Assessing anatomical variations of the inferior mesenteric artery via three-dimensional CT angiography and laparoscopic colorectal surgery: a retrospective observational study.

To assess the anatomy of the inferior mesenteric artery (IMA) and its branches by reviewing laparoscopic left-sided colorectal cancer surgery videos and comparing them with preoperative three-dimensional computed tomography (3D-CT) angiography, to verify the accuracy of 3D-CT vascular reconstruction techniques. High-definition surgical videos and preoperative imaging data of 200 patients who underwent laparoscopic left-sided colorectal cancer surgery were analysed, and the alignment of the IMA and its branches in relation to the inferior mesenteric vein (IMV) was observed and summarized. The above two methods were used to measure the length of the IMA and its branches. Of 200 patients, 47.0% had the sigmoid arteries (SAs) arise from the common trunk with the superior rectal artery (SRA), and 30.5% had the SAs arise from the common trunk with the left colic artery (LCA). In 3.5% of patients, the SAs arising from both the LCA and SRA. The LCA, SA, and SRA emanated from the same point in 13.5% of patients, and the LCA was absent in 5.5% of patients. The range of D cm (IMA length measured by intraoperative silk thread) and d cm (IMA length measured by 3D-CT vascular reconstruction) in all cases was 1.84-6.62 cm and 1.85-6.52 cm, respectively, and there was a significant difference between them. (p < 0.001). The lengths between the intersection of the LCA and IMV measured intraoperatively were 0.64-4.29 cm, 0.87-4.35 cm, 1.32-4.28 cm and 1.65-3.69 cm in types 1A, 1B, 1C, and 2, respectively, and there was no significant difference between the groups (p = 0.994). There was only a significant difference in the length of the IMA between the 3D-CT vascular reconstruction and intraoperative observation data, which can provide guidance to surgeons in preoperative preparation.

Does transanal drainage tubes placement have an impact on the incidence of anastomotic leakage after rectal cancer surgery? a systematic review and meta-analysis.

BACKGROUND: Whether Transanal drainage tubes (TDTs) placement reduces the occurrence of anastomotic leakage (AL) after rectal cancer (RC) surgery remains controversial. Most existing meta-analyses rely on retrospective studies, while the prospective studies present an inadequate level of evidence. METHODS: A systematic review and meta-analysis of prospective studies on TDTs placement in RC patients after surgery was conducted. The main analysis index was the incidence of AL, Grade B AL, and Grade C AL, while secondary analysis index was the incidence of anastomotic bleeding, incision infection, and anastomotic stenosis. A comprehensive literature search was performed utilizing the databases Cochrane Library, Embase, PubMed, and Web of Science. We recorded Risk ratios (RRs) and 95% confidence intervals (CI) for each included study, and a fixed-effect model or random-effect model was used to investigate the correlation between TDTs placement and four outcomes after RC surgery. RESULTS: Seven studies (1774 participants, TDT 890 vs non-TDT 884) were considered eligible for quantitative synthesis and meta-analysis. The meta-analysis revealed that the incidence of AL was 9.3% (83/890) in the TDT group and 10.2% (90/884) in the non-TDT group. These disparities were found to lack statistical significance (P = 0.58). A comprehensive meta-analysis, comprising four studies involving a cumulative sample size of 1259 participants, revealed no discernible disparity in the occurrence of Grade B AL or Grade C AL between the TDT group and the non-TDT group (Grade B AL: TDT 34/631 vs non-TDT 26/628, P = 0.30; Grade C AL: TDT 11/631 vs non-TDT 27/628, P = 0.30). Similarly, the incidences of anastomotic bleeding (4 studies, 876 participants), incision infection (3studies, 713 participants), and anastomotic stenosis (2studies, 561 participants) were 5.5% (24/440), 8.1% (29/360), and 2.9% (8/280), respectively, in the TDT group, and 3.0% (13/436), 6.5% (23/353), and 3.9% (11/281), respectively, in the non-TDT group. These differences were also determined to lack statistical significance (P = 0.08, P = 0.43, P = 0.48, respectively). CONCLUSION: The placement of TDTs does not significantly affect the occurrence of AL, Grade B AL, and Grade C AL following surgery for rectal cancer. Additionally, TDTs placement does not be associated with increased complications such as anastomotic bleeding, incision infection, or anastomotic stenosis. TRIAL REGISTRATION: PROSPERO: CRD42023427914.

