Systematic analysis of cuproptosis abnormalities and functional significance in cancer.

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.

Population-based screening for colorectal cancer in Wuhan, China.

Fecal DNA test has emerged as a non-invasive alternative for colorectal cancer (CRC) screening in average-risk population. However, there is currently insufficient evidence in China to demonstrate the effectiveness of population-based CRC screening using fecal DNA based test. Here, a large-scale real-world study for CRC screening was implemented in Wuhan, Hubei province, China. A total of 98,683 subjects aged between 45 and 60 years were screened by a fecal DNA test (ColoTect®) which detected methylation status of SDC2, ADHFE1, and PPP2R5C. Participants who tested positive were advised to receive diagnostic colonoscopy. 4449 (4.5%) subjects tested positive for fecal DNA test, and 3200 (71.9%) underwent colonoscopy. Among these, 2347 (73.3%) had abnormal colonoscopy findings, of which 1330 (56.7%) subjects received pathological diagnosis. Detection rates for CRC and advanced precancerous lesions were 1.3% and 2.3%, respectively. Detection rates for nonadvanced adenomas and polyps were 14.0% and 21.6%, respectively. 28.0% of all colonoscopies showed colorectal neoplasm but lack pathological diagnosis. 6.1% showed other abnormalities such as enteritis. In conclusion, preliminary real-world evidence suggested that fecal DNA tests had promising diagnostic yield in population-based CRC screening. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=192838, identifier ChiCTR2300070520.

Colonic stent as a bridge to surgery versus emergency rection for malignant left-sided colorectal obstruction: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The role of self-expanding metal stent (SEMS) implantation as a bridge to surgery in malignant left-sided colorectal obstruction (MLCO) remains controversial. OBJECTIVE: To evaluate the safety of SEMS implantation versus emergency surgery (ER) in the treatment of MLCO. METHODS: Four major literature databases (Cochrane Library, Embase, PubMed, and Web of Science) were searched to collect articles published before April 20, 2023. After determining random or fixed-effect models based on heterogeneity tests, odds ratios (RR) or standardized mean differences (SMD) with their respective 95% confidence intervals (CI) were calculated. RESULTS: Nineteen randomized controlled studies were included. The main outcomes included overall tumor recurrence rate, 30-day mortality rate, and overall incidence of complications. Secondary outcomes included mortality-related indicators, tumor recurrence-related indicators, surgery-related indicators, and other relevant indicators. The study found that there was no significant difference in the 30-day mortality rate between the SEMS group and the er group. However, the SEMS group had a lower overall incidence of complications (RR = 0.787, P = .004), lower incision infection rate (RR = 0.472, P = .003), shorter operation time (SMD = -0.591, P = .000), lower intraoperative blood loss (SMD = -1.046, P = .000), lower intraoperative transfusion rate (RR = 0.624, P = .021), lower permanent stoma rate (RR = 0.499, P = .000), lower overall stoma rate (RR = 0.520,P = .000), shorter hospital stay (SMD = -0.643, P = .014), and more lymph node dissections during surgery (SMD = 0.222, 95% CI: 0.021-0.423, P = .031), as well as a higher primary anastomosis rate (RR = 0.472, 95% CI: 0.286-0.7 77, P = .003), among other advantages. However, the SEMS group had a higher overall tumor recurrence rate (RR = 1.339, P = .048). CONCLUSION: SEMS has significant advantages over er in relieving clinical symptoms and facilitating postoperative recovery in MLCO, but does not reduce the tumor recurrence rate. Neoadjuvant chemotherapy combined with SEMS may provide a new approach to the treatment of MLCO.

A deep learning-based system for mediastinum station localization in linear EUS (with video).

