Identification and Analysis of Subtypes of Liver Cancer Based on Genes Related to E3 Ubiquitin Ligases and Deubiquitinating Enzymes.

Recent studies have reported a correlation between ubiquitination or deubiquitination and cancer development. But mechanisms underlying the roles of genes associated with E3 ubiquitin ligases and deubiquitinating enzymes (DUB) in liver cancer remain to be explored. We analyzed and screened differentially expressed genes related to E3 ubiquitin ligases and DUB in liver cancer on the basis of public databases. Cluster analysis was utilized to classify liver cancer samples into different subtypes. Survival analysis, immune analysis, and pathway enrichment analysis were performed on the subtypes. We constructed a protein-protein interaction network using STRING to screen hub genes. Finally, we used the Connectivity Map (CMap) database to predict targeted small molecules. The results show that a total of 139 differentially expressed E3/DUB genes in liver cancer were screened. Then, liver cancer was classified into two subtypes, cluster 1 and cluster 2, based on E3-related and DUB-related genes. Patients in cluster 1 had higher survival rates and immune levels than those in cluster 2. Four hub genes (RPSA, RPS5, RPL30, and RPL8) significantly affecting the survival of the two subtypes of liver cancer patients were identified based on cluster 1 and cluster 2. Finally, the CMap database predicted that small-molecule drugs including probenecid, dexamethasone, and etomidate may improve the prognosis of liver cancer patients. These findings may offer a reference for risk stratification studies and drug development in liver cancer.

Fusobacterium nucleatum Affects Cell Apoptosis by Regulating Intestinal Flora and Metabolites to Promote the Development of Colorectal Cancer.

Background/Aims: Intestinal flora, especially Fusobacterium nucleatum (Fn), can affect the development of colorectal cancer (CRC). In this study, we examined the composition of intestinal flora and their metabolites in the tissues, serum and feces of CRC patients. Materials and Methods: CRC tissues, adjacent normal colonic tissues, fecal and serum samples were collected from CRC patients who received surgical treatment between January 2018 and January 2020. Fecal and serum samples were collected from healthy individuals for comparison. In addition, fecal samples were collected from BALB/c female mice. SW480, a human CRC cell line, was utilized for in vitro studies. The experiments involved 1H-NMR-based metabolomics analysis, targeted and untargeted mass spectrometry analysis, and intestinal flora 16S rDNA V4 region sequencing. Results: The abundance of Bacteroides and propionic acid concentration were decreased and that of Lactobacillus and lactic acid concentration were increased in CRC tissues. In addition, the abundances of Ruminococcus, Prevotella, and Sutterell were decreased in CRC patients. The levels of leucine and isoleucine were decreased in the serum and tumor tissues of CRC patients. Aspartate, glutamate and glutathione levels were elevated in the tissues of CRC patients only. The serum glutamine, tyrosine, valine, alanine, and histidine levels were decreased significantly. Lactic acid inhibited and propionic acid promoted apoptosis among SW480 CRC cells. Conclusion: Fn affected the apoptosis of CRC cells and promoted the progression of CRC by affecting the distribution of intestinal flora, which altered the concentrations of metabolites such as lactic acid, propionic acid. Intestinal flora could regulate amino acid metabolism.

Talin1 knockdown prohibits the proliferation and migration of colorectal cancer cells via the EMT signaling pathway.

[This retracts the article DOI: 10.3892/ol.2019.10902.].

Efficient detection and post-surgical monitoring of colon cancer with a multi-marker DNA methylation liquid biopsy.

Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylation markers and is capable of quantitative analysis of plasma samples with as little as 0.05% tumor DNA. In a cohort of 179 plasma samples from colorectal cancer (CRC) patients, adenoma patients, and healthy controls, the sensitivity and specificity of the mqMSP assay were 84.9% and 83.3%, respectively. In a head-to-head comparative study, the mqMSP assay also performed better for detecting early-stage (stage I and II) and premalignant polyps than a published SEPT9 assay. In an independent longitudinal cohort of 182 plasma samples (preoperative, postoperative, and follow-up) from 82 CRC patients, the mqMSP assay detected ctDNA in 73 (89.0%) of the preoperative plasma samples. Postoperative detection of ctDNA (within 2 wk of surgery) identified 11 of the 20 recurrence patients and was associated with poorer recurrence-free survival (hazard ratio, 4.20; P = 0.0005). With subsequent longitudinal monitoring, 14 patients (70%) had detectable ctDNA before recurrence, with a median lead time of 8.0 mo earlier than seen with radiologic imaging. The mqMSP assay is cost-effective and easily implementable for routine clinical monitoring of CRC recurrence, which can lead to better patient management after surgery.

