Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Adjuvant chemotherapy does not improve cancer-specific survival for pathologic stage II/III rectal adenocarcinoma after neoadjuvant chemoradiotherapy and surgery: evidence based on long-term survival analysis from SEER data.

PURPOSE: Adjuvant chemotherapy is controversial in rectal cancer, especially after neoadjuvant chemoradiotherapy (NCRT). This retrospective study aims at evaluating adjuvant chemotherapy's long-term survival benefits in stage II and stage III rectal adenocarcinoma (RC). METHODS: This study obtained data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2010 and 2015. The survival analyses used the Kaplan-Meier method and were compared by log-rank test. The factors that affect survival outcomes were analyzed by univariate and multivariate Cox regression. The propensity score matching (1:4) was used to ensure the balance of variables between different groups. RESULTS: The median follow-up time for overall patients was 64 months. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were 51.3% and 67.4% in the adjuvant chemotherapy (-) group and 73.9% and 79.6% in the adjuvant chemotherapy ( +) group (p < 0.001, p = 0.002). However, subgroup analysis showed adjuvant chemotherapy after NCRT improved the 5-year OS but not CSS rates in stage II and stage III RC (p = 0.003, p = 0.004; p = 0.29, p = 0.3). Univariate and multivariate analyses found adjuvant chemotherapy after NCRT was an independent prognosis factor of OS but not CSS (HR 0.8, 95%CI 0.7-0.92, p < 0.001; p = 0.276). CONCLUSION: The survival benefits from adjuvant chemotherapy were associated with the status of NCRT for pathological stage II and III RC. For patients who did not receive NCRT, adjuvant chemotherapy is needed to significantly improve long-term survival rates. However, adjuvant chemotherapy after NCRT did not significantly improve long-term CSS.

The benefits of adjuvant chemotherapy are associated with the kind of neoadjuvant therapy in stage ypI rectal cancer: evidence based on population analysis.

PURPOSE: The oncological role of adjuvant chemotherapy (ACT) remains debated in locally advanced rectal cancer (RC) after neoadjuvant therapy (NAT), especially ypI RC. In this study, we used population-based data to evaluate the benefits of ACT in stage ypI RC after NAT and surgery. Moreover, we tried to differentiate what kind of NAT (radiotherapy alone or chemoradiotherapy) was administered because this may affect the further efficacy of ACT. METHODS: All patients with stage ypI primary rectal malignancy were diagnosed in the SEER database between 2004 and 2017. The Kaplan-Meier method was applied to estimate the effects of ACT in survival analysis. Cox regression was performed to calculate the hazard ratio (HR) and the prognosis factors of survival. Propensity score matching (PSM) was used to balance the parameters between therapy groups. RESULTS: The overall cohort's median follow-up time was 105 months. For 5-year OS and CSS, there were no significant differences between the ACT ( +) and ACT (-) groups (p = 0.105; p = 0.788). However, subgroup analyses according to the kind of NAT found that ACT improved overall survival (OS) and cancer-specific survival (CSS) in patients who received neoadjuvant radiotherapy (nRT) (p < 0.001, p = 0.015). Among patients who received neoadjuvant chemoradiotherapy (nCRT), no significant survival benefits were found between the ACT ( +) and ACT (-) groups (p = 0.526, p = 0.288). CONCLUSION: Our population-based cohort study suggested that the efficacy of ACT was associated with the kind of NAT. The ACT provides survival benefits in stage ypI RC for patients who received nRT. However, among patients who received nCRT, ACT did not improve long-term survival.

Adjuvant chemotherapy improves long-term survival in pathologic stage III rectal mucinous adenocarcinoma after pre-operative chemoradiotherapy.

