Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Validation of a real-time biliopancreatic endoscopic ultrasonography analytical device in China: a prospective, single-centre, randomised, controlled trial.

BACKGROUND: Endoscopic ultrasonography (EUS) is a key procedure for the diagnosis of biliopancreatic diseases. However, the performance among EUS endoscopists varies greatly and leads to blind spots during the operation, which can impair the health outcomes of patients. We previously developed an artificial intelligence (AI) device that accurately identified EUS standard stations and significantly reduced the difficulty of ultrasonography image interpretation. In this study, we updated the device (named EUS-IREAD) and validated its performance in improving the quality of EUS procedures. METHODS: In this single-centre, randomised, controlled trial, we updated EUS-IREAD so it consisted of five learning models to identify eight EUS stations and 24 anatomical structures. The trial was done at the Renmin Hospital of Wuhan University (Wuhan, China) and included patients aged 18 years or older with suspected biliopancreatic (pancreas and biliopancreatic duct) lesions due to clinical symptoms, radiological findings, or laboratory findings, and with a high risk of pancreatic cancer. Patients were randomly assigned (1:1) by a dedicated research assistant using a computer-generated random number series (with a block size of four) to undergo the EUS procedure with or without the assistance of EUS-IREAD. Endoscopists in the EUS-IREAD-assisted group were required to observe all standard stations and anatomical structures according to the prompts by the AI device. Data collectors, the independent data anaylsis team, and patients were masked to group allocation. The primary outcome was the missed scanning rate of standard stations between the two groups, which was assessed in patients who underwent EUS procedure in accordance with the assigned intervention (per protocol). This trial is registered with ClinicalTrials.gov, NCT05457101. FINDINGS: Between July 9, 2022, and Feb 28, 2023, 290 patients (mean age 55·93 years [SD 14·06], 152 [52%] male, and 138 [48%] female) were randomly assigned and analysed, including 144 in the EUS-IREAD-assisted group and 146 in the control group. The EUS-IREAD-assisted group had a lower missed scanning rate of stations than the control group (4·5% [SD 0·8] vs 14·3% [1·0], -9·8% [95% CI -12·2 to -7·5]; odds ratio 3·6 [95% Cl 2·6 to 4·9]; p<0·0001). No significant adverse event was found during the study. INTERPRETATION: Our study confirms the capability of EUS-IREAD to monitor the blind spots and reduce the missed rate of stations and structures during EUS procedures. The EUS-IREAD has the potential to play an essential part in EUS quality control. FUNDING: Innovation Team Project of Health Commission of Hubei Province and College-enterprise Deepening Reform Project of Wuhan University.

Preoperative automatic reminder systems and impact on quality and compliance with colonoscopy preparation: A multicenter randomized controlled trial.

OBJECTIVES: Traditional preoperative reminding services have been applied to enhance the quality of bowel preparation for colonoscopy. In this study we aimed to evaluate the effectiveness of an automated electronic reminder system (E-reminder) on improving bowel preparation and the quality of preoperative education before colonoscopy. METHODS: From August 2021 to March 2022, 833 outpatients aged 50-75 years who underwent colonoscopy were included and randomly assigned to the E-reminder group and the control group. While the control group received routine preoperative education. The E-reminder group received automatic phone call, text message reminders and web services regarding the details of bowel preparation before the colonoscopic examination. The quality of bowel preparation was evaluated by the Boston Bowel Preparation Scale (BBPS) score and the previously validated objective evaluation scale of automatic BBPS (e-BBPS). RESULTS: In manual assessment, the rate of adequate bowel preparation was improved in the E-reminder group of intention-to-treat population using BBPS (60.7% vs 54.5%, P = 0.01). The percentage of objective evaluated adequate bowel preparation using e-BBPS in the E-reminder group of per-protocol population was significantly higher than that in the control group (76.9% vs 69.2%, P = 0.02). CONCLUSIONS: E-reminder was an effective tool to improve the quality of bowel preparation and compliance with medical instructions. It may be regarded as an efficient and convenient education tool, improving the quality of medical service.