Highly multiplexed quantifications of 299 somatic mutations in colorectal cancer patients by automated MALDI-TOF mass spectrometry.

BACKGROUND: Detection of somatic mutations in tumor tissues helps to understand tumor biology and guide treatment selection. Methods such as quantitative PCR can analyze a few mutations with high efficiency, while next generation sequencing (NGS) based methods can analyze hundreds to thousands of mutations. However, there is a lack of cost-effective method for quantitatively analyzing tens to a few hundred mutations of potential biological and clinical significance. METHODS: Through a comprehensive database and literature review we selected 299 mutations associated with colorectal cancer. We then designed a highly multiplexed assay panel (8-wells covering 299 mutations in 109 genes) based on an automated MADLI-TOF mass spectrometry (MS) platform. The multiplex panel was tested with a total of 319 freshly frozen tissues and 92 FFPE samples from 229 colorectal cancer patients, with 13 samples also analyzed by a targeted NGS method covering 532 genes. RESULTS: Multiplex somatic mutation panel based on MALDI-TOF MS detected and quantified at least one somatic mutation in 142 patients, with KRAS, TP53 and APC being the most frequently mutated genes. Extensive validation by both capillary sequencing and targeted NGS demonstrated high accuracy of the multiplex MS assay. Out of 35 mutations tested with plasmid constructs, sensitivities of 5 and 10% mutant allele frequency were achieved for 19 and 16 mutations, respectively. CONCLUSIONS: Automated MALDI-TOF MS offers an efficient and cost-effective platform for highly multiplexed quantitation of 299 somatic mutations, which may be useful in studying the biological and clinical significance of somatic mutations with large numbers of cancer tissues.

A rare case of eosinophilic cholangiopathy.

Eosinophilic cholangiopathy is termed as a rare, benign, and self-limiting disease. Moreover, the interference of malignant tumor to diagnosis and the changing process of disease make the accurate treatment proposal challenging. A significant number of patients require surgery for the definitive diagnosis and resolution of symptoms. We put forward a case of eosinophilic cholangiopathy infiltrating the gallbladder and bile duct with bone marrow involved, coupled with peripheral eosinophilia. The patient underwent a successful treatment using laparoscopic cholecystectomy and steroids, instead of extrahepatic bile duct excision with Roux-en-Y hepaticojejunostomy. The patient gets an accurate treatment in a minimally invasive manner. In conclusion, surgery refers to not only a diagnostic methodology but also a treatment. When the bile duct and gallbladder are involved at the same time, and cannot distinguish benign and malignant diseases, laparoscopic cholecystectomy is feasible, the effect is the same, and the symptoms of eosinophilic cholecystitis are relieved.

A systematic evaluation of stool DNA preparation protocols for colorectal cancer screening via analysis of DNA methylation biomarkers.

Objectives: Colorectal cancer (CRC) screening using stool samples is now in routine use where tumor DNA methylation analysis for leading markers such as NDRG4 and SDC2 is an integral part of the test. However, processing stool samples for reproducible and efficient extraction of human genomic DNA remains a bottleneck for further research into better biomarkers and assays. Methods: We systematically evaluated several factors involved in the processing of stool samples and extraction of DNA. These factors include: stool processing (solid and homogenized samples), preparation of DNA from supernatant and pellets, and DNA extraction with column and magnetic beads-based methods. Furthermore, SDC2 and NDRG4 methylation levels were used to evaluate the clinical performance of the optimal protocol. Results: The yield of total and human genomic DNA (hgDNA) was not reproducible when solid stool scraping is used, possibly due to sampling variations. More reproducible results were obtained from homogenized stool samples. Magnetic beads-based DNA extraction using the supernatant from the homogenized stool was chosen for further analysis due to better reproducibility, higher hgDNA yield, lower non-hgDNA background, and the potential for automation. With this protocol, a combination of SDC2 and NDRG4 methylation signals with a linear regression model achieved a sensitivity and specificity of 81.82 and 93.75%, respectively. Conclusions: Through the systematic evaluation of different stool processing and DNA extraction methods, we established a reproducible protocol for analyzing tumor DNA methylation markers in stool samples for colorectal cancer screening.

LINC01413/hnRNP-K/ZEB1 Axis Accelerates Cell Proliferation and EMT in Colorectal Cancer via Inducing YAP1/TAZ1 Translocation.

