IGJ suppresses breast cancer growth and metastasis by inhibiting EMT via the NF­κB signaling pathway.

Breast cancer metastasis is the primary cause of mortality of patients with breast cancer. The present study aimed to explore the role and underlying mechanisms of IGJ in the invasion and metastasis of breast cancer. The Cancer Genome Atlas database was utilized to analyze the differential gene expression profiles in patients with breast cancer with or without metastasis; the target gene, joining chain of multimeric IgA and IgM (JCHAIN, also known as IGJ, as referred to herein), with significant expression and with prognostic value was screened. The expression levels of IGJ in human breast cancer paired tissues and cell lines were detected using reverse transcription­quantitative PCR and western blot analysis. IGJ differential expression was detected in paired human breast cancer tissues using immunohistochemistry. The role of IGJ in breast cancer was verified using CCK­8, invasion and migration assays, and scratch tests in vivo and in vitro. Further exploration of the role and mechanism of IGJ in breast cancer was conducted through Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes analysis, western blot analysis and immunofluorescence experiments. Through the analysis of gene expression profiles, it was found that IGJ was poorly expressed in patients with breast cancer with metastasis compared to patients with non­metastatic breast cancer. The overexpression of IGJ was associated with an improved distant metastasis­free survival and overall survival (OS). COX multivariate regression analysis demonstrated that IGJ was an independent prognostic factor for the OS and relapse­free survival of patients with breast cancer. In comparison to healthy breast cancer adjacent tissues and cell lines, IGJ was poorly expressed in breast cancer tissues and cell lines (P<0.05). Further analyses indicated that the overexpression of IGJ suppressed the proliferation, invasion and metastasis of breast cancer cells in vivo and in vitro by inhibiting the occurrence of epithelial­to­mesenchymal transition (EMT) and suppressing the nuclear translocation of p65. Finally, rescue experiments indicated that IGJ restricted the proliferation and metastasis of breast cancer cells by regulating the NF­κB signaling pathway. On the whole, the present study demonstrates that IGJ suppresses the invasion and metastasis of breast cancer by inhibiting both the occurrence of EMT and the NF­κB signaling pathway. These findings may provide novel biomarkers and potential therapeutic targets for the treatment of metastatic breast cancer.

FGFR blockade boosts T cell infiltration into triple-negative breast cancer by regulating cancer-associated fibroblasts.

Background: Since T cell exclusion contributes to tumor immune evasion and immunotherapy resistance, how to improve T cell infiltration into solid tumors becomes an urgent challenge. Methods: We employed deep learning to profile the tumor immune microenvironment (TIME) in triple negative breast cancer (TNBC) samples from TCGA datasets and noticed that fibroblast growth factor receptor (FGFR) signaling pathways were enriched in the immune-excluded phenotype of TNBC. Erdafitinib, a selective FGFR inhibitor, was then used to investigate the effect of FGFR blockade on TIME landscape of TNBC syngeneic mouse models by flow cytometry, mass cytometry (CyTOF) and RNA sequencing. Cell Counting Kit-8 (CCK-8) assay and transwell migration assay were carried out to detect the effect of FGFR blockade on cell proliferation and migration, respectively. Cytokine array, western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) were employed to investigate the potential mechanism by which FGFR inhibition enhanced T cell infiltration. Results: Blocking FGFR pathway by Erdafitinib markedly suppressed tumor growth with increased T cell infiltration in immunocompetent mouse models of TNBC. Mechanistically, FGFR blockade inhibited cancer-associated fibroblasts (CAFs) proliferation, migration and secretion of vascular cell adhesion molecule 1 (VCAM-1) by down-regulating MAPK/ERK pathway in CAFs, thus promoting T cell infiltration by breaking physical and chemical barriers built by CAFs in TIME. Furthermore, we observed that FGFR inhibition combined with immune checkpoint blockade therapy (ICT) greatly improved the therapeutic response of TNBC tumor models. Conclusions: FGFR blockade enhanced ICT response by turning immune "cold" tumor into "hot" tumor, providing remarkable implications of FGFR inhibitors as adjuvant agents for combinatorial immunotherapy.

