Deafness-associated tRNAPhe mutation impaired mitochondrial and cellular integrity.

Defects in mitochondrial RNA metabolism have been linked to sensorineural deafness that often occurs as a consequence of damaged or deficient inner ear hair cells. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAPhe 593T > C mutation that changed a highly conserved uracil to cytosine at position 17 of the DHU-loop. The m.593T > C mutation altered tRNAPhe structure and function, including increased melting temperature, resistance to S1 nuclease-mediated digestion, and conformational changes. The aberrant tRNA metabolism impaired mitochondrial translation, which was especially pronounced by decreases in levels of ND1, ND5, CYTB, CO1, and CO3 harboring higher numbers of phenylalanine. These alterations resulted in aberrant assembly, instability, and reduced activities of respiratory chain enzyme complexes I, III, IV, and intact supercomplexes overall. Furthermore, we found that the m.593T > C mutation caused markedly diminished membrane potential, and increased the production of reactive oxygen species in the mutant cell lines carrying the m.593T > C mutation. These mitochondrial dysfunctions led to the mitochondrial dynamic imbalance via increasing fission with abnormal mitochondrial morphology. Excessive fission impaired the process of autophagy including the initiation phase, formation, and maturation of the autophagosome. In particular, the m.593T > C mutation upregulated the PARKIN-dependent mitophagy pathway. These alterations promoted an intrinsic apoptotic process for the removal of damaged cells. Our findings provide critical insights into the pathophysiology of maternally inherited deafness arising from tRNA mutation-induced defects in mitochondrial and cellular integrity.

Peripheral vertigo and subsequent risk of depression and anxiety disorders: a prospective cohort study using the UK Biobank.

BACKGROUND: Peripheral vertigo is often comorbid with psychiatric disorders. However, no longitudinal study has quantified the association between peripheral vertigo and risk of psychiatric disorders. Furthermore, it remains unknown how the white matter integrity of frontal-limbic network relates to the putative peripheral vertigo-psychiatric disorder link. METHODS: We conducted a cohort study including 452,053 participants of the UK Biobank with a follow-up from 2006 through 2021. We assessed the risks of depression and anxiety disorders in relation to a hospitalization episode involving peripheral vertigo using Cox proportional hazards models. We also examined the associations of peripheral vertigo, depression, and anxiety with MRI fractional anisotropy (FA) in a subsample with brain MRI data (N = 36,087), using multivariable linear regression. RESULTS: Individuals with an inpatient diagnosis of peripheral vertigo had elevated risks of incident depression (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.79-2.67) and anxiety (HR 2.11; 95% CI 1.71-2.61), compared to others, particularly within 2 years after hospitalization (HR for depression 2.91; 95% CI 2.04-4.15; HR for anxiety 4.92; 95% CI 3.62-6.69). Depression was associated with lower FA in most studied white matter regions, whereas anxiety and peripheral vertigo did not show statistically significant associations with FA. CONCLUSIONS: Individuals with an inpatient diagnosis of peripheral vertigo have increased subsequent risks of depression and anxiety disorders, especially within 2 years after hospitalization. Our findings further indicate a link between depression and lower microstructural connectivity as well as integrity beyond the frontal-limbic network.

Seasonal purification efficiency, greenhouse gas emissions and microbial community characteristics of a field-scale surface-flow constructed wetland treating agricultural runoff.