Does the setting of local government economic growth targets promote or hinder urban carbon emission performance? Evidence from China.

Growth target management drives China's economic expansion, leading to potential carbon emission externalities. This study examines the impact of economic growth target setting on carbon emission performance in 257 Chinese localities from 2004 to 2020. Using cluster standard error regression, 2SLS instrumental variable regression, and the spatial Durbin model, the results show that moderate growth targets improve urban carbon emission performance. Conversely, aggressive targets do not enhance regional carbon emission performance. Moderate growth targets foster innovation in green technology, while aggressive ones encourage investment in fixed assets and new city growth, impeding performance. Cities in the eastern and western regions, with larger populations and less reliance on natural resources, benefit more from effective economic development targets. The establishment of local targets negatively affects neighboring regions' carbon emissions performance, particularly at a spatial scale of 100 to 200 km. This paper contributes to understanding the environmental consequences of growth target setting and offers insights for balancing economic growth with carbon emission governance in emerging market countries.

Elongating the role of renewable energy and sustainable foreign direct investment on environmental degradation.

Climatic variations and GHG emissions are the most debated issues of the current age economically, socially, politically and environmentally. An internationally legally binding treaty on climate change, the "Paris Agreement" is followed by G-8 countries to maintain environmental sustainability with green development. The research investigates the relationship of GHG emissions with renewable energy (RE), foreign direct investment (FDI), total population (TP), and trade (TR). The time span of 22 years is used for analytical purposes covering the period from 2000 to 2021 b y addressing the literary gap. The analytical procession found total population and trade increase GHG emissions because of its modern fundamental layers toxic human activities and polluted trade practices. The decreasing behavior toward GHG emissions has been determined by FDI and RE. The findings of this research have confirmed the long-run relationship among variables. They are evidence that the eco-innovative steps by G-8 countries significantly reduce GHG emissions directly or indirectly. Furthermore, the analytical outcomes indicate that innovative green development in renewable energy sector can reduce the GHG emissions pressure from this sector and contribute to net zero emissions. The extracting results have suggested policies for environmental practitioners and economic developers.

A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer.

The objective of this study is to explore the effects of thymalfasin for injection on perioperative immune function and long-term prognosis of patients with colorectal cancer (CRC). In total, 400 patients who entered the groups from February 2019 to January 2021 and underwent radical resection of CRC in the Fourth Hospital of Hebei Medical University were the study subjects. They were separated into experimental group (0-199, XELOX chemotherapy and thymalfasin for injection) and control group (200-400, XELOX chemotherapy) by random number table, and the experimental group was randomly divided into conventional-dose group (n = 100, 1.6 mg of thymalfasin for injection, twice a week) and high-dose group (n = 100, 1.6 mg of thymalfasin for injection, thrice a week) according to a ratio of 1:1, to analyze the effects of different treatment schemes on perioperative immune function and long-term prognosis of CRC patients. Compared with control group, the conventional-dose group and high-dose group had notably lower incidences of perioperative infection (P < 0.05), with no significant difference in both groups (P > 0.05). The experimental group had significantly lower overall incidence of early and late postoperative complications, local recurrence rate and the incidence of distant metastasis, and higher perioperative immune function indexes and median disease free survival (DFS) (P < 0.05). The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment for such patients, which can benefit patients.

Potential impact of platelet-to-lymphocyte ratio on prognosis in patients with colorectal cancer: A systematic review and meta-analysis.

