Preoperative inflammation and nutrition-based comprehensive biomarker for predicting prognosis in resectable colorectal cancer.

Background: Colorectal cancer (CRC) remains a major global health concern, with significant morbidity and mortality rates. In this study, we aimed to develop a comprehensive blood indicator based on systemic inflammation and nutritional condition to predict the prognosis of resectable CRC patients. Methods: A retrospective cohort of 210 CRC patients who underwent radical resection at the First Affiliated Hospital of Chongqing Medical University, China, between January 2015 and December 2017, was included in the analysis. Baseline characteristics, preoperative blood markers, including neutrophil count, monocyte count, lymphocyte count, platelets, albumin, and CEA were retrospectively reviewed. Various blood indicators, such as NLR, PLR, MLR, SIRI and OPNI were calculated. The least absolute shrinkage and selection operator (LASSO) method was employed to select indicators to establish a novel comprehensive biomarker (named PSI). Kaplan-Meier survival curves and log-rank tests were used to evaluate the prognostic impact of preoperative OPNI, SIRI, and PSI. Univariate and multivariate Cox regression model were conducted to identify independent prognostic factors for CRC. The receiver operating characteristic (ROC) method assessed the predictive ability of PSI, stage, OPNI, and SIRI. Results: Patients with higher preoperative OPNI and lower SIRI values had significantly better overall survival (OS). PSI was identified as an independent prognostic factor for OS in both univariate and multivariate analysis. Patients with medium (28.3-43.4) and high (>43.4) PSI scores exhibited superior OS compared to those with low (≤ 28.3) PSI scores. PSI showed higher predictive ability (AUC: 0.734) than individual indicators alone (OPNI: 0.721, SIRI: 0.645, stage: 0.635). Conclusion: The novel indicator, PSI, based on preoperative SIRI and OPNI, demonstrated significant prognostic value for resectable CRC patients. PSI outperformed individual indicators and could serve as a reliable tool for prognostic evaluation in CRC patients.

High preoperative CEA and systemic inflammation response index (C-SIRI) predict unfavorable survival of resectable colorectal cancer.

BACKGROUND: CEA and systemic inflammation were reported to correlate with proliferation, invasion, and metastasis of colorectal cancer. This study investigated the prognostic significance of the preoperative CEA and systemic inflammation response index (C-SIRI) in patients with resectable colorectal cancer. METHODS: Two hundred seventeen CRC patients were recruited from Chongqing Medical University, the first affiliated hospital, between January 2015 and December 2017. Baseline characteristics, preoperative CEA level, and peripheral monocyte, neutrophil, and lymphocyte counts were retrospectively reviewed. The optimal cutoff value for SIRI was defined as 1.1, and for CEA, the best cutoff values were 4.1 ng/l and 13.0 ng/l. Patients with low levels of CEA (< 4.1 ng/l) and SIRI (< 1.1) were assigned a value of 0, those with high levels of CEA (≥ 13.0 ng/l) and SIRI (≥ 1.1) were assigned a value of 3, and those with CEA (4.1-13.0 ng/l) and SIRI (≥ 1.1), CEA (≥ 13.0 ng/l), and SIRI (< 1.1) were assigned a value of 2. Those with CEA (< 4.1 ng/l) and SIRI (≥ 1.1) and CEA (4.1-13.0 ng/l) and SIRI (< 1.1) were assigned a value of 1. The prognostic value was assessed based on univariate and multivariate survival analysis. RESULTS: Preoperative C-SIRI was statistically correlated with gender, site, stage, CEA, OPNI, NLR, PLR, and MLR. However, no difference was observed between C-SIRI and age, BMI, family history of cancer, adjuvant therapy, and AGR groups. Among these indicators, the correlation between PLR and NLR is the strongest. In addition, high preoperative C-SIRI was significantly correlated with poorer overall survival (OS) (HR: 2.782, 95% CI: 1.630-4.746, P < 0.001) based on univariate survival analysis. Moreover, it remained an independent predictor for OS (HR: 2.563, 95% CI: 1.419-4.628, p = 0.002) in multivariate Cox regression analysis. CONCLUSION: Our study showed that preoperative C-SIRI could serve as a significant prognostic biomarker in patients with resectable colorectal cancer.

