Real-time use of artificial intelligence for diagnosing early gastric cancer by magnifying image-enhanced endoscopy: a multicenter diagnostic study (with videos).

BACKGROUND AND AIMS: Endoscopy is a pivotal method for detecting early gastric cancer (EGC). However, skill among endoscopists varies greatly. Here, we proposed a deep learning-based system named ENDOANGEL-ME to diagnose EGC in magnifying image-enhanced endoscopy (M-IEE). METHODS: M-IEE images were retrospectively obtained from 6 hospitals in China, including 4667 images for training and validation, 1324 images for internal tests, and 4702 images for external tests. One hundred eighty-seven stored videos from 2 hospitals were used to evaluate the performance of ENDOANGEL-ME and endoscopists and to assess the effect of ENDOANGEL-ME on improving the performance of endoscopists. Prospective consecutive patients undergoing M-IEE were enrolled from August 17, 2020 to August 2, 2021 in Renmin Hospital of Wuhan University to assess the applicability of ENDOANGEL-ME in clinical practice. RESULTS: A total of 3099 patients undergoing M-IEE were enrolled in this study. The diagnostic accuracy of ENDOANGEL-ME for diagnosing EGC was 88.44% and 90.49% in internal and external images, respectively. In 93 internal videos, ENDOANGEL-ME achieved an accuracy of 90.32% for diagnosing EGC, significantly superior to that of senior endoscopists (70.16% ± 8.78%). In 94 external videos, with the assistance of ENDOANGEL-ME, endoscopists showed improved accuracy and sensitivity (85.64% vs 80.32% and 82.03% vs 67.19%, respectively). In 194 prospective consecutive patients with 251 lesions, ENDOANGEL-ME achieved a sensitivity of 92.59% (25/27) and an accuracy of 83.67% (210/251) in real clinical practice. CONCLUSIONS: This multicenter diagnostic study showed that ENDOANGEL-ME can be well applied in the clinical setting. (Clinical trial registration number: ChiCTR2000035116.).

Real-time artificial intelligence for detecting focal lesions and diagnosing neoplasms of the stomach by white-light endoscopy (with videos).

BACKGROUND AND AIMS: White-light endoscopy (WLE) is the most pivotal tool to detect gastric cancer in an early stage. However, the skill among endoscopists varies greatly. Here, we aim to develop a deep learning-based system named ENDOANGEL-LD (lesion detection) to assist in detecting all focal gastric lesions and predicting neoplasms by WLE. METHODS: Endoscopic images were retrospectively obtained from Renmin Hospital of Wuhan University (RHWU) for the development, validation, and internal test of the system. Additional external tests were conducted in 5 other hospitals to evaluate the robustness. Stored videos from RHWU were used for assessing and comparing the performance of ENDOANGEL-LD with that of experts. Prospective consecutive patients undergoing upper endoscopy were enrolled from May 6, 2021 to August 2, 2021 in RHWU to assess clinical practice applicability. RESULTS: Over 10,000 patients undergoing upper endoscopy were enrolled in this study. The sensitivities were 96.9% and 95.6% for detecting gastric lesions and 92.9% and 91.7% for diagnosing neoplasms in internal and external patients, respectively. In 100 videos, ENDOANGEL-LD achieved superior sensitivity and negative predictive value for detecting gastric neoplasms from that of experts (100% vs 85.5% ± 3.4% [P = .003] and 100% vs 86.4% ± 2.8% [P = .002], respectively). In 2010 prospective consecutive patients, ENDOANGEL-LD achieved a sensitivity of 92.8% for detecting gastric lesions with 3.04 ± 3.04 false positives per gastroscopy and a sensitivity of 91.8% and specificity of 92.4% for diagnosing neoplasms. CONCLUSIONS: Our results show that ENDOANGEL-LD has great potential for assisting endoscopists in screening gastric lesions and suspicious neoplasms in clinical work. (Clinical trial registration number: ChiCTR2100045963.).