The effect of authentic leadership and organizational climate on the volunteering behavior of college students: A moderated mediation model.

This study explored the role of volunteers' psychological capital and family concern in the effect of the authentic leadership and organization's climate on volunteering behavior in volunteer organizations. A questionnaire survey was used to investigate 945 college student volunteers from volunteer organizations in Chinese colleges at three time points. The results found that authentic leadership and the climate in the volunteer organization were significantly and positively related to volunteers' psychological capital and volunteering behavior, and family concern was significantly and positively related to authentic leadership in volunteer organizations and volunteers' psychological capital. Authentic leadership and climate in volunteer organizations positively affected volunteering behavior, not only directly but also indirectly, through the mediating role of volunteers' psychological capital. Moreover, family concern played a moderating role in the indirect effect of authentic leadership and the climate in volunteer organizations on volunteering behavior through volunteers' psychological capital. Specifically, when the college students' family concern increased, the positive indirect effect of the authentic leadership and climate in volunteer organizations on volunteering behavior through volunteers' psychological capital increased.

ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance.

Palmitoylation is essential for the classic hallmarks of cancers through regulating protein stability and protein-protein interactions. ZDHHC22, as a well-known member of palmitoyltrans-ferase family, its role has not been revealed in cancer. We found ZDHHC22 expression was significantly lower in estrogen receptor (ER) negative breast cancer (BrCa) tissues and cell lines, and its expression was positively corelated with the clinical prognosis of BrCa patients. The lower expression of ZDHHC22 might be caused by its promoter methylation. ZDHHC22 inhibited the proliferation capability of BrCa cells both in vitro and in vivo, depending on its encoding palmitoyltransferase activity. In terms of the mechanisms, ZDHHC22 reduced mTOR stability via palmitoylation and decreased the activation of the AKT signaling pathway. Furthermore, ectopic expression of ZDHHC22 could restore the sensitivity to tamoxifen therapy in MCF-7R cells. Collectively, ZDHHC22 may serve as a prognostic biomarker and therapeutic target, providing the theoretical foundation for exploring specific palmitoylation drugs targeted, especially for endocrine therapy-resistant BrCa patients.

The Promotion of Creativity of Vocational College Students: The Role of Parent-Child Relationship, Emotional Intelligence, and Grit.

Objective: To examine whether emotional intelligence played a mediation role in the association between parent-child relationship and vocational college student's creativity, and whether grit moderated this mediating process. Methods: 663 vocational college students participated in this study and completed four questionnaires at three time points, which included measures of parent-child relationship, creativity, emotional intelligence, and grit. Results: (1) Emotional intelligence mediated the relationship between parent-child relationship and vocational college student's creativity; (2) grit moderated the mediating role of emotional intelligence between parent-child relationship and vocational college student's creativity. Conclusion: Parent-child relationship had both direct effects on vocational college student's creativity and indirect effects through emotional intelligence. Grit moderates the effect of emotional intelligence on vocational college student's creativity.

ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer.

Tumor microenvironment (TME) is vital for the occurrence and development of breast cancer (BRCA). However, it remains challenging to understand the dynamic modulation of the stromal and immune components comprehensively in TME. Herein, we used ESTIMATE and CIBERSORT algorithm to estimate the number of stromal and immune components and the abundance of tumor-infiltrating immune cells (TICs) in 582 BRCA cases from gene expression omnibus (GEO) database. We employed three regression models including univariable Cox proportion, LASSO regression model and multivariate Cox regression, and identified 7 immune-specific genes related to BRCA survival. Of 7 genes, ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2) attracts our attention for significantly predicting prognosis of BRCA patients. Further analysis indicated that ATP2C2 expression was closely related to the clinicopathological features (age, T- and N-staging) and negatively correlated with patients' survival in BRCA. Gene Set Enrichment Analysis (GSEA) was performed to reveal pathway enrichment between ATP2C2high and ATP2C2low groups. The low ATP2C2 expression groups' genes were mainly enriched for immune-related activities, while those in the ATP2C2 high-expression group were largely enriched in metabolic-related pathways. Notably, Pearson's correlation analysis identified that ATP2C2 expression was positively correlated with T follicular helper (Tfh) cells, and negatively correlated with gamma delta (γδ) T cell, suggesting that ATP2C2 might be accountable for the maintenance of immune-dominant status for TME. To sum up, this study comprehensively analyzed the TME and shed light on prognostic immune-related biomarkers for BRCA. In particular, ATP2C2 might be helpful for predicting the prognosis of BRCA patients, which provided an extra insight for BRCA treatment.

