The association between the body roundness index and the risk of colorectal cancer: a cross-sectional study.

BACKGROUND: Colorectal cancer (CRC), has a link between obesity, especially visceral fat. The body roundness index (BRI) can more accurately assess body fat and visceral fat levels. It is, however, unknown whether BRI is associated with CRC risk. METHODS: 53,766 participants were enrolled from the National Health and Nutrition Examination Survey (NHANES). Analysing the corelation between BRI and CRC risk was performed using logistic regression. Stratified analyses revealed the association based on the population type. Receiver operating characteristic curve (ROC) was performed for predicting CRC risk using different anthropometric indices. RESULTS: The risk of CRC mounting apparently with elevated BRI for participants with CRC compared to normal participants (P-trend < 0.001). The association persisted even after adjusting for all covariates (P-trend = 0.017). In stratified analyses, CRC risk increased with increasing BRI, especially among those who were inactive (OR (95% CI): Q3 3.761 (2.139, 6.610), P < 0.05, Q4 5.972 (3.347, 8.470), P < 0.01), overweight (OR (95% CI): Q3 2.573 (1.012, 7.431), P < 0.05, Q4 3.318 (1.221, 9.020), P < 0.05) or obese (OR (95% CI): Q3 3.889 (1.829, 8.266), P < 0.001, Q4 4.920 (2.349, 10.308), P < 0.001). ROC curve showed that BRI had a better ability in forecasting the risk of CRC than other anthropometric indices such as body weight etc. (all P < 0.05). CONCLUSIONS: CRC risk and BRI have a positive and significant relationship, particularly in inactive participants with BMI ≥ 25 kg/m2. It is hoped that these results will raise awareness of the importance of reducing visceral fat deposition.

CircRNA circ-ATAD1 suppresses miR-618 maturation to participate in colorectal cancer.

BACKGROUND: CircRNA circ-ATAD1 has been characterized as an oncogenic circRNA in gastric cancer, while its role in colorectal cancer (CRC) is unknown. This study was carried out to explore the role of circ-ATAD1 in CRC. METHODS: Paired CRC and adjacent non-tumor tissue samples collected from 64 CRC patients were subjected to RNA extractions and RT-qPCRs to analyze the expression of circ-ATAD1, premature miR-618, and mature miR-618 in CRC. The effects of circ-ATAD1 overexpression on miR-618 maturation were analyzed by transfecting circ-ATAD1 expression vector into CRC cells, followed by determining the expression of premature miR-618 and mature miR-618 using RT-qPCR. The subcellular location of circ-ATAD1 was analyzed by nuclear fractionation assay, and the interaction between circ-ATAD1 and premature miR-618 was analyzed by RNA pull-down assay. The roles of circ-ATAD1, premature miR-618, and mature miR-618 in regulating CRC cell proliferation were explored by CCK-8 assay. RESULTS: Circ-ATAD1 was upregulated in CRC and predicted poor survival. In addition, circ-ATAD1 was inversely correlated with mature miR-618 but not premature miR-618. In CRC cells, circ-ATAD1 overexpression decreased the level of mature miR-618 but not premature miR-618. Circ-ATAD1 was detected in both the nucleus and cytoplasm. A direct interaction between circ-ATAD1 and miR-618 was observed. Moreover, circ-ATAD1 overexpression reduced the inhibitory effects of miR-618 overexpression on cell proliferation. CONCLUSION: Circ-ATAD1 is overexpressed in CRC and may suppress miR-618 maturation to participate in CRC.

Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide accompanying with the high rate of recurrence. Accumulating reports have documented the significance of circular RNAs (circRNAs) in carcinogenesis and development of HCC. This study aimed to establish the mechanism underlying circ-HOMER1 involvement in HCC. To this end, we identified a binding site for miR-1322 via bioinformatics, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and dual-luciferase reporter assays providing evidence of a direct link between circ-HOMER1 and miR-1322. Similarly, the target gene of miR-1322 was investigated. Moreover, we determined the specific function of circ-HOMER1 in HCC with the aid of qRT-PCR based on patient clinical records, Cell Counting Kit-8, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, and wound-healing and transwell assays. Notably, circ-HOMER1 was upregulated in both HCC cells and tissues. This aberrant expression pattern was closely correlated with larger tumor size, higher tumor-node-metastasis stage, and poorer prognosis for the patients with HCC. Moreover, silenced circ-HOMER1 inhibited cell proliferation, migration, and invasion concomitant with the promotion of apoptosis in HCC cells, and vice versa. Mechanistically, circ-HOMER1 enhanced the inhibition of miR-1322 on CXCL6 in HCC. Furthermore, we found that circ-HOMER1 promoted HCC cell growth and aggressiveness by miR-1322/CXCL6 axis. This study may provide a potential prognostic indicator and therapeutic target for patients with HCC.