Background: Numerous studies have confirmed that inflammation promotes the occurrence, development and prognosis of colorectal cancer (CRC). Objective: This study focuses on the potentially prognostic value of the platelet-to-lymphocyte ratio (PLR) in CRC patients. Data Sources: This study was registered at PROSPERO (ID: CRD42020219215). Relative studies were searched on PubMed, Cochrane Library, Embase, Web of Science, and clinical trial databases by two back-to-back reviewers. Study Selection and Intervention: Studies were screened according to the predetermined inclusion and exclusion criteria, comparing prognosis differences between low PLR levels and high PLR levels for CRC patients. Main Outcome Measures: Studies were integrated and compared to analyze the value of PLR in predicting overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), disease-free survival (DFS) and recurrence-free survival (RFS) of CRC. Results: Outcomes were compared using Review Manager (version 5.4) software from Cochrane Collaboration. A total of 27 literary works, including 13,330 patients, were incorporated into our study. The final results showed that higher PLR levels had worse OS (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.21-1.62, P < 0.00001), DFS (HR = 1.44, 95% CI = 1.09-1.90, P = 0.01) and RFS (HR = 1.48, 95% CI = 1.13-1.94, P = 0.005) than lower PLR levels, respectively. However, there was no evidence of significance for PFS (HR = 1.14, 95% CI = 0.84-1.54, P = 0.40) and CSS (HR = 1.16, 95% CI = 0.88-1.53, P = 0.28) in the final meta-analysis. Limitations: Our study has the following limitations. First of all, we only included literature published in English, which means that some publication bias may be inevitable. In addition, our study used aggregate data, not individual data; furthermore, we did not define the exact cut-off value representing the PLR level. Conclusion: An elevated PLR seems to be an adverse prognostic factor affecting survival outcomes in patients with CRC. Meanwhile, more prospective studies are required to confirm our conclusion.PROSPERO ID: CRD42020219215.

Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR 2100043775.

Nomogram for benign anastomotic stricture after surgery for rectal cancer.

BACKGROUND: Benign anastomotic stricture remains among the most prevalent complications following surgery for rectal cancer. OBJECTIVE: This study is aimed at identifying risk factors of anastomotic stricture as well as generating an effective nomogram for the stricture. METHODS: Design: This is a retrospective study. SETTING: This study was conducted from January 2015 to December 2019 in a single tertiary center for rectal cancer. PATIENTS: A total of 117 rectal cancer patients after surgery without recurrence were enrolled in this study, of which 39 with anastomotic stricture and 78 without stricture. MAIN OUTCOME MEASURES: Their clinical and pathological data were collected. Multiple logistic regression analysis was conducted to identify risk factors for anastomotic stricture and to generate the nomogram prediction model. RESULTS: Multivariate analysis of the primary cohort led to the identification of LCA (left colic artery) preservation (OR, 0.074; P = 0.0015), protective stoma (OR, 5.353; P = 0.012), anastomotic leakage (OR, 12.027; P = 0.005), and anastomotic distance (OR, 7.578; P = 0.012) as independent risk factors for anastomotic stricture. The following predictive model was derived: Logit (anastomotic stricture) = 0.074∗ LCA + 5.353∗ Protective stoma +12.027∗ Anastomotic leakage + 7.578∗ Anastomotic distance. Assessment of the predictive model revealed that the area under the curve (AUC) was 0.871, while the cutoff value was 15.444 with a sensitivity of 64.1% and a specificity of 94.8%. LIMITATIONS: The main limitation is the research design of a retrospective and case-controlled study with a small sample size from a single center. CONCLUSIONS: LCA preservation, protective stoma, anastomotic leakage, and anastomotic distance may affect the occurrence of anastomotic stricture following surgery for rectal cancer. The nomogram model generated in the present study can be valuable in the prediction of anastomotic stricture. This study has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR 2100043775).

Methylation detection of circulating tumor cell miR-486-5p/miR-34c-5p in the progression of colorectal cancer.