Achieving Total Enteroscopy by Consecutive Bidirectional Double-balloon Enteroscopy Procedures.

OBJECTIVE: To investigate the feasibility and safety of achieving total enteroscopy by consecutive bidirectional double-balloon enteroscopy (DBE) procedures. METHODS: The demographic data, indication, initial insertion route, examination time for each insertion and the entire procedure, total enteroscopy rate, diagnostic yield and adverse events of patients who attempted to achieve total enteroscopy by consecutive bidirectional DBE procedures from January 2014 to December 2019 were retrospectively analyzed. RESULTS: A total of 189 patients were included, and the total enteroscopy rate was 87.3%. Initiating the DBE procedure via the retrograde approach as the initial insertion route achieved a higher total enterosocpy rate (90.9% vs. 78.9%, P=0.023), with shorter overall examination time (134.2±36.2 vs. 156.9±47.6 min, P=0.017) and shorter examination time for the opposite insertion route (23.8±19.9 vs. 53.1±27.6 min, P=0.000) compared with anteograde approach as the initial insertion route. The overall diagnostic yield was 37.6%. The diagnostic yield for successfully achieving total enteroscopy was higher, when compared to the yield for not successfully achieving total enteroscopy (39.4% vs. 25%, P=0.029). The overall rate of adverse events was 2.1% (4/189). There was no significant difference in adverse event rate between the overall examination time ≥2 h group and <2 h group (2.1% vs. 2.0%, P=0.593). CONCLUSION: Consecutive bidirectional DBE procedure is an effective and safe strategy for achieving total enteroscopy with a considerable success rate. This may be a promising option and alternative to traditional methods, and helpful to more promptly establish a definite diagnosis. The retrograde approach, as the initial insertion route, is preferred in clinical practice.

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5ß1/FAK/ERK pathway.

Gastric cancer (GC) is one of the most common malignancies and its prognosis is extremely poor. This study identifies a novel oncogene, microfibrillar-associated protein 2 (MFAP2) in GC. With integrative reanalysis of transcriptomic data, we found MFAP2 as a GC prognosis-related gene. And the aberrant expression of MFAP2 was explored in GC samples. Subsequent experiments indicated that silencing and exogenous MFAP2 could affect motility of cancer cells. The inhibition of silencing MFAP2 could be rescued by another FAK activator, fibronectin. This process is probably through affecting the activation of focal adhesion process via modulating ITGB1 and ITGA5. MFAP2 regulated integrin expression through ERK1/2 activation. Silencing MFAP2 by shRNA inhibited tumorigenicity and metastasis in nude mice. We also revealed that MFAP2 is a novel target of microRNA-29, and miR-29/MFAP2/integrin α5ß1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression. In conclusion, our data identified MFAP2 as a novel oncogene in GC and revealed that miR-29/MFAP2/integrin α5ß1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression.

Randomised controlled trial of WISENSE, a real-time quality improving system for monitoring blind spots during esophagogastroduodenoscopy.

OBJECTIVE: Esophagogastroduodenoscopy (EGD) is the pivotal procedure in the diagnosis of upper gastrointestinal lesions. However, there are significant variations in EGD performance among endoscopists, impairing the discovery rate of gastric cancers and precursor lesions. The aim of this study was to construct a real-time quality improving system, WISENSE, to monitor blind spots, time the procedure and automatically generate photodocumentation during EGD and thus raise the quality of everyday endoscopy. DESIGN: WISENSE system was developed using the methods of deep convolutional neural networks and deep reinforcement learning. Patients referred because of health examination, symptoms, surveillance were recruited from Renmin hospital of Wuhan University. Enrolled patients were randomly assigned to groups that underwent EGD with or without the assistance of WISENSE. The primary end point was to ascertain if there was a difference in the rate of blind spots between WISENSE-assisted group and the control group. RESULTS: WISENSE monitored blind spots with an accuracy of 90.40% in real EGD videos. A total of 324 patients were recruited and randomised. 153 and 150 patients were analysed in the WISENSE and control group, respectively. Blind spot rate was lower in WISENSE group compared with the control (5.86% vs 22.46%, p<0.001), and the mean difference was -15.39% (95% CI -19.23 to -11.54). There was no significant adverse event. CONCLUSIONS: WISENSE significantly reduced blind spot rate of EGD procedure and could be used to improve the quality of everyday endoscopy. TRIAL REGISTRATION NUMBER: ChiCTR1800014809; Results.

