NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways.

OBJECTIVE: To investigate the role of NudCD1 in spindle assembly checkpoint regulation and in the prognosis of colorectal cancer.  METHODS: Immunohistochemical staining was used to detect in situ expression of NudCD1 in 100 colorectal cancer tissue samples. A chi-square test was used to analyse the correlation between the NudCD1 protein expression level of the cancer tissues and clinicopathological features. The Kaplan-Meier survival analysis was used to assess the correlation between the NudCD1 mRNA expression and the three-year survival of patients with colorectal cancer. The impact of NudCD1 on the development of colorectal cancer and the underlying molecular mechanisms were assessed by flow cytometry cell cycle and apoptosis assays after lentiviral overexpression of NudCD1 in two colorectal cancer cell lines. Quantitative real-time PCR was used to assess mRNA expression of the cellular spindle assembly checkpoint genes BUB1, BUBR1, MAD1, CDC20 and MPS1, as well as the downstream genes LIS1, DYNC1H1, and DYNLL1 in the NudC/LIS1/dynein pathway. RESULTS: Compared with normal intestinal tissue (8.00% with high expression), the expression of NudCD1 protein in colorectal cancer tissue was significantly higher (58.00% with high expression, P < 0.01). In addition, expression of NudCD1 significantly correlated with the degree of tumour differentiation and the TNM staging (P < 0.01), as well as the depth of invasion of the primary tumour and lymph node metastasis (P < 0.05). However, there was no correlation with gender, age, tumour site, gross type, tumour size or distant metastasis. The Kaplan-Meier survival analysis showed that patients with high NudCD1 expression in colorectal cancer tissues had a significantly shorter survival time than those with low expression of NudCD1 (P < 0.01). Compared with the transfection of the empty vector, colon cancer HT-29 cells with overexpressed NudCD1 had significantly increased mRNA levels of BUBR1, MPS1 and LIS1. The DNA synthesis phase (S phase) was significantly shorter in cells overexpressing NudCD1 than in the control group (43.83% ± 1.57%, P < 0.05), while there was no difference in apoptosis in the two groups. CONCLUSION: NudCD1 can serve as a valuable prognostic marker for colorectal cancer. It may be involved in the regulation of spindle-assembly checkpoint-gene expression and the LIS1 pathway of colorectal cancer cells.

Prolonged Capecitabine Chemotherapy Following Capecitabine and Oxaliplatin (CAPOX) Regimen Chemotherapy Failed to Improve Survival of Stage III Colorectal Cancer After Radical Resection.

BACKGROUND Colorectal cancer (CRC) is considered to be a worldwide health problem because of its increasing incidence and prevalence. Surgery offers an opportunity for cure, but the postoperative recurrence rate is still high despite the advancement of chemotherapy. This study aimed to assess the efficacy and safety of prolonged capecitabine chemotherapy following CAPOX chemotherapy for stage III  CRC after radical surgery. MATERIAL AND METHODS This study included 212 patients with stage III CRC undergoing open radical surgery from July 2010 to June 2015. Among those patients, 104 patients received prolonged capecitabine chemotherapy (prolonged group) following 8 cycles of CAPOX regimen chemotherapy, while the other 108 patients (control group) received no prolonged chemotherapy. The prolonged chemotherapy consisted of capecitabine (1000 mg/m² per day for 2 weeks) and was repeated every 3 weeks for 8 cycles at most. Long-term survival and toxicities were retrospectively compared. RESULTS Patient characteristics did not differ between the 2 groups. For all patients, no significant difference was found in the 3-year disease-free survival (DFS) (P=0.7775) or 3-year overall survival (OS) rates between the 2 groups (P=0.5787). The prolonged group had significantly higher frequency of hand-foot syndrome (P=0.0267) and paresthesia (P=0.0164). In further subgroup analyses, no benefit for 3-year DFS or 3-year OS of prolonged capecitabine chemotherapy was found in colon cancer or rectal cancer. CONCLUSIONS Prolonged capecitabine chemotherapy following CAPOX regimen chemotherapy failed to improve the survival of patients with stage III CRC after radical surgery.

[Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia].

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.

Mast cell specific immunological biomarkers and metabolic syndrome among middle-aged and older Chinese adults.