PURPOSE: The benefits of adjuvant chemotherapy remain debated rectal mucinous adenocarcinoma (MC). Our study aims to delve into the efficacy of adjuvant chemotherapy in pathologic stage III rectal MC by a large population-based database. METHODS: The Chi-square test was performed to examine the parameters between treatment groups. The overall survival (OS) and cancer-specific survival (CSS) of treatment groups were conducted by using the Kaplan-Meier method. The impact of factors on survival was assessed using Cox regression analyses. To balance the covariates and reduce the selection bias, we employed propensity score matching (PSM) to narrow the differences between treatment groups. RESULTS: The median follow-up time for overall patients was 80 months. In the pre-operative chemoradiotherapy (pre-CRT) group, patients who received adjuvant chemotherapy had significantly better 5-year OS and CSS. Multivariate analyses found that adjuvant chemotherapy was associated with better OS (p < 0.001, HR (95% CI): 0.66 (0.51-0.86)) and CSS (p = 0.012, HR (95% CI): 0.71 (0.54-0.93)). However, adjuvant chemotherapy was not an independent prognosis factor in both OS (p = 0.149, HR (95% CI): 0.76 (0.53-1.1); Supplement Table 1) and CSS (p = 0.183, HR (95% CI): 0.74 (0.48-1.15)) in patients who did not receive pre-CRT. After PSM, similar results were found in the pre-CRT and the no pre-CRT groups. CONCLUSION: In conclusion, our population-based retrospective cohort study indicates that the effects of adjuvant chemotherapy were associated with the pre-CRT status in patients with stage III rectal MC. In patients who underwent pre-CRT, the receipt of adjuvant chemotherapy was associated with better survival outcomes. Conversely, adjuvant chemotherapy does not seem to confer significant survival benefits to patients without pre-CRT.

Surgical and oncological outcomes of robotic- versus laparoscopic-assisted distal gastrectomy with D2 lymphadenectomy for advanced gastric cancer: a propensity score­matched analysis of 1164 patients.

BACKGROUND: Studies on surgical outcomes after robotic surgery are increasing; however, long-term oncological results of studies comparing robotic-assisted distal gastrectomy (RADG) versus laparoscopic-assisted distal gastrectomy (LADG) for advanced gastric cancer (AGC) are still limited. This study aimed to assess the surgical and oncological outcomes of RADG and LADG for the treatment of AGC. METHODS: A total of 1164 consecutive AGC patients undergoing RADG or LADG were enrolled between January 2015 and October 2021. Propensity score-matched (PSM) analysis was performed to minimize selection bias. The perioperative and oncological outcomes between the two groups were compared. RESULTS: Patient's characteristics were comparable between the two groups after PSM. RADG group represented a longer operative time (205.2 ± 43.1 vs 185.3 ± 42.8 min, P < 0.001), less operative blood loss (139.3 ± 97.8 vs 167.3 ± 134.2 ml, P < 0.001), greater retrieved lymph nodes (LNs) number (31.4 ± 12.1 vs 29.4 ± 12.3, P = 0.015), more retrieved LNs in the supra-pancreatic areas (13.4 ± 5.0 vs 11.4 ± 5.1, P < 0.001), and higher medical costs (13,608 ± 4326 vs 10,925 ± US $3925, P < 0.001) than LADG group. The overall complication rate was 13.7% in the RADG group and 16.6% in the LADG group, respectively; the difference was not significantly different (P = 0.242). In the subgroup analysis, the benefits of RADG were more evident in high BMI patients. Moreover, the 3-year overall survival (75.5% vs 73.1%, P = 0.471) and 3-year disease-free survival (72.9% vs 71.4%, P = 0.763) were similar between the two groups. CONCLUSION: RADG appears to be a safe and feasible procedure and could serve as an alternative treatment for AGC in experienced centers.

Multi-objective optimization of Stinger PDC cutter breaking rock parameters under intrusion-cutting action using Taguchi-based gray relational analysis.

To enhance the efficiency of the Stinger Polycrystalline Diamond Compact (PDC) cutter in breaking hard rocks, this study focuses on optimizing the cutter intrusion-cutting rock breaking parameters. A numerical calculation model for the rotational breaking of granite by a Stinger PDC cutter was established. A comprehensive statistical examination was performed to assess the influence of various factors on intrusion ability (IA), tangential force (TF), and mechanical specific energy (MSE). The Taguchi method was used to determine the optimal settings for each factor, while analysis of variance was employed to assess the significance and relative impact of these factors on the target outcomes. In addition, the multi-objective function was optimized using the gray relational analysis method. The primary process parameters obtained for the various performance characteristics are the cone top angle (α), the cone top radius (r), the cutter diameter (d), the cutter back inclination angle (ß), and weight on bit (P). The impact ratios of these parameters are 6.20%, 7.66%, 3.93%, 17.20%, and 65.02%, respectively. The optimal geometrical parameters are α = 60°, r = 2 mm, and d = 15 mm, while the optimal working parameters are ß = 30° and P = 800 N. In the optimal case, IA and MSE were reduced by 55.335% and 15.809%, respectively, compared to the initial case. Despite a 15.706% increase in TF, the overall GRG increased for all three evaluation criteria, with an overall increase in efficiency of 18.229%. The results of this paper can provide guidance for the design of Stinger cutter PDC drill bits.