Gray matter reduction related to decreased serum creatinine and increased triglyceride, Hemoglobin A1C, and low-density lipoprotein in subjects with obesity.

PURPOSE: Altered brain volume and metabolic variables have been found in subjects with obesity. However, the role of metabolic parameters in gray matter volume (GMV) has been poorly investigated. This study aimed to investigate the relationship between the metabolic parameters and brain volume in subjects with obesity. METHODS: Thirty-seven subjects with obesity and 39 age and sex matched normal-weight controls were included in this study. Eighteen of the 37 participants who underwent sleeve gastrectomy were included in the longitudinal analysis. Blood samples and high-resolution 3T T1-weighted magnetic resonance images were collected. Metabolic parameters in plasma and GMV were measured. RESULTS: Multiple linear regression analysis showed that gray matter reduction in several cognition-related cortices including right angular gyrus, superior occipital cortex, superior parietal cortex, and cerebellum was related to decreased creatinine, as well as increased triglyceride, HbA1c, and low-density lipoprotein in plasma in subjects with obesity. Weight loss after the surgery induced significant recovery of altered metabolic parameters and decreased gray matter volume. Furthermore, changes in the four metabolic parameters before and after the surgery were associated with changes in gray matter volume. CONCLUSION: Our results suggest that the gray matter reduction is related to decreased creatinine as well as increased triglyceride, HbA1c, and low-density lipoprotein in plasma in subjects with obesity.

Laparoscopic resections of colorectal cancer and synchronous liver metastases: a case controlled study.

PURPOSE: To investigate the efficacy and safety of laparoscopic simultaneous resections of colorectal cancer and synchronous colorectal liver metastases (SCRLM), relative to open surgery. METHODS: Between 1 January 2009 and 20 April 2014, 20 of 25 patients who underwent laparoscopic simultaneous colorectal cancer and SCRLM resections were matched with 20 of 29 patients who underwent an open approach, based on prognostic propensity scores. Perioperative results and survival outcomes were compared. RESULTS: The laparoscopic and open groups were comparable in demographics, cancer characteristics, surgery characteristics, and chemotherapy treatment. No postoperative mortality occurred in either group. The estimated blood loss and postoperative stay were significantly greater in the open group than in the laparoscopic group (all, p < .05). All other perioperative results and postoperative complications were similar between the two groups, as well as three-year overall and disease-free survival rates. CONCLUSIONS: The postoperative complications and survival rates of patients given laparoscopic simultaneous colorectal cancer and SCRLM resections were similar to those treated with an open approach, but with greater short-term benefits. Laparoscopy in this setting by an experienced surgical team appears safe and effective, and is a feasible alternative to an open approach for selected patients.

Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer.

BACKGROUND: Genetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied. METHODS: We genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients. RESULTS: We identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence-free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples. CONCLUSIONS: Our study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility.