Effect of enhanced patient instructions on Helicobacter pylori eradication: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: To improve Helicobacter pylori (H. pylori) eradication rate, enhanced patient instructions (EPI) such as telephone-based re-education, short-message service, and Wechat have been proposed with conflicting results. The aim of this meta-analysis was to evaluate the effect of EPI on H. pylori eradication. METHODS: The PROSPERO registered number of this study is CRD42021278536. PubMed, Embase, and CENTRAL database were searched to identify relevant randomized controlled trials (RCTs) from inception to September 2021. Meta-analysis was performed to estimate the pooled relative risk (RR) with 95% confidence intervals (CI) using a random-effects model. Trial sequential analysis (TSA) was conducted to determine the robustness of the H. pylori eradication rate. RESULTS: Nine RCTs were included. Compared with patients receiving only regular instructions, patients received EPI showed significantly higher H. pylori eradication rate (n = 8 RCTs, ITT analysis: RR = 1.20, 95% CI: 1.06-1.35; PP analysis: RR = 1.12, 95% CI:1.02-1.23) and better patient compliance (n = 8 RCTs, RR = 1.23, 95% CI: 1.09-1.39), as well as higher patient satisfaction (n = 3 RCTs, RR = 1.42, 95% CI: 1.14-1.76). However, there were no significant difference between groups in the incidence of total adverse events (n = 6 RCTs, RR = 0.66, 95%CI: 0.40-1.08) and symptom relief rates (n = 2 RCTs, RR = 1.17, 95% CI: 0.89-1.54). The TSA result indicated that the effect was robust. CONCLUSIONS: Evidence from our meta-analysis shows that EPI intervention may be a promising strategy to improve H. pylori eradication rate, patient compliance, and patient satisfaction.

Evaluation of the effects of an artificial intelligence system on endoscopy quality and preliminary testing of its performance in detecting early gastric cancer: a randomized controlled trial.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is a prerequisite for detecting upper gastrointestinal lesions especially early gastric cancer (EGC). An artificial intelligence system has been shown to monitor blind spots during EGD. In this study, we updated the system (ENDOANGEL), verified its effectiveness in improving endoscopy quality, and pretested its performance in detecting EGC in a multicenter randomized controlled trial. METHODS: ENDOANGEL was developed using deep convolutional neural networks and deep reinforcement learning. Patients undergoing EGD in five hospitals were randomly assigned to the ENDOANGEL-assisted group or to a control group without use of ENDOANGEL. The primary outcome was the number of blind spots. Secondary outcomes included performance of ENDOANGEL in predicting EGC in a clinical setting. RESULTS: 1050 patients were randomized, and 498 and 504 patients in the ENDOANGEL and control groups, respectively, were analyzed. Compared with the control group, the ENDOANGEL group had fewer blind spots (mean 5.38 [standard deviation (SD) 4.32] vs. 9.82 [SD 4.98]; P < 0.001) and longer inspection time (5.40 [SD 3.82] vs. 4.38 [SD 3.91] minutes; P < 0.001). In the ENDOANGEL group, 196 gastric lesions with pathological results were identified. ENDOANGEL correctly predicted all three EGCs (one mucosal carcinoma and two high grade neoplasias) and two advanced gastric cancers, with a per-lesion accuracy of 84.7 %, sensitivity of 100 %, and specificity of 84.3 % for detecting gastric cancer. CONCLUSIONS: In this multicenter study, ENDOANGEL was an effective and robust system to improve the quality of EGD and has the potential to detect EGC in real time.

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: The association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) has been shown in many observational studies, but these conclusions remain controversial. Hence, we performed a meta-analysis to elucidate the association. METHODS: A comprehensive search was conducted on relevant studies published from inception to December 31, 2018, in PubMed, EMBASE, and Web of Science databases. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled by random-effect model, generic inverse variance method. Subgroup and sensitivity analyses were also done. Publication bias was estimated by the funnel plot, Begg's test, and Egger's test. RESULTS: Fifteen studies (eleven cross-sectional, two case-control, and two cohort studies) were included in this meta-analysis. The pooled OR of NAFLD in patients with H. pylori infection was 1.19 (95% CI: 1.11-1.29, P < 0.00001) when compared with the patients without H. pylori infection. Similar results were observed when the subgroup analyses were stratified by different geographical locations, study designs, and confounders adjustment. In subgroup analysis stratified by different H. pylori testing methods, the correlation still exists when using UBT, serology, RUT, or SAT, but there was no statistically significant difference when using multiple detection methods (OR = 2.96, 95% CI: 0.37-23.94, P = 0.31). Sensitivity analyses showed that our results were robust. No evidence of substantial publication bias was detected. CONCLUSIONS: Current evidence indicated that a positive association between H. pylori infection and the risk of NAFLD. Further prospective studies are warranted to strengthen the association and to clarify whether there is a causative link between them.

