (miR-34a) serves as a tumor suppressor in a number of different types of cancer. The present study was performed to investigate the involvement of miR-34a in bladder cancer. In the present study, miR-34a was downregulated in patients with bladder cancer compared with the healthy controls in bladder biopsies and plasma. Downregulation of miR-34a distinguished between patients with bladder cancer and the healthy controls. miR-34a expression was associated with tumor metastasis; however, not with tumor size. Transfection of miR-34a mimics upregulated the expression of phosphatase and tensin homolog (PTEN) in bladder cancer cells, and decreased cell migration and invasion. miR-34a may inhibit bladder cancer cell migration and invasion by upregulating PTEN. miR-34a may additionally serve as a potential therapeutic target for bladder cancer.

Comparison of photoselective green light laser vaporisation versus traditional transurethral resection for benign prostate hyperplasia: an updated systematic review and meta-analysis of randomised controlled trials and prospective studies.

OBJECTIVE: To assess the efficacy and safety of green-light laser photoselective vaporisation of the prostate (PVP) compared with transurethral resection of the prostate (TURP) for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). DESIGN: Systematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. DATA SOURCES: PubMed, EMBASE, the Cochrane Library until October 2018. ELIGIBILITY CRITERIA: Randomised controlled trials and prospective studies comparing the safety and efficacy of PVP versus TURP for LUTS manifesting through BPH. DATA EXTRACTION AND SYNTHESIS: Perioperative parameters, complications rates and functional outcomes including treatment-related adverse events such as International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), postvoid residual (PVR), quality of life (QoL) and International Index of Erectile Function (IIEF). RESULTS: 22 publications consisting of 2665 patients were analysed. Pooled analysis revealed PVP is associated with reduced blood loss, transfusion, clot retention, TUR syndrome, capsular perforation, catheterisation time and hospitalisation, but also with a higher reintervention rate and longer intervention duration (all p<0.05). No significant difference in IPSS, Qmax, QoL, PVR or IIEF at 3, 24, 36 or 60 months was identified. There was a significant difference in QoL at 6 months (MD=-0.08; 95% CI -0.13 to -0.02; p=0.007), and IPSS (MD = -0.10; 95% CI -0.15 to -0.05; p<0.0001) and Qmax (MD=0.62; 95% CI 0.06 to 1.19; p=0.03) at 12 months, although these differences were not clinically relevant. CONCLUSION: PVP is an effective alternative, holding additional safety benefits. PVP has equivalent long-term IPSS, Qmax, QoL, PVR, IIEF efficacy and fewer complications. The main drawbacks are dysuria and reintervention, although both can be managed with non-invasive techniques. The additional shortcoming is that PVP does not acquire histological tissue examination which removes an opportunity to identify prostate cancer.

One-shot dilation versus serial dilation technique for access in percutaneous nephrolithotomy: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to systematically review the outcomes of the use of one-shot dilation (OSD) and serial tract dilation for percutaneous nephrolithotomy (PCNL). METHODS: A systematic review and meta-analysis was conducted. The randomised controlled trials (RCTs) included in the study were identified from EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials. The last search was performed on 30 April 2018. Summary effects were calculated as risk ratios (RRs) with 95% CIs or mean differences (MDs) with 95% CIs. The endpoints included access time, fluoroscopy time, successful dilation rate, stone-free rate, postoperative decrease in haemoglobin levels, transfusion rate, complication rate and length of postoperative hospital stay. RESULTS: A total of seven RCTs were included in the study, with clinical data reported for 697 patients. The overall access time was approximately 110 s shorter in the OSD group than in the serial dilation group (MD, -110.14; 95% CI -161.99 to -58.30; p<0.0001). The fluoroscopy time was shorter with OSD in all RCTs. In addition, the decrease in postoperative haemoglobin levels was approximately 2.3g/L less in patients in the OSD group than in those in the serial dilation group (MD, -0.23; 95% CI-0.39 to -0.07; p=0.004). No relationship was found between the successful dilation rate, stone-free rate, transfusion rate, or complication rate and the method of tract dilation. CONCLUSION: OSD is a safe and efficacious tract dilation technique that can reduce the access time, fluoroscopy time and postoperative decrease in haemoglobin level. No difference was found in the successful dilation rate, stone-free rate, transfusion rate or rate of complications between the OSD and serial dilation groups. The difference in the length of postoperative hospital stay was uncertain. OSD may be a better method of tract creation for PCNL.