The main aim of this study is to explore whether these mast cell specific immunological biomarkers [immunoglobulin E (IgE), chymase and tryptase] is an independent risk factor of MetS and whether the combined action of these biomarkers increased the associations with MetS. Three mast cell-specific immunological biomarkers were measured using enzyme linked immunosorbent assay (ELISA). One-way analysis of covariance and logistic regression models were used for analyzing the associations between immunological biomarkers with MetS. A total of 340 participants, 82 (24.1%) individuals had diabetes mellitus, 31 (9.1%) had MetS (without diabetes mellitus) and 110 had MetS plus diabetes mellitus. After adjusting by multivariable (age, gender, smoking, and family history for hypertension), compared with no diabetes mellitus or MetS group (reference group), hs-CRP was associated with diabetes mellitus [OR (odds ratio): 2.29 (1.15-4.57, 95% CI (confidence interval), p=0.019] and MetS plus diabetes mellitus [OR: 2.20 (1.05-4.61, 95% CI), p=0.036], IgE was associated with MetS plus diabetes mellitus [OR: 2.38 (1.13-5.02, 95% CI), p=0.023]. After adjusting by multivariable, compared with reference group, most of combined elevated inflammatory or immunological biomarkers were significantly associated with diabetes mellitus or MetS with or without diabetes mellitus. Patients with established diabetes mellitus or MetS had different inflammatory or immunological cytokine profile (such as hs-CRP, IgE, chymase, tryptase), which indicated that there is an alteration in the function of the immune system in diabetes mellitus or MetS patient. But these results are requested to be further demonstrated for large sample population-based cohort study.

High Blood Glucose Levels Correlate with Tumor Malignancy in Colorectal Cancer Patients.

BACKGROUND Research shows that type 2 diabetes mellitus (T2DM) affects the risk and prognosis of colorectal cancer (CRC). Here, we conducted a retrospective study to investigate whether the clinicopathological features of CRC patients correlate with their blood glucose levels. MATERIAL AND METHODS We enrolled 391 CRC patients hospitalized in our center between 2008 and 2013. Data of their first fasting plasma glucose (FPG) and 2-h postprandial glucose (2hPPG) level after admission, their clinicopathological features, and survival were collected. The correlations between blood glucose level and clinicopathological features were analyzed by Pearson chi-square analysis. Patient survival was analyzed by Kaplan-Meier and Cox-regression analysis. RESULTS There were 116 out of the 391 CRC patients who had high blood glucose level (H-G group, 29.67%), among which 58 (14.83%), 18 (4.60%), and 40 (10.23%) were diabetes mellitus (DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG), respectively, while 275 (70.33%) patients had normal glucose level (N-G group). Compared with the N-G group, patients in the H-G group had larger tumor diameters and lower tumor differentiation (p<0.05). A higher ratio of patients in the H-G group also had more advanced TNM staging and more ulcerative CRC gross type (p<0.05). No significant difference was observed in patient overall survival among different glucose groups. No effect of insulin therapy on CRC development and patient survival was observed. CONCLUSIONS Blood glucose level in CRC patients correlates significantly with local tumor malignancy, but no significant effect on distant metastasis and patient overall survival was observed.

Prophylactic hepatic artery infusion chemotherapy improved survival after curative resection in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: To explore the effect of prophylactic hepatic artery infusion chemotherapy (HAIC) on survival probability after curative resection in patients with hepatocellular carcinoma (HCC). METHODOLOGY: 85 patients with HCC were randomly assigned to HAIC group (42 cases) and control group (43 patients), all the database of two groups had no significant difference. Patients in HAIC groups underwent hepatic artery infusion chemotherapy (5-FU 1000 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1 and Gemcitabine 1000 mg/m2 on day 1 and 8) starting 3 weeks after operation with intervals of 4 weeks. All patients were followed up for 3 years and intrahepatic recurrence-free survival, disease-free survival rate and overall survival rate were recorded. RESULTS: Intrahepatic recurrence rate of HAIC group and the control group was respectively 19.05% and 39.53%, P < 0.05. Disease-free survival rate was respectively 57.14% and 44.19%, P < 0.05. Overall survival rate was 66.67% and 46.51%, P < 0.05. All patients in HAIC group tolerated the therapy. No adverse effect above grade 3 was reported in HAIC group. CONCLUSION: HAIC effectively and safely prevents intrahepatic recurrence and improves the prognosis of patients with HCC after curative resection.