Controlling nonpoint source pollution (NPSP) is very important for protecting the water environment, and surface-flow constructed wetlands (SFCWs) have been widely established to mitigate NPSP loads. In this study, the pollutant removal efficiencies, greenhouse gas (GHG) emissions, and chemical and microbial community properties of the sediment in a large-scale SFCW established beside a plateau lake (Qilu Lake) in southwestern China to treat agricultural runoff were evaluated over a year. The SFCW performed best in terms of nitrogen removal in autumn (average efficiency of 63.5% at influent concentrations of 9.3-35.4 mg L-1) and demonstrated comparable efficiency in other seasons (23.7-40.0%). The removal rates of total phosphorus (TP) and chemical oxygen demand (COD) were limited (18.6% and 12.4% at influent concentrations of 1.1 and 45.5 mg L-1 on average, respectively). The SFCW was a hotspot of CH4 emissions, with an average flux of 31.6 mg m-2·h-1; moreover, CH4 emissions contributed the most to the global warming potential (GWP) of the SFCW. Higher CH4 and N2O fluxes were detected in winter and in the front-end section of the SFCW with high pollutant concentrations, and plant presence increased CH4 emissions. Significant positive relationships between nutrient and heavy metal contents in the SFCW sediment were detected. The microbial community compositions were similar in autumn and winter, with Thiobacillus, Lysobacter, Acinetobacter and Pseudomonas dominating, and this distribution pattern was clearly distinct from those in spring and summer, with high proportions of Spirochaeta_2 and Denitratisoma. The microbial co-occurrence network in spring was more complex with stronger positive correlations than those in winter and autumn, while it was more stable in autumn with more keystone taxa. Optimization of the construction, operation and management of SFCWs treating NPSP in lake watersheds is necessary to promote their environmental benefits.

tRFTars: predicting the targets of tRNA-derived fragments.

BACKGROUND: tRNA-derived fragments (tRFs) are 14-40-nucleotide-long, small non-coding RNAs derived from specific tRNA cleavage events with key regulatory functions in many biological processes. Many studies have shown that tRFs are associated with Argonaute (AGO) complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools for accurately predicting tRF target genes. METHODS: We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous AGO-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including the sequence context of each site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF prediction models. RESULTS: We first identified features that globally influenced tRF targeting. Among these features, the most significant were the minimum free folding energy (MFE), position 8 match, number of bases paired in the tRF-mRNA duplex, and length of the tRF, which were consistent with previous findings. Our constructed model yielded an area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977-0.983) in the training process and an AUC = 0.847 (0.83-0.861) in the test process. The model was applied to all the sites with perfect Watson-Crick complementarity to the seed in the 3' untranslated region (3'-UTR) of the human genome. Seven of nine target/nontarget genes of tRFs confirmed by reporter assay were predicted. We also validated the predictions via quantitative real-time PCR (qRT-PCR). Thirteen potential target genes from the top of the predictions were significantly down-regulated at the mRNA levels by overexpression of the tRFs (tRF-3001a, tRF-3003a or tRF-3009a). CONCLUSIONS: Predictions can be obtained online, tRFTars, freely available at http://trftars.cmuzhenninglab.org:3838/tar/ , which is the first tool to predict targets of tRFs in humans with a user-friendly interface.

The platelet to lymphocyte ratio is a potential inflammatory marker predicting the effects of adjuvant chemotherapy in patients with stage II colorectal cancer.

BACKGROUND: The effects of adjuvant chemotherapy in patients with stage II colorectal cancer (CRC) has been in controversy for a long time. Our study aimed to find an effective inflammatory marker to predict the effects of chemotherapy. METHODS: Seven hundred eight stage II CRC patients in our institution were included. The subpopulation treatment effect pattern plot (STEPP) analysis was used to determine the optimal inflammatory marker and cut-off value. Propensity score matching (PSM) was performed to balance discrepancy between the chemotherapy and non-chemotherapy group. Survival analyses based on overall survival (OS) and cancer-specific survival (CSS) were performed with Kaplan-Meier methods with log-rank test and Cox proportional hazards regression. The restricted mean survival time (RMST) was used to measure treatment effect. RESULTS: The platelet to lymphocyte ratio (PLR) was chosen as the optimal marker with a cut-off value of 130 according to STEPP. In OS analysis, PLR was significantly associated with the effects of chemotherapy (interaction p = 0.027). In the low-PLR subgroup, the chemotherapy patients did not have a longer OS than the non-chemotherapy patients (HR: 0.983, 95% CI: 0.528-1.829). In the high-PLR subgroup, the chemotherapy patients had a significantly longer OS than the non-chemotherapy patients (HR: 0.371, 95% CI: 0.212-0.649). After PSM, PLR was still associated with the effects of chemotherapy. In CSS analysis, PLR was not significantly associated with the effects of chemotherapy (interaction p = 0.116). In the low-PLR subgroup, the chemotherapy patients did not have a longer CSS than the non-chemotherapy patients (HR: 1.016, 95% CI: 0.494-2.087). In the high-PLR subgroup, the chemotherapy patients had a longer CSS than the non-chemotherapy patients (HR: 0.371, 95% CI: 0.212-0.649). After PSM, PLR was not associated with the effects of chemotherapy. CONCLUSIONS: PLR is an effective marker to predict the effects of chemotherapy in patients with stage II CRC.

Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data.

BACKGROUND: Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). METHODS: The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan-Meier curves. RESULTS: The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177-0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205-0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. CONCLUSIONS: Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

A nomogram for predicting bowel obstruction in preoperative colorectal cancer patients with clinical characteristics.

BACKGROUND: Bowel obstruction (BO) is a complication that commonly affects patients with colorectal cancer (CRC). BO causes severe outcomes, and its treatment leads to a dilemma for many surgeons. Moreover, the factors correlated to BO in preoperative CRC patients remain unclear. The objectives of this study were to investigate the clinical characteristics of BO to identify risk predictors and to construct a BO prediction model with preoperative CRC patients. METHODS: A large-scale, retrospective cohort, population-based study analyzed the data of 11,814 patients obtained from the Surveillance, Epidemiology, and End Results and Medicare claims-linked databases (SEER-M database). Patients aged ≥ 66 years and primarily diagnosed with CRC from 1992 to 2009 were divided into BO and non-BO groups. Cox proportional hazards regression models were used to determine predictors, and then, a nomogram was constructed by those predictors. RESULTS: A total of 11,814 patients (5293 men and 6251 women) were identified. In multivariate analysis, 14 factors were found to be associated with BO including age, race, marital status, residence location, T category, M category, primary tumor site, histologic type, histologic grade, tumor size, history of alcoholism, chemotherapy, radiotherapy, abdominal pain, and anemia. A nomogram predicting the 90- and 180-day rates of BO was built for the preoperative CRC patients with a C-index of 0.795. CONCLUSIONS: This study identified 14 BO-related factors, and a statistical model was constructed to predict the onset of BO in preoperative CRC patients. The obtained data may guide decision-making for the intervention of patients at risk for BO.

Prognostic value of gastric cancer-associated gene signatures: Evidence based on a meta-analysis using integrated bioinformatics methods.

Selecting differentially expressed genes (DEGs) based on integrated bioinformatics analyses has been used in previous studies to explore potential biomarkers in gastric cancer (GC) with microarray and RNA sequencing data. However, the genes obtained may be inaccurate because of noisy data and errors, as well as insufficient clinical sample sizes. Thus, we aimed to find robust and strong DEGs with prognostic value for GC, where the robust rank aggregation method was employed to select significant DEGs from eight Gene Expression Omnibus data sets with a total of 140 up-regulated and 206 down-regulated genes. Network data mining was then used to screen hub genes, and 11 genes were filtered using Fisher's exact test. Based on these results, we built a prognostic signature with seven genes (FBN1, MMP1, PLAU, SPARC, COL1A2, COL2A1 and ATP4A) using stepwise multivariate Cox proportional hazard regression. According to the risk score for each patient, we found that high-risk group patients had significantly worse survival results compared with those in the low-risk group (log-rank test P-value < 0.001). This seven-gene signature was then validated with an external data set. Thus, we established a signature based on seven DEGs with prognostic value for GC patients using multi-steps bioinformatics methods, which may provide novel insights and potential biomarkers for prognosis, as well as possibly serving as new therapeutic targets in clinical applications.

A panel consisting of three novel circulating lncRNAs, is it a predictive tool for gastric cancer?