AIMS: This study set out to examine the expression and methylation levels of miR-486-5p/miR-34c-5p and its mechanism of action based on the microRNA methylation level of circulating tumor cells (CTCs) in colorectal cancer (CRC) through clinical data and tissue detection. METHODS: EGFR and EpCAM immunophospholipid magnetic spheres (EpCAM-IML/EGFR-IML) were synthesized by the thin film method to capture CTCs in peripheral blood. The expression of miR-486-5p/miR-34c-5p was detected via real-time fluorescent quantitative PCR (RT-PCR). Methylation-specific PCR was implemented to detect the methylation level of miR-486-5p/miR-34c-5p, and 5-Aza-dC was used for demethylation treatment to detect the effect of changes in methylation levels on the tumor cells development. Cell Counting Kit-8 (CCK-8) analysis, transwell assay, and flow cytometry were used to determine the effects of demethylation and overexpression on the proliferation, invasion, migration, and apoptosis of CRC cells. RESULTS: The results showed that the expression and methylation levels of the miR-486-5p/miR-34c-5p isolated from CTCs were low and the methylation level was high in tumor cells and tissues. In CRC cell lines, demethylation and overexpression of miR-486-5p/miR-34c-5p could effectively inhibit the proliferation, invasion and migration of tumor cells, and facilitate tumor apoptosis (p < 0.05). CONCLUSION: The constructed CTCs sorting system has characteristics of high specificity and high sensitivity, is a supplement to tissue samples, and has guiding significance for the clinical rational use of drugs and personalized therapy.

Evaluating technological innovation impact: an empirical analysis of the offshore wind sector.

This study analyzed the determinants that impact innovation on offshore wind energy (OSW) for a select group of countries, applying mixed-method approaches for a period between 2011 and 2021. The OSW sector witnessed cost reductions in recent years; therefore, this study analyzed how these factors impact technological innovation in the OSW sector. The fixed effects results proved trademark, carbon emissions, offshore wind capacity, and electricity from renewable energy, technical and scientific journals are significant and impact innovation regarding offshore wind energy. The maximum likelihood (MLE) coefficients are more robust than the restricted maximum likelihood (MREL) and better explained the significance of the variables in spurring OSW innovation. Ultimately, the interaction term "cross" came out significant in the analysis. It signified the importance of the interaction variables in scaling innovation. Similarly, the study forecasted OSW capacity additions to grow to more than 28GW by 2036, at a 48.8% growth rate, from the current over 55 G.W. capacity. Additionally, the infrastructure development of the OSW sector via a fitted line between total global offshore capacity and the development projects observed a negative relationship among these dual factors evaluated in the OSW, showing a decreasing trend of capacity additions among countries, as well as the fitted line relationship between total country OSW capacity and operational projects showed that China leads the globe with operational OSW projects. At the same time, Brazil is the new leader in the world regarding OSW capacity. The general analysis of the parameters of the OSW infrastructure plan showed the sector is declining regarding secured projects, development projects, operational projects, and capacities additions in some countries. However, global total capacity additions are on a steady path, declining a bit. This is attributable to the pandemic that slowed the global economy. This study will serve as a reference document for policy formulators regarding scaling up innovation for offshore wind energy.

Threat shapes visual context sensitivity selectively through low-spatial-frequency channels.

Threat has long been supposed to affect human cognitive processing including visual size perception. Whether such threat-related modulation effect varies as a function of spatial frequency is largely unexplored. Here we used low- or high-pass filtered threatening animal and fearful face images as primes and measured their effects on the processing of the Ebbinghaus illusion. Results showed that threatening-animal primes relative to neutral ones significantly decreased the illusion magnitude in low-spatial-frequency rather than in high-spatial-frequency ranges. However, fearful- and neutral-face primes had a comparable effect on the illusion magnitude in both spatial frequency ranges. Notably, when inhibitory transcranial magnetic stimulation was applied to the left temporo-parietal junction (TPJ), fearful-face primes significantly decreased the illusion magnitude in low-spatial-frequency rather than in high-spatial-frequency ranges. However, the opposite pattern of results was observed with right TPJ stimulation. The findings suggest that threat shapes basic aspects of visual perception in a spatial frequency-specific manner, possibly via magnocellular projections from both subcortical and cortical fear-processing systems to early visual cortex.