Spleen-preserving distal pancreatectomy or distal pancreatectomy with splenectomy?: Perioperative and patient-reported outcome analysis.

GOALS: We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. BACKGROUND: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. STUDY: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses, estimated blood loss, intraoperative transfusion, and operative time between the 2 groups. More perioperative complications occurred in the DPS group than in the SPDP group (P=0.0344). Consequently, postoperative hospital stay was significantly shorter in the SPDP group than in the DPS group (P=0.0273). In the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (P=0.047). More patients in the DPS group felt fatigue (P=0.0481) and poor health condition (P=0.0371). Less newly developed (P=0.0193) and aggravated diabetes mellitus (P=0.0361) were also observed in the SPDP group. Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts, and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. CONCLUSIONS: In addition to frequent higher grade complications, prolonged hospital stays, and severe hematological abnormalities, DPS seemed to result in poor health condition based on the follow-up survey. Even an effort to preserve an adult spleen in distal pancreatectomy is worthwhile.

Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy. METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014). CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

Optimal selection of methods for mini-invasive treatment of extrahepatic bile duct stones.

BACKGROUND/AIMS: This study aims to identify the optimal mini-invasive treatment for extrahepatic bile duct stones. METHODOLOGY: One hundred and seventy eight patients with EHBD stones were randomized into 4 groups: laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) plus T-tube drainage (group LT), LC and LCBDE with endonasobiliary drainage (ENBD) tube (group LE), and endoscopic sphincterotomy with ENBD followed by LC (group EE) and T-tube drainage of open CBDE (group OT). Demographic data, perioperative findings, postoperative outcomes, hospital expense, gastrointestinal quality of life index (GIQLI) scores and cost per quality-adjusted life year (QALY) were analyzed. RESULTS: The operating time was longest in group EE. There was less bleeding in group OT and EE. Group LE and EE had shorter hospital stay and recovery time of intestinal motility. The postoperative white blood cell count and serum C-reaction protein level were higher in group LT and OT. Postoperatively, the mean GIQLI scores in group LE and EE were higher. Mean cost were highest in group EE. Patients in group LE had lowest cost per QALY. CONCLUSIONS: The modified laparoscopic procedure, LC combined with LCBDE followed by a primary closure over the ENBD tubes, appears to be the best option for patients with EHBD stones.

Endoscopic Biliary Stenting Versus Percutaneous Transhepatic Biliary Stenting in Advanced Malignant Biliary Obstruction: Cost-effectiveness Analysis.

BACKGROUND/AIMS: This study aims to compare the clinical outcomes and costs between endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary stenting (PTBS). METHODOLOGY: We randomly assigned 112 patients with unresectable malignant biliary obstruction 2006 and 2011 to receive EBS or PTBS with self-expandable metal stent (SEMS) as palliative treatment. PTBS was successfully performed in 55 patients who formed the PTBS group (failed in 2 patients). EBS was successfully performed in 52 patients who formed the EBS group (failed in 3 patients). The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. RESULTS: Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the BBS group (P < 0.05). There was no significant difference in effectiveness of biliary drainage (P = 0.9357) or survival time between two groups (P = 0.6733). Early complications occurred in PTBS group was significantly lower than in EBS group (3/55 vs 11/52, P = 0.0343). Late complications in the EBS group did not differ significantly from PTBS group (7/55 vs 9/52, P = 0.6922). The survival curves in the two groups showed no significant difference (P = 0.5294). Conclusions: 3.

RENAL PROTECTIVE EFFECT AND CLINICAL ANALYSIS OF VITAMIN B 6 IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: To investigate the protective effect and possible mechanisms of vitamin B 6 against renal injury in patients with sepsis. Methods: A total of 128 patients with sepsis who met the entry criteria in multiple centers were randomly divided into experimental (intravenous vitamin B 6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen, serum creatinine, and renal resistance index monitored by ultrasound) were compared between the two groups. Results: After 7 d of treatment, the IL-6, IL-8, TNF-α, and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the blood urea nitrogen, serum creatinine, and renal resistance index values in the experimental group were significantly lower than those in the control group ( P < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality ( P > 0.05). However, the intensive care unit length of stay and the total hospitalization expenses in the experimental group were significantly lower than those in the control group ( P < 0.05). Conclusion: The administration of vitamin B 6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.