Early detection is vital for prolonging 5-year survival for patients with gastric cancer (GC). Numerous studies indicate that circulating long non-coding RNAs (lncRNAs) can be used to diagnose malignant tumours. This study aimed to investigate the capacity of novel lncRNAs for diagnosing GC. A lncRNA microarray assay was used to screen differentially expressed lncRNAs between plasma of patients with GC and healthy controls. Plasma samples from 100 patients with healthy controls were used to construct a multiple-gene panel. An additional 50 pairs of GC patients with healthy controls were used to evaluate the diagnostic accuracy of the panel. Expression levels of lncRNAs were quantified through real-time polymerase chain reaction. The receiver operating characteristic curve and area under curve (AUC) were used to estimate the diagnostic capacity. We identified three lncRNAs, CTC-501O10.1, AC100830.4 and RP11-210K20.5 that were up-regulated in the plasma of GC patients with AUCs 0.724, 0.730 and 0.737, respectively (P < .01). Based on the logistic regression model, the combined AUC of the three lncRNAs was 0.764. The AUC of the panel was 0.700 in the validation cohort. These findings indicate that plasma lncRNAs can serve as potential biomarkers for detection of GC.

Impact of timing of adjuvant chemotherapy on survival in stage III colon cancer: a population-based study.

BACKGROUND: There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant chemotherapy are unknown. METHODS: Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS). RESULTS: A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9-12 weeks: hazard ratio [HR] = 1.222, 95% confidence interval [CI] = 1.063-1.405; 13-16 weeks: HR = 1.252, 95% CI = 1.041-1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663-2.331). The efficacies of adjuvant chemotherapy within 5-8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921-1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763-1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy (p < 0.05). CONCLUSIONS: Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.

Racial/ethnic disparities in the adjuvant chemotherapy of locally advanced colon cancer patients.

BACKGROUND: Most race/ethnicity-oriented investigations focus on Caucasian Americans (whites) and African Americans (blacks), leaving Asians, Hispanic white (Hispanics), and other minorities less well studied. Adjuvant chemotherapy (CT) after curative resection is critical to patients with locally advanced colon cancer (LACC). We studied the racial disparities in the adjuvant CT of LACC to aid in selecting optimal treatments for people from different races/ethnicities in this era of precision medicine. METHODS: Patients with American Joint Committee on Cancer (AJCC) stage II or III colon cancer (CC) (together termed as LACC) were included based on Surveillance, Epidemiology, and End Results cancer registry-Medicare linked databases. The log-rank test and Cox multivariate regression analysis were performed to investigate the racial/ethnic disparities in cohorts divided according to the regimen of adjuvant CT. RESULTS: In the LACC patients who did not receive adjuvant CT, Asian patients had better survival than other groups (all, P <0.05). For the fluoropyrimidine cohort, the survival of Asian patients was better than that of whites, blacks, and other minorities (all, P <0.05). For the fluoropyrimidine with oxaliplatin cohort, other minorities had superior survival to other groups (all, P <0.05). Similar findings were demonstrated for patients with AJCC stage II and III CC, and the observed better survival persisted after adjustments in the Cox models. CONCLUSIONS: Among LACC patients not receiving adjuvant CT, Asians achieved better survival than other races/ethnicities. Superior survival was also observed for Asians in the fluoropyrimidine cohort and for other minorities in the fluoropyrimidine with oxaliplatin cohort for AJCC stage III CC.