The lncRNA BCYRN1 Functions as an Oncogene in Human Glioma by Downregulating miR-125a-5p in vitro.

INTRODUCTION: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) are deregulated in many cancers and exert their functions through multiple cancer-related biological processes. Glioma is the most common primary malignant central nervous system tumor and has a high fatality rate in adults. In current study, we aimed to determine the role and functional mechanism of the lncRNA BCYRN1 in glioma. METHODS: Gain-of-function and loss-of function approaches were used to investigate the function of BCYRN1. The effects of BCYRN1 on glioma cell proliferation, migration and invasion were evaluated using MTS, Transwell and wound-healing assays. The correlation between the expression of BCYRN1 and miR-125a-5p was verified by quantitative real-time PCR. RESULTS: The upregulation of BCYRN1 promoted the proliferation, migration and invasion of glioma cells. Meanwhile, the knockdown of BCYRN1 had the opposite effects. BCYRN1 was negatively correlated with miR-125a-5p. Additionally, TAZ, the endogenous target of miR-125a-5p, could be regulated by BCYRN1 in RNA and protein levels. A miR-125a-5p inhibitor restored BCYRN1 siRNA function in glioma. CONCLUSION: The present study indicates that BCYRN1 promotes glioma cell proliferation, invasion and migration in vitro. Mechanistically, upregulated expression of BCYRN1 in glioma acts as a sponge to sequester the endogenous tumor suppressor miR-125a-5p and to further increase the expression TAZ. Our findings suggest that BCYRN1 is a novel oncogene and a new therapeutic target for glioma.

Wang's Forceps-Assisted Percutaneous Insertion and Fixation of Peritoneal Dialysis Catheter.

Percutaneous insertion of peritoneal dialysis catheters is theoretically most preferred by nephrologists because of the advantages of bedside performing, surgery independence, and minimal injury over other procedures of catheter placement such as open surgical dissection or laparoscopic operation. However, blindly placing catheters in the percutaneous procedure brings the risk of catheter malposition or bowel perforation; this largely retarded it's implementation. We had previously developed a novel technique termed "Wang's forceps-assisted catheter insertion and fixation," which had been successfully applied in the open surgical catheter insertion and displaced catheter reposition in our center. In this study, we further explored the possibility of applying the Wang's forceps in the procedure of percutaneous catheter insertion both in porcine model and patients with end stage renal disease (ESRD). A total of three miniature pigs successfully received percutaneous catheter insertion using Seldinger's technique with Wang's forceps assistance. The catheters were all placed in the right position and functioning well in dialysate drainage. This novel method of percutaneous catheter insertion was then performed on 20 ESRD patients. The procedure showed effective time-saving with the average operating time of 29.2 ± 3.53 min and was well tolerated by patients with minimal pain and injury. During a follow-up time of 6 months, no complications of catheter displacement, leakage, or blockade occurred. Our preliminary observation demonstrates that utilization of Wang's forceps in a percutaneous procedure conferred benefits of accurately placing and fixing catheters while preserving the merits of minimal invasion and simple performance.

Identification of the appropriate fixation site to avoid peritoneal catheter migration based on a mechanical analysis.

AIM: To conduct mechanical analysis on the relationship between abdominal wall fixation point and the displacement of catheter top, and establish the finite element model for the complex forces and conditions that the catheter wears in human abdominal cavity, in order to provide the scientific basis for optimizing the catheter position in abdominal wall fixation method. METHODS: Using the PIPE59 finite elements to divide units, and taking the lower part of catheter, that is, below interior polyester cuff to simulate and compute the displacement formula. RESULTS: The whole model includes a total of 1701 units. Periodic load was used to simulate the dynamic pressure that peritoneal dialysis catheter gets in abdominal cavity. The load direction was perpendicular to the catheter axis. We used pressure amplitude, duration and frequency as the boundary conditions, and adjusted the fixation point of the catheter lower part at the same time, thus calculating the extreme displacement value of the catheter top end with changing parameter conditions. We also did fitted regression on the results and obtained the displacement formula: y = 0.2 × 0.87x (y: the end displacement of peritoneal dialysis catheter, x: the distance between fixation point and the interior polyester cuff), R2: .982. Simulation the catheter maximal displacement on flat surface demonstrated that additional catheter fixation at the site of 9 cm or more below the internal cuff significantly restricted the catheter migration. CONCLUSIONS: The optimal position of fixation point in peritoneal dialysis is about 9 cm away from the interior polyester cuff.