Efficacy and safety of apatinib monotherapy for patients with advanced breast cancer: a systematic review and meta-analysis.

Background: Patients with advanced breast cancer usually have poor prognosis. Apatinib is a small-molecule tyrosine kinase inhibitor, and the reports regarding the efficacy and safety of apatinib monotherapy for advanced breast cancer in the current literature are controversial. Therefore, we performed a systematic review and meta-analysis to collect and pool efficacy and safety data of apatinib monotherapy for advanced breast cancer with the aim of providing up-to-date evidence to aid clinical practice. Methods: This study was registered at PROSPERO (CRD42020190049). Three literature databases, including PubMed, EMBASE, and Cochrane Library, were searched. For evaluating efficacy, the objective response rate and disease control rate were extracted or calculated. Safety was evaluated in terms of the proportions of patients with grade 3 or 4 treatment-related adverse events. The pooled proportions of the outcomes and their 95% confidence interval were shown. The Kaplan-Meier curves of overall survival and progression-free survival were pooled from the extracted data of the included studies. Furthermore, pooled medians for overall survival and progression-free survival were calculated. A p-value of < 0.05 was considered statistically significant. Results: Six studies were included and deemed eligible for further quality evaluation and analysis. The pooled objective response rate and disease control rate were 20.4% and 71.6%, respectively. The pooled proportions of four hematologic adverse events ranged from 2.6% to 6.9%. The pooled proportions of hypertension, hand-foot syndrome, transaminase increased, and proteinuria ranged from 4.1% to 24.3%, and other non-hematologic adverse events were <1%. The pooled median progression-free survival and overall survival were 4.00 and 10.43 months, respectively, in cases of advanced breast cancer treated with apatinib. Conclusions: This study confirms the reliable efficacy of apatinib monotherapy for advanced breast cancer. However, non-hematologic grade 3-4 adverse events, especially hypertension, are more frequently observed during apatinib treatment than during treatment with other tyrosine kinase inhibitors, such as sunitinib or sorafenib. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020190049.

Identification of Hypoxia-Related Subtypes, Establishment of Prognostic Models, and Characteristics of Tumor Microenvironment Infiltration in Colon Cancer.

Background: Immunotherapy is a treatment that can significantly improve the prognosis of patients with colon cancer, but the response to immunotherapy is different in patients with colon cancer because of the heterogeneity of colon carcinoma and the complex nature of the tumor microenvironment (TME). In the precision therapy mode, finding predictive biomarkers that can accurately identify immunotherapy-sensitive types of colon cancer is essential. Hypoxia plays an important role in tumor proliferation, apoptosis, angiogenesis, invasion and metastasis, energy metabolism, and chemotherapy and immunotherapy resistance. Thus, understanding the mechanism of hypoxia-related genes (HRGs) in colon cancer progression and constructing hypoxia-related signatures will help enrich our treatment strategies and improve patient prognosis. Methods: We obtained the gene expression data and corresponding clinical information of 1,025 colon carcinoma patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct hypoxia subtypes (subtype A and subtype B) according to unsupervised clustering analysis and assessed the clinical parameters, prognosis, and TME cell-infiltrating characteristics of patients in the two subtypes. We identified 1,132 differentially expressed genes (DEGs) between the two hypoxia subtypes, and all patients were randomly divided into the training group (n = 513) and testing groups (n = 512). Following univariate Cox regression with DEGs, we construct the prognostic model (HRG-score) including six genes (S1PR3, ETV5, CD36, FOXC1, CXCL10, and MMP12) through the LASSO-multivariate cox method in the training group. We comprehensively evaluated the sensitivity and applicability of the HRG-score model from the training group and the testing group, respectively. We explored the correlation between HRG-score and clinical parameters, tumor microenvironment, cancer stem cells (CSCs), and MMR status. In order to evaluate the value of the risk model in clinical application, we further analyzed the sensitivity of chemotherapeutics and immunotherapy between the low-risk group and high-risk group and constructed a nomogram for improving the clinical application of the HRG-score. Result: Subtype A was significantly enriched in metabolism-related pathways, and subtype B was significantly enriched in immune activation and several tumor-associated pathways. The level of immune cell infiltration and immune checkpoint-related genes, stromal score, estimate score, and immune dysfunction and exclusion (TIDE) prediction score was significantly different in subtype A and subtype B. The level of immune checkpoint-related genes and TIDE score was significantly lower in subtype A than that in subtype B, indicating that subtype A might benefit from immune checkpoint inhibitors. Finally, an HRG-score signature for predicting prognosis was constructed through the training group, and the predictive capability was validated through the testing group. The survival analysis and correlation analysis of clinical parameters revealed that the prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. There were also significant differences in immune status, mismatch repair status (MMR), and cancer stem cell index (CSC), between the two risk groups. The correlation analysis of risk scores with IC50 and IPS showed that patients in the low-risk group had a higher benefit from chemotherapy and immunotherapy than those in the high-risk group, and the external validation IMvigor210 demonstrated that patients with low risk were more sensitive to immunotherapy. Conclusion: We identified two novel molecular subgroups based on HRGs and constructed an HRG-score model consisting of six genes, which can help us to better understand the mechanisms of hypoxia-related genes in the progression of colon cancer and identify patients susceptible to chemotherapy or immunotherapy, so as to achieve precision therapy for colon cancer.

Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.

Low-spatial-frequency priming potentiates the high-level mechanisms of contextual influence.

The context sensitivity of visual size perception can be enhanced by prior exposure to low-spatial-frequency (LSF) relative to high-spatial-frequency information. Whether LSF priming affects low- or high-level mechanisms of contextual influence remains to be clarified. By using the Ebbinghaus illusion, which is a classic example of context-dependent size perception, we reduced the lightness contrast of surrounding inducers relative to the background and the shape similarity of the central target and surrounding inducers to diminish or eliminate low-level contour interaction and high-level size contrast, respectively. The results showed that LSF-related enhancement of context influence was unaffected by a change to the surround elements' contrast but not by a change to the shape similarity between the target and surround. The findings provide evidence that LSF priming primarily affects high-level rather than low-level mechanisms of contextual influence, possibly by weakening the suppressive function of feedback connections from higher visual regions to the early visual cortex.

ADAMTS8 Inhibits Cell Proliferation and Invasion, and Induces Apoptosis in Breast Cancer.

INTRODUCTION: A disintegrin and metallopeptidase with thrombospondin motifs (ADAMTSs), whose expression is dysregulated in various cancers, is implicated in cancer development. Herein, we aimed to investigate the functional role of ADAMTS8 in breast cancer (BC) and explore the underlying mechanisms. METHODS: The protein expression of ADAMTS8 in BC cell lines and tumor tissues from BC patients was quantified by Western blot. ADAMTS8 overexpression was induced by transfection with pEZ-M90-ADAMTS8 plasmid using lipofectamine 2000. To generate ADAMTS8 stable knockdown cells, MDA-MB-231 cells were transfected with psi-H1-ADAMTS8siRNA plasmids. Cell counting kit-8 (CCK-8) assay, wound-healing assay, transwell assay and flow cytometry assay were employed to analyze the effects of ADAMTS8 on the proliferation, migration, invasion and apoptosis of BC cells. Chemosensitivity also was assessed using CCK-8 assay. The expressions of ß-catenin, MMP-7 and c-Myc were measured by Western blot. RESULTS: Our results showed that ADAMTS8 expression was significantly lower in BC tissues than that in adjacent non-tumor tissues. Overexpression of ADAMTS8 in MDA-MB-453 cells could inhibit the cell proliferation, migration and invasion and promote apoptosis. ADAMTS8 knockdown displayed the reverse effect in MDA-MB-231 cells. Consistently, in vivo data showed that ADAMTS8 overexpression led to a reduction in tumor growth. In addition, chemosensitivity testing in MDA-MB-453 cells transfected with pEZ-M90-ADAMTS8 plasmid indicated that cisplatin inhibited cell growth dramatically. Furthermore, attenuated ß-catenin, MMP-7 and c-Myc level was detected after ADAMTS8 overexpression. CONCLUSION: These results indicate that increased ADAMTS8 expression could modify the progression of BC by inhibiting cell proliferation and invasion while promoting the apoptosis of BC cells. Thus, ADAMTS8 represents a potential therapeutic target for BC therapy.

