Zhining Fan

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

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Publications (20)63.84 Total impact

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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; · 3.33 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; · 3.43 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. · 0.34 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. · 0.34 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; · 4.27 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.
    Journal of biomedical research. 05/2013; 27(3):215-219.
  • Xiao-Wei Tang, Shu Huang, Zhining Fan
    Scandinavian Journal of Gastroenterology 04/2013; · 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; · 2.51 Impact Factor
  • The American Journal of Gastroenterology 11/2012; 107(11):1755. · 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; · 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. · 0.34 Impact Factor
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    ABSTRACT: BACKGROUND: Specialized intestinal metaplasia (SIM) mucosa observed in Barrett's esophagus (BE) has been a hot research topic due to the close relationship with adenocarcinoma of esophagus (ACE). Earlier studies found that SIM mucosa was similar to normal intestinal epithelium on morphology and histology. The signal pathway involved in conformation of intestinal epithelium may be a critical initiator for BE. METHODS: The expressions of key regulators (Tcf4, Cdx2, Hes1 and Math1) in Wnt and Notch signal pathways were measured in 41 paired esophageal biopsies. Cell morphological changes in normal esophagus were compared among groups treated by acid, bile acid and the mixture of both media. RESULTS: The expression levels of regulators (Tcf4, Cdx2, Hes1 and Math1) were found significantly increased in SIM, C≥3Mn and high-grade dysplasia (HGD) groups. Distinct ultrastructure changes and highly expressed key regulators were also detected at the seventh day for group treated by 400μmol bile acid. CONCLUSIONS: Aberrant expressed regulators in Wnt and Notch pathways were observed in BE tissue and normal esophageal cells treated by acid, bile acid and the mixture of both media. This study provided preliminary data to understand the mechanism of BE conformation.
    Gastroentérologie Clinique et Biologique 08/2012; · 0.80 Impact Factor
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    ABSTRACT: Cyclooxygenase-2 (COX-2) involves in multiple processes in carcinogenesis, including inflammation, apoptosis inhibition, immune response suppression, tumor cell invasion, and angiogenesis. COX-2 is overexpressed in various cancers, including gastric cancer. COX-2 is encoded by prostaglandin endoperoxide synthase 2 (PTGS2) gene. We hypothesized that potentially functional polymorphisms in PTGS2 may contribute to gastric cancer risk. To assess this hypothesis, we conducted a case-control study with 1681 gastric cancer cases and 1916 control subjects in a Chinese population to evaluate the association between a polymorphism in 3'-untranslated region of PTGS2, rs5275, and the risk of gastric cancer. Logistic regression analysis revealed that variant allele (C) of rs5275 was significantly associated with an increased risk of gastric cancer (per allele odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29, p = 0.030). This association was more prominent in females (per allele OR = 1.42, 95% CI = 1.11-1.81, p = 0.005) and nonsmokers (per allele OR = 1.35, 95% CI = 1.14-1.59, p = 0.001). Interestingly, we detected a negative interaction between rs5275 and smoking on the gastric cancer risk (p = 0.007). Our findings indicate that PTGS2 rs5275T/C may be a candidate genetic marker for gastric cancer susceptibility.
    DNA and cell biology 03/2012; 31(7):1252-7. · 2.28 Impact Factor
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    ABSTRACT: Pyogenic liver abscess (PLA) is a serious, life threatening condition with a high mortality rate that represents a diagnostic and therapeutic challenge. The aim of this study was to collect demographic data and clinical, laboratory and microbiological characteristics of PLA patients treated between 2000 and 2010. We also aimed to collect information regarding our management experience of these cases. As a retrospective review, 47 patients with PLA in a tertiary referral center were examined to determine their demographic characteristics, clinical features, and laboratory, imaging, and microbiologic findings as well as the treatment outcome. Cryptogenic PLA was the most frequently identified type of PLA, while benign biliary tract disease was the most frequently identifiable cause of PLA (18/47 patients; 38.3%). Leukocytosis and elevated alanine transaminase were common laboratory findings and were observed in 35 (74.5%) and 22 (46.8%) patients, respectively. Increased fibrinogen was also detected in 11 of 15 investigated cases (73.3%). Notably, infection-induced thrombocytopenia occurred in 8 patients (17%). Diabetes mellitus was associated with the occurrence of infection induced shock when compared to the non-diabetic group (p<0.05). Patients with two or more comorbid diseases had longer hospitalizations when compared to patients with one comorbid disease or those without comorbidities (p<0.001). The number of days needed to establish diagnosis was correlated with the length of hospitalization (p<0.001). The overall hospital mortality rate was 2.1% (1/47). Characteristics of PLA patients from the past 10 years are presented. The number of days needed to establish a PLA diagnosis was correlated with the length of the hospital stay. The hospital stay of PLA patients can be further improved by early diagnosis and effective treatments during the early stages of PLA progression.