The efficacy of chemotherapy and operation in patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Colorectal neuroendocrine carcinoma (CRNEC) is a rare type of malignancy and is quite aggressive with dismal prognosis. Neither large-scale retrospective studies nor prospective studies have been performed to evaluate the prognostic value of adjuvant chemotherapy in patients with CRNEC. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, 318 elderly patients who were diagnosed with high-grade colorectal neuroendocrine tumors were included. The survival benefit was evaluated using a Cox proportional hazards model and propensity score-matched techniques. RESULTS: Among patients with stage I-III CRNEC, there was also no significant difference in cancer-specific survival (CSS) (P = 0.898) or overall survival (OS) (P = 0.539) between the 5-fluorouracil (5-FU) and the no chemotherapy groups. Meanwhile, the etoposide + platinum (EP) regimen showed no improved survival in patients with stage I-III CRNEC compared with the no chemotherapy group. For stage IV CRNEC, there was no significant difference between operation group and no operation group in CSS (P = 0.317) or OS (P = 0.385). Both 5-FU and EP regimens improved the CSS (for 5-FU, hazard ratio [HR] = 0.257, 95% confidence interval [CI] = 0.134-0.491, P < 0.001; for EP, HR = 0.348, 95% CI = 0.192-0.631, P = 0.001) and OS (for 5-FU, HR = 0.274, 95% CI = 0.149-0.502, P < 0.001; for EP, HR = 0.345, 95% CI = 0.194-0.612, P < 0.001) of patients in stage IV CRNEC. CONCLUSIONS: Our findings demonstrated that neither the 5-FU based nor EP chemotherapy regimens improved the CSS or OS for patients with stage I-III CRNEC. And for stage IV CRNEC, chemotherapy is an independent prognostic factor for CSS and OS, while operation could not improve the CSS or OS for patients with stage IV CRNEC.

The preoperative neutrophil to lymphocyte ratio is a superior indicator of prognosis compared with other inflammatory biomarkers in resectable colorectal cancer.

BACKGROUND: Growing evidence has indicated that some inflammatory markers, including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), can be used as indicators in the prognosis of colorectal cancer (CRC). However, there is controversy concerning what is the best predictor of prognosis in CRC. METHODS: A cohort of 1744 CRC patients in our institution was analyzed retrospectively. Harrell's concordance index (c-index) and Bayesian information criterion (BIC) were used to determine the optimal cut-off values of inflammatory markers and compare their predictive capacity. The association of inflammatory markers with overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model. RESULTS: The multivariate analysis indicated that among these inflammatory markers, NLR (< 2.0 vs. ≥ 2.0) was the only independent prognostic factor for poor OS [hazard ratio (HR) = 0.758, 95% confidence intervals (CI) = 0.598-0.960, P = 0.021)] and CSS (HR = 0.738, 95% CI = 0.573-0.950, P = 0.018). Among these inflammatory markers, the c-index and BIC value for NLR were maximum and minimum for OS, respectively. In addition, the c-index was higher and the BIC value was smaller in TNM staging combined with NLR compared with the values obtained in TNM staging alone. CONCLUSION: NLR is a superior indicator of prognosis compared with LMR, PLR, and PNI in CRC patients, and NLR may serve as an additional indicator based on the current tumor staging system.

Prognostic value of pretreatment standardized uptake value of F-18-fluorodeoxyglucose PET in patients with gastric cancer: a meta-analysis.

BACKGROUND: F-18- fluorodeoxyglucose Positron emission tomography (18FDG-PET) has been widely used in clinical practice. However, the prognostic value of the pretreatment standardized uptake value (SUV) for patients with gastric cancer remains controversial. METHODS: Major databases were systematically searched. The quality of the included studies was assessed using the Newcastle-Ottawa scale; the PET protocols were also evaluated. The pooled hazard ratio (HR) for overall survival (OS) and recurrence-free survival (RFS) were used to estimate the effect size. Data from the included studies were analyzed using Review Manager Software version 5.2. RESULTS: Eight studies with 1080 patients were included. The pooled HR for OS of six studies including 672 patients was 1.72 (95% CI [1.28-2.3], p = 0.0004, I2 = 0%), indicating that patients with high SUVs may have poor prognosis. The pooled HR for RFS was 1.70 (95% CI [1.20-2.39], p = 0.003, I2 = 0%). Subgroup analysis based on the cutoff values determining method indicated that the receiver operating characteristic (ROC) method could better define the cutoff value. Subgroup analysis based on the therapeutic strategies used subsequently indicated the significant prognostic value of SUV. CONCLUSION: In conclusion, our meta-analysis indicated that pretreatment SUV in primary lesions can be an important prognostic factor for overall survival and recurrence-free survival in patients with gastric cancer. High SUVs may indicate poor prognosis.

MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer, and tumor growth associated with down-regulation of sec23a expression.