Background and Objectives: EUS is a crucial diagnostic and therapeutic method for many anatomical regions, especially in the evaluation of mediastinal diseases and related pathologies. Rapidly finding the standard stations is the key to achieving efficient and complete mediastinal EUS imaging. However, it requires substantial technical skills and extensive knowledge of mediastinal anatomy. We constructed a system, named EUS-MPS (EUS-mediastinal position system), for real-time mediastinal EUS station recognition. Methods: The standard scanning of mediastinum EUS was divided into 7 stations. There were 33 010 images in mediastinum EUS examination collected to construct a station classification model. Then, we used 151 videos clips for video validation and used 1212 EUS images from 2 other hospitals for external validation. An independent data set containing 230 EUS images was applied for the man-machine contest. We conducted a crossover study to evaluate the effectiveness of this system in reducing the difficulty of mediastinal ultrasound image interpretation. Results: For station classification, the model achieved an accuracy of 90.49% in image validation and 83.80% in video validation. At external validation, the models achieved 89.85% accuracy. In the man-machine contest, the model achieved an accuracy of 84.78%, which was comparable to that of expert (83.91%). The accuracy of the trainees' station recognition was significantly improved in the crossover study, with an increase of 13.26% (95% confidence interval, 11.04%-15.48%; P < 0.05). Conclusions: This deep learning-based system shows great performance in mediastinum station localization, having the potential to play an important role in shortening the learning curve and establishing standard mediastinal scanning in the future.

Diagnostic value of endoscopic ultrasonography in periampullary duodenal tumours.

Introduction: The objective of this study was to investigate the diagnostic value of endoscopic ultrasonography (EUS) for tumours around the duodenal ampullary. Patients and Methods: A retrospective analysis was performed on cases diagnosed and treated in our hospital from October 2016 to August 2021 due to the lesions around the duodenal ampulla. All patients received EUS, abdominal enhanced computed tomography (CT) and magnetic resonance imaging combined with magnetic resonance cholangiopancreatography (MRI-MRCP). Pathological diagnosis was used to verify the accuracy of the imaging findings. The detection rates of periampullary tumours by EUS, abdominal enhanced CT and MRI-MRCP were determined and compared. Results: A total of 86 patients were included in this study. According to the pathological diagnosis, the detection rate of EUS was 87% (36/41) for periampullary tumour lesions with a tumour diameter <1 cm, which was significantly higher than that of MRI-MRCP (59%, 24/41) (P = 0.003) and CT (44%, 18/41) (P < 0.001). For periampullary tumour lesions with a tumour diameter ≥1 cm, the detection rate of MRI-MRCP was 93% (42/45), which was significantly higher than that of EUS (78%, 35/45) (P = 0.036) and CT (76%, 34/45) (P = 0.02). Conclusions: EUS can accurately detect tumour lesions around the ampullary part of the duodenum with minimal gas interference. For periampullary tumour lesions <1 cm, EUS has better diagnostic accuracy than abdominal-enhanced CT and MRI-MRCP. In addition, a biopsy of the lesion can be performed at the same time during the EUS examination. Therefore, EUS has an important clinical significance and value in the diagnosis of duodenal periampullary tumours.

Comparison of vonoprazan-based with rabeprazole-based dual therapy for treatment-naive patients of Helicobacter pylori infection: a prospective, multi-center, randomized controlled study.

BACKGROUND: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan-amoxicillin (VA) and 14-day rabeprazole-amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. METHODS: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. RESULTS: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). CONCLUSIONS: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication.

Effect of wet-heparinized suction on the quality of mediastinal solid tumor specimens obtained by endoscopic ultrasound-guided fine-needle aspiration: a retrospective study from a single center.

BACKGROUND: Mediastinal lesions are diagnosed sometimes by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Wet-heparinized suction technique has been used to improve the quality of abdominal solid tumor samples obtained by EUS-FNA. The aim of the study is to assess the effect of wet-heparinized suction on the quality of mediastinal solid tumor samples and to evaluate the safety of the method. METHODS: The medical records, EUS-FNA records, pathologic data, and follow-up data between the patients who suspected mediastinal lesions with wet-heparinized suction and conventional suction were retrospectively and comparatively analyzed. Adverse events at 48 h and 1 week after EUS-FNA were evaluated. RESULTS: Wet-heparinized suction contributed to more tissue specimens (P < 0.05), superior tissue integrity (P < 0.05), and a longer length of white tissue core (P < 0.05). In addition, the more complete the tissue bar was, the higher the rate of successful sample (P < 0.05). Moreover, the total length of the white tissue bar at the first puncture was remarkably longer in the Experimental group (P < 0.05). No significant difference in red blood cell contamination in paraffin sections was found between the two groups (P > 0.05). There was no complication after discharge in both groups. CONCLUSION: Wet-heparinized suction can improve the quality of mediastinal lesion samples obtained by EUS-FNA and increase the success rate of sampling. In addition, it will not aggravate blood contamination in paraffin sections while ensuring a safe puncture.