The benefit of adjuvant chemotherapy in pathological T1-3N0M0 rectal mucinous adenocarcinoma: no improvement survival outcomes based on long-term survival analysis of large population data.

Background: Currently, the benefits of the administration of adjuvant chemotherapy (AT) in pathological low-risk rectal mucinous adenocarcinoma (RM) with T1-3N0M0 are unclear. The objective of this study is to retrospectively investigate the clinical significance of AT in terms of survival outcomes for patients with pathological T1-3N0M0 RM using data from a large population. Methods: The patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) Program. The Chi-squared test was used to analyze categorical variables. The survival curves were compared using the log-rank test and the Kaplan-Meier method. A multivariate proportional hazards regression (Cox) model was applied to identify the independent prognostic factors of survival outcomes. Propensity score matching (PSM) was utilized to eliminate the differences between groups and estimate AT's effect. Results: The median follow-up duration for the rectal cancer (RC) cohort was 116 months. Multivariate analyses revealed that RM was a significant adverse prognostic factor, correlating with poorer overall survival (OS) and cancer-specific survival (CSS) for RC [hazard ratio (HR): 1.226, 95% confidence interval (CI): 1.094-1.375, P<0.001; HR: 1.446, 95% CI: 1.242-1.683, P<0.001]. Among patients with RM, the rates of 5-year OS and CSS were 68.6% and 79.3% in the AT (-) group, respectively. Additionally, the AT (+) group exhibited similar rates of 65.6% for 5-year OS and 74% for CSS (P=0.80, P=0.26). Subtype analysis according to preoperative therapy status showed that AT also did not significantly affect survival outcomes (P=0.65, P=0.34; P=0.90, P=0.76). Conclusions: Our study found that RM is a poor prognostic factor in pathological T1-3N0M0 RC. However, AT does not appear necessary to improve survival outcomes of pathological T1-3N0M0 RM.

Risk stratification of stage II rectal mucinous adenocarcinoma to predict the benefit of adjuvant chemotherapy following neoadjuvant chemoradiation and surgery.

Background: The treatment strategy for stage II rectal mucinous adenocarcinoma (RMA) recommends neoadjuvant chemoradiotherapy (NCR) followed by total mesorectal excision (TME). However, the necessity of adjuvant chemotherapy (AC) remains controversial. Materials and methods: Chi-square test was used to assess the relationship between pathological classification, AC and clinicopathological characteristics. Kaplan-Meier (KM) curves and the log-rank test were utilized to analyze differences in overall survival (OS) and cancer-specific survival (CSS) among different groups. Cox regression identified prognostic factors. Nomogram was established utilizing the independent prognostic factors. X-tile divided patients into three risk subgroups. Results: Compared to RMA, rectal adenocarcinoma (RA) demonstrates longer OS and CSS in all and non-AC stage II patients, with no difference in OS and CSS for AC stage II patients. Propensity score matching analyses yielded similar results. Stratified analysis found that AC both improve OS of RA and RMA patients. Age, gender, pathologic T stage, regional nodes examined, and tumor size were identified as independent prognostic factors for RMA patients without AC. A nomogram was constructed to generate risk scores and categorize RMA patients into three subgroups based on these scores. KM curves revealed AC benefits for moderate and high-risk groups but not for the low-risk group. The external validation cohort yielded similar results. Conclusions: In summary, our study suggests that, compared to stage II RA patients, stage II RMA patients benefit more from AC after NCR. AC is recommended for moderate and high-risk stage II RMA patients after NCR, whereas low-risk patients do not require AC.

Effect of fasudil on clinical outcomes of pulmonary hypertension: a systematic review and meta-analysis.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition with high mortality, categorized into 5 Groups based on distinct etiologies. Fasudil, a potent vasodilator targeting the RhoA/Rho kinase pathway, holds promise for diverse PH pathologies. However, a comprehensive systematic evaluation of its clinical benefits remains elusive. METHODS: We conducted a systematic search across several databases. Meta-analysis using odds ratio and mean difference was performed, with an assessment of studies' quality and pooled evidence. RESULTS: Studies on Group-2 and -3 PH reports eligible data for meta-analysis. Inclusion of 3269 patients with Group-3 PH demonstrated that fasudil significantly increased effective events, FEV1, 6-minute walking distance (6MWD) and arterial PaO2, and decreased mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP); Inclusion of 197 patients with Group-2 PH suggested that fasudil significantly increased 6MWD and PaO2, and decreased PASP. Subgroup analysis revealed no significant difference between dosages of 30 and 60 mg/day, while durations and methods of fasudil administration might affect therapeutic effectiveness in patients with Group-3 PH. CONCLUSIONS: By providing comprehensive and robust evidence, our study favor the beneficial effects of fasudil by enhancing FEV1, 6MWD and PaO2, and reducing mPAP and PASP on patients with Group-3 PH, suggesting fasudil as a viable treatment recommendation for these patients and highlighting the need for further studies to inform healthcare policies. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42022308947.