A study on the effect of using the video teach-back method in continuous nursing care of stroke patients.

Objective: To explore the effect of a video teach-back method on continuous family nursing care of stroke patients. Methods: Stroke patients hospitalized in our hospital between March 2020 and March 2023 who met the inclusion criteria were randomly divided into an intervention group (n = 45), who received routine health education plus video teach-back training of caregivers, and a control group (n = 45), who received routine health education only. The effects on nursing-related variables were compared between the two groups. Results: Total scores representing the caring ability of caregivers in the intervention group increased significantly over time relative to baseline and were higher than those of the control group. Scores representing the care burden of caregivers in the intervention group decreased significantly over time and were lower than those of the control group. Conclusion: The teach-back method combined with video education improves the nursing ability of family caregivers and can improve the self-care ability of stroke patients.

Hematological benefits after spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis.

BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: The demographics and final diagnoses were similar between the two groups. There were no significant differences in estimated blood loss, intraoperative transfusion and operative time between the two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. CONCLUSIONS: In addition to frequent higher-grade complications, prolonged hospital stays, DPS appeared to result in severer hematological abnormalities. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

Spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis.

BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We aimed to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses estimated blood loss, intraoperative transfusion and operative time between the two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). On the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (p = 0.047). More patients in the DPS group felt fatigue (p = 0.0481) and poorer health condition (p = 0.0371). Less newly developed (p = 0.0193) and aggravated diabetes mellitus (p = 0.0361) were also observed in SPDP group. CONCLUSIONS: In addition to frequent higher-grade complications, and prolonged hospital stays, DPS appeared to result in poorer health condition based on follow-up survey. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

Percutaneous transhepatic biliary stenting vs. surgical bypass in advanced malignant biliary obstruction: cost- effectiveness analysis.

BACKGROUND/AIMS: This study aims to compare the clinical outcomes and costs between percutaneous transhepatic biliary stenting (PTBS) and surgical bypass. METHODOLOGY: We randomly assigned 142 patients with unresectable malignant biliary obstruction between 2005 and 2010 to receive PTBS or surgical bypass as palliative treatment. PTBS was successfully performed in 70 patients who formed the PTBS group (failed in 7 patients). Sixty five patients underwent surgical bypass treatment. Additional gastrojejunostomy was performed in five patients. The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. RESULTS: Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the surgical group (p<0.05). There was no significant difference in effectiveness of biliary drainage (p=0.9307) or survival time between two groups (p=0.4826). Early complications of PTBS group was significantly lower than surgical group (3/75 vs. 11/65, p=0.0342). Late complication in PTBS group did not differ significantly from surgical group (9/70 vs. 6/65, p=0.6823). The survival curves in the two groups showed no significant difference (p=0.1032). CONCLUSIONS: PTBD is a better palliative treatment than surgical bypass for unresectable malignant biliary obstruction for its high effectiveness of biliary drainage and acceptable expense and complication.

ARID2 mitigates hepatic steatosis via promoting the ubiquitination of JAK2.

Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem. However, the complicated pathogenesis of NAFLD contributes to the deficiency of effective clinical treatment. Here, we demonstrated that liver-specific loss of Arid2 induced hepatic steatosis and this progression could be exacerbated by HFD. Mechanistic study revealed that ARID2 repressed JAK2-STAT5-PPARγ signaling pathway by promoting the ubiquitination of JAK2, which was mediated by NEDD4L, a novel E3 ligase for JAK2. ChIP assay revealed that ARID2 recruited CARM1 to increase H3R17me2a level at the NEDD4L promoter and activated the transcription of NEDD4L. Moreover, inhibition of Jak2 by Fedratinib in liver-specific Arid2 knockout mice alleviated HFD-induced hepatic steatosis. Downregulation of ARID2 and the reverse correlation between ARID2 and JAK2 were also observed in clinical samples. Therefore, our study has revealed an important role of ARID2 in the development of NAFLD and provided a potential therapeutic strategy for NAFLD.

