Dongkai Zhou

Meta-analysis: the use of carbon dioxide insufflation vs. room air insufflation for gastrointestinal endoscopy

Carbon dioxide (CO2) insufflation has been proposed as an alternative to air insufflation to distend the lumen in gastrointestinal (GI) endoscopy.

A Meta-Analysis of Randomized Controlled Trials of Low-Volume Polyethylene Glycol plus Ascorbic Acid versus Standard-Volume Polyethylene Glycol Solution as Bowel Preparations for Colonoscopy

Background Standard-volume polyethylene glycol (PEG) gut lavage solutions are safe and effective, but they require the consumption of large volumes of fluid. A new lower-volume solution of PEG plus ascorbic acid has been used recently as a preparation for colonoscopy. Aim A meta-analysis was performed to compare the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. Study Electronic and manual searches were performed to identify randomized controlled trials (RCTs) that compared the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. After a methodological quality assessment and data extraction, the pooled estimates of bowel preparation efficacy during bowel cleansing, compliance with preparation, willingness to repeat the same preparation, and the side effects were calculated. We calculated pooled estimates of odds ratios (OR) by fixed- and/or random-effects models. We also assessed heterogeneity among studies and the publication bias. Results Eleven RCTs were identified for analysis. The pooled OR for preparation efficacy during bowel cleansing and for compliance with preparation for low-volume PEG plus ascorbic acid were 1.08 (95% CI = 0.98–1.28, P = 0.34) and 2.23 (95% CI = 1.67–2.98, P<0.00001), respectively, compared with those for standard-volume PEG. The side effects of vomiting and nausea for low-volume PEG plus ascorbic acid were reduced relative to standard-volume PEG. There was no significant publication bias, according to a funnel plot. Conclusions Low-volume PEG plus ascorbic acid gut lavage achieved non-inferior efficacy for bowel cleansing, is more acceptable to patients, and has fewer side effects than standard-volume PEG as a bowel preparation method for colonoscopy.

Genome-wide analysis of long noncoding RNA (lncRNA) expression in colorectal cancer tissues from patients with liver metastasis

The liver is the most frequent site of metastasis in colorectal cancer (CRC), in which long noncoding RNAs (lncRNAs) may play a crucial role. In this study, we performed a genome‐wide analysis of lncRNA expression to identify novel targets for the further study of liver metastasis in CRC. Samples obtained from CRC patients were analyzed using Arraystar human 8 × 60K lncRNA/mRNA v3.0 microarrays chips to find differentially expressed lncRNAs and mRNAs. The results were confirmed by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). The differentially expressed lncRNAs and mRNAs were identified through fold change filtering. Gene ontology (GO) and pathway analyses were performed using standard enrichment computational methods. In the CRC tissues from patients with liver metastasis, 2636 lncRNAs were differentially expressed, including 1600 up‐regulated and 1036 down‐regulated over two‐fold compared with the CRC tissues without metastasis. Among the 1584 differentially expressed mRNAs, 548 were up‐regulated and 1036 down‐regulated. GO and pathway analysis of the up‐regulated and down‐regulated mRNAs yielded different results. The up‐regulated mRNAs were associated with single‐organism process (biological process), membrane part (cellular component), and transporter activity (molecular function), whereas the down‐regulated mRNAs were associated with cellular process, membrane, and binding, respectively. In the pathway analysis, 27 gene pathways associated with the up‐regulated mRNAs and 51 gene pathways associated with the down‐regulated mRNAs were targeted. The significant changes in NQO2 (NM_000904) mRNA and six associated lncRNAs were selected for validation by qRT‐PCR. Aberrantly expressed lncRNAs may play an important role in the liver metastasis of CRC. The further study can provide useful insights into the biology and, ultimately, the prevention of liver metastasis.

The lncRNA HOXA11-AS functions as a competing endogenous RNA to regulate PADI2 expression by sponging miR-125a-5p in liver metastasis of colorectal cancer

Several long non-coding RNAs (lncRNAs) play important roles in the regulation of liver metastasis in colorectal cancer (CRC) patients. We previously described the potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR-125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis in CRC patients. In the present study, we verified the significant upregulation of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a positive correlation between HOXA11-AS and PADI2 and a negative correlation with miR-125a-5p in the regulation of liver metastasis in CRC cell lines. Overall, we conclude that HOXA11-AS promotes liver metastasis in CRC by functioning as a miR-125a-5p sponge and describe a novel HOXA11-AS–miR-125a-5p–PADI2 regulatory network involved in CRC liver metastasis.