Adjuvant Radiotherapy Is Not Necessary for Stage III Mucinous Rectal Cancer: Evidence Based on Long Survival Analysis from SEER Data.

BACKGROUND: Although rectal mucinous adenocarcinoma (RMC) is less sensitive to radiotherapy, adjuvant radiotherapy is still recommended for RMC patients. This study aimed to explore whether adjuvant radiotherapy is necessary for stage III RMC. METHODS: Data of patients with stage III RMC were obtained from the National Cancer Institute's SEER database (2004-2015). The survival rates were calculated by Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were used to assess the impact of clinicopathological parameters on overall survival (OS) and cancer-specific survival (CSS). RESULTS: RMC has a worse T and N stage at diagnosis than rectal adenomatous carcinoma (RAC) (all p < 0.001). Multivariate Cox regression analyses revealed that histopathological type MC was an independent poor prognostic factor for OS (HR 1.27; 95%CI 1.14-1.41; p < 0.001) and CSS (HR 1.34; 95%CI 1.18-1.51; p < 0.001). Subgroup analysis based on different treatment regimens showed no significant difference between chemotherapy group and chemotherapy plus radiotherapy group. After the propensity score matching, no significant difference was also found in OS and CSS between chemotherapy group and chemotherapy plus radiotherapy group. CONCLUSIONS: RMC is an independent poor prognostic factor for OS and CSS. Adjuvant radiotherapy for RMC was not beneficial in improving survival outcomes.

Development and validation of a clinical survival model for young-onset colorectal cancer with synchronous liver-only metastases: a SEER population-based study and external validation.

Background: The morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM. Methods: The YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly (1488 and 639 patients, respectively). Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model's predictive accuracy. The calibration plots were used to determine the Nomogram's discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram's net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software. Results: The Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score<234) had significantly better survival outcomes than middle-risk (234-318) and high-risk (>318) patients (P < 0.001). Conclusion: A nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment.

The Influence of Casing-Sand Adhesion on Cementing Bond Strength.

In the petroleum industry, one of the most serious problems encountered during cementing is the failure at the bonding interface. Many measures including casing-sand adhesion have been developed to improve cementing bond strength. However, due to the lack of detailed study of the technique, many questions remain. The primary goal of this study is to investigate the influence of casing-sand adhesion on cementing bond strength, and to optimize parameters. An orthogonal experiment and a supplementary experiment were conducted. The results indicated that casing-sand adhesion can improve the cementing bond strength. The priority orders of key factors are: sand grain size, sand coverage, adhesive curing temperature and adhesive curing time. The optimal parameters recommended for application are: 1.6mm~1.9mm sand grain size, 60%~70% sand coverage, 30°C curing temperature and 60 hours curing time.

Synthesis and anticancer activities of 5,6,7-trimethylbaicalein derivatives.

The aim of this study was to develop potential anticancer agents based on a naturally occurring baicalein, a flavonoid from Scatellariae radix. Cinnamic acid derivatives were converted to corresponding chlorides and then condensed with 3,4,5-trimethoxyphenol in the presence of BF(3) x Et(2)O to give chalcones. Intramolecular cyclization of these intermediates by the actions of DMSO/I(2) afforded the desired trimethylbaicalein derivatives. Cell viability after treatment with the tested compound for 2 d was determined by a colorimetric MTT assay. The results indicated that most of the derivatives showed improved inhibition of proliferation of Hep G2 cells. Compound 9 was the most potent, in which the cell viability was reduced to <2% at the 25 microM level. In the case of Hep 3B cells, 8a, 8b and 8f showed moderate inhibition of their proliferation and 25 microM was required to reduce the viability to ca. 30%. On the other hand, prostate DU145 cells were more resistant. Most of the derivatives caused a 60% inhibition of DU145 cells only at a concentration of 100 microM or above.