No abstract

Background Lymph node metastasis and tumor progression depend on lymphovascular invasion (LVI). This study aimed to investigate the prognostic role of LVI in patients with stage III colorectal cancer (CRC) and to develop a prognostic nomogram. Material/Methods A retrospective study included 437 patients with stage III CRC. The impact of LVI on overall survival (OS) was analyzed with the Kaplan-Meier method and Cox regression model. A nomogram was constructed, and its predictive accuracy was evaluated using the concordance index (C-index) and the calibration plot. Results LVI was found in 19.7% of cases of stage III CRCs and was significantly correlated with high tumor grade (poor differentiation) and advanced tumor stage (all P<0.05). Patients age, a family history of cancer in a first-degree relative, pre-treatment levels of carcinoembryonic antigen (CEA), prognostic nutritional index (PNI), histological tumor grade, tumor-node-metastasis (TNM) stage, and LVI were independent prognostic indicators (all P<0.05). Compared with the LVI(−) group, patients in the LVI(+) group showed a 1.748-fold increased risk of death (P=0.004) and a significantly reduced OS rate (P<0.001). In the prognostic nomogram, the C-index was significantly increased with LVI compared with the TNM stage alone (0.742 vs. 0.593; P<0.001). Calibration plots showed good fitness of the nomogram for prediction of survival. Comparison of the nomograms with and without LVI showed that inclusion of LVI improved the C-index from 0.715 to 0.742. Conclusions LVI was an indicator of more aggressive biological behavior and poor prognosis in patients with stage III CRC.

Background: PXR (Pregnane X Receptor) and CAR (Constitutive Androstane Receptor) are termed as xenobiotic receptors, which are known as core factors in regulation of the transcription of metabolic enzymes and drug transporters. However, accumulating evidence has shown that PXR and CAR exert their effects on energy metabolism through the regulation of gluconeogenesis, lipogenesis and β-oxidation. Therefore, in this review, we are trying to summary recent advances to show how xenobiotic receptors regulate energy metabolism. Methods: A structured search of databases has been performed by using focused review topics. According to conceptual framework, the main idea of research literature was summarized and presented. Results: For introduction of each receptor, the general introduction and the critical functions in hepatic glucose and lipid metabolism have been included. Recent important studies have shown that CAR acts as a negative regulator of lipogenesis, gluconeogenesis and β -oxidation. PXR activation induces lipogenesis, inhibits gluconeogenesis and inhabits β-oxidation. Conclusion: In this review, the importance of xenobiotic receptors in hepatic glucose and lipid metabolism has been confirmed. Therefore, PXR and CAR may become new therapeutic targets for metabolic syndrome, including obesity and diabetes. However, further research is required to promote the clinical application of this new energy metabolism function of xenobiotic receptors.

Some studies have demonstrated that Rab11-family interacting proteins (Rab11-FIPs) are connected with the tumorigenesis, and they may act as tumor promoters in some cancers. The clinicopathological significance of Rab11-family interacting protein 4 (Rab11-FIP4) expression and its possible effects on pancreatic cancer (PC) are still undiscovered. In this study, Rab11-FIP4 protein expression level in 60 PC specimens and pair-matched non-cancerous samples were detected by immunohistochemistry analysis. The results were analysed and compared with each patients' clinical data. Rab11-FIP4 expression in PC tissues increased significantly more than that of adjacent non-cancerous tissues (P=0.0001). Overexpression of Rab11-FIP4 in the PC tissues was significantly related to tumor size (P=0.0001), histological grade (P=0.028), metastasis (P=0.001) and TNM stage (P=0.004) but not with age (P=0.832), gender (P=0.228) or tumor site (P=0.875). Kaplan-Meier survival analysis showed that overexpression of Rab11-FIP4 was significantly related to overall survival time (P=0.0036). In addition, Rab11-FIP4 in PANC-1 pancreatic cancer cells were successfully knocked-out using the CRISPR/Cas9 system. Rab11-FIP4 knockout in PANC-1 cells inhibited cell growth, invasion and metastasis, and arrested cell cycle progression, but did not alter apoptosis. Our findings suggest that overexpression of Rab11-FIP4 predicts poor clinical outcomes for pancreatic cancer and contributes to pancreatic tumor progression.

Hitherto, it has been identified that numerous basic-helix-loop-helix (bHLH) transcription factors play vital roles in tumor initiation and progression. Atonal homolog 8 (ATOH8) is a member of the bHLH family of transcription factors, which participates in embryogenesis and the development of various tissues. Several studies have demonstrated that ATOH8 is involved in the progression of malignancies; however, the effects of ATOH8 in colorectal cancer (CRC) remain unknown. The aim of the present study was to explore the expression and function of ATOH8 in CRC. The present study included 106 paired CRCs and peritumoral samples. The expression of ATOH8 was evaluated by immunohistochemistry, and the results were compared with the clinical outcomes of the patients. Furthermore, cell proliferation, cell cycle distribution, wound healing and cytotoxicity assays were performed in colon cancer cell line SW620. Immunohistochemical analyses revealed that the expression of ATOH8 in CRC tissues was significantly increased compared with the peritumoral tissues, and that the high expression of ATOH8 was associated with a high serum carcinoembryonic antigen (CEA) level and a worse overall survival. In vitro assays revealed that ATOH8 knockdown in colon cancer cells inhibited cell proliferation, induced cell cycle arrest at the S phase, and increased the percentage of apoptotic cells and sensitivity to 5-fluorouracil (5-FU). The present study suggests that ATOH8 promotes the progression of CRC and may potentially serve as a novel prognostic predictor and potential therapeutic target in CRC.