Oncologic outcomes of laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective cohort study from China.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has been indicated to be safe, feasible, and oncologically efficacious for the treatment of early gastric cancer by both retrospective and prospective studies. Although some reports have demonstrated that LAG was also a safe and technically feasible procedure for advanced gastric cancer (AGC), its oncologic outcomes have not yet been confirmed in a multicenter, large-scale study. The aim of this study was to evaluate the oncologic outcomes of LAG for AGC on a multicenter basis in China. METHODS: Data of 1,184 consecutive patients with locally AGC who underwent LAG with curative intent between February 2003 and December 2009 were collected from the Chinese Laparoscopic Gastrointestinal Surgery Study group database and retrospectively analyzed. Survival rates were estimated by the Kaplan-Meier method. Risk factors for recurrence and survival were evaluated by Cox regression models. RESULTS: Postoperatively, 121 patients (10.2%) experienced complications, and 1 patient died (0.1%). Median follow-up was 12 months. Recurrence was observed in 185 patients (16.7%), including hematogenous (31 patients), peritoneal (52), locoregional (25), distant lymph node (LN) (8), mixed (63), and uncertain (6) recurrences. The cumulative 3-year overall survival and disease-free survival rates were 75.3 and 69.0%, respectively. The 3-year overall survival and disease-free survival rates were 89.7 and 88.9% for stage I tumors, 85.0 and 77.0 % for stage II, 60.5 and 59.3% for stage III. Independent risk factors for recurrence were tumor size > 40 mm, intraoperative blood transfusion, and advanced tumor stage. For survival, age > 65 years, tumor size > 40 mm, and advanced tumor stage were independent risk factors. CONCLUSIONS: In addition to being safe and technically feasible, LAG for locally AGC could also yield acceptable short-term oncologic outcomes.

Correlation between Complement C1q A Chain (C1QA) and Macrophages in the Progression of Carotid Atherosclerosis.

Background: There is increasing evidence that macrophages are involved in the development of carotid atherosclerosis (CAS), but the specific mechanism is still unclear. We aimed to explore the key genes that play a regulatory role on macrophages in the progression of CAS. Methods: From 2021 August to 2023 August, GEO datasets GSE100927 and GSE43292 were downloaded and the key gene modules related to CAS were identified by weighted Gene co-expression network analysis (WGCNA). Kyoto Encyclopedia of Genes and Genes (KEGG) pathway analysis was performed on the genes of the key modules to identify common gene enrichment pathways. Differential expression analysis of pathway-related genes was performed by the "limma" package of R software. Case groups were categorized into high and low expression groups based on the expression levels of key genes, and ssGSEA immune infiltration analysis was performed. Results: The turquoise module of GSE100924 (threshold=12) and the brown module of GSE43292 (threshold=7) were obtained through WGCNA analysis. The analysis of KEGG showed that the differentially expressed genes in the turquoise and brown modules were co-enriched in the staphylococcus aureus infection signaling pathway. Differential expression analysis identified 18 common differentially expressed genes, all of which were highly expressed in the case group. C1QA is the gene of interest. According to ssGSEA analysis, the high expression group of C1QA showed a significant increase in the number of macrophages (GSE43292, P=0.0011; GSE100927, P=0.025). Conclusion: This study identified the key gene C1QA involved in regulating macrophage functional activity during the CAS process, providing new ideas for effective control of CAS.

Molecular characterization, clinical value, and cancer-immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer.

BACKGROUND: This research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC). METHODS: The data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool. RESULTS: SRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib. CONCLUSION: In conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Bromodomain-containing protein 9 activates proliferation and epithelial-mesenchymal transition of colorectal cancer via the estrogen pathway in vivo and in vitro.

Background: Bromodomain-containing protein 9 (BRD9) has been reported to be upregulated in multiple malignancies and facilitate cancer progression. However, there is a paucity of data relating to its expression and biological role in colorectal cancer (CRC). Therefore, this current study examined the prognostic role of BRD9 in CRC and the underlying mechanisms involved. Methods: Real-time polymerase chain reaction (PCR) and Western blotting were used to examine the expression of BRD9 in paired fresh CRC and para-tumor tissues from colectomy patients (n=31). Immunohistochemistry (IHC) was performed to assess BRD9 expression in 524 paraffin-embedded archived CRC samples. The clinical variables are including age, sex, carcinoembryonic antigen (CEA), location of tumor, T stage, N stage, and TNM classification. The effect of BRD9 on the prognosis of CRC patients was explored by Kaplan-Meier and Cox regression analyses. Cell counting kit 8 (CCK-8), clone formation assay, transwell assay, and flow cytometry were used to determine CRC cell proliferation, migration, invasion, and apoptosis, respectively. Xenograft models in nude mice were established to investigate the role of the BRD9 in vivo. Results: BRD9 mRNA and protein expression levels were significantly upregulated in CRC cells compared to normal colorectal epithelial cells (P<0.001). IHC analysis of 524 paraffin-embedded archived CRC tissues showed that high BRD9 expression was significantly associated with TNM classifications, CEA, and lymphatic invasion (P<0.01). Univariate and multivariate analyses indicated that BRD9 [hazard ratio (HR): 3.04, 95% confidence interval (CI): 1.78-5.20; P<0.01] expression and sex (HR: 6.39, 95% CI: 3.94-10.37; P<0.01) were independent prognostic factors for overall survival in the entire cohort. Overexpressing BRD9 promoted CRC cell proliferation, while silencing BRD9 inhibited the proliferation of CRC cells. Furthermore, we showed that BRD9 silencing significantly inhibited epithelial-mesenchymal transition (EMT) via the estrogen pathway. Finally, we demonstrated that silencing BRD9 significantly inhibited the proliferation and tumorigenicity of SW480 and HCT116 cells in vitro and in vivo in nude mice (P<0.05). Conclusions: This study demonstrated that BRD9 high could be an independent prognostic risk factor for CRC. Furthermore, the BRD9/estrogen pathway may contribute to the proliferation of CRC cells and EMT, suggesting that BRD9 may be a novel molecular target in the therapeutic treatment of CRC.

