Zhining Fan

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (29)98.07 Total impact

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    ABSTRACT: To evaluate the efficacy of endoscopic purse-string suture (EPSS) with metallic clips and endoloop for the gastric wall defect after postoperative perforation. Clinical data of 25 patients with gastric tumors(1 of gastric adenocarcinoma, 24 of gastric gastrointestinal stromal tumor, GIST) undergoing EPSS in Jiangsu Province People's Hospital and The Second Affiliated Hospital of Nanjing Medical University from January 2013 to May 2014 were retrospectively analyzed. During the procedure, EPSS was performed in 8 cases with perforation after endoscopic submucosal dissection(ESD), and in 17 cases with active perforation after endoscopic full-thickness resection. Twenty-five patients underwent EPSS successfully. The procedure time was 35.0-75.0(49.8±10.1) min. No severe operational and postoperative complications occurred. Tumor resection margin were all negative. Time to withdraw gastrointestinal decompression drainage tube was 1-3(1.3±0.8) d. Postoperative hospital stay was 2-10(4.8±2.1) d and total cost was 10-31(19±0.5) thousand Yuan. One month after the procedure, all the patients received follow-up with no complaint of discomfort, and endoscopy confirmed that all the lesions healed. EPSS with metallic clips and endoloop is effective and safe to close the gastric wall defect after full-thickness resection.
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    ABSTRACT: Histopathology is the gold standard for diagnosis of esophageal carcinoma. Based on two photon excited fluorescence (TPEF) and second harmonic generation (SHG), multiphoton microscopy (MPM) has become a novel optical tool adjunct to current histopathological techniques without any exogenous contrast agents. We thus investigated the potential of using TPEF and SHG techniques for differentiating cancer tissues from cancer tissues after paclitaxel-eluting stent implantation and normal esophageal tissues which are fresh and unstained without dying from the VX2 esophageal carcinoma rabbit models. Comparisons were made between MPM imaging and gold standard sections for each specimen stained with hematoxylin-eosin (H&E). Our results indicated that the MPM imaging technique could identify and distinguish among normal esophageal tissues, cancer tissues, as well as cancer tissues after stent implantation. Therefore, MPM potentially offers a powerful tool to not only diagnose esophageal cancer but also monitor stent-therapy efficacy. SCANNING 9999:1-6, 2015. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.
    Scanning 02/2015; DOI:10.1002/sca.21192 · 1.29 Impact Factor
  • Limei Ma, Zhining Fan
    Endoscopy 12/2014; 46(12):1123. DOI:10.1055/s-0034-1378102 · 5.20 Impact Factor
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    ABSTRACT: Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients' clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.
    Tumor Biology 09/2014; 35(12). DOI:10.1007/s13277-014-2526-4 · 2.84 Impact Factor
  • Yin Zhang, Yu Sheng, Zhining Fan
    Endoscopy 08/2014; 46(8):713. DOI:10.1055/s-0034-1377309 · 5.20 Impact Factor
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    ABSTRACT: AbstactBackground and AimThe gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel disease. This study aimed to evaluate the safety, feasibility and efficacy of FMT through mid-gut for refractory Crohn's disease (CD).Methods We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey-Bradshaw Index (HBI) score ≥ 7 were enrolled for this study. All included patients were treated with single FMT through mid-gut and assessed during follow-up.ResultsMetagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7 % (26/30) and 76.7 % (23/30) respectively, which was higher than other assessment points within 15-month follow-up. Patients’ body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.Conclusions This is a pilot study with the largest sample of patients with refractory CD underwent single FMT. The results demonstrated that FMT through mid-gut might be a safe, feasible, and efficient rescue therapy for refractory CD.
    Journal of Gastroenterology and Hepatology 08/2014; 30(1). DOI:10.1111/jgh.12727 · 3.33 Impact Factor
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    ABSTRACT: Esophageal perforation is a rare complication of endoscopic retrograde cholangiopancreatography and the perforation is usually too large to close with endoclips. We developed an endoscopic procedure for the perforations. A gastroscope fitted with a cap was inserted into the esophagus to perform the clip closure. The closure procedure was divided in 3 steps: step 1 is large clip closure; step 2 is small clip closure; and step 3 is the nasogastric tube placement for drainage. A total of 4 patients underwent a cap-assisted clip closure and the procedures were completed successfully within 30 minutes. The cure was achieved in all the 4 patients after a relatively short period of hospital stay and no patient complained of closure-related complication. The cap-assisted clip closure procedure is effective, safe, and easy to carry out for the closure of large esophageal perforations. It may also be applied to perform the closure of large perforations at other sites of the digestive tract.