Consensus on the digestive endoscopic tunnel technique.

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

Doxorubicin combined with Notch1-targeting siRNA for the treatment of gastric cancer.

Notch1, a transmembrane receptor that has a notable role in gastric cancer (GC) as an oncogene, has been reported to be involved in doxorubicin resistance. Thus, Notch1 is a potential therapeutic target for GC. In the present study, the protein levels of Notch1 intracellular domain (NICD; a marker of Notch1 activation) in human GC cell lines and tumor tissues was measured by western blotting. Next, the effects of Notch1 depletion in SGC7901 cells were evaluated. Finally, the efficacy of Notch1 small interfering RNA (siRNA) combined with doxorubicin therapy for GC was examined in vitro and in vivo. The results revealed that NICD levels were high in GC cells, and that the inhibition of NICD by transfection with Notch1 siRNA induced apoptosis and inhibited proliferation. Ectopic downregulation of Notch1 expression enhanced the sensitivity of GC tumors to doxorubicin, which suppressed the development of GC. These data demonstrated that Notch1 was a significant regulator of cell proliferation and apoptosis in GC. Thus, the combination of doxorubicin with Notch1 siRNA is a potential strategy for the treatment of GC.

Wnt6 contributes tumorigenesis and development of colon cancer via its effects on cell proliferation, apoptosis, cell-cycle and migration.

Wnt proteins have been reported to contribute to the progression of various types of cancer. Wnt6 is a member of the Wnt family and may promote tumorigenesis in gastrointestinal cancer and cervical cancer. In the present study, the expression of Wnt6 in human colon cancer cell lines was evaluated, in order to investigate the role of Wnt6 in the development of colon cancer. Additionally, the effects of Wnt6 upregulation or downregulation on proliferation, apoptosis, cell cycle and cell migration of colon cancer cells have been investigated. Furthermore, western blot analysis was employed to evaluate the expression of Wnt6, B-cell lymphoma 2-associated X protein (Bax), caspase-3 and matrix metalloproteinase (MMP)2. The results of the present study demonstrated that the expression of Wnt6 was increased in HCT116 and SW480 cells compared with the remaining colon cancer cell lines. Furthermore, overexpression Wnt6 resulting from transfection of pGPU6/GFP/Neo-Wnt6-Homo-1 plasmid promoted the proliferation, cell cycle and migration of HCT116 and SW480 cells, but inhibited cell apoptosis in vitro. The expression of caspase-3 and MMP2 was increased, whereas the expression of Bax was decreased in response to upregulation of Wnt6. These results suggested that Wnt6 may serve a vital function in the development of colon cancer.

Aberrant high expression level of MORC2 is a common character in multiple cancers.

Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types using immunohistochemical staining and analysis of messenger RNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, esophagus, and bladder). We also found that the MORC2 expression level in high-grade cancer tissues was much more elevated and associated with unfavorable pathological characteristics, poor overall survival, and disease-free survival in several kinds of cancers such as non-small cell lung cancer and breast cancer. Gene set enrichment analysis was used to predict the genes modulated by MORC2, and the results showed that dysregulation of MORC2 in tumor may take part in the cell cycle regulation and genomic instability. We observed that MORC2 knockdown would arrest the cell cycle progress, and the genome of tumors with high MORC2 expression contained more point mutations and gene copy number variation, which validates our gene set enrichment analysis results. The results also showed that MORC2 knockdown would significantly inhibit the proliferation, colony forming, migration, and invasion in multiple cancer cell lines. Taken together, these results highlight the importance of MORC2 in tumorigenesis and cancer progression, and it may act as a potential diagnostic marker and therapeutic target for these diseases.

Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs

Abstract Background The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. Aims This research aimed to determine the clinical and virological features of the rare pattern. Methods A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. Results The amino acid variability within major hydrophilic region, especially the “a” determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the “a” determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. Conclusions In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs.

BACKGROUND: The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. AIMS: This research aimed to determine the clinical and virological features of the rare pattern. METHODS: A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. RESULTS: The amino acid variability within major hydrophilic region, especially the "a" determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the "a" determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. CONCLUSIONS: In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

Sequence analysis of the HBV S protein in Chinese patients with coexisting HBsAg and anti-HBs antibodies.

The coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in patients with hepatitis B virus (HBV) infection has been discovered and explained for several decades, but debate still exists. This study was to explore the relationship between this special serological pattern and mutations in S gene region. Fifteen patients with coexisting HBsAg and anti-HBs were selected as the experimental group, and 27 patients with HBsAg positive only were selected as the control group. The S gene region was amplified and sequenced. No significant differences were observed between the two groups with regard to age, gender, alanine aminotransferase level, HBsAg titer, genotype, and HBV DNA level. The patients from the two groups were infected with HBV of the genotype B and C. Compared with the control group, the experimental group showed a higher variability in amino acid within the N-terminal region and the MHR, especially the "a" determinant. The most frequent change in patients from the experimental group was located at positions s126. The coexistence of HBsAg and anti-HBs might be associated with the increased amino acid mutations in the "a" determinant. Further studies should be performed to determine the clinical implication of this serological pattern, including the binding of anti-HBs to HBsAg, escape from immune system, and efficacy of antiviral therapy.

Phosphatase and Tensin Homolog (PTEN) Represses Colon Cancer Progression through Inhibiting Paxillin Transcription via PI3K/AKT/NF-κB Pathway.

The tumor suppressor gene phosphatase and tensin homolog (PTEN) is frequently mutated in colon cancer. However, the potential contribution of loss of PTEN to colon cancer progression remains unclear. In this study, we demonstrated that PTEN overexpression or knockdown in Lovo colon cancer cells decreased or increased paxillin expression, respectively. Moreover, paxillin reversed PTEN-mediated inhibition of Lovo cell invasion and migration. Overexpression of PTEN in an orthotropic colon cancer nude mice model inhibited tumor formation and progression. In addition, PTEN protein level was negatively correlated with that of paxillin in human colon cancer tissues. Mechanistically, we identified three NF-κB binding sites on paxillin promoter and confirmed that paxillin was a direct transcriptional target of NF-κB. Our findings reveal a novel mechanism by which PTEN inhibits the progression of colon cancer by inhibiting paxillin expression downstream of PI3K/AKT/NF-κB pathway. Thereby, PTEN/PI3K/AKT/NF-κB/paxillin signaling cascade is an attractive therapeutic target for colon cancer progression.

Thymoquinone Pretreatment Overcomes the Insensitivity and Potentiates the Antitumor Effect of Gemcitabine Through Abrogation of Notch1, PI3K/Akt/mTOR Regulated Signaling Pathways in Pancreatic Cancer.

BACKGROUND: The gemcitabine-insensitivity remains the main challenge for pancreatic cancer treatment. Thymoquinone, the predominant bioactive ingredient of Nigella sativa, has been shown to possess promising anti-cancer and chemo-sensitizing effects on pancreatic cancer, however, its meticulous mechanism is still indistinct. AIM: The objective of the present study was to investigate the potency of thymoquinone in combination with gemcitabine in inducing apoptosis and preventing the development of gemcitabine-insensitivity in pancreatic cancer cells. METHODS: The anti-tumor effects of thymoquinone and gemcitabine were analyzed via evaluation of alterations of cell viability, tumor weight, apoptosis-related proteins, caspase-3, -9 activities and NF-κB DNA binding activity in pancreatic cancer cells in vitro and PANC-1 cells orthotopic xenograft in vivo. RESULTS: Thymoquinone pretreatment following gemcitabine treatment synergistically caused an increase in pancreatic cancer cells apoptosis and tumor growth inhibition both in vitro and in vivo. The novel combinational regimen also contributes to alterations of multiple molecular signaling targets, such as the suppression of Notch1, NICD accompanying with up-regulation of PTEN, the inactivation of Akt/mTOR/S6 signaling pathways, and the suppression of phosphorylation and nuclear translocation of p65 induced by TNF-α. Thymoquinone pretreatment and gemcitabine also induced down-regulation of anti-apoptotic Bcl-2, Bcl-xL, XIAP and up-regulation and activation of pro-apoptotic molecules including Caspase-3, Caspase-9, Bax and increased release of cytochrome c. CONCLUSIONS: This novel modality of thymoquinone pretreatment can enhance the anti-cancer activity of gemcitabine and may be a promising option in the treatment of pancreatic cancer.

Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo.

Gastric cancer is the second most common cause of cancer-related deaths worldwide. Doxorubicin-based chemotherapeutic regimes have been the mainstay of systemic treatment for disseminated gastric cancer for numerous years. However, the efficacy of doxorubicin is severely limited due to chemoresistance. Chemoresistance is a tightly regulated process, under the control of numerous signal transduction pathways. Amongst these, the mitogen-activated protein kinase (MAPK) pathway has received much attention. This study assessed whether the p38 MAPK pathway is involved in doxorubicin resistance in gastric cancer cells. Doxorubicin alone or combined with the p38 MAPK pathway inhibitor SB203580 was used to treat gastric cancer cells (SGC7901 and BGC823 lines). The effect of doxorubicin on the growth and apoptosis of gastric cancer cells in the presence or absence of SB203580 was investigated by western blot analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, Annexin V-FITC/propidium iodide staining followed by flow cytometry analysis, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Next, the effects of doxorubicin and SB203580, on the sensitivity of BGC-823 cells were assessed in a tumor xenograft model. The results showed that the p38 MAPK inhibitor significantly increases gastric cancer cell sensitivity to doxorubicin. Doxorubicin in combination with SB203580 significantly reduced cell viability (P<0.01) and increased cell death (P<0.01), which may be associated with the inactivation of the p38 MAPK signaling pathway, followed by the induced expression of the pro-apoptotic protein Bax and a concomitant decrease in Bcl-2 expression. These findings suggest that p38 MAPK is involved in gastric cancer cell survival, and that the inhibition of p38 MAPK signaling can reduce the tolerance of gastric cancer cells to doxorubicin treatment.

Fujinon intelligent color enhancement for the diagnosis of early esophageal squamous cell carcinoma and precancerous lesion.

BACKGROUND/AIMS: Esophageal squamous cell carcinoma is a common malignant tumor in recent years, and the key for improving the survival rate is early diagnosis and treatment. Computed virtual chromoendoscopy with the Fujinon intelligent color enhancement (FICE) system was reported to improve visualization of neoplastic and non-neoplastic lesions in gastroscopy and colonoscopy. The purpose of this study was to evaluate the value of FICE in the diagnosis of early esophageal squamous cell carcinoma and precancerous lesions. MATERIALS AND METHODS: Two hundred fifty-seven patients with suspicious lesions of the esophagus were examined successively by FICE, magnifying FICE, Lugol chromoendoscopy, and magnifying Lugol chromoendoscopy in the hospital. The lesions and the intrapapillary capillary loop (IPCL, microvessels at the surface of esophageal carcinoma) were observed and compared with the pathologic diagnosis that was regarded as the golden standard. RESULTS: The positive rates of early esophageal squamous cell carcinoma were 92.6% and 88.9% as examined by FICE and Lugol chromoendoscopy (p>0.05), and 96.3% and 92.6% as examined by magnifying FICE and magnifying Lugol chromoendoscopy (p>0.05), respectively. The magnifying FICE could observe the IPCL of the esophagus clearly. Early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia were mainly type IV and type V. Low-grade intraepithelial neoplasia and esophagitis were type II and type III, and normal esophagus was type I; however, the observation of the IPCL by magnifying Lugol chromoendoscopy was not clear. CONCLUSION: Fujinon intelligent color enhancement and magnifying FICE are complements to Lugol chromoendoscopy and magnifying Lugol chromoendoscopy in the diagnosis of early esophageal lesions.