Long non-coding RNAs (lncRNAs) are crucial molecules in tumorigenesis and tumor growth in various human cancers, including colorectal cancer (CRC). Studies have revealed that lncRNAs can regulate cellular processes in cancers by interacting with proteins, for example RNA-binding proteins (RBPs). In this study, we recognize a novel lncRNA called LINC01413 that is upregulated in CRC tissues through lncRNAs microarray. Subsequently, we confirmed that an elevated level of LINC01413 expression in CRC tissues was strongly correlated to clinicopathological features, such as tumor size, tumor stage, lymph node metastasis, and distant metastasis, and its association with poor overall survival was also revealed. Additionally, LINC01413 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Also, silenced LINC01413 restrains tumor growth in vivo. Moreover, LINC01413 binds with hnRNP-K and induces YAP1 (yes-associated protein 1)/TAZ1 (tafazzin) nuclear translocation to regulate the expression of ZEB1 in CRC cells. Taken together, this research suggested LINC01413 as a positive regulator in CRC progression through the LINC01413/hnRNP-K/TAZ1/YAP1/ZEB1 axis, broadening a new view on CRC treatment.

Fusobacterium nucleatum Promotes the Progression of Colorectal Cancer Through Cdk5-Activated Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: Growing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: CRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations. RESULTS: The abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/ß-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/ß-catenin signaling in relation to the progression of CRC. CONCLUSION: The results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/ß-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.

Talin1 knockdown prohibits the proliferation and migration of colorectal cancer cells via the EMT signaling pathway.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second highest cause of cancer-associated death worldwide. Talin1 activates integrins, which mediate cell adhesion, proliferation, tumorigenesis and metastasis. The aim of the present study was to determine talin1 expression levels in colorectal cancer (CRC) and investigate the role of talin1 in CRC proliferation and invasion in vitro and in vivo. Talin1 protein expression levels were detected in human CRC and adjacent normal tissues by immunohistochemistry. Talin1 short hairpin RNA and control vectors were designed and stably transfected into HCT116 CRC cells. Cell proliferation was determined by MTT assay. Cell migratory and invasive capabilities were detected by wound-healing and Matrigel invasion assays. The expression of proteins in the epithelial-to-mesenchymal transition signaling pathway was determined by western blotting and reverse transcription-quantitative PCR. The effect of talin1 on tumor growth was explored in vivo using BALB/c nude mice. Immunohistochemical analysis of CRC and adjacent normal tissue revealed that talin1 expression was upregulated in CRC. Talin1 knockdown significantly reduced the proliferation, migration and invasive ability of HCT116 cells compared with the control. Protein levels of phosphorylated STAT3 and vimentin were significantly lower in talin1-knockdown HCT116 cell lines compared with the control, whereas protein levels of E-cadherin were increased. Interleukin-6 mRNA levels were significantly increased in patients' blood samples compared with blood samples from healthy controls, as well as in CRC compared with adjacent normal tissue. In vivo experiments demonstrated that talin1 knockdown reduced CRC tumor growth and weight in nude mice. In conclusion, Talin1 knockdown may prevent the proliferation and migration of CRC cells by downregulating various factors involved in the epithelial-to-mesenchymal transition process, such as phosphorylated STAT3 and vimentin; therefore, talin1 may provide a novel therapeutic target for CRC.

Knock-Down of HOXB8 Prohibits Proliferation and Migration of Colorectal Cancer Cells via Wnt/ß-Catenin Signaling Pathway.

BACKGROUND There has been no research on the mechanism of HOXB8 action on colorectal cancer so far. This study was designed to investigate the mechanism of HOXB8 regulating colorectal cancer cell proliferation and invasion in vivo and in vitro. MATERIAL AND METHODS HOXB8 shRNA, HOXB8 overexpression, and negative control vector were designed and stably transfected into HCT116 cells. MTT assays were performed to detect cell proliferation. Western blot was utilized to detect HOXB8 expression level in HCT116 stable cells. The invasive and migration abilities were detected by Transwell assay and wound-healing assay. RESULTS HOXB8 knockdown inhibited cell proliferation. The invasiveness of HCT116 cells was significantly reduced following HOXB8 depletion compared with that in the shRNA control group, whereby the rates were reduced by 67% in HOXB8 knockdown group. The wound-healing rate of HOXB8 over-expression cells was significantly increased comparing with that of cells in the blank control group (P<0.05). HOXB8 knockdown promotes apoptosis of HCT116 cells. The expression of E-cadherin was restrained in the HOXB8 over-expression group and increased in the HOXB8 knockdown group. CONCLUSIONS Knock-down of HOXB8 prohibits the proliferation and migration of colorectal cancer cells via the Wnt/ß-catenin signaling pathway and the downregulation of various factors, such as MMP2, c-Myc, CyclinD1,and vimentin. Our data suggested that HOXB8 has great potential to be developed as a novel therapeutic agent for the treatment of human colorectal cancer.