Prophylactic adjuvant hepatic arterial infusion chemotherapy reduced hepatic metastases from Stage III colorectal cancer after curative resection.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of Stage III colorectal cancer patients after curative resection. METHODOLOGY: We randomly assigned 287 Stage III colorectal cancer patients after curative resection between 2002 and 2008 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (combined therapy) or 6 cycles of systemic chemotherapy alone (monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 2-hour infusion of Oxaliplatin (85mg/m2) on day 1 followed by folinic acid 200mg/m2 as a 2-hour infusion on days 2 and 3 and by 5-fluorouracil 2400mg/m2 as a 48-hour infusion on days 2 and 3. The treatment repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year disease-free survival (Combined therapy, 75.00%; Monotherapy, 63.27%; p=0.0035), overall survival (Combined therapy, 84.29%; Monotherapy, 65.31%; p=0.0006) and liver metastases-free survival (Combined therapy, 80.00%; Monotherapy, 69.39%; p=0.0451). CONCLUSIONS: HAIC effectively and safely prevents metachronous liver metastases and improves the prognosis of patients with Stage III colorectal cancer after curative resection.

Endostatin inhibits angiogenesis in hepatocellular carcinoma after transarterial chemoembolization.

BACKGROUND/AIMS: This study aims to investigate the influence of endostatin on angiogenesis in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). METHODOLOGY: Ninety-five patients with HCC were enrolled. Twenty-six patients received initial liver resection without preoperative TACE (non-TACE), 24 received preoperative TACE without endostatin (TACE), 22 received endostatin (15mg/m2) right after TACE intravenously (TACE-V) and 23 received endostatin (15mg/m2) through the hepatic artery during TACE (TACE-A). TACE was performed using Gemcitabine 1000mg/m2 (emulsified with lipiodol, 10-12mL), cisplatin 40 mg/m2 and 5-fluorouracil 500mg/m2 through the hepatic artery feeding the tumor. Patients received liver resection 4 weeks after second course of TACE. RESULTS: The mean microvessel density (MVD) was 32.23±12.71, 57.46±18.38, 44.36±15.13 and 43.48±15.59 in non-TACE, TACE, TACE-V and TACE-A group respectively. The positive rate of vascular endothelial growth factor (VEGF) expression was 46.15%, 91.67%, 77.27% and 73.91% in non-TACE, TACE, TACE-V and TACE-A groups, respectively. Compared to the non-TACE group, MVD and VEGF expression in TACE, TACE-V and TACE-A groups were significantly higher (p<0.05). MVD and VEGF expression in the TACE-V and TACE-A groups were significantly lower than in the TACE group (p<0.05). CONCLUSIONS: Endostatin could significantly repress angiogenesis in HCC after TACE by down-regulating expression of VEGF.

Delayed administration of D-Ala2-D-Leu5-enkephalin, a delta-opioid receptor agonist, improves survival in a rat model of sepsis.

Sepsis is the major cause of death in intensive care units, despite enormous efforts in the development of antimicrobial therapies. Sepsis is mediated by early [e.g., tumor necrosis factor (TNF)-α and interleukin (IL)-1ß] and late [e.g., high-mobility group box 1 protein (HMGB1)] proinflammatory cytokines. HMGB1, which is secreted into extracellular milieu by activated macrophages or passively released by destroyed macrophages, stimulates intensive inflammatory responses. D-Ala2-D-Leu5-enkephalin (DADLE), a synthetic δ-opioid receptor agonist, has been shown to protect rats from sepsis. Here we elucidated the mechanism for protective effect of DADLE against sepsis. Sepsis was established in Sprague-Dawley rats by means of cecal ligation and puncture (CLP). In this model, the serum levels of TNF-α and IL-1ß were increased after 2-3 h, while those of HMGB1 were increased after 18 h. Administration of DADLE (5 mg/kg) concurrently with CLP improved survival, which was associated with the decreases in the serum levels of TNF-α, IL-1ß and HMGB1. Importantly, DADLE administrated 4 h after CLP showed comparable protective effect as the concurrent administration, with decreased serum HMGB1 levels. Moreover, peritoneal macrophages isolated from rats were challenged with lipopolysaccharide (LPS). Concurrent or delayed DADLE administration at 10(-6) M suppressed the LPS-induced cell death. DADLE also suppressed the release of HMGB1 from macrophages that was induced by LPS, TNF-α or interferon-γ. In conclusion, DADLE protects rats from sepsis probably by decreasing the serum level of HMGB1. We propose DADLE as a candidate for septic shock therapy, even if it is administered after the onset of sepsis.