Telomere Length as a Prognostic Factor for Overall Survival in Colorectal Cancer Patients.

BACKGROUND/AIMS: The stabilization of telomere length has important roles in the carcinogenesis of colorectal cancer. A systemic review and meta-analysis of published studies was performed to assess the prognostic role of telomere length in colorectal cancer. METHODS: Pubmed and Embase were searched for eligible studies on the association between telomere length and overall survival in colorectal cancer patients. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (95%CI) was calculated using fixed-effects or random-effects model according to the magnitude of between-study heterogeneity. RESULTS: Seven individual studies with a total of 956 colorectal cancer patients were included. Long telomere length in cancer tissues was marginally associated with poorer overall survival (Random-effects HR = 1.85, 95% 0.90 to 3.83, P = 0.09). When using studies with adjusted estimates, long telomere length in cancer tissues was independently and significantly associated with poorer overall survival (Fixed-effects HR = 2.70, 95% 1.51 to 4.84, P = 0.001). However, short telomere length in peripheral blood leukocytes was independently and significantly associated with poorer overall survival (Fixed-effects HR = 2.01, 95% 1.46 to 2.77, P < 0.001). CONCLUSIONS: There is some evidence for telomere length as a prognostic factor for overall survival in colorectal cancer patients. More studies with large number of participants are needed to further assess the prognostic significance of telomere length in colorectal cancer patients.

A Study on the Mechanism of Low-Expressed Cancer Stem Cell Marker Lgr5 in Inhibition of the Proliferation and Invasion of Colorectal Carcinoma.

The present study intends to explore the influence of Lgr5 as a marker of tumor stem cells after siRNA interference on the proliferation and invasion of colorectal carcinoma (CRC) and its mechanism. The tissue samples were taken for biopsy from 32 cases of patients and 32 cases of normal subjects by colonoscopy. Real-time quantitative PCR was used to detect the differential expression of Lgr5. After siRNA interference of Lgr5 in CRC cell line CT-26 cells, RT-PCR method was used to detect the mRNA expression level of Lgr5 after interference of CT-26 cells. CCK8 method was used to observe the influence of Lgr5 interference on the proliferation, colony formation, and invasion of CT-26 cells. RT-PCR and Western blot were used to detect the E-cadherin mRNA and protein levels in CT-26 cells. Lgr5 expression level in CRC tissue was significantly higher than that in the corresponding para-carcinoma tissue and the control group, and the differences were statistically significant (P < 0.05). Lgr5 mRNA expression level in tissue with lymph node metastasis was significantly higher than that in the tissue without lymph node metastasis, and the difference was statistically significant (P < 0.05). Compared with the control group, CT-26 cell proliferation, colony formation, and migration capability after Lgr5 siRNA transfection were all significantly reduced, and the differences were statistically significant (P < 0.05). CT-26 cells after Lgr5 interference were found with significantly reduced E-cadherin mRNA and protein levels. Lgr5 facilitates the cell proliferation, colony formation, and migration of colorectal carcinoma, which may be closely related to the expression level of E-cadherin.

Peritoneal catheter fixation to the abdominal wall in surgical catheter implantation to prevent malfunction.