[Zhu's trocar placement in laparoscopic appendectomy in the treatment of complicated appendicitis].

OBJECTIVE: To evaluate the feasibility and efficacy of Zhu's trocar placement (ZTP) in laparoscopic appendectomy (LA) in the treatment of complicated appendicitis. METHODS: Clinical data of 139 complicated appendicitis patients undergoing LA at the First Affiliated Hospital of Wenzhou Medical University from June 2013 to December 2017 were retrospectively analyzed. ZTP-LA group comprised 59 cases and its procedure was as follows: 10 mm umbilical trocar was used as lens port; 12 mm trocar at crossing point of umbilical hole horizontal line and right midclavicular line was used as main operating port; 5 mm trocar at the crossing point of horizontal line 0-3 cm below umbilicus and right anterior axillary line was used as assist operating port with the drainage function for Douglas fossa and right iliac fossa; The operator and the assistant stood on the right side and the left side of the patient respectively. Traditional three-port group comprised 80 cases (8 cases converted to laparotomy, 72 cases enrolled finally) and its procedure was as follows: 10 mm lens port below umbilicus; 10-12 mm main operating port at lateral border of left lower rectus abdominis; 5 mm assist operating port above pubis; The operator and the assistant stood on left side of the patient. The operative time, time to oral semi-fluid, postoperative hospital stay, cost during hospitalization, and postoperative morbidity of complication were compared between two groups. RESULTS: Baseline data such as gender, age, WBC count, percentage of leukocyte, pathological finding and type were not significantly different between two groups(all P>0.05). The conversion rate in ZTP-LA was significantly lower than that in traditional three-port group [0%(0/59) vs. 10.0%(8/80),χ²=4.552,P=0.033]. Compared with traditional three-port group, ZTP-LA group showed shorter operative time [(47.8±20.1) minutes vs. (66.0±27.3) minutes, t=4.383,P<0.001], shorter time to oral semi-fluid [(35.0±20.7) hours vs. (59.3±32.8) hours, t=5.158,P<0.001], shorter postoperative hospital stay [(4.1±1.6) days vs. (5.5±2.2) days, t=4.162, P<0.001], lower postoperative morbidity of complication [3.4% (2/59) vs. 18.1%(13/72), χ²=6.879, P=0.009], lower incidence of postoperative intra-abdominal abscess [0%(0/59) vs. 11.1%(8/72), χ²=5.179, P=0.023], lower incidence of paralytic ileus [1.7%(1/59) vs. 12.5%(9/72), χ²=3.946, P=0.047] and less cost during hospitalization[(13 585±2909) yuan vs.(16 861±5334) yuan, t=4.463, P<0.001]. CONCLUSION: ZTP-LA is safe, feasible and effective with advantages of faster recovery and less cost in the treatment of complicated appendicitis.

Sleeve gastrectomy with duodenojejunal end-to-side anastomosis in the treatment of type 2 diabetes: the initial experiences in a Chinese population with a more than 4-year follow-up.