Detection value of endoscopic ultrasound-guided 19G fine-needle wet-heparinized suction for pancreatic solid tumors: a randomized controlled trial.

Background: Conventional endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has some inevitable flaws in the detection of pancreatic solid tumors, such as an incomplete histological structure of the obtained pancreatic biopsy tissues and blood coagulation. Heparin can prevent blood coagulation, thus improving the structural integrity of the specimen. However, whether the combination of EUS-FNA and wet heparin can improve the detection of pancreatic solid tumors needs to be further explored. Hence, this study aimed to compare the EUS-FNA combined with wet heparin and the conventional EUS-FNA, and analyze the detection value of EUS-FNA combined with wet heparin for pancreatic solid tumors. Methods: The clinical data of 52 patients with pancreatic solid tumors who had received EUS-FNA at the Wuhan Fourth Hospital from August 2019 to April 2021 were selected. Patients were divided into a heparin group and a conventional wet-suction group using a randomized number table. The total length of biopsy tissue strips, total length of white tissue core in pancreatic biopsy lesions [according to macroscopic on-site evaluation (MOSE)], total length of white tissue core in each biopsy tissue, erythrocyte contamination in the paraffin sections, and postoperative complications were compared between the groups. The receiver operating characteristic curve was used to reflect the detection value of EUS-FNA combined with wet heparin for pancreatic solid tumors. Results: The heparin group had a longer total length of biopsy tissue strips (P<0.05) and total length of white tissue core (P<0.05) than the conventional group. There was a positive correlation between the total length of white tissue core and the total length of biopsy tissue strips in both groups (conventional wet-suction group: r=0.470, P<0.05; heparin group: r=0.433, P<0.05). The heparin group had milder erythrocyte contamination in the paraffin sections (P<0.05). The total length of white tissue core in the heparin group had the highest diagnostic performance, with a Youden index of 0.819 [area under the curve (AUC) =0.944]. Conclusions: Our research shows that wet-heparinized suction improves the quality of pancreatic solid tumor tissue biopsy obtained by 19G fine-needle aspiration and is a safe and efficient aspiration method in conjunction with MOSE for tissue biopsy. Trial Registration: Chinese Clinical Trial Registry ChiCTR2300069324.

circ_0006089 Facilitates Gastric Cancer Progression via Decoying miR- 515-5p and Up-regulating CXCL6.

BACKGROUND: Gastric cancer (GC) is the most common cancer globally. Recent research has suggested that circular RNAs (circRNAs) play crucial roles in GC tumorigenesis and progression. The present study is performed to clarify the possible mechanism of circRNA has_circ_0006089 (circ_0006089) in GC. METHODS: The differentially expressed circRNAs were screened out by analyzing the dataset GSE83- 521. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect circ_0006089, miR-515-5p and CXCL6 expression levels in GC tissues and cell lines. CCK-8, BrdU and Transwell assays were adopted to examine the biological function of circ_0006089 in GC cells. The interaction between miR-515-5p and circ_0006089, as well as between CXCL6 and miR-515-5p, was confirmed through bioinformatics, RNA immunoprecipitation (RIP) assay, dual-luciferase reporter gene assay and RNA pull-down assay. RESULTS: Circ_0006089 was significantly upregulated in GC tissues and cells, and miR-515-5p was remarkably downregulated. After knocking down circ_0006089 or overexpressing miR-515-5p, the growth, migration and invasion of GC cells were markedly reduced. In terms of mechanism, miR-515- 5p was verified to be the target of circ_0006089, and CXCL6 was validated as miR-515-5p's downstream target gene. Inhibiting miR-515-5p reversed the inhibitory effect knocking down circ_0006089 had on GC cell proliferation, migration and invasion. CONCLUSION: Circ_0006089 facilitates the malignant biological behaviors of GC cells via the miR-515- 5p/CXCL6 axis. Circ_0006089 can probably act as one of the important biomarkers and therapeutic targets in GC treatment strategies.

Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis.

The present work focused on exploring the role and underlying molecular mechanism of action of the non-coding RNA (miRNA/circRNA) in colorectal cancer (CRC). Here, we found that miR-653 was dramatically upregulated in CRC tissues and cells. CRC Patients with high miR-653 level possessed poor prognosis. miR-653 elevated proliferation, migration, and invasion, meanwhile suppressed apoptosis of CRC cells. Furthermore, circSETD3 directly sponged miR-653 and negatively regulate miR-653 to affect proliferation, migration, invasion, and apoptosis of CRC cells. Moreover, miR-653 served as carcinoma-promoting gene via targeting KLF6, and circSETD3 knockdown significantly reversed the inhibitory effect of KLF6 overexpression on CRC cells. In addition, hypoxia obviously increased expression of miR-653. Knockdown of miR-653 decreased the effects of hypoxia on CRC cell proliferation, migration and invasion. Taken together, these findings indicated that circSETD3/miR-653/KLF6 axis may be an effective therapeutic target for CRC patients.

Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study.

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Comparison of high-dose dual therapy with bismuth-containing quadruple therapy in Helicobacter pylori-infected treatment-naive patients: An open-label, multicenter, randomized controlled trial.

OBJECTIVE: Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial. METHOD: Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. RESULTS: A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p > 0.05). CONCLUSION: High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.

A deep learning-based system for bile duct annotation and station recognition in linear endoscopic ultrasound.

BACKGROUND: Detailed evaluation of bile duct (BD) is main focus during endoscopic ultrasound (EUS). The aim of this study was to develop a system for EUS BD scanning augmentation. METHODS: The scanning was divided into 4 stations. We developed a station classification model and a BD segmentation model with 10681 images and 2529 images, respectively. 1704 images and 667 images were applied to classification and segmentation internal validation. For classification and segmentation video validation, 264 and 517 videos clips were used. For man-machine contest, an independent data set contained 120 images was applied. 799 images from other two hospitals were used for external validation. A crossover study was conducted to evaluate the system effect on reducing difficulty in ultrasound images interpretation. FINDINGS: For classification, the model achieved an accuracy of 93.3% in image set and 90.1% in video set. For segmentation, the model had a dice of 0.77 in image set, sensitivity of 89.48% and specificity of 82.3% in video set. For external validation, the model achieved 82.6% accuracy in classification. In man-machine contest, the models achieved 88.3% accuracy in classification and 0.72 dice in BD segmentation, which is comparable to that of expert. In the crossover study, trainees' accuracy improved from 60.8% to 76.3% (P < 0.01, 95% C.I. 20.9-27.2). INTERPRETATION: We developed a deep learning-based augmentation system for EUS BD scanning augmentation. FUNDING: Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Hubei Province Major Science and Technology Innovation Project, National Natural Science Foundation of China.

Deep learning-based pancreas segmentation and station recognition system in EUS: development and validation of a useful training tool (with video).