BACKGROUND: MicroRNA-21 (miR-21) is up-regulated in many cancers, including colorectal cancer (CRC). Nevertheless, the function of miR-21 in CRC and the mechanism underlying that function is still unclear. METHODS: After analyzing the expression of miR-21 and Sec23A in CRC cell lines, we transfected the highest miR-21 expressing cell line, SW-480, with a plasmid containing an miR-21 inhibitor and the lowest miR-21 expressing cell line, DLD-1, with a plasmid containing an miR-21 mimic and measured the effects on the expression of Sec23A and on cell proliferation, migration, and invasion. We also evaluated the effect of knocking down Sec23A on miR-21 expression and its effects on cell proliferation, migration, and invasion. Finally, we assessed the effect of miR-21 in a xenograft tumor model in mice. Tumor tissues from these mice were subjected to immunohistochemical staining to detect the expression of Sec23A. RESULTS: Genetic deletion of miR-21 suppressed the proliferation, migration, and invasion of SW-480 cells, while over-expression of miR-21 promoted proliferation, migration, and invasion of DLD-1 cells. Inhibition of miR-21 increased the expression of Sec23A protein in SW-480 cells while over-expression of miR-21 significantly suppressed the expression of Sec23A protein and Sec23A mRNA in DLD-1 cells. Knockdown of Sec23A increased the expression of miR-21 in SW480 and DLD-1 cells and their proliferation (DLD-1 only), migration, and invasion. Over-expression of miR-21 promoted tumor growth in BALB/c nude mice and suppressed tumor expression of Sec23A. CONCLUSION: These findings provide novel insight into the molecular functions of miR-21 in CRC, which may serve as a potential interesting target.

Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis.

BACKGROUND: The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy. RESULTS: Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects). CONCLUSION: Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.

Meta-analysis of the laparoscopic versus open colorectal surgery within fast track surgery.

BACKGROUND: Laparoscopic methods and fast-track surgery (FTS) can enhance recovery and reduce postoperative hospital stay. However, whether laparoscopic surgery can provide short-term benefits within FTS is controversial. Thus, we conducted a meta-analysis of published studies to evaluate the effect of laparoscopic colorectal surgery within FTS. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies. Endpoints were duration of postoperative hospital stay, time to first bowel movement, total postoperative complication rate, readmission rate, mortality within 30 days after surgery, and conversation rate of laparoscopic surgery. RESULTS: Four randomized controlled trials and six clinical controlled trials (1510 patients) were eligible for analyses. Duration of postoperative hospital stay (weighted mean difference, -1.65 days; p < 0.001), time to first bowel movement (-1.13 days; p < 0.001), total postoperative complication rate (risk ratio [RR], 0.65; p < 0.001), readmission rate (0.46; p < 0.001), and mortality (0.45; p < 0.001) were significantly reduced in the laparoscopic surgery group. Overall conversion rate of laparoscopic surgery was 11.1%. Subgroup analyses based on each FT element demonstrated that studies without the element "prevention of hypothermia," "no bowel preparation," or "no routine use of drains" did not show significant differences between two groups with regard to duration of postoperative hospital stay or total prevalence of postoperative complications. CONCLUSION: Within FTS, laparoscopic methods can significantly shorten postoperative hospital stay, accelerate postoperative recovery, and enhance safety in colorectal surgery. The FT elements "prevention of hypothermia," "no bowel preparation," and "no routine use of drains" may play important parts in the combined effect of these two methods.

Clinicopathological and prognostic significance of circulating tumor cells in patients with gastric cancer: a meta-analysis.