Land Use Conflict Identification Coupled with Ecological Protection Priority in Jinan City, China.

Land use conflicts exacerbate soil erosion and reduce biodiversity, which is detrimental to sustainable development. Multiple methods such as multi-criteria evaluation and landscape pattern indexes can identify land use conflicts, but few studies conform to the concept of green development. The concept of green development gives priority to ecological protection and coordinates the relationship between production development, food production and ecological protection to achieve sustainable development. Taking Jinan City (China) as the study area, we identified the ecological source areas by evaluating the importance of ecosystem service functions and ecological sensitivity, then extracted and optimized the ecological corridor network (using the minimum cumulative resistance model and gravity model), and constructed the ecological security pattern. Spatial overlay analysis of cultivated land, construction land, and the ecological security pattern was performed to identify the types and intensity of land use conflicts. Spatially, we found that ecological land was in more serious conflict with cultivated land than construction land. Different types of land use conflicts have significant differences in spatial distribution. The key to land use conflict mediation in Jinan City is to balance food security with the improvements in the quality of the ecological environment. Hence, it is necessary to delineate the main functional zones and formulate tailored land use conflict mediation strategies in each zone. The method for land use conflict identification proposed here follows the principle of giving priority to ecological protection, providing a scientific reference for the utilization and protection of territorial space in other similar areas.

Identification of the shared gene signature and biological mechanism between type 2 diabetes and colorectal cancer.

Background: The correlation of type 2 diabetes mellitus (T2DM) with colorectal cancer (CRC) has garnered considerable attention in the scientific community. Despite this, the molecular mechanisms underlying the interaction between these two diseases are yet to be elucidated. Hence, the present investigation aims to explore the shared gene signatures, immune profiles, and drug sensitivity patterns that exist between CRC and T2DM. Methods: RNA sequences and characteristics of patients with CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. These were investigated using weighted gene co-expression network analysis (WGCNA) to determine the co-expression networks linked to the conditions. Genes shared between CRC and T2DM were analyzed by univariate regression, followed by risk prognosis assessment using the LASSO regression model. Various parameters were assessed through different software such as the ESTIMATE, CIBERSORT, AND SSGSEA utilized for tumor immune infiltration assessment in the high- and low-risk groups. Additionally, pRRophetic was utilized to assess the sensitivity to chemotherapeutic agents in both groups. This was followed by diagnostic modeling using logistic modeling and clinical prediction modeling using the nomogram. Results: WGCNA recognized four and five modules that displayed a high correlation with T2DM and CRC, respectively. In total, 868 genes were shared between CRC and T2DM, with 14 key shared genes being identified in the follow-up analysis. The overall survival (OS) of patients in the low-risk group was better than that of patients in the high-risk group. In contrast, the high-risk group exhibited higher expression levels of immune checkpoints The Cox regression analyses established that the risk-score model possessed independent prognostic value in predicting OS. To facilitate the prediction of OS and cause-specific survival, the nomogram was established utilizing the Cox regression model. Conclusion: The T2DM + CRC risk-score model enabled independent prediction of OS in individuals with CRC. Moreover, these findings revealed novel genes that hold promise as therapeutic targets or biomarkers in clinical settings.

Management of esophagogastric fistula caused by adjustable gastric band erosion: A case report and literature review.