    Surgical laparoscopy, endoscopy & percutaneous techniques 04/2014; 24(3). DOI:10.1097/SLE.0b013e318293c4b6 · 0.88 Impact Factor
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    ABSTRACT: Stents are recommended in patients with dysphagia caused by esophageal stricture, but an ideal stent does not currently exist. Thus, studies on new esophageal stents are necessary, and suitable animal models are desperately needed for these studies. The aim of this study was to establish a model of malignant esophageal stricture in rabbit for studies on stent innovation. A total of 38 New Zealand white rabbits were used in this study. Using the endoscopic submucosal injection technique, VX2 fragments were inoculated into the submucosal layer of the rabbit thoracic esophagus, and an endoscopic follow-up was subsequently performed to observe the tumor development and progression. The self-expandable metal stents were randomly deployed in rabbits with severe esophageal stricture to investigate the safety and feasibility of the animal models for stenting. An endoscopic implantation procedure for VX2 tumors was completed in 34/38 rabbits, and tumor development was confirmed in 30/34 animals. The success rate of the endoscopic implantation and tumor development were 89.4% (95% CI, 79.6% to 99.2%) and 88.2% (95% CI, 76.9% to 99.5%) respectively. During the endoscopic follow-up period, severe esophageal stricture occurred in 22/30 rabbits with a rate of 73.3% (95%CI, 57.5% to 89.1%), and 12/22 models received stent placement. During and after stent implantation, no severe stent-related complication or mortality occurred in the animal models. The rabbits that received stent placement survived longer than those without stent implantation (the mean survival time: 53.9 days versus 40.3 days, P = 0.016). The endoscopic method is a safe and effective method for establishing a malignant esophagostenosis model in rabbits. This model can simulate the human body environment for stent deployment and is an excellent tool for the study of stent innovation for the treatment of esophageal cancer.
    Journal of Translational Medicine 02/2014; 12(1):40. DOI:10.1186/1479-5876-12-40 · 3.99 Impact Factor
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    ABSTRACT: This study was undertaken to establish a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma (ESC) by endoscopic and surgical implantation of VX2 tumors. Fragments of a VX2 tumour were endoscopically implanted in the submucosal layer of the thoracic esophagus of 32 New Zealand white rabbits, while 34 animals received surgical implantation into the muscular layer. Then, the animals were studied endoscopically and pathologically. The safety and efficiency of the two methods and the pathological features of the animal models were analyzed. Both the endoscopic and the surgical method had a relatively high success rate of tumor implantation [93.7% (30/32) vs. 97.1% (33/34)] and tumor growth [86.7% (26/30) vs. 81.8% (27/33)], and the variation in the results was not statistically significant (P>0.05). Compared with those produced by the surgical method, the models produced by the endoscopic method had a higher rate of severe esophageal stricture [61.5% (16/26) vs. 29.6% (8/27)] and of intra-luminal tumor growth [73.1% (19/26) vs. 37.0% (10/27)], and had a lower rate of tumor invasion of adjacent organs [53.8% (14/26) vs. 81.5% (22/27)]; all of these results were statistically significant (P<0.05). However, the difference in the survival time and the rates of tumor regional/distant metastasis [38.5% (10/26) vs. 51.8% (14/27)] between the two methods were not statistically significant (P>0.05). The endoscopic and surgical methods are both safe and effective for establishment of VX2 tumors in the rabbit esophagus. The models produced by the two methods have different pathologic features mimicking that of human ESC. We recommend the models for studies on surgical procedures and minimally invasive treatments.
    PLoS ONE 01/2014; 9(1):e85326. DOI:10.1371/journal.pone.0085326 · 3.53 Impact Factor
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    ABSTRACT: Gastric submucosal tumors (SMTs) originating from the muscularis propria layer are treated endoscopically. Successful closure of the wall defect is a critical step. This study evaluated the safety and feasibility of the endoscopic purse-string suture (EPSS) method using an endoloop and several metallic clips after endoscopic full-thickness resection (EFTR) or perforation due to endoscopic submucosal dissection (ESD). From December 2009 to April 2013, 30 patients with SMTs originating from the muscularis propria layer who received EFTR or ESD were retrospectively analyzed. After successful tumor resection, an endoloop was anchored onto the circumferential margin of the gastric defect with several metallic clips and tightened gently. Patient characteristics, tumor size, en bloc resection, and postoperative complications were evaluated. For all 30 patients, EPSS was successfully performed after EFTR or perforation due to ESD. The mean diameter of the resected specimen was 1.9 cm. No severe complications occurred during or after the procedure. The lesions were healed 1 month after the procedure, as confirmed endoscopically. The EPSS method using an endoloop and clips is an effective and safe technique for closing the gastric defect after EFTR or perforation due to ESD.