The prognostic significance of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in patients with gastric cancer (GC) is controversial. The aims of our meta-analysis are to assess its correlation with clinicopathological characteristics and prognostic significance in GC. PubMed, Embase, the Cochrane database, the Science citation index, the CNKI database and the references of relevant studies were systematically searched (up to November, 2013). Using the random-effect model, the meta-analysis was completed with odds ratio (OR), risk ratio, hazard ratio (HR) and 95% confidence intervals (CI) as effect values. Twenty-six studies containing 2,566 patients with GC were analyzed. The overall analysis showed that the incidence difference of tumor cells (CTCs/DTCs) was significant when comparing the stage I/II group to the stage III/IV group (OR = 0.36, CI [0.23, 0.56]), the Lauren diffuse group to the intestinal group (OR = 2.06, CI [1.06, 4.00]), the poorly differentiated group to the well/moderate group (OR = 1.65, CI [1.10, 2.50]), the lymphatic involvement positive group to the positive group (OR = 2.92, CI [1.00, 8.55]). The detection of CTCs/DTCs was significantly related with the disease-free survival of patients (HR = 3.42, CI [2.39, 4.91]) and the detection of CTCs in peripheral blood was significantly related with the overall survival of patients (HR = 2.13, CI [1.13, 4.03]). Our meta-analysis indicates that detection of CTCs/DTCs is associated with prognosis for patients with GC and thus could act as a basis for GC staging.

Anti-epidermal growth factor receptor-targeted therapy in upper gastrointestinal tract cancers: a meta-analysis.

This meta-analysis evaluated the efficacy and safety of anti-epidermal growth factor receptor (EGFR) treatment of patients with upper gastrointestinal (GI) tract cancers. A systematic search of multiple databases identified seven randomized controlled trials. Anti-EGFR combination therapy improved disease control rate (DCR) in all patients and progression-free survival (PFS) in patients receiving the same dose of standard therapy as patients receiving standard therapy alone. Combinations of anti-EGFR with non-capecitabine chemotherapy further improved DCR, whereas combinations with capecitabine masked the benefits of DCR and worsened PFS. Overall survival was apparently lower in patients without metastasis, and PFS was apparently improved in patients with squamous cell carcinoma of the esophagus and esophagogastric junction. Anti-EGFR treatment was associated with higher rates of cardiac events, hand-foot syndrome, rash, hypomagnesemia, diarrhea and mucositis and lower rates of neutropenia. Combinations of anti-EGFR agents with non-capecitabine chemotherapy or better supportive care may benefit patients with upper GI tract cancers.

Aspirin and nonsteroidal anti-inflammatory drugs after but not before diagnosis are associated with improved breast cancer survival: a meta-analysis.

PURPOSE: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer survival is still controversial. The aim of our meta-analysis was to assess the survival benefit of NSAIDs. METHODS: A literature search was conducted in PubMed and EMBASE (to September 2014). A meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (CIs) as the effect measures. Subgroup analyses were based on time of NSAID use (before and after diagnosis), medication type (aspirin and other nonaspirin NSAIDs), and study design (cohort and case-control studies). RESULTS: There were 16 eligible studies. Use of NSAIDs after diagnosis was significantly inversely associated with relapse/metastasis (HR 0.69, 95% CI 0.59-0.80) and tended toward potentially protective effects on all-cause mortality, although significance was not reached (HR 0.79, 95% CI 0.61-1.02). In cohort studies, the association between post-diagnostic use of NSAIDs and breast cancer survival was stronger with reduced heterogeneity (breast-cancer-specific mortality: HR 0.65, 95% CI 0.48-0.89, I(2) = 65.3%; all-cause mortality: HR 0.73, 95% CI 0.57-0.92, I(2) = 83.2%; relapse/metastasis: HR 0.73, 95% CI 0.61-0.86, I(2) = 48.3%). Aspirin use after diagnosis was significantly associated with breast-cancer-specific mortality (HR 0.69, 95% CI 0.50-0.96) and relapse/metastasis (HR 0.75, 95% CI 0.56-1.00), and tended toward a protective effect on all-cause mortality, although significance was not reached (HR 0.79, 95% CI 0.60-1.03). Including cohort studies only, we obtained similar results and post-diagnostic use of aspirin was significantly associated with all-cause mortality (HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: NSAIDs and aspirin after but not before diagnosis were associated with improved breast cancer survival, including breast-cancer-specific mortality, all-cause mortality, and relapse/metastasis.