Laparoscopic adjustable gastric banding (LAGB) is commonly used in the treatment of morbid obesity. However, with clinical application and long-term follow-up, the shortcomings of this procedure were also exposed, bringing about surgery-related complications include dysphagia, intragastric band migration, slippage, and gastric band erosion. Lower esophageal and gastric fistula is a rare but dangerous complication after LAGB. We describe a case of esophagogastric fistula occurring twelve years after a laparoscopic band procedure and its successful management in a multidisciplinary and staged manner, followed by a short review of the literature.

Murine neonatal dermal fibroblast acquires a lymphoid tissue organizer cell-like activity upon synergistic activation of TNF-α receptor and LTß receptor.

Tertiary lymphoid organs (TLOs) are ectopic aggregates of immune cells. As accumulating studies demonstrate TLOs as a predictor of better prognosis in certain cancers, targeting TLO formation, which is tightly regulated by the lymphoid tissue organizer cells (LTOs), has become intriguing in cancer treatment. However, the clinical outcome of these attempts is limited, because the approaches for activating tumor adjacent LTO is lack and little is known about what type of self-cell can be used as LTO to initiate TLO formation. Here we demonstrate that co-stimulation with membrane-bound ligand LTα1ß2 and soluble TNF-α could induced an LTO-like activity in murine neonatal dermal fibroblast, featured by high expression of cell migration-associated chemokines and adhesion molecules that resemble typical LTO gene signature. Furthermore, the LTO-phenotypic dermal fibroblast could enhance the attachment and survival of T and B cell and proliferation of T cell. These findings suggest dermal fibroblast as a promising target for TLO induction to improve cancer immunotherapy.

The risk factors of postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy and laparoscopic distal gastrectomy: a propensity score matching analysis.

Postoperative nausea and vomiting (PONV) is a common side effect after laparoscopic surgery. The aim of the study is to investigate the variables that could predict PONV in patients who underwent laparoscopic gastrectomy. We divided patients who underwent laparoscopic gastrectomy into PONV and No-PONV groups. Propensity score matching (PSM) was applied to adjust confounding factors for further validation, and ordinal logistic regression analysis was used to identify predictors for PONV. In the ordinal logistic regression analysis, the preoperative neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]: 3.19, 95% confidence interval [CI]: 1.38-7.38; p < 0.01) was identified as an independent risk factor for the presence of PONV and a predictor of the severity of PONV (OR: 3.44, 95% CI: 1.67-5.20; p < 0.01) in 94 PSM patients. Besides, NLR was positively correlated with the PONV score (r = 0.534, p < 0.001). In the receiver-operating characteristic (ROC) curve analysis, an NLR with an optimal cutoff value of 1.59 predicted severe PONV with a sensitivity of 72% and specificity of 81%. The NLR was an independent risk factor for the presence of PONV, and a high NLR tends to be positively associated with the severity of PONV after laparoscopic gastrectomy.

Potentially functional genetic variants in KDR gene as prognostic markers in patients with resected colorectal cancer.

Angiogenesis plays a key role in the development and treatment response of various tumors. The signaling transductions mediated by the binding of vascular endothelial growth factor (VEGF) to its receptor KDR (kinase insert domain receptor) is the most important pathway in tumor angiogenesis. Single nucleotide polymorphisms (SNPs) in VEGF have been extensively implicated in the etiology and treatment outcome of colorectal cancer (CRC). However, no study has been reported evaluating the role of KDR SNPs in CRC prognosis. We herein assessed the association between four potentially functional KDR SNPs and tumor recurrence in a Chinese population with 408 surgically resected CRC patients. The most significant SNP was for rs10013228 located in the KDR gene promoter. Compared with the homozygous wild-type genotype, the variant-containing genotypes of this SNP were significantly associated with a reduced recurrence risk with a hazard ratio (HR) of 0.53 (95% confidence interval [CI] 0.30-0.95, P = 0.032). Moreover, a borderline significant association was noted for another promoter SNP, rs2071559, with an HR of 0.67 (95% CI 0.42-1.07, P = 0.092). In stratified analysis, the associations of both SNPs were more prominent in patients receiving chemotherapy (HR = 0.47, 95% CI 0.23-0.94, P = 0.033 for rs10013228 and HR = 0.55, 95% CI 0.32-0.95, P = 0.032 for rs2071559). Further analysis revealed a protective effect on patient recurrence by chemotherapy (HR = 0.56, 95% CI 0.32-1.01, P = 0.046), which was more evident in patients with the variant-containing genotypes of each of the two SNPs (HR = 0.09, 95% CI 0.02-0.55, P = 0.009 for rs10013228 and HR = 0.39, 95% CI 0.18-0.86, P = 0.020 for rs2071559). Collectively, our findings suggest SNPs in the KDR gene modulate CRC recurrence, especially in those receiving chemotherapy.

Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis.

Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.

Identification and functional analysis of ligands for natural killer cell activating receptors in colon carcinoma.

Natural killer (NK) cells play important roles in the immune defense against tumor cells. The function of NK cells is determined by a balance between activating and inhibitory signals. DNAX accessory molecule-1 (DNAM-1) and NK group 2 member D (NKG2D) are major NK cell activating receptors, which transduce activating signals after binding their ligands CD155, CD112 and major histocompatibility complex class I-related chains A and B (MICA/B). However, the expression and functions of these ligands in colon carcinoma are still elusive. Here, we show the higher expression of CD155, CD112 and MICA/B in colon carcinoma tissues, although no correlations between the ligands expression and patient clinicopathological parameters were found. The subsequent cytotoxicity assay indicated that NK cells effectively kill colon carcinoma cells. Functional blocking of these ligands and/or receptors with antibodies led to significant inhibition of NK cell cytotoxicity. Importantly, expression of DNAM-1 and NKG2D was reduced in NK cells of colon cancer patients, and this reduction could directly suppress the activation of NK cells. Moreover, colon cancer patients have higher serum concentrations of sCD155 and sMICA/B (soluble ligands, secreted or shed from cells) than those in healthy donors (sCD155, 127.82 ± 44.12 vs. 63.67 ± 22.30 ng/ml; sMICA, 331.51 ± 65.23 vs. 246.74 ± 20.76 pg/ml; and sMICB, 349.42 ± 81.69 vs. 52.61 ± 17.56 pg/ml). The up-regulation of these soluble ligands may down-regulate DNAM-1 and NKG2D on NK cells, ultimately leading to the inhibition of NK cytotoxicity. Colon cancer might be a promising target for NK cell-based adoptive immunotherapy.

Study on the Mechanism of Platelet-Released Clusterins Inducing Restenosis after Carotid Endarterectomy by Activating TLR3/NF-κb p65 Signaling Pathway.

This study aimed to explore the role of clusterin released by platelet aggregation in restenosis after carotid endarterectomy. 35 patients who underwent carotid endarterectomy due to carotid artery stenosis were enrolled in this study. They were admitted to the Third Affiliated Hospital of Qiqihar Medical University from January 2018 to January 2019. All the patients were divided into two groups: the restenosis group and the nonrestenosis group, according to the follow-up results within 12 months. Peripheral blood was collected on the first day, 6 months, and 12 months after operation. The expression of CLU in serum of plasma and platelet culture medium was detected by an ELISA experiment. The vascular endothelial cells were cultured in vitro with 100 ng/mL of human recombinant CLU added to the medium. Cell proliferation, migration, and invasion were detected by CCK8, scratch, and Transwell invasion tests. The expression level of TLR3 and NF-κb p65 proteins in cells was detected by western blot. TLR3 knockout plasmids in vascular endothelial cell lines were transfected. Cell proliferation and migration were detected by CCK8 and the scratch assay. The CLU content in peripheral blood plasma and supernatant of platelet culture medium was significantly higher in the restenosis group than that of the control group (p=0.003) 6 months after operation (p=0.047) and 12 months after operation (p=0.011). When CLU was added to vascular endothelial cell culture medium, the proliferation and migration were significantly enhanced. The TLR3/NF-κb p65 protein expression level in cells also significantly increased. After the transfection of TLR3 knockout plasmids into vascular endothelial cell lines, CLU cannot promote the proliferation and migration of vascular endothelial cells. Platelet-released clusterin can induce vascular endothelial cell proliferation and migration by activating the TLR3/NF-kb p65 signaling pathway, leading to carotid artery restenosis after carotid endarterectomy.