    Surgical Endoscopy 01/2014; 28(6). DOI:10.1007/s00464-013-3404-7 · 3.31 Impact Factor
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    ABSTRACT: Pancreaticobiliary maljunction (PBM) is an unusual anomalous condition in which the pancreatic duct and bile duct merge outside the duodenal wall and form a long common channel. Pancreas divisum (PD) is a congenital anomaly in which the dorsal and ventral pancreatic ducts fail to fuse. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosing PD and magnetic resonance cholangiopancreatography (MRCP) is the non-invasive choice. In this study, four cases of patients with unusual PBM in addition to PD are described. The patients presented with abdominal pain, which was caused by distal biliary stricture diagnosed by MRCP. The patients received ERCP and had a good prognosis.
    Experimental and therapeutic medicine 01/2014; 7(1):8-10. DOI:10.3892/etm.2013.1403 · 0.94 Impact Factor
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    ABSTRACT: Primary immunodeficiency is a disease characterized by reduced levels of serum immunoglobulins and multiple clinical manifestations. Patients with primary immunodeficiency frequently present with gastrointestinal symptoms, such as diarrhea, malabsorption and weight loss. The mainstay of treatment is replacement therapy with intravenous immunoglobulin (IVIG). In the current study, we report the case of a 23-year-old man with symptoms of chronic diarrhea, malabsorption and weight loss that had been apparent for two years. Subsequent to being diagnosed with possible primary immunodeficiency, the patient was treated with 30 mg/day oral prednisone for one month. The prednisone was then tapered weekly by 5 mg until withdrawal. Three months later, the patient's clinical symptoms disappeared and his quality of life improved. During the subsequent nine months follow-up, the patient was able to work without suffering any effects from his illness. The body weight of the patient increased and plasma albumin levels were normal. In conclusion, this study describes the case of a patient with primary immunodeficiency-related gastrointestinal symptoms who responded well to oral prednisone treatment.
    Experimental and therapeutic medicine 08/2013; 6(2):616-618. DOI:10.3892/etm.2013.1178 · 0.94 Impact Factor
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    ABSTRACT: Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3'-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC. © 2013 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 07/2013; 52. DOI:10.1002/mc.22062 · 4.27 Impact Factor
  • Gastrointestinal Endoscopy 05/2013; 77(5):AB191. DOI:10.1016/j.gie.2013.03.448 · 4.90 Impact Factor
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    ABSTRACT: Recent studies showed that pseudogenes can regulate the expression of their coding gene partners by competing for miRNAs. The E2F family plays a crucial role in the control of cell cycle checkpoint. E2F3P1 is a pseudogene of E2F3. Few studies focused on genetic variations on pseudogenes. In this study, we performed a case-control study to assess the association between single nucleotide polymorphisms (SNPs) in E2F3P1 and hepatocellular carcinoma (HCC) risk in 1050 hepatitis B virus (HBV)-positive HCC cases and 1050 chronic HBV carriers. Logistic regression analysis was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and HCC risk. We found that the variant CT/TT genotypes of rs1838149 were associated with a significantly decreased risk of HCC (adjusted OR = 0.66, 95% CIs = 0.51-0.86, P = 0.002) compared to those with wildtype CC homozygote. Furthermore, the AA genotype of rs9909601 had an increased HCC risk with an adjusted OR of 1.41 (95% CIs = 1.07-1.86), and the A allele of rs9909601 was significantly associated with HCC risk compared to those with the G allele (adjusted OR = 1.17, 95% CIs = 1.03-1.33, P = 0.017). These results indicate that genetic variations in the pseudogene E2F3P1 may confer HCC risk.