Risk factors associated with suicide among hepatocellular carcinoma patients: A surveillance, epidemiology, and end results analysis.

BACKGROUND: Throughout the world, hepatocellular carcinoma (HCC) remains the primary type of liver cancer. The suicide risk was higher among patients with HCC than the general population. Hence, the purpose of this study was to confirm the suicide rates, standardized mortality ratios (SMRs), and the potential risk factors associated with suicide among HCC patients. METHODS: HCC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database during 1975-2016. Suicide rates and SMRs among these patients were calculated, and the general population of the United States (U.S.) during 1975-2016 was used as a reference. Univariable and multivariable Cox regression were taken to find out the underlying risk factors of suicide in HCC patients. RESULTS: There were 70 suicides identified among 102,567 individuals with HCC observed for 160,500.88 person years. The suicide rate was 43.61 per 100,000 person-years, and SMR was 2.26 (95% CI: 1.78-2.84). On Cox regression, year of diagnosis (1975-1988 vs. 2003-2016, HR: 3.00, 95% CI: 1.01-8.89, P = 0.047; 1989-2002 vs. 2003-2016, HR: 1.92, 95% CI: 1.10-3.34, P = 0.021), gender (male vs. female, HR: 8.72, 95% CI: 2.73-27.81, P < 0.001), age at diagnosis (63-105 years old vs. 0-55 years old, HR: 2.28, 95% CI: 1.21-4.31, P = 0.011), race (white race vs. American Indian/Alaska Native, Asian/Pacific Islander, HR: 3.02, 95% CI: 1.35-6.76, P = 0.007) were independent risk factors of suicide among HCC patients. CONCLUSIONS: Diagnosed in the early years (1975-2002), male sex, the older age (63-105 years old), white race, survival months (＜2 months) were significantly associated with suicide among HCC patients. For the sake of preventing suicide behaviors, the government, clinicians, and family members should take adequate measures to decrease the rate of suicide, especially in patients with high-risk factors of suicide.

Immunoglobulin superfamily member 10 is a novel prognostic biomarker for breast cancer.

BACKGROUND: Immunoglobulin superfamily member 10 (IGSF10) is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary. Currently, the role and possible mechanism of IGSF10 in breast cancer remain unclear. METHOD: By applying real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), the expression of IGSF10 in breast cancer cells and tissues was detected. We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas (TCGA), and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients. The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis (GSEA). RESULTS: According to TCGA data, qRT-PCR and IHC experiments, levels of the IGSF10 mRNA and protein were significantly decreased in breast cancer tissues. IGSF10 expression was significantly correlated with age, tumor size, and tumor stage. Moreover, shorter overall survival (OS) and relapse-free survival (RFS) correlated with lower IGSF10 expression, according to the survival analysis. The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS (hazard ratio (HR) = 1.793, 95% confidence interval (CI) [1.141-2.815], P = 0.011) and RFS (HR = 2.298, 95% CI [1.317-4.010], P = 0.003) of patients with breast cancer. Based on the GSEA, IGSF10 was involved in DNA repair, cell cycle, and glycolysis. IGSF10 was also associated with the PI3K/Akt/mTOR and mTORC1 signaling pathways. CONCLUSIONS: This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time. Therefore, further studies are needed to understand the mechanism of IGSF10 in breast cancer.

Prognostic value of systemic immune-inflammation index in patients with urologic cancers: a meta-analysis.