BACKGROUND: Gastric bypass has been thought to be associated with a risk of gastric cancer, particularly in Asia. Sleeve gastrectomy with duodenojejunal end-to-side anastomosis (SG-DJESA) was suggested to be a better-designed procedure to avoid this risk, and it also has other advantages. OBJECTIVE: We aimed to evaluate the clinical efficacy and feasibility of SG-DJESA in the treatment of nonobese patients with type 2 diabetes (T2D). SETTING: University Hospital, China. METHODS: We present prospective data from 7 consecutive T2D patients with gastric precancerosis who underwent SG-DJESA from December 15, 2011 to June 8, 2013. The group had a mean body mass index of 27.7 kg/m2. The glycometabolic parameters, including fasting plasma glucose, 2-hour postprandial plasma glucose, fasting insulin, fasting C-peptide, glycated hemoglobin, lipometabolic parameters, and anemia-related indicators were collected at baseline and at 1, 3, 6, 12, 24, and 48 months postoperatively. Remission was defined according to the "outcome reporting standards" conducted by the American Society for Metabolic and Bariatric Surgery. RESULTS: Along with a decrease in antidiabetic medication requirements, body mass index, fasting plasma glucose, 2-hour postprandial plasma glucose, and glycated hemoglobin decreased significantly at each postoperative time point, compared with the preoperative baseline (P<.05, respectively). Four patients (4/7, 57.1%) achieved a complete remission of T2D at 12 months and maintained remission at the 4-year follow-up time; 1 patient (1/7, 14.3%) achieved a partial remission at 6 months but had recurrence at 12 months postoperatively; and the other 2 patients (2/7, 28.6%) achieved improvement during the follow-up time. There were no deaths during the follow-up period. One patient had a postoperative anastomotic bleed and recovered under conservative treatment. Another patient had iron deficiency anemia 8 weeks after surgery and recovered after taking an oral iron supplement for 1 month. No other serious perioperative complications or postoperative malnutrition occurred. CONCLUSIONS: SG-DJESA is an effective and safe procedure for nonobese patients with T2D and could be recommended as a treatment option for T2D patients with gastric precancerosis. A larger sample size may be required for better evaluation.

Pitavastatin suppressed liver cancer cells in vitro and in vivo.

Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy.

Berberine modulates cisplatin sensitivity of human gastric cancer cells by upregulation of miR-203.

Chemotherapeutic resistance is the main reason of the failure in clinical treatment of gastric cancer. Berberine (BER) is the active compound of traditional Chinese medicine Huang Lian. The aim of this present study is to evaluate the effect of BER on cisplatin resistance in gastric cancer cells and to investigate its possible mechanism. Gastric cancer cell lines SGC-7901 and BGC-823 and their respective cisplatin-resistant variants SGC-7901/DDP and BGC-823/DDP were used in this study. We found that BER treatment significantly reversed cisplatin sensitivity and induced caspase-dependent apoptosis in SGC-7901/DDP and BGC-823/DDP cells; BER treatment induced miR-203 expression, and overexpression of miR-203 mimicked the cisplatin-sensitizing effect of BER. Importantly, we showed that miR-203 was able to target the 3'UTR of Bcl-w. Therefore, we conclude that BER treatment reduces cisplatin resistance of gastric cancer cells by modulating the miR-203/Bcl-w apoptotic axis. BER may be a novel agent to enhance chemotherapeutic responses in cisplatin-resistant gastric cancer patients.

Long-Term Oncologic Outcomes of Laparoscopic versus Open Surgery for Middle and Lower Rectal Cancer.

BACKGROUND: Laparoscopic surgery for middle and lower rectal cancer remain controversial because anatomical and complex surgical procedures specifically influence oncologic outcomes. This study analyzes the long-term outcomes of laparoscopic versus open surgery for middle and lower rectal cancer. METHODS: Patients (laparoscopic: n = 129, open: n = 152) who underwent curative resection for middle and lower rectal cancer from 2003 to 2008 participated in the study. The same surgical team performed all operations. The mean follow up time of all patients was 74.3 months. RESULTS: No statistical difference in local recurrence rate (7.8% vs. 7.2%; log-rank = 0.024; P = 0.876) and distant recurrence rate (20.9% vs.16.4%; log-rank = 0.699; P = 0.403) between laparoscopic and open groups were observed within 5 years. The 5-year overall survival rates of the laparoscopic and open groups were 72.9% and 75.7%, respectively; no significant statistical difference was observed between them (log-rank = 0.163; P = 0.686). The 5-year survival rates between groups were not different between stages: Stage I (92.6% vs. 86.7%; log-rank = 0.533; P = 0.465); stage II (75.8% vs. 80.5%; log-rank = 0.212; P = 0.645); and Stage III (63.8% vs. 69.1%, log-rank = 0272;P = 0.602). However, significant statistical difference amongst different stages were observed (log-rank = 1.802; P = 0.003). CONCLUSION: Laparoscopic and open surgery for middle and lower rectal cancer offer equivalent long-term oncologic outcomes. Laparoscopic surgery is feasible in these patients.

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis.