BACKGROUND AND AIMS: EUS is considered one of the most sensitive modalities for pancreatic cancer detection, but it is highly operator-dependent and the learning curve is steep. In this study, we constructed a system named BP MASTER (pancreaticobiliary master) for EUS training and quality control. METHODS: The standard procedure of pancreatic EUS was divided into 6 stations. We developed a station classification model and a pancreas/abdominal aorta/portal confluence segmentation model with 19,486 images and 2207 images, respectively. Then, we used 1920 images and 700 images for classification and segmentation internal validation, respectively. To test station recognition we used 396 videos clips. An independent data set containing 180 images was applied for comparing the performance between models and EUS experts. Seven hundred sixty-eight images from 2 other hospitals were used for external validation. A crossover study was conducted to test the system effect on reducing difficulty in ultrasonographics interpretation among trainees. RESULTS: The models achieved 94.2% accuracy in station classification and .836 dice in segmentation at internal validation. At external validation, the models achieved 82.4% accuracy in station classification and .715 dice in segmentation. For the video test, the station classification model achieved a per-frame accuracy of 86.2%. Compared with EUS experts, the models achieved 90.0% accuracy in classification and .77 and .813 dice in blood vessel and pancreas segmentation, which is comparable with that of experts. In the crossover study, trainee station recognition accuracy improved from 67.2% to 78.4% (95% confidence interval, .058-1.663; P < .01). CONCLUSIONS: The BP MASTER system has the potential to play an important role in shortening the pancreatic EUS learning curve and improving EUS quality control in the future.

Overexpression of the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 is associated with the poor prognosis of patients with colorectal cancer.

Tumor necrosis factor receptor-associated protein-1 (TRAP-1), a mitochondrial chaperone, contributes significantly to the progression of cancer. However, the understanding of its involvement in the clinicopathological characteristics and prognosis of colorectal cancer (CRC) remains limited. The aim of the present study was to assess the significance of TRAP-1 expression in CRC. The expression of TRAP-1 was evaluated in corresponding cancerous, paracancerous, lymph node and distant metastatic tissues of 256 cases of CRC by immunohistochemistry. The associations between TRAP-1 expression and the clinicopathological parameters and survival rates of patients was assessed. Out of 256 patients with CRC, TRAP-1 expression was detected in 203 (79.3%). TRAP-1 expression was significantly increased in cancerous tissue compared with that in corresponding paracancerous tissues (P<0.001). Overexpression of TRAP-1 was significantly associated with differentiation (P=0.011), depth of invasion (P=0.006), lymph node metastasis (P<0.001) and tumor-node-metastasis stage (P<0.001). In patients with high TRAP-1 expression, the 5-year overall survival (OS) rate was 38.0%, in contrast to 56.5% in patients with low TRAP-1 expression (P=0.003). Similarly, the 5-year progression-free survival (PFS) was 26.6% for patients with high TRAP-1 expression and 53.3% for patients with low TRAP-1 expression (P<0.001). Multivariate analyses indicated the TRAP-1 expression is an independent prognostic factor for poorer OS [P=0.015; hazard ratio (HR), 1.914] and PFS (P<0.001; HR, 2.534). Thus, TRAP-1 may serve as a potential biomarker for predicting the prognosis of patients with CRC. Specifically, overexpression of TRAP-1 may predict progression and poor survival in cases of CRC.

Plasma levels of interleukin 18, interleukin 10, and matrix metalloproteinase-9 and -137G/C polymorphism of interleukin 18 are associated with incidence of in-stent restenosis after percutaneous coronary intervention.

This study aims to investigate the relationship between the levels of IL-18, IL-10, and MMP-9 and -137G/C polymorphism of interleukin 18 with the risk of in-stent restenosis (ISR). The study population consisted of 68 patients with ISR, 173 in non-ISR group, treated with drug-eluting stent and evaluated by coronary angiography post-procedure and at follow-up, and also 109 without angiographic evidence of coronary artery disease (CAD) which formed a reference control group (non-CAD group). The sequential plasma IL-18, IL-10, and MMP-9 levels were assessed at admission, 24 h, and 2 weeks after percutaneous coronary intervention. The -137G/C polymorphism of IL-18 was genotyped by the ligase detection reaction-polymerase chain reaction. Plasma IL-18 and MMP-9 increased significantly from admission, peaking after 24 h and fall after 2 weeks. Compared with the non-ISR group, the ISR group had higher levels of IL-18 and MMP-9, but IL-10 level was the opposite. The -137GG genotype of IL-18 was significantly higher than of the CG and CC genotypes. A significant higher frequency of -137G allele or GG genotype of IL-18 was observed in patients with ISR group compared with the non-ISR group. There is correlation between the changes of IL-18, IL-10, MMP-9, and ISR. IL-18 promoter -137G/C polymorphism influences IL-18 levels and the susceptibility to ISR, suggesting that IL-18-mediated pathways are causally involved in the process of ISR.