Background The non-HDL-cholesterol to HDL-cholesterol (NHDLC/HDLC) ratio is closely related to a variety of dyslipidemia-related diseases. This study examined the relationship between the NHDLC/HDLC ratio and non-alcoholic fatty liver (NAFLD) in children and adolescents. Methods This cross-sectional survey included a total of 7759 eligible Chinese children and adolescents (5692 boys and 2067 girls) who received routine medical examinations. The anthropometric and laboratory data of the subjects were collected. NAFLD was diagnosed by liver ultrasonography. Binary logistic regression analysis was performed on the NHDLC/HDLC ratio, NHDLC, HDLC and NAFLD. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic significance of the above parameters for NAFLD. Results The total prevalence of NAFLD was 4.36%, and the prevalence in boys was higher than that in girls (5.61% vs. 1.9%, P < 0.001). The prevalence of NAFLD was positively correlated with the NHDLC/HDLC ratio (P < 0.001). The binary logistic regression analysis demonstrated that the OR was 8.61 (95% CI, 5.90–12.57, P < 0.001) in tertile 3 (highest NHDLC/HDLC ratio) compared with tertile 1 (lowest NHDLC/HDLC ratio). After adjustment for age, sex, body mass index (BMI), alanine aminotransferase (ALT), uric acid (UA), total bilirubin (TB), fasting plasma glucose (FPG) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the OR for tertile 3 (OR = 1.83, 95% CI, 1.04–3.22, P = 0.035) was still significantly higher than that of tertile 1. The area under the curve (AUC) of the NHDLC/HDLC ratio of boys was 0.787, which was significantly greater than NHDLC and HDLC (0.719 and 0.726, P < 0.001). For girls, the AUC of the NHDLC/HDLC ratio was 0.763, which was also significantly greater than NHDLC (0.661, P < 0.001). The cutoff point of the NHDLC/HDLC ratio was 2.475 in boys and 2.695 in girls. In addition, the AUC of the NHDLC/HDLC ratio was 0.761 in subjects with normal ALT levels (ALT ≤40 U/L), which was significantly higher than NHDLC (0.680, P < 0.001) and HDLC (0.724, P = 0.007). For subjects with elevated ALT levels (ALT > 40 U/L), the AUC of the NHDLC/HDLC ratio (0.746) was also significantly greater than NHDLC (0.646, P < 0.001). Conclusions The NHDLC/HDLC ratio was positively correlated with NAFLD in Chinese children and adolescents. It may serve as an effective indicator to help identify NAFLD in children and adolescents.

Background: The non-HDL-cholesterol to HDL-cholesterol (NHDLC/HDLC) ratio is closely related to a variety of dyslipidemia-related diseases. This study aimed to inspect the relationship between the NHDLC/HDLC ratio and non-alcoholic fatty liver (NAFLD) in children and adolescents.Methods: In this cross-sectional survey, a total of 7,759 eligible Chinese children and adolescents (5,692 boys and 2,067 girls) received routine medical examinations. The anthropometric and laboratory data of the subjects were collected. NAFLD was diagnosed by liver ultrasonography. Binary logistic regression analysis was performed on the NHDLC/HDLC ratio, NHDLC, HDLC and NAFLD. Receiver operating characteristic (ROC) curve analysis was exploited to compare the diagnostic significance of the above parameters for NAFLD.Results: The total prevalence of NAFLD was 4.36%, and the prevalence in boys was higher than that in girls (5.61% vs. 1.9%, P < 0.001). The prevalence of NAFLD was positively correlated with the NHDLC/HDLC ratio (P < 0.001). The binary logistic regression analysis demonstrated that the OR was 8.61 (95% CI, 5.90-12.57, P < 0.001) in tertile 3 (highest NHDLC/HDLC ratio) compared with tertile 1 (lowest NHDLC/HDLC ratio). After adjustment for age, sex, body mass index (BMI), alanine aminotransferase (ALT), uric acid (UA), total bilirubin (TB), fasting plasma glucose (FPG) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the OR for tertile 3 (OR=1.83, 95% CI, 1.04-3.22, P = 0.035) was still significantly higher than that of tertile 1. The area under the curve (AUC) of the NHDLC/HDLC ratio of boys was 0.787, which was significantly greater than that of NHDLC and HDLC (0.719 and 0.726, P < 0.001). For girls, the AUC of the NHDLC/HDLC ratio was 0.763, which was also significantly greater than that of NHDLC (0.661, P < 0.001). Furthermore, the cutoff point of the NHDLC/HDLC ratio was 2.475 in boys and 2.695 in girls. In addition, the AUC of the NHDLC/HDLC ratio was 0.761 in subjects with normal ALT levels (ALT ≤ 40 U/L), which was significantly higher than that of NHDLC (0.680, P < 0.001) and HDLC (0.724, P = 0.007). For subjects with elevated ALT levels (ALT > 40 U/L), the AUC of the NHDLC/HDLC ratio (0.746) was also significantly greater than that of NHDLC (0.646, P < 0.001)Conclusions: The NHDLC/HDLC ratio was positively correlated with NAFLD in Chinese children and adolescents. It may serve as an effective indicator to help identify NAFLD in children and adolescents.

No abstract