Hepatitis B virus X protein inhibits p53-mediated upregulation of mitofusin-2 in hepatocellular carcinoma cells.

The hepatitis B virus X (HBx) protein has many significant roles in hepatocellular carcinoma (HCC). Our previous research demonstrated that mitofusion-2 (Mfn2), a potential tumor suppressor gene in HCC, is a novel direct target of p53 that exerts apoptotic effects via the mitochondrial apoptotic pathway. However, the relationship between HBx and Mfn2 expression in the development of HCC is unknown. We found that HBx had little direct effect on the expression of Mfn2 or p53 in HCC cells not treated with doxorubicin. However, HBx inhibited the upregulation of Mfn2 in HBx-transfected HCC cells simultaneously treated with doxorubicin or cotransfected with p53 plasmid, as evidenced by Western Blot and real-time PCR. Through electrophoretic mobility shift analysis, we confirmed that HBx interfered with the binding event of the p53 protein and the p53 binding site-oligo of the Mfn2 promoter. Moreover, luciferase assays revealed that the activity of the Mfn2 promoter did not increase when transfected with HBx plasmid in doxorubicin-treated HepG2 cells. These results indicate that HBx impacts p53-mediated transcription of Mfn2, providing insight into the negative effect of HBx against p53-dependent chemotherapeutic agents, such as doxorubicin, used in the treatment of HCC.

Long non-coding RNA CASC15 is upregulated in hepatocellular carcinoma and facilitates hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for one-sixth of all malignant tumors, and the mortality rate of HCC ranks second among all cancer-related deaths. Increasing evidence has recently shown that long non-coding RNAs (lncRNAs) play an important role in cancer occurrence and progression, including HCC. Cancer susceptibility candidate 15 (CASC15), a lncRNA, has been reported to be involved in melanoma progression and phenotype switching. However, the function of CASC15 in human HCC is still unknown. In the present study, we evaluated expression of CASC15 and its potential functions in HCC. The expression of CASC15 in HCC tissues was quantitated by the reverse-transcription quantitative polymerase chain reaction, which showed that CASC15 was overexpressed in 59% (48/82) of HCC tissues compared with corresponding adjacent normal tissues, and the CASC15 expression level was significantly correlated with metastasis (P=0.012), tumor size (P=0.037), and TNM stage (P=0.013). Kaplan-Meier survival curves showed that high CASC15 expression was associated with poor prognosis in HCC patients (P<0.05). Moreover, a knockdown model of CASC15 was established, which showed that CASC15 significantly impaired HCC cell proliferation, migration, and invasion. CASC15 knockdown also induced cell apoptosis in vitro and impaired tumor growth in vivo. In conclusion, CASC15 plays an important role in the progression of HCC, acting as an oncogene. High expression of CASC15 is correlated with a poor prognosis, suggesting that CASC15 may be a predictive biomarker of HCC.

Expression and Clinical Significance of the Novel Long Noncoding RNA ZNF674-AS1 in Human Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) play crucial roles in cancer occurrence and progression. However, the relationship between the expression levels of lncRNAs and the hepatocellular carcinoma (HCC) process is unclear. The goal of this study was to determine the expression level of ZNF674-AS1, a newly found lncRNA, in HCC and its clinical association. The expression of ZNF674-AS1 in 137 pairs of tumorous and adjacent normal tissues from patients with HCC was detected by quantitative real-time reverse transcription polymerase chain reaction. Additionally, the potential associations between its level in HCC tissue and clinicopathological features were analyzed. The expression of ZNF674-AS1 in the HCC cell lines HepG2, HCCLM3, SK-Hep1, HuH7, Hep3B, and MHCC97H was significantly downregulated compared with that in the normal liver cell line QSG-7701. The expression of ZNF674-AS1 was downregulated in 72% (99/137) of HCC tissues compared with that in paired adjacent normal tissues (p < 0.01). The results showed that the ZNF674-AS1 expression level was significantly correlated with metastasis (p = 0.041), clinical stage (p = 0.039), and histopathologic grading (p = 0.045). In addition, the Kaplan–Meier survival curves revealed that low ZNF674-AS1 expression was associated with poor prognosis in patients with HCC. Our data suggest that ZNF674-AS1 may play some role during cancer occurrence and progression and may be a new biomarker for HCC.