The lncRNA FEZF1-AS1 Promotes the Progression of Colorectal Cancer Through Regulating OTX1 and Targeting miR-30a-5p.

Long noncoding RNAs (lncRNAs) participate in and regulate the biological process of colorectal cancer (CRC) progression. Our previous research identified differentially expressed lncRNAs in 10 CRC tissues and 10 matched nontumor tissues by next-generation sequencing (NGS). In this study, we identified an lncRNA, FEZF1 antisense RNA 1 (FEZF1-AS1), and further explored its function and mechanism in CRC. We verified that FEZF1-AS1 is highly expressed in CRC tissues and cell lines. Through functional experiments, we found that reduced levels of FEZF1-AS1 significantly suppressed CRC cell migration, invasion, and proliferation and inhibited tumor growth in vivo. Mechanistically, we discovered that reduced levels of the lncRNA FEZF1-AS1 inhibited the activation of epithelial-mesenchymal transition (EMT); the overexpression of orthodenticle homeobox 1 (OTX1) partially rescued the FEZF1-AS1-induced inhibition of protein expression. It indicated that FEZF1-AS1 may play a role in the occurrence and development of CRC by regulating the FEZF1-AS1/OTX1/EMT pathway. Furthermore, it was reported that FEZF1-AS1 is located in both the nucleus and cytoplasm of HCT116 cells. Dual-luciferase reporter assays verified that FEZF1-AS1 directly binds miR-30a-5p and negatively regulated each other. Further, we showed that 5'-nucleotidase ecto (NT5E) is a direct target of miR-30a-5p, and the inhibition of miR-30a-5p expression partially rescued the inhibitory effect of FEZF1-AS1 on NT5E. Our results indicated that the mechanism by which FEZF1-AS1 positively regulates the expression of NT5E is through sponging miR-30a-5p. Our study demonstrated that lncRNA FEZF1-AS1 is involved in the development of CRC and may serve as a diagnostic and therapeutic target for CRC patients.

Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3ß pathway.

Isochorismatase domain-containing 1 (ISOC1) is a coding gene that contains an isochorismatase domain. The precise functions of ISOC1 in humans have not been clarified; however, studies have speculated that it may be involved in unknown metabolic pathways. Currently, it is reported that ISOC1 is associated with breast cancer. In this research, the aim is to investigate the critical role of ISOC1 in colorectal cancer (CRC) and to explore its biological function and mechanism in colon cancer cells. In 106 paired clinical samples, we found that the levels of ISOC1 expression were widely increased in cancer tissues compared with matched adjacent non-tumor tissues and that increased expression of ISOC1 was significantly associated with tumor size, tumor invasion, local lymph node metastasis and Tumor, Node and Metastasis (TNM) stage. Moreover, higher expression levels of ISOC1 were correlated with shorter disease-free survival in patients 2 years after surgery. In vitro, ISOC1 knockdown inhibited the proliferation and migration and induced the apoptosis of colon cancer cells, and in vivo, the xenograft tumors were also inhibited by ISOC1 silencing. We also used MTS, Transwell and cell apoptosis assays to confirm that ISOC1 plays a critical role in regulating the biological functions of colon cancer cells through the AKT/GSK-3ß pathway. Additionally, the results of confocal microscopy and western blot analysis indicated that ISOC1 knockdown could promote p-STAT1 translocation to the nucleus.