BACKGROUND: Several studies have reported that the systemic immune-inflammation index (SII) is associated with the prognosis of patients with urologic cancers (UCs). The aim of this study was to systematically evaluate the prognostic value of SII in UC patients. METHODS: We searched public databases for relevant published studies on the prognostic value of SII in UC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled to assess the relationships between SII and overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), overall response rate (ORR) and disease control rate (DCR). RESULTS: A total of 14 studies with 3074 patients were included. From the pooled results, we found that high SII was associated with worse overall survival (OS) in patients with UC (HR 2.58, 95% CI 1.59-4.21). Patients with high SII values also had poorer PFS (HR 1.92, 95% CI 1.29-2.88) and CSS (HR 2.58, 95% CI 1.36-4.91) as well as lower ORRs (HR 0.40, 95% CI 0.22-0.71) than patients with low SII values. In addition, the subgroup analysis of OS and PFS showed that the prognosis of patients with high SII was worse than that of patients with low SII. CONCLUSIONS: SII might be a promising noninvasive predictor in patients with UC. However, more samples and multicenter studies are needed to confirm the effectiveness of SII in predicting the prognosis of patients with UC.

Circular RNA 0001073 Attenuates Malignant Biological Behaviours in Breast Cancer Cell and Is Delivered by Nanoparticles to Inhibit Mice Tumour Growth.

BACKGROUND: Circular RNAs (circRNAs) are a special class of noncoding RNAs that are involved in gene regulation and compete with mRNA for miRNA binding sites. The roles of circRNAs in cancer, especially breast cancer (BC), are poorly understood. MATERIALS AND METHODS: The expression levels of circRNA 0001073 (circ-1073) in BC cells (BCCs) and tissues and peritumoural tissues were detected by real-time quantitative reverse transcription-polymerase chain reaction. Kaplan-Meier analysis and receiver operating characteristic curves were used to evaluate relapse-free survival (RFS) and the diagnostic value of circ-1073 for BC, respectively. The biological functions of circ-1073 were determined by cell counting kit-8 assays, colony formation assays, flow cytometry, wound-healing assays, transwell assays, and xenograft model studies. RNA immunoprecipitation assays were conducted to identify the connection between circ-1073 and human antigen R (HuR). RESULTS: Low circ-1073 expression was discovered in BCCs and BC tissues compared with normal mammary epithelial cells and peritumoural tissues, respectively. Circ-1073 downregulation was significantly associated with an unfavourable prognosis, including a shorter RFS, in BC patients. Circ-1073 is a valuable diagnostic biomarker for BC. Circ-1073 overexpression significantly inhibited BCC proliferation and induced apoptosis by increasing Cleaved Caspase-3/9 levels. Moreover, circ-1073 upregulation significantly suppressed cell mobility and epithelial-mesenchymal transition. Notably, xenograft tumour growth was inhibited by the intratumoural injection of nanoparticles containing the circ-1073 plasmid or by circ-1073 overexpression, and this inhibition was accompanied by HuR upregulation. CONCLUSION: Circ-1073 functions as a tumour suppressor in BC, suggesting its potential as a novel therapeutic target in BC.

CircEHMT1 inhibits metastatic potential of breast cancer cells by modulating miR-1233-3p/KLF4/MMP2 axis.

CircRNA is a kind of covalent head-to-tail looped RNA and plays an important role in tumor development. However, the identification of new potential targetable circRNAs to inhibit cancer development is still a huge challenge. In this study, we found that circEHMT1 inhibited migration and invasion of breast cancer cells. Mechanistically, we identified miR-1233-3p as a target of circEHMT1, and the circEHMT1/miR-1233-3p axis regulated matrix metalloprotease 2 (MMP2) by modulating the transcription factor Krϋppel-like factor 4 (KLF4). In summary, we showed that circEHMT1 has potential as a prognostic factor in breast cancer and played a tumor suppressor role via the circEHMT1/miR-1233-3p/KLF4/MMP2 axis.

The Prognostic Value of Circulating Soluble Programmed Death Ligand-1 in Cancers: A Meta-Analysis.