Saccharomyces boulardii as an adjuvant therapy for Helicobacter pylori eradication: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND AND AIMS: Whether Saccharomyces boulardii (S boulardii) as an adjuvant therapy are beneficial to H pylori eradication remains controversial. The aim of the study was to update and determine the effects of S boulardii as an adjuvant therapy on H pylori eradication rates and adverse effects. METHODS: We searched PubMed, Embase, CENTRAL, and Web of Science to collect all randomized controlled trials assessing the effects of S boulardii as an adjuvant therapy for H pylori eradication from inception to February 2019. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis was performed to control the risk of type I and type II errors. RESULTS: Eighteen trials with 3592 patients were eligible for meta-analysis. Compared with standard eradication regimen, the S boulardii supplementation could significantly improve eradication rates [risk ratio (RR) = 1.09, 95% confidence interval (CI):1.05-1.13; moderate quality evidence] and reduce the incidence of total side effects (RR = 0.47, 95%CI:0.36-0.61; low quality evidence), as well as some gastrointestinal adverse effects, especially diarrhea (RR = 0.33, 95%CI:0.23-0.47; low quality evidence) and constipation (RR = 0.37, 95%CI:0.23-0.57; moderate quality evidence). In addition, the need for discontinuation rate in S boulardii supplementation group was significantly lower than in the control group (RR = 0.33, 95%CI:0.16-0.69, P = .003; moderate quality evidence). The TSA results for overall eradication rates and total side effects indicated that the effects were conclusive. CONCLUSIONS: Our meta-analysis shows that S boulardii supplementation on standard eradication therapy significantly increased H pylori eradication rates and reduced the incidence of total side effects and some gastrointestinal adverse effects during eradication therapy.

Development and Evaluation of a Surveillance System for Follow-Up After Colorectal Polypectomy.

Importance: The adherence of physicians and patients to published colorectal postpolypectomy surveillance guidelines varies greatly, and patient follow-up is critical but time consuming. Objectives: To evaluate the accuracy of an automatic surveillance (AS) system in identifying patients after polypectomy, assigning surveillance intervals for different risks of patients, and proactively following up with patients on time. Design, Setting, and Participants: In this diagnostic/prognostic study, endoscopic and pathological reports of 47 544 patients undergoing colonoscopy at 3 hospitals between January 1, 2017, and June 30, 2022, were collected to develop an AS system based on natural language processing. The performance of the AS system was fully evaluated in internal and external tests according to 5 guidelines worldwide and compared with that of physicians. A multireader, multicase (MRMC) trial was conducted to evaluate use of the AS system and physician guideline adherence, and prospective data were collected to evaluate the success rate in contacting patients and the association with reduced human workload. Data analysis was conducted from July to September 2022. Exposures: Assistance of the AS system. Main Outcomes and Measures: The accuracy of the system in identifying patients after polypectomy, stratifying patient risk levels, and assigning surveillance intervals in internal (Renmin Hospital of Wuhan University), external 1 (Wenzhou Central Hospital), and external 2 (The First People's Hospital of Yichang) test sets; the accuracy of physicians and their time burden with and without system assistance; and the rate of successfully informed patients of the system were evaluated. Results: Test sets for 16 106 patients undergoing colonoscopy (mean [SD] age, 51.90 [13.40] years; 7690 females [47.75%]) were evaluated. In internal, external 1, and external 2 test sets, the system had an overall accuracy of 99.91% (95% CI, 99.83%-99.95%), 99.54% (95% CI, 99.30%-99.70%), and 99.77% (95% CI, 99.41%-99.91%), respectively, for identifying types of patients and achieved an overall accuracy of at least 99.30% (95% CI, 98.67%-99.63%) in the internal test set, 98.89% (95% CI, 98.33%-99.27%) in external test set 1, and 98.56% (95% CI, 95.86%-99.51%) in external test set 2 for stratifying patient risk levels and assigning surveillance intervals according to 5 guidelines. The system was associated with increased mean (SD) accuracy among physicians vs no AS system in 105 patients (98.67% [1.28%] vs 78.10% [18.01%]; P = .04) in the MRMC trial. In a prospective trial, the AS system successfully informed 82 of 88 patients (93.18%) and was associated with reduced burden of follow-up time vs no AS system (0 vs 2.86 h). Conclusions and Relevance: This study found that an AS system was associated with improved adherence to guidelines among physicians and reduced workload among physicians and nurses.