Clinical analysis for the application of endoscopic ultrasonography in the diagnosis of patients with a retroperitoneal space-occupying lesion.

OBJECTIVE: To report our experience and to evaluate the application of endoscopic ultrasonography (EUS) in the qualitative diagnosis of retroperitoneal space-occupying lesions. METHODS: Twenty-six patients with retroperitoneal space-occupying lesions confirmed by CT or MRI were studied. All the patients underwent endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) at the Department of Gastroenterology, Xiangyang Central Hospital, Hubei Province, China from August 2009 to August 2011. Different parameters were evaluated, such as complications of EUS-FNA, the ratio of definite pathological diagnosis, and the pathologic types of all the specimens. RESULTS: Of the 26 patients, 24 had definite pathological diagnosis; the ratio of histodiagnosis was 92.3%. There were no complications such as hemorrhage, infection, or injury to the abdominal viscera in the process of EUS-FNA. Eight patients had benign tumors, with a ratio of 33.3%, and 16 patients had malignant tumors, with a ratio of 66.7%. Two patients had no definite pathological diagnosis because of the shortness of tissue sample. Eight patients did not undergo operation due to the diagnosis of benign tumors. CONCLUSION: The EUS-FNA has the advantage of lower complications, and higher diagnostic ratio, which is valuable in the qualitative diagnosis of retroperitoneal space-occupying lesions.

Prognostic significance of hERG1 expression in gastric cancer.

Previous studies have demonstrated that human ether-à-go-go-related potassium channel (hERG1) is highly expressed in many tumor cell lines, as well as in primary human cancers, and, hence, have a critical role in cell cycle progress and proliferation. In this study, hERG1 expression was investigated in gastric cancer by immunohistochemistry and/or reverse transcription polymerase chain reaction (RT-PCR). It was discovered that hERG1, which was negatively expressed in surrounding non-tumor tissues, switched to aberrantly positive expression in gastric cancer. Statistically, there were significant differences in hERG1 protein expression according to factors such as serosal invasion, venous invasion, lymph node metastases, other organ metastases, and stage. The mean survival time for the hERG1-positive expression group was significantly shorter than the negative group, the survival rates for the positive group were significantly lower than the negative group, and hERG1 expression was found to be an independent prognostic factor. In summary, hERG1 channel was proved to be a potential biomarker for gastric cancer invasion and survival.

Promoter polymorphism of interleukin-18 in angiographically proven coronary artery disease.

Interleukin 18 (IL-18) is a pro-atherogenic cytokine associated with the occurrence of various cardiac complications. The IL-18 gene has a functional -137 G/C polymorphism (rs187238) in the promoter region. Using the ligase detection reaction-polymerase chain reaction, we genotyped a cohort of patients in Chinese Han population in Xiangfan region. Case patients of coronary artery disease and control patients were identified by coronary angiography. The plasma IL-18 concentrations were measured by ELISA. A significant increase of G allele or GG-genotype was observed in 241 case patients compared to 145 control individuals (frequency of G allele = 0.90 vs 0.83, p=0.004; frequency of GG-genotype = 0.81 vs 0.68, p = 0.005). In case patients, G allele carriers in multi-vessel disease patients had a higher occurrence rate when compared to single-vessel disease patients, but no significant difference was detected (frequency of G allele = 0.92 vs 0.88, p=0.107; frequency of GG-genotype = 0.84 vs 0.75, p = 0.089). IL-18 protein concentration of the -137GG genotype was much higher than concentration of the CG and CC genotype (case patients: 229.1+/-131.5 vs 122.7+/-73.6 pg/ml, P < 0.001; control patients: 65.9+/-31.6 vs 42.4+/-19.5 pg/ml, P < 0.001). To conclude, IL-18 promoter -137G/C polymorphism influences IL-18 levels and the occurrence of coronary artery disease, suggesting that IL-18 is causally involved in the development of atherosclerosis.