Recombinant human trefoil factor 3 ameliorates bowel injury: its anti-inflammatory effect on experimental necrotizing enterocolitis.

Aim. Recombinant human trefoil factor 3 (intestinal trefoil factor) has been suggested to be partially protective against necrotizing enterocolitis (NEC), but the mechanisms of this protection have not been defined. We investigated whether the protective effects of rhTFF3 are the result of an anti-inflammatory response. Methods. The rats were killed on day 4, the distal ileum was harvested for morphological studies and immunohistochemistry for NF- κ B (p65), and the amounts of IL-1 ß , IL-6, and IL-10 in the intestinal tissue were measured using commercial ELISA assay kits. Results. In the neonatal NEC, IL-1 ß , IL-6, and IL-10 were significantly higher than in normal group. In normal group, IL-1 ß and IL-6 were significantly decreased, and the amount of IL-10 was markedly increased compared with NEC group. In the NEC model, immunohistochemical staining for NF- κ B (p65) was demonstrated to be of a strong brown color and was distributed in the intestinal epithelium. Treatment with rhTFF3 significantly decreased the immunoreactivity of NF- κ B (p65) in the NEC model. Conclusions. Intestinal inflammation was ameliorated after rhTFF3 was injected. rhTFF3 may protect against the intestinal injury of the neonatal rat NEC model by suppression of the inflammatory response.

PTEN inhibits the invasion and metastasis of gastric cancer via downregulation of FAK expression.

The tumor suppressor gene phosphatase and tensin homolog (PTEN) is essential in inhibiting tumor growth and metastasis. However, the mechanism by which PTEN restricts gastric cancer progression and metastasis remains largely elusive. Here we demonstrated that PTEN overexpression or knockdown in gastric cancer cells led to the downregulation or upregulation of focal adhesion kinase (FAK), and decreased or increased cell invasion, respectively. Moreover, FAK overexpression could rescue the inhibition of cell invasion by PTEN. These results were further confirmed in orthotropic gastric cancer nude mice model. In addition, in human gastric cancer tissues, PTEN protein level was conversely correlated with FAK protein level. Mechanistically, we found that PTEN inhibited PI3K/NF-κB pathway and inhibited the DNA binding of NF-κB on FAK promoter. Taken together, our data reveal a novel mechanism that PTEN inhibits the growth and invasion of gastric cancer via the downregulation of FAK expression and suggest that exploiting PTEN/PI3K/NF-κB/FAK axis is a promising approach to treat gastric cancer metastasis.

[Diagnosis of obscure gastrointestinal bleeding among different age groups by double balloon enteroscope].

OBJECTIVE: To investigate the diagnostic value of double balloon enteroscope (DBE) on obscure gastrointestinal bleeding(OGIB) and to analyze etiological characteristics among different age groups. METHODS: The clinical data of patients undergoing DBE due to OGIB in the Department of Gastroenterology in Renmin Hospital of Wuhan University from January 2007 to January 2012 were retrospectively analyzed and compared among different age groups. Patients were divided into the young group(age≤40, n=86), the middle age group(aged 41-59, n=81), and the elderly group (age≥60, n=49). The detection of bleeding origin by DBE was compared between different age groups. RESULTS: Diagnosis rates in young, middle age, elderly group were 83.7%(72/86), 87.7%(71/81), 81.6%(40/49) without statistical differences(P>0.05). Complication rates in the young, middle age, and elderly group were 1.2%(1/86), 2.5%(2/81), 2.0%(1/49) without statistic difference(P>0.05). The most common cause in young group was diverticulum/replica malformation while the most common location was ileum. The most common cause in both middle age and elderly group was tumor. CONCLUSIONS: DBE is an effective and safe method for diagnosis of OGIB among different age groups. Each age group has its etiological characteristics. Diagnosis and therapeutic strategy based on age-related characteristics is worthy of further investigation.