    Gut and liver 06/2011; 5(2):221-7. · 1.31 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2010; 71(5).
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    Faming Zhang, Guozhong Ji, Zhining Fan
    The Lancet Oncology 07/2009; 10(6):541-2. · 25.12 Impact Factor
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    Journal of gastrointestinal and liver diseases: JGLD 04/2009; 18(1):5-7. · 1.86 Impact Factor
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    ABSTRACT: Transforming growth factor-beta (TGF-beta)-Smad signaling pathway participates in the regulation of a variety of cellular activities. Unlike the high incidences of Smad4 mutation or deletion in pancreatic cancer and gastrointestinal cancers, Smad4 gene is seldom mutated or deleted in hepatocellular carcinoma (HCC). The role of TGF-beta-Smad4 signaling pathway in leading to carcinogenesis of liver cells remains unknown. In this study, we succeeded in silencing Smad4 using lentiviral-mediated Smad4 RNA interference (RNAi). We investigated the role of Smad4 in TGF-beta1-induced cell proliferation and apoptosis of HCC cell line SMMC-7721. We determined cell proliferation, apoptosis, and expression of p21, p16, p53 and caspase 3. Results showed that TGF-beta1 not only had a significant anti-proliferation effect but also induced cellular apoptosis in SMMC-7721 cells. These effects induced by TGF-beta1 were almost completely blocked by the knockdown of Smad4. Western blot analysis revealed that p16 was up-regulated and caspase 3 was activated by silencing of Smad4, and the expression of p21 and wild-type p53 were not affected. These results suggest that TGF-beta1-induced cell growth inhibition by up-regulating p16 expression and cellular apoptosis by activating caspase 3 was Smad4-dependent. Additionally, the knock down of a specific gene using lentiviral-mediated RNAi appears to be a promising tool and strategy for analyzing endogenous gene function.
    Oncology Reports 12/2008; 20(5):1053-9. · 2.30 Impact Factor
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    ABSTRACT: The ileum generally works well, whereas Meckel’s diverticulum (MD) has complications including bleeding, obstruction, intussusception, diverticulitis, and perforation. Our knowledge of the pathological features of the MD muscular layer and mucosa is limited. We report a rare case of giant MD that was diagnosed by double-balloon enteroscopy (DBE). The pathological features of the mucosa were evaluated by investigation for Helicobacter pylori; and the nuclear proliferation antigen Ki-67, the gastrointestinal cancer-associated biomarker TRAK1, synaptophysin, and neurofilament were used to precisely define the mucosa and neuronal and ganglion cell components. The pathophysiology of MD is discussed and a literature review is presented. We believe that this is the first report of a systematic histochemical analysis of the mucosa and myenteric plexus of MD and the normal ileum. The present investigation may provide novel evidence of pathological abnormalities resulting in the complex complications of MD. KeywordsMeckel’s diverticulum-Ki-67-TRAK1-Synaptophysin-Neurofilament
    Clinical Journal of Gastroenterology 3(2):92-96.
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a highly malignant cancer characterized by rapid progression, easy metastasis and frequent recurrence. Previous studies have shown that the Smad4 signaling pathway plays an important role in the cell growth and apoptosis of HCC. However, the effect of Smad4 signaling on the invasion and migration of HCC cells remains unclear. The present study aimed to examine the effects of the transforming growth factor (TGF)-β1-Smad4 signaling pathway on the migration of HCC cells. Lentiviral vectors expressing miRNA against Smad4 were constructed to block the expression of Smad4 in HCC cells, and transwell units were used to investigate the invasive potential of SMMC-7721 cells before and after TGF-β1 treatment. mRNA levels of matrix metalloproteinase (MMP)-2 and -9 were analyzed by reverse-transcription PCR, and concentrations of vascular endothelial growth factor (VEGF), p-JNK, p-p38 and p-Erk1/2 proteins were analyzed by Western blotting. The results indicate that TGF-β1 induced cellular invasion in the SMMC-7721 cells. These effects were almost completely blocked by the knockdown of Smad4. Reverse-transcription PCR and Western blot analysis revealed that MMP-2, VEGF, p-JNK and p-p38 were up-regulated by the silencing of Smad4, while the expression of MMP-9 and p-Erk1/2 was not affected by Smad4 silencing with or without TGF-β1 stimulation. These findings suggest that TGF-β1-induced SMMC-7721 cell invasion by the up-regulation of MMP-2 and VEGF is Smad4-dependent. The activation of MMP-2 and VEGF may be an important mechanism by which Smad4 is involved in metastasis. TGF-β1-Smad4 signaling may regulate SMMC-7721 cell migration through the activation of the MAPK pathway.
    Molecular Medicine Reports 3(2):295-9. · 1.17 Impact Factor