    05/2013; 27(3):215-219. DOI:10.7555/JBR.27.20130019
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  • Xiao-Wei Tang, Shu Huang, Zhining Fan
    Scandinavian Journal of Gastroenterology 04/2013; DOI:10.3109/00365521.2012.763179 · 2.33 Impact Factor
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    ABSTRACT: Several potential functional polymorphisms in the DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln (rs25487), Arg194Trp (rs1799782), Arg280His (rs25489) and X-ray repair cross-complementing group 3 (XRCC3) T241M (rs861539) have been implicated in colorectal cancer (CRC) risk, but the results are conflicting. Here, we performed a meta-analysis of 23 published case control datasets and assessed genetic heterogeneity between those datasets. All the case-control studies published from January 2000 to June 2012 on the association between those polymorphisms and CRC risk were identified by searching the electronic literature Medline. Statistical analysis was performed with the software programs Review Manager (version 4.2). For overall CRC, no significant association was observed, the pooled odds ratios for XRCC1 Arg399Gln, Arg194Trp, Arg280His, and XRCC3 T241M were 1.02 (95 % CI: 0.93, 1.12), 1.03 (95 % CI: 0.94, 1.14), 0.98 (95 % CI: 0.85, 1.13) and 1.03 (95 % CI: 0.85, 1.26), respectively. Furthermore, no significant association was observed in subgroup analyses based on ethnicity. The results suggested that these four SNPs evaluated are not associated with risk of CRC.
    Molecular Biology Reports 12/2012; DOI:10.1007/s11033-012-2471-5 · 1.96 Impact Factor
  • The American Journal of Gastroenterology 11/2012; 107(11):1755. DOI:10.1038/ajg.2012.251 · 9.21 Impact Factor
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    ABSTRACT: Recombinant immunotoxins consisting of small antibody fragments fused to cytotoxic moieties are being evaluated for use in prospective antibody-targeted cancer therapies. A receptor tyrosine kinase known as c-Met is overexpressed in a vast range of human malignancies, making it an ideal target for antibody-mediated delivery of numerous cytotoxic agents. A single Fab molecule capable of binding to human c-Met with high affinity and specificity was previously identified using antibody phage-display technology. In order to develop a molecule to increase both the cytotoxicity and anti-tumor activity of the anti-c-Met molecule, a recombinant immunotoxin anti-c-Met/PE38KDEL was constructed and expressed by fusing the human anti-c-Met single-chain variable fragment (ScFv) with a modified Pseudomonas exotoxin A (PE38KDEL). Purified anti-c-Met/PE38KDEL was demonstrated to specifically bind to cells of c-Met-positive human hepatoma cell lines, causing a proliferation defect by inducing caspase-3/8-mediated apoptosis, as observed by in vitro assays. Furthermore, anti-c-Met/PE38KDEL administration was shown to inhibit the growth of hepatocellular carcinoma xenografts in vivo through suppression of Ki-67 expression and enhancement of tumor cell apoptosis rates. Cumulatively, the current findings demonstrate the successful construction of a recombinant immunotoxin capable of accurately targeting c-Met-positive human hepatoma cell lines both in vitro and in vivo, providing a novel compound with potential for applications as an alternative therapy for c-Met-positive cancer management.
    Immunology letters 09/2012; 149(1-2). DOI:10.1016/j.imlet.2012.09.006 · 2.91 Impact Factor
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    ABSTRACT: Normal saline is the most popular agent used during endoscopic submucosal injection. However, endoscopists have never identified an optimal submucosal injection solution, which is not only safe and cost-effective but has a unique lifting ability with endoscopic submucosal cushion and causes less tissue damage. This study aimed to evaluate the effectiveness and microscopic characteristics of a blood solution, including whole blood and plasma solution, as a submucosal cushioning agent, compared with normal saline. Endoscopic submucosal dissection (ESD) procedures in pig stomachs were performed by injecting plasma solution (n=4) and normal saline (n=4). A total of 38 patients with gastrointestinal neoplasms underwent endoscopic musocal resection (EMR) procedures. Of 38 EMRs, 7 used whole blood injection, and 31 of 38 acting as the control group used normal saline. A tissue damage scoring system was developed based on injection-induced hydrops and tears for the evaluation of tissue damage. In animal experiments, the lifting time of the injection with normal saline in the pig colon was shorter than that of the group with plasma solution (18.25±5.44 min vs. 6.5±2.38 min, P=0.007). In animal experiments with ESD procedures in the stomach, the hydrops in the normal saline injection group were more extensive than those in the group with plasma (P=0.011). The degree of tearing in the group with normal saline was observed to be less than that in the group with plasma (P=0.008). In patients with EMR, using the histological scoring method, it was determined that the degree of hydrops in the group with normal saline injection was more extensive than that in the group with whole blood (P<0.001). The effective submucosal tearing in the group with normal saline was less than that in the group with blood (P<0.001). The blood solution, including whole blood and plasma solution, as a novel submucosal injection agent, may outperform normal saline with a unique lifting ability, less pronounced tissue damage and marked effective submucosal blunt dissection.
    Experimental and therapeutic medicine 09/2012; 4(3):419-424. DOI:10.3892/etm.2012.626 · 0.94 Impact Factor