Exploring the challenge of early gastric cancer diagnostic AI system face in multiple centers and its potential solutions.

BACKGROUND: Artificial intelligence (AI) performed variously among test sets with different diversity due to sample selection bias, which can be stumbling block for AI applications. We previously tested AI named ENDOANGEL, diagnosing early gastric cancer (EGC) on single-center videos in man-machine competition. We aimed to re-test ENDOANGEL on multi-center videos to explore challenges applying AI in multiple centers, then upgrade ENDOANGEL and explore solutions to the challenge. METHODS: ENDOANGEL was re-tested on multi-center videos retrospectively collected from 12 institutions and compared with performance in previously reported single-center videos. We then upgraded ENDOANGEL to ENDOANGEL-2022 with more training samples and novel algorithms and conducted competition between ENDOANGEL-2022 and endoscopists. ENDOANGEL-2022 was then tested on single-center videos and compared with performance in multi-center videos; the two AI systems were also compared with each other and endoscopists. RESULTS: Forty-six EGCs and 54 non-cancers were included in multi-center video cohort. On diagnosing EGCs, compared with single-center videos, ENDOANGEL showed stable sensitivity (97.83% vs. 100.00%) while sharply decreased specificity (61.11% vs. 82.54%); ENDOANGEL-2022 showed similar tendency while achieving significantly higher specificity (79.63%, p < 0.01) making fewer mistakes on typical lesions than ENDOANGEL. On detecting gastric neoplasms, both AI showed stable sensitivity while sharply decreased specificity. Nevertheless, both AI outperformed endoscopists in the two competitions. CONCLUSIONS: Great increase of false positives is a prominent challenge for applying EGC diagnostic AI in multiple centers due to high heterogeneity of negative cases. Optimizing AI by adding samples and using novel algorithms is promising to overcome this challenge.

Association Between Non-alcoholic Fatty Liver Disease and Risk of Stroke: A Systematic Review and Meta-Analysis.

Background/Objectives: Recent observational studies have explored the association between non-alcoholic fatty liver disease (NAFLD) and stroke with controversial results. We therefore performed a meta-analysis to investigate this possible association. Methods: PubMed, EMBASE and Web of Science database were searched from inception until December 2019, and updated on May 2021. Random-effects meta-analyses were performed by generic inverse variance method. Subgroup and sensitivity analyses were also conducted. The PROSPERO registered number of this study is CRD42020167330. Results: Twenty observational (15 cohort, 4 cross-sectional, and 1 case-control) studies with 17,060,388 participants were included in the meta-analysis. Meta-analysis of data from 18 studies with 17,031,672 participants has shown that NAFLD was associated with mildly increased risk of stroke (OR = 1.18, 95% CI: 1.08-1.30, P = 0.0005). Similar results were observed in most of the subgroup analyses we performed. Sensitivity analyses did not alter these findings. Meta-analysis of data from 3 studies with 29,614 participants has shown that insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke. Conclusions: We found that NAFLD was associated with increased risk of stroke. However, there was insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke. To better understand any association, future well-designed prospective studies that take fully account of specific population, type of stroke, and confounding factors are warranted. Systematic Review Registration: Unique Identifier: CRD42020167330.

A deep learning and natural language processing-based system for automatic identification and surveillance of high-risk patients undergoing upper endoscopy: A multicenter study.