Regional portal hypertension, systemic lymphadenopathy, and splenomegaly associated with autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, characterised by elevated serum IgG4 levels. AIP is associated with many other diseases, including retroperitoneal fibrosis, sclerosing cholangitis, and sialoadenitis. Here, we report an interesting case of a 45-year-old male who presented with haematemesis, melena, and fever, accompanied by hepatosplenomegaly, systemic lymphadenopathy, diffuse swelling of the pancreas, portal hypertension, and multiple enlarged retroperitoneal lymph nodes on abdominal computed tomography (CT). The patient did not have a history of viral hepatitis or cirrhosis. Laboratory testing revealed an elevated IgG (3000 mg/dL). He underwent surgery for uncontrolled active upper gastrointestinal bleeding. We found splenomegaly, with a plump pancreas and involved peripheral lymph nodes, so a splenectomy was performed, and the pancreatic tail and some of the lymph nodes were biopsied. All of the resected tissues were infiltrated by large numbers of IgG4-positive plasma cells. Therefore, this patient was diagnosed with AIP associated with portal hypertension, systemic lymphadenopathy, and splenomegaly. The patient received no other treatment after the splenectomy. By the 6-month follow-up, the patient had recovered, the serum IgG had decreased to normal, and enhanced CT showed a normal pancreas. We speculate that splenectomy may be a new method of treating AIP.

miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer

Improvements in survival rates for pancreatic cancer have been slow and the morality rate continues to increase in patients. MicroRNA (miR)-448 is reported to be significantly downregulated in several types of cancer. In this study, Rab2B is target of miR-488 was confirmed by bioinformatics analysis and validated using a luciferase reporter assay. A total of 72 cases of pancreatic cancer in patients diagnosed at The First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China) were enrolled, and cancer specimens and their adjacent normal tissues were collected for analysis. The expression levels of miR-448 and Rab2B in these tissues and in pancreatic cancer cell lines were quantified using reverse transcription-polymerase chain reaction analysis. miR-448 overexpression was achieved by cell transfection. Protein expression was assessed using western blot analysis. Cell viability, cell cycle and apoptosis were analyzed using CCK-8 assay and flow cytometry, respectively. The results revealed a negative correlation between miR-448 and Rab2B in the pancreatic tissues and cell lines. The results of bioinformatics analysis indicated that miR-448 directly targeted Rab2B. Aberrant miR-448 levels in PANC-1 cells downregulated the expression of Rab2B, and significantly decreased cell proliferation and promoted apoptosis of cancer cells. It was also found that miR-448 mimics resulted in G0/G1 cell cycle arrest and affected the expression of cell cycle regulators, including cyclin D1, p21 and p27. In addition, the miR-448 mimics led to inactivation of the Akt/Mammalian target of rapamycin signaling pathway. The miR-448 mimics induced apoptosis and activated the expression of caspase-3, caspase-9 and poly(ADP-ribose) polymerase. The results suggested that miR-448 was a negative regulator of Rab2B and promoted cell cycle arrest and apoptosis in pancreatic cancer.

High Expression of ITGA3 Promotes Proliferation and Cell Cycle Progression and Indicates Poor Prognosis in Intrahepatic Cholangiocarcinoma

Integrin subunit alpha 3 (ITGA3) interacts with a beta 1 subunit to form a member of the integrin family. Integrins are heterodimeric integral membrane proteins that serve as cell surface adhesion proteins. In this research, we investigated the biological function of this protein in human intrahepatic cholangiocarcinoma (ICC) for the first time. Here, using Western blotting and immunohistochemistry assays, we discovered that ITGA3 was overexpressed in ICC cell lines and ICC patients. Moreover, we found ITGA3 expression correlated with several clinicopathological features, including tumor size, lymph node metastasis, and the TNM stage. Patients with high ITGA3 expression underwent a worse prognosis after complete resection compared with patients with low ITGA3 expression in terms of overall survival. Furthermore, we demonstrated that ITGA3 could significantly promote ICC cell proliferation and cell cycle progression in vitro. However, as a classical cell surface adhesion molecule, we found ITGA3 correlated negatively with the migration and invasion of ICC cell lines, which differs from other malignant tumors. Generally, these findings suggest that ITGA3 may play a role as a potential oncogene in ICC and suppression of ITGA3 expression may establish a novel target for guiding the therapy of ICC patients.