BACKGROUND: What benefits and toxicities patients acquire from the use of bevacizumab combined with firstline chemotherapy remains controversial. This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: Several databases, including PubMed, Embase, and Cochrane Library, were searched up to April 30, 2013. Eligible studies were only randomized, controlled trials (RCTs) with a direct comparison between mCRC patients treated with and without bevacizumab. Overall risk ratio (RR), hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials. RESULTS: Six RCTs, including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group, were included. Overall, the addition of bevacizumab to first-line chemotherapy increased overall response rate (ORR) by 4.5%, prolonged both progression-free survival (PFS) and overall survival (OS), and increased the rate of total Grades 3 or 4 adverse events (G3/4AEs) by 6.9%. Significant differences were found in ORR (RR = 1.22 (95% CI 1.01-1.46), P = 0.03), PFS (HR = 0.60 (95% CI 0.47-0.77), P < 0.0001), OS (HR = 0.83 (95% CI 0.70-0.97), P = 0.02), and any G3/4AEs (OR = 1.56 (95% CI 1.29-1.89), P < 0.00001). CONCLUSION: Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC, because of conferring a significant improvement in ORR, PFS, and OS, even though it increased adverse events.

Duodenal-jejunal bypass for the treatment of type 2 diabetes in Chinese patients with an average body mass index<24 kg/m2.

BACKGROUND: It is frequently reported that bariatric surgery often leads to resolution of type 2 diabetes mellitus (T2 DM). Limited experience with duodenal-jejunal bypass (DJB) for the treatment of T2 DM has shown controversial results. We present the first study of DJB for T2 DM patients in China. The objective of this study was to evaluate the effects of DJB in nonobese Chinese patients with T2 DM. METHODS: From March 2009 to March 2011, a total of 10 T2 DM patients with an average body mass index (BMI) of 23.8 ± 1.2 kg/m(2) were enrolled in the study. DJB was performed in all patients. BMI and glycometabolic parameters were collected at baseline and 1, 3, 6, 12, and 24 months postoperatively. Remission of T2 DM was defined as a glycosylated hemoglobin (HbA1c) level of<7% without diabetic medication. RESULTS: Remission of T2 DM was observed in 1 (10%) of 10 T2 DM patients at 6 months. Without increasing antihyperglycemic agents, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose, and HbA1c decreased significantly at each postoperative time point, compared with the preoperative baseline. BMI statistically decreased at 1 and 3 months, but did not reach statistical significance at 6, 12, and 24 months. CONCLUSIONS: DJB can improve glycemic control in nonobese T2 DM patients without significant weight loss but may not be effective enough to induce remission of T2 DM in nonobese Chinese patients. A larger sample size and more constrictive inclusion criteria may be required for better evaluation.

[The role of glucagon-like peptide-1 and its receptor in the mechanism of metabolic surgery].

At present, surgery has become one of the treatments for type 2 diabetes, but it is still unclear about the therapeutic mechanism. Many experiments has proved that the anatomical and physiological structure has been altered leading to significant changes related to the secretion of gastrointestinal hormones and neuropeptides. These molecular are related to the metabolism of glucose, functions of islet cells and sensitivity of insulin. Intensive studies of glucagon-like peptide-1 (GLP-1) play an important role in the surgical treatment of diabetes and now it has gained increasing recognition. However, GLP-1 must be combined with GLP-1 receptor (GLP-1R) to execute its function. In this paper we reviewed the role of GLP-1 and its receptor in the mechanism of metabolic surgery.

[Duodenojejunal bypass in treatment for 7 cases with non-severe obese type 2 diabetes mellitus].

OBJECTIVE: To investigate the efficacy and feasibility of duodenojejunal bypass(DJB)on non-severe obese patients with type 2 diabetes mellitus(T2DM). METHODS: The body mass index (BMI), fasting plasma glucose(FPG), 2h-postprandial plasma glucose(2hPG), fasting insulin(F-ins), fasting c-peptide(F-CP), glycated hemoglobin and hypoglycemic agents dose changes were tested in 7 patients with non-severe obese T2DM undergoing DJB, preoperatively and within 24 weeks after surgery during the follow-up. Data were collected and the clinical outcomes of T2DM were analyzed. RESULTS: In 7 cases of non-obese T2DM who underwent DJB, one patient was weaned off hypoglycemic agents with normal FPG, 2hPG and HbA1c postoperatively. Five required significantly lower dosage. No significant improvement in 1 case. Complete remission rate of hyperglycemia was 1/7, effective rate was 6/7, and effective rate of HbA1c was 5/7. No significant changes in BMI were observed between the preoperative and postoperative phases. CONCLUSION: Plasma glucose level can be markedly reduced by duodenojejunal bypass in non-obese T2DM, independent of weight loss, and the mechanism remains unclear.