Background: Timely identification and regular surveillance of patients at high risk are crucial for early diagnosis of upper gastrointestinal cancer. However, traditional manual surveillance method is time-consuming, and current surveillance rate is below 50%. Here, we aimed to develop a surveillance system named ENDOANGEL-AS (automatic surveillance) for automatic identification and surveillance of high-risk patients. Methods: 7874 patients from Renmin Hospital of Wuhan University between May 1 and July 31, 2021 were used as the training set, 6762 patients between August 1 and October 31, 2021 as the internal test set, and 7570 patients from two other hospitals between August 1 and October 31, 2021 as the external test sets. We first extracted descriptions of abnormalities from endoscopic and pathological reports based on natural language processing techniques to identify individuals. Then patients were classified at nine risk levels according to endoscopic and pathological findings, and a deep learning model was trained to identify demarcation line (DL) in gastric low-grade intraepithelial neoplasia (LGIN) using 1561 white-light still images for risk stratification of gastric LGIN. Finally, patients undergoing upper endoscopy were classified and assigned one of ten surveillance intervals according to guidelines. The performance of ENDOANGEL-AS was evaluated and compared with physicians. Findings: Patient identification module achieved an accuracy of 100% and 99.91% in internal and external test sets, respectively. Risk level classification module achieved an accuracy of 100% and 99.85% in the internal and external test sets, respectively. DL identification module achieved an accuracy of 87.88%. ENDOANGEL-AS on surveillance interval assignment achieved an accuracy of 99.23% and 99.67% in internal and external test sets, respectively. ENDOANGEL-AS had significantly higher accuracy compared with physicians (99.00% vs 38.87%, p < 0.001). The accuracy (63.67%, p < 0.001) of endoscopists with the assistance of ENDOANGEL-AS was significantly improved. Interpretation: We established a surveillance system that can automatically identify patients and assign surveillance intervals with high accuracy and good transferability. Funding: This work was partly supported by a grant from the Hubei Province Major Science and Technology Innovation Project (2018-916-000-008) and the Fundamental Research Funds for the Central Universities (2042021kf0084).

An exploration of aptamer internalization mechanisms and their applications in drug delivery.

INTRODUCTION: As 'chemical antibodies', aptamers have some advantages, such as lack of immunogenicity, rapid tissue penetration, cell internalization and so on. Consequently, more and more aptamers have been screened out by the systematic evolution of ligands through exponential enrichment for the desired cells or membrane receptors. On the basis of the result, researchers use aptamers to guide drug targeting to the desired cells and internalization in vivo. AREAS COVERED: In this review, we explore the mechanisms of cargo- or aptamer-mediated internalization, and then briefly summarize five strategies for exploring the mechanism of aptamer internalization. Finally, we focus on four types of applications involving aptamer internalization: aptamers as drugs, aptamers as chemical drug-delivery systems, aptamer-based chimeras and aptamer-conjugated nanoparticles or block copolymer micelles. EXPERT OPINION: Two aptamer-internalization mechanisms are known, namely receptor-mediated endocytosis and macropinocytosis. The latter mechanism, which is has only been verified in the internalization of nucleolin aptamer shuttles between the nucleus and cytoplasm, may be important for nuclear internalization and cargo molecule escape from the endosomal compartment. Thus, it is feasible to use some strategies to further explore the macropinocytosis internalization mechanism and then to screen for aptamers similar to the nucleolin aptamer for use with the desired cell types as a targeted delivery tool.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death.

The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3-kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC-823 and SGC-7901), and the activities were concentration and time-dependent. Up-regulation of PTEN expression in BGC-823 cells by PEAK8-PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC-823 cells to etoposide and doxorubicin. Pretreatment of BGC-823 and SGC-7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB-alpha degradation, NFkappaB activation, phosphorylation of Akt, MDM-2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl-1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase-3, caspase-9 activation and poly ADP-ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells.

[Impact of PI3K /Akt /mdm2 signaling pathway on the sensitivity of gastric cancer cell line SGC7901 to doxorubicin].

OBJECTIVE: To explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SGC7901 cells to doxorubicin. METHODS: Gastric cancer cell line SGC7901 cells were exposed to doxorubicin and specific PI3K inhibitor wortmannin. Cell apoptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53. RESULTS: The level of apoptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PI3K activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression. CONCLUSION: PI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.

Interference of P-REX2a may inhibit proliferation and reverse the resistance of SGC7901 cells to doxorubicin.