BACKGROUND: Catheter failure, especially catheter displacement and obstruction remain the major barriers for peritoneal dialysis. We have developed a new surgery technique of catheter fixation on the lower abdominal wall in the catheter planting to avert the catheter mechanical complications. METHOD: A retrospective study was performed on 93 patients; among them, 52 patients underwent the traditional method of surgery for catheter insertion and 41 patients received additional catheter fixation. Comparisons of complications including infection, leak, infusion pains, catheter displacement, and obstruction occurred during a follow-up period of 6 months, were made between the fixed and non-fixed groups. RESULTS: Catheter fixation cost more time than the conventional operating procedure (94.2 ± 14.6 min vs. 83 ± 13.3 min, p = 0.043). Complications of infection, leak, and infusion pain that occurred in the fixed and unfixed groups are comparable. Catheter fixation reduced the complications of catheter displacement or obstruction to 0 episode in the fixed group, whereas those complications were encountered by 7 patients in the unfixed group (0/41 vs. 7/52, p = 0.022). All these 7 patients received re-exploration and catheter replacement with further catheter fixation. In the following time until now (ranging from 3 to 16 months), no catheter dysfunction was observed. CONCLUSIONS: These results suggest that catheter fixation is effective in preventing catheter displacement and obstruction in peritoneal dialysis.

Exogenous stem cell factor improves interstitial cells of Cajal restoration after blockade of c-kit signaling pathway.

OBJECTIVE: Interstitial cells of Cajal (ICC) have been endowed with considerable intrinsic plasticity. Blockade of the c-kit signaling pathway results in the shift of ICC towards a smooth muscle-like phenotype. Little is known about stem cell factor (SCF), the ligand of c-kit, and the role it plays in the process of restoration. The aim of this study was to determine whether exogenous SCF can promote ICC replenishment following the blockade of c-kit signaling. MATERIAL AND METHODS: Neutralizing anti-c-kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. Jejunal muscle strips were cultured up to 7 days. Electrical rhythmic changes were monitored and ICC were examined by immunohistochemistry. Expression of c-kit mRNA was detected by reverse transcriptase-polymerase chain reaction, and expression of Kit protein was detected by Western blot. RESULTS: When c-kit receptors were blocked, ICC nearly disappeared from the jejunum accompanied by the loss of electrical slow waves. By day 7, after in vitro culture with SCF (100 ng/ml), the amplitude of muscle strip slow waves was restored to 0.19 +/- 0.07 mV (p < 0.05), whereas the frequency recovered to 13.7 +/- 3.32/min (p < 0.01). Furthermore, labeling for c-kit(+) cells in the myenteric plexus increased and c-kit mRNA and protein expression were up-regulated compared to that of non-treatment with SCF. CONCLUSIONS: The c-kit signaling pathway, activated by SCF, is the critical pathway associated with the control of ICC survival and proliferation. The restoration of ICC number and jejunal electrical rhythm, resulting from blockade of the c-kit signaling pathway, could be facilitated by local SCF administration.

Effects of LPS, PLA(2) and OFR on proton translocation across inner mitochondrial membrane and H(+)-ATPase in the liver.

OBJECTIVE: To elucidate the effects of lipopolysaccharide (LPS), phospholipase A(2) (PLA(2)) and oxygen free radical (OFR) on proton transmembrane translocation and H(+)-ATPase. METHODS: The normal rats were sacrificed for preparetion liver mitochondria and submitochondrial particles for experiments in vitro. Submitochondrial particles were incubated with LPS (100 &mgr;g/mL), PLA(2) (10 u/mL) and FeSO(4)/Vit C (30/90 &mgr;mol/L) at 30 degrees C for 30 min. The proton translocation of submitochondrial particles (SMPs) were assayed with the fluorescent probe ACMA (9-amino-6-chloro-2 methoxya cridine). The mitochondria were incubated with different concentration of LPS, PLA(2) and FeSO(4)/Vit C. The H(+)-ATPase, PLA(2) and malondialdehyde (MDA) were assayed. RESULTS: The fluorescent quenching of ACMA and H(+)-ATPase activity in high dose was significantly decreased after treatment with LPS, PLA(2), FeSO(4)/Vit C (P<0.05). The mitochondrial PLA(2) activity and MDA content were significantly increased after treatment with LPS (P<0.01). CONCLUSIONS: FeSO(4)/Vit C in low dose causes increases H(+)-ATPase activity. LPS, PLA(2), FeSO(4)/Vit C might be the important factors changing H(+)-ATPase and proton translocation across the membrane.