A novel messenger RNA and long noncoding RNA signature associated with the progression of nonmuscle invasive bladder cancer.

AIM: To explore the molecular mechanism of nonmuscle invasive bladder cancer (NMIBC), matched normal, and cancer tissues of 10 NMIBC were examined for RNA sequencing. METHODS: We profiled the messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression of patients with NMIBC. Differentially expressed mRNAs and lncRNAs were screened between cancer and normal tissues and validated by quantitative polymerase chain reaction (qPCR), and lncRNA-mRNA-miRNA interaction network was constructed. RESULTS: A total of 91 upregulated and 190 downregulated genes and 34 upregulated and 58 downregulated lncRNAs were screened from the sequencing result. The differentially expressed mRNAs were enriched in focal adhesion, rap1 signaling pathway, Hippo signaling pathway, PI3K-Akt signaling pathway, extracellular matrix (ECM)-receptor interaction, Ras signaling pathway, and mitogen-activated protein kinases signaling pathway, of which some pathways were involved in the cancer development. In the RNA sequencing, KIT and laminin subunitγ γ3 (LAMC3) were significantly downregulated in the NMIBC group compared with the normal group. The results of quantitative reverse transcription PCR showed that the expression of LAMC3 and KIT were significantly decreased in the NMIBC group compared with the normal group. The lncRNA-mRNA-miRNA interaction network was constructed by Cytoscape software to further investigate the interaction correlations. The results implied that KIT and LAMC3 might regulate the lncRNAs (such as ENST00000445707, ENST00000501122, ENST00000505254, ENST00000528986, ENST00000557661, ENST00000602964, ENST00000614517, ENST00000620864, and ENST00000623414) by the miRNAs (such as hsa-let-7f-2-3p, hsa-miR-125a-3p, hsa-miR-134-3p, hsa-miR-191-5p, hsa-miR-210-5p, hsa-miR-30a-5p, hsa-miR-30d-5p, hsa-miR-30e-5p, hsa-miR-92a-2-5p, and hsa-miR-95-3p), and finally played a role in the development of NMIBC cancer. CONCLUSION: Altogether, our study preliminarily indicated that KIT and LAMC3 might play a crucial role in the development of NMIBC cancer via a complex mRNA-lncRNA-miRNA regulatory network.

Hypothermic Machine Perfusion Versus Static Cold Storage in Deceased Donor Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Static cold storage (SCS) and hypothermic machine perfusion (HMP) are two primary options for renal allograft preservation. Compared with SCS, HMP decreased the incidence of delayed graft function (DGF) and protected graft function. However, more evidence is still needed to prove the advantages of the HMP. In this study, the outcomes of kidney grafts from the two preservation methods were compared by conducting a systematic review and meta-analysis. Randomized controlled trials (RCTs) comparing the effect of hypothermic machine perfusion and static cold storage in deceased donor kidney transplantation were identified through searches of the MEDLINE, EMBASE, and Cochrane databases between January 1, 1980 and December 30, 2017. The primary endpoints were delayed graft function and graft survival. Secondary endpoints included primary non-function (PNF), graft renal function, duration of DGF, acute rejection, postoperative hospital stay and patient survival. Summary effects were calculated as risk ratio (RR) with 95% confidence interval (CI) or mean difference (MD) with 95% confidence intervals (CI). A total of 13 RCTs were included, including 2048 kidney transplant recipients. The results indicated that compared with SCS, HMP decreased the incidence of DGF (RR 0.78, 95% CI 0.69-0.87, P < 0.0001), and improved the graft survival at 3 years (RR 1.06, 95% CI 1.02-1.11, P = 0.009). There was no significant difference in other endpoints. HMP might be a more desirable method of preservation for kidney grafts. The long-term outcomes of kidney allografts stored by hypothermic machine perfusion still need to be further investigated.