Drug resistance inhibits the efficacy of doxorubicin in gastric cancer. Phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by binding to and inactivating phosphatase and tensin homolog (PTEN), which functions as a tumor promoter in a number of types of cancer. However, there is no research concerning the association between P-REX2a expression and drug resistance in gastric cancer. In the present study, the expression of P-REX2a in clinical gastric cancer tissues was detected, and the mechanism of doxorubicin resistance in the gastric cancer cell line SGC7901 was investigated. Using reverse transcription-quantitative polymerase chain reaction and western blotting, it was demonstrated that the mRNA and protein expression of P-REX2a was increased in gastric cancer tissues. MTT assays were also used to determine proliferation, and proliferation was revealed to be reduced following transfection of P-REX2a small interfering (si)RNA. When the cells were treated with 0.3 µM doxorubicin for 24 h, the rate of apoptosis in the siRNA-transfected groups significantly increased and no marked changes in of PTEN and Akt expression were observed. By contrast, the activity of PTEN increased, and the expression of p-Akt (S473) decreased in the P-REX2a siRNA-transfected group compared with the control. The detection of PTEN enzymatic activity in the present study was based on phosphatidylinositol-3,4,5-trisphosphate. Therefore, it was concluded that P-REX2a may participate in the generation of resistance to doxorubicin in gastric cancer, and this may be associated with the upregulation of the PI3K/Akt signaling pathway via inactivation of PTEN.

Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines.

Recently, an interesting relationship between potassium channels and cancer has evolved. The aim of this study is to investigate expression of Eag1 potassium channel in gastric cancer and its role in cancer cells growth. The expression of Eag1 for gasric cancer patients and cell lines as well as gastric adenoma was investigated by immunohistochemistry and reverse transcription polymerase chain reaction. In addition, imipramine was used to identify the involvement of Eag1 in the growth of SGC-7901 and BGC-823 cells. Frequency of positive expression of Eag1 protein was 70.5% (67/95) and Eag1 mRNA was 68.2% (15/22) in gastric cancer primary tissues. Eag1 mRNA was positively expressed in two gastric cell lines. Eag1 protein and mRNA were negatively expressed in paired non-cancerous matched tissues and 5 cases of adenoma tissues. The expression level of Eag1 protein was associated with lymph node metastasis (P = 0.049) and stage (P = 0.039), but had no correlation with sex, age, differentiation grades, and other organs metastases. Imipramine significantly inhibited the proliferation of SGC-7901 and BGC-823 cells at 12 h and 24 h detected by cells number counting and MTT assay (P < 0.01). The study indicates Eag1 is aberrantly expressed in gastric cancer tissues and cell lines and associated with cancer lymph node metastasis and stage and play an important role in the proliferation of gastric cancer cells.

Diagnostic accuracy of the 14C-urea breath test in Helicobacter pylori infections: a meta-analysis.

OBJECTIVES: To summarize and appraise the available literature regarding the use of the 14C-urea breath test in the diagnosis of Helicobacter pylori infections in adult patients with dyspepsia and to calculate pooled diagnostic accuracy measures. METHODS: We systematically searched the PubMed, EMBASE, Cochrane Library, Chinese Journals Full-text (CNKI) and CBMDisc databases to identify published data regarding the sensitivity, specificity, and other measures of diagnostic accuracy of the 14C-urea breath test in the diagnosis of Helicobacter pylori infections in adult patients with dyspeptic symptoms. Risk of bias was assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies)-2 tool. Statistical analyses were performed using Meta-Disc 1.4 software and STATA. RESULTS: Eighteen studies met the inclusion criteria. Pooled results indicated that the 14C-urea breath test showed a diagnostic sensitivity of 0.96 (95% CI 0.95 to 0.96) and specificity of 0.93 (95% CI 0.91 to 0.94). The positive like ratio (PLR) was 12.27 (95% CI 8.17 to 18.44), the negative like ratio (NLR) was 0.05 (95% CI 0.04 to 0.07), and the area under the curve was 0.985. The DOR was 294.95 (95% CI 178.37 to 487.70). The 14C-urea breath test showed sufficient sensitivity and specificity for diagnosing Helicobacter pylori infection, but unexplained heterogeneity after meta-regression and several subgroup analyses remained. CONCLUSIONS: The UBT has high accuracy for diagnosing H. pylori infections in adult patients with dyspepsia. However, the reliability of these diagnostic meta-analytic estimates is limited by significant heterogeneity due to unknown factors.