BACKGROUND: Studies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results. OBJECTIVE: This meta-analysis was performed to assess the association between sPD-L1 and the prognosis of cancer patients. METHODS: Published articles in Pubmed, EMBASE, and Cochrane clinical trial databases were searched from the inception to September 2020. Overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) data were evaluated using a hazard ratio (HR) at 95% confidence interval (95% CI). RESULTS: A total 31 studies involving 17 tumors and 3,780 patients were included. The overexpression of sPD-L1 was associated with shorter OS (HR 1.85, 95% CI 1.59-2.15, I2 = 33%). High sPD-L1 had worse PFS (HR 2.40, 95% CI 1.55-3.72, I2 = 83%), and worse DFS (HR 2.92, 95% CI 2.02-4.29, I2 = 40%), without significant statistical difference in RFS (HR 2.08, 95% CI 0.99-4.40, I2 = 0%). CONCLUSIONS: High sPD-L1 levels were associated with worse survival prognosis in cancer patients. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers in the future.

Different Expression Characteristics of LAG3 and PD-1 in Sepsis and Their Synergistic Effect on T Cell Exhaustion: A New Strategy for Immune Checkpoint Blockade.

The impairment of immunity characterized by T cell exhaustion is the main cause of death in patients with sepsis after the acute phase. Although PD-1 blockade is highly touted as a promising treatment for improving prognosis, the role of PD-1 plays in sepsis and particularly its different roles in different periods are still very limited. A recent study revealed LAG3 can resist the therapeutic effect of PD-1 blockade in tumor, which inspired us to understand their role in sepsis. We enrolled 26 patients with acute sepsis from 422 candidates using strict inclusion criteria. Follow-up analysis revealed that the expression levels of PD-1 were rapidly increased in the early stage of sepsis but did not change significantly as infection continued (P < 0.05). However, the expression of LAG3 was contrary to that of PD-1. Compared with LAG3 or PD-1 single-positive T cells, T cells coexpressing LAG3 and PD-1 were significantly exhausted (P < 0.05). The proportion of coexpressing T cells was negatively correlated with the total number of lymphocytes (r = -0.653, P = 0.0003) and positively correlated with the SOFA score (r = 0.712, P < 0.0001). In addition, the higher the proportion of coexpressing T cells was, the longer the hospital stay and the higher the mortality. These results showed that LAG3 and PD-1 had a potential synergistic effect in regulating the gradual exhaustion of T cells in sepsis, which seriously affected the clinical prognosis of patients. Therefore, LAG3 and PD-1 double-positive T cells are an important indicator for immunity detection and prognostic evaluation. In the future, precision therapy may pay more attention to the different expression patterns of these two molecules.

Laparoscopic hepatectomy versus radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis.

Aim: To compare the effectiveness of laparoscopic hepatectomy (LH) with that of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: We conducted a literature search without a language restriction to identify relevant available articles that had been published with the EMBASE and PubMed databases and the Cochrane Library. Studies comparing the outcomes of LH versus RFA for HCC were eligible for inclusion. Results: A total of 10 studies with 1570 patients was included in this meta-analysis. The pooled results revealed that LH was superior to RFA in terms of the 5-year overall survival rate (OR=0.53, 95% CI=0.40, 0.69, p<0.001). In the subgroup analysis of small HCCs, there was still a significantly better 5-year overall survival rate in the LH group compared with the RFA group (OR=0.47, 95% CI=0.33, 0.66, p<0.001). Additionally, the LH group had better 1- and 3-year disease-free survival rate and a lower local recurrence rate, compared with the RFA group. However, the complication rate was higher in the LH group than the RFA group (OR=0.64, 95% CI=0.46, 0.89, p=0.008). Conclusion: Patients who underwent LH had a better long-term prognosis and a lower recurrence rate than those who received RFA. However, we did not obtain conclusive evidence for the superiority of LH over RFA for the treatment of HCCs due to the inclusion of retrospective studies in the present meta-analysis, and well-designed RCTs are needed.

Increasing negative lymph node count is independently associated with improved long-term survival in resectable perihilar cholangiocarcinomas.

To evaluate the prognostic value of numbers of negative lymph nodes (NLNs) for patients with perihilar cholangiocarcinomas.The surveillance, epidemiology, and end results database was used to screen for patients with perihilar cholangiocarcinomas. Kaplan-Meier and Cox regression analyses were used for statistical evaluations. Subsequently, propensity score matching (PSM) was performed to confirm the results.A total of 938 patients with perihilar cholangiocarcinomas met the inclusion criteria. The cut-off number for the grouping of patients with different numbers of NLNs was 17. Both the univariate and multivariate survival analyses demonstrated that there was a significant improvement in terms of cancer-specific survival for patients with >17 NLNs, compared with patients with ≤17 NLNs. Then, the above results were confirmed via a PSM procedure. Additionally, the independent prognostic value of NLNs was evaluated in subgroup univariate and multivariate analyses of patients with stage I or stage II tumors.The numbers of NLNs were evaluated and determined to be important independent prognostic factors for the cancer-specific survival of patients with perihilar cholangiocarcinomas.

A four-miRNA signature as a novel biomarker for predicting survival in endometrial cancer.

BACKGROUND: The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. The aim of this study was to identify new miRNA prognostic biomarkers in endometrial cancer (EC) and to develop an expression-based miRNA signature to provide survival risk prediction for EC patients. METHODS: From TCGA database, the miRNA datasets of EC and clinical information were downloaded in April 2018. Using univariate and multivariate Cox regression analyses identify prognostic factors. Using area under the curve (AUC) of receiver operating characteristic (ROC) curve assess the sensitivity and specificity of prognostic model. RESULTS: 530 patients were randomly divided into training set and testing set. Among 561 differentially expressed miRNAs, 4 miRNAs (miR-4758, miR-876, miR-142, miR-190b) were demonstrated to be predictive biomarkers of overall survival (OS) for EC patients in training set. Based on the risk score of 4-miRNA model, patients in the training set were divided into high-risk and low-risk groups with significantly different OS. This 4-miRNA model was validated in testing and entire set. The AUC for the ROC curves in the entire set was 0.704. Meanwhile, multivariate Cox regression combined with other traditional clinical parameters indicated that the 4-miRNA model can be used as an independent OS prognostic factor. Functional enrichment analysis revealed that these miRNAs are involved in biological processes and pathways that are closely related to cancer. CONCLUSION: A robust 4-miRNA signature as an independent prognostic factor for OS in EC patients was established.

Comparison of endoscopic papillary large balloon dilation with and without a prior endoscopic sphincterotomy for the treatment of patients with large and/or multiple common bile duct stones: a systematic review and meta-analysis.

AIM: To compare endoscopic papillary large balloon dilation (EPLBD) alone with EPLBD following endoscopic sphincterotomy (EST) in patients with large and/or multiple common bile duct stones. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library database to identify relevant available articles until July 19, 2018. Complete common bile duct stone (CBDS) removal rate, frequency of mechanical lithotripsy (ML) usage, total procedure time and intra- and postoperative adverse events were analyzed. We used RevMan 5.3 to perform the pooled analyses. RESULTS: Seven RCTs matched the selection criteria. A total of 369 patients underwent EPLBD alone, and 367 patients underwent EPLBD following EST. Our meta-analysis revealed that there were no significant differences in terms of initial success rate (OR =0.69, 95% CI=0.44-1.09, P=0.11), frequency of ML usage (OR =1.18, 95% CI=0.68-2.05, P=0.55), rate of post-endoscopy pancreatitis (PEP) (OR =0.88, 95% CI=0.43-1.78, P=0.72), total procedure time (MD =1.52, 95% CI=-0.13-3.17, P=0.07), or other intra- and postoperative adverse events between the groups for patients with large and/or multiple CBDSs. CONCLUSIONS: EPLBD alone was comparable to EPLBD with prior EST in patients with large and/or multiple CBDSs. Further studies are required to confirm the mechanisms of PEP in patients who accept EPLBD during endoscopic retrograde cholangiopancreatography (ERCP).

Transradial vs transfemoral access in patients with hepatic malignancy and undergoing hepatic interventions: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare transradial access (TRA) approach with transfemoral access (TFA) approach in patients undergoing hepatic interventions. METHODS: We conducted a comprehensive search of the PubMed, Embase, and the Cochrane Library database to identify relevant available articles. Patients' preference, success rate, intra- and postoperative outcomes were analyzed. The risk difference (RD), relative risk (RR), and weighted mean difference (WMD) values were reported with 95% confidence intervals (CIs). We used RevMan 5.3 to perform the pooled analyses. RESULTS: Nine cohort studies were included. A total of 1096 procedures were performed in 877 patients. Of those, 545 procedures (49.7%) were performed by TRA, and 551 procedures (50.3%) were performed by TFA. Patients were significantly prefer the TRA (86.5%) to the TFA (13.5%) (RD = 0.88, P < .00001). The procedure time in TRA groups was longer (WMD = 3.36, 95% CI 1.24-5.47, P = .002). But there were no significant difference in terms of success rate, fluoroscopy time, radiation dosage, contrast volume, and postoperative vascular complications. CONCLUSION: For patients suffer from primary or secondary hepatic malignancy and undergoing hepatic interventions, the present meta-analysis demonstrated that patients prefer the TRA approach to the TFA approach. But the procedure time is longer in TRA group.

Downregulated miR-1247-5p associates with poor prognosis and facilitates tumor cell growth via DVL1/Wnt/ß-catenin signaling in breast cancer.

The abnormal expression of microRNAs is a key hallmark of breast cancer. Nevertheless, the biological roles of miR-1247-5p in breast cancer remain unknown. In this study, we revealed that miR-1247-5p expression was markedly decreased in breast cancer. It was a valuable diagnostic biomarker for breast cancer with the area under the curve of more than 0.80. Reduced miR-1247-5p expression was significantly correlated with patient age, tumor size, and poor prognosis in The Cancer Genome Atlas cohort including 839 breast cancer patients. Multivariate Cox regression analysis demonstrated that miR-1247-5p was an independent prognostic indicator for overall survival (hazard radio [HR] = 1.683, 95% confidence interval [CI] = 1.087-2.606, p = 0.020) and recurrence-free survival (HR = 2.496, 95% CI = 1.576-3.951, p < 0.001). Moreover, functional studies showed that overexpression of miR-1247-5p inhibited proliferation and induced apoptosis in breast cancer cells. Bioinformatics analysis and mechanistic investigations revealed that Dishevelled 1 (DVL1) was a direct target of miR-1247-5p. Inhibition of DVL1 by miR-1247-5p resulted in the suppression of Wnt/ß-catenin signaling, whereas overexpression of DVL1 abrogated the miR-1247-5p-mediated effect. These data reveal that miR-1247-5p, as an oncosuppressor in breast cancer, may be a promising prognostic biomarker and therapeutic target.

Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta-analysis.

BACKGROUND: TAS-102 has been applied to metastatic colorectal cancer (mCRC) patients who had received at least two prior regimens of standard chemotherapy. This meta-analysis is designed to assess the efficacy and safety of TAS-102 in patients with mCRC. METHODS: We searched randomized controlled trials (RCTs) through PubMed, Embase, Web of Science and Cochrane clinical trial databases and clinicaltrial.gov from database initiation to March 2018. The overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and incidence of adverse events were summarized with the use of hazard ratio (HR) or risk ratio (RR). RESULTS: Three RCTs with 1318 patients were included. Results showed that TAS-102 significantly improved OS (HR 0.70, 95% confidence interval [CI] 0.62-0.79) and PFS (HR 0.46, 95% CI 0.40-0.52) in patients who were intolerant or refractory to fluoropyrimidine, irinotecan and oxaliplatin. The pooled odds ratio of DCR was 4.15 (95% CI 3.18-5.43). Notably, there were significant OS benefits both in patients with KRAS mutation (HR 0.76, 95% CI 0.63-0.92) and those with wild-type KRAS (HR 0.66, 95% CI 0.55-0.79). These benefits were also observed in patients with different numbers of metastatic sites. However, patients with >18 months since the diagnosis of first metastases seemed to have better OS (HR 0.65, 95% CI 0.55-0.77). The most common toxicities associated with TAS-102 were neutropenia (RR 116.51, 95% CI 23.51-577.33), leucopenia (RR 67.70, 95% CI 13.63-336.29), anemia (RR 4.28, 95% CI 2.70-6.79) and diarrhea (RR 5.10, 95% CI 1.40-18.61). CONCLUSION: TAS-102 significantly improves OS, PFS and DCR in refractory mCRC patients with tolerable toxicity. Meanwhile, the OS benefits have nothing to do with KRAS status and the number of metastatic sites.