Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

MiRNA detection in cervical exfoliated cells for missed high-grade lesions in women with LSIL/CIN1 diagnosis after colposcopy-guided biopsy.

BACKGROUND: Low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by colposcopy guided biopsy is recommended conservative follow-up, although some of these lesions are actually high-grade lesions, which are missed on an initial colposcopy. Therefore, in this work, we evaluate the potential role of miRNA detection in cervical exfoliated cells in a clinic-based population for predicting missed high-grade lesions in women diagnosed with LSIL/CIN1 after colposcopy-guided biopsy. METHODS: A total number of 177 women with a diagnosis of LSIL/CIN1 obtained by colposcopy-guided biopsy were grouped into two categories according to the histology of the conization specimens: consistent LSIL/CIN1 group (surgical pathology consistent with colposcopic diagnosis) and missed high-grade lesion group (surgical pathology found high-grade lesion). The expression of eight miRNAs, such as miRNA195, miRNA424, miRNA375, miRNA218, miRNA34a, miRNA29a, miRNA16-2, and miRNA20a was detected by real time-quantitative polymerase chain reaction (RT-qPCR) in cervical exfoliated cells of the 177 patients. Pearson Chi-Square was used to compare the performance efficiency of patients' characteristics. Nonparametric Man-Whitney U test was used to assess differences in miRNA expression. The receiver operating characteristic (ROC) curve was used to assess the performance of miRNA evaluation in detecting missed high-grade lesions. RESULTS: Among the 177 women with biopsy-confirmed CIN1, 15.3% (27/177) had CIN2+ in the conization specimen (missed high-grade lesion group) and 84.7% (150/177) had CIN1-(consistent LSIL/CIN1 group). The relative expression of miRNA-195 and miRNA-29a in the missed high-grade lesion group was significantly lower than that in the consistent LSIL/CIN1 group. The relative expression of miRNA16-2 and miRNA20a in the missed high-grade lesion group was significantly higher than that in the consistent LSIL/CIN1 group. No significant difference was observed between these two groups regarding the other four miRNAs. Of these significant miRNAs, miRNA29a detection achieved the highest Youden index (0.733), sensitivity (92.6%), positive predictive value (46.2%), negative predictive value (98.3%) and higher specificity (80.7%) when identifying missed high-grade lesions. CONCLUSIONS: Detection of miRNA might provide a new triage for identifying a group at higher risk of missed high-grade lesions in women with colposcopy diagnosis of LSIL/CIN1.

Mortality Risk Attributed to Ambient Temperature in Nanjing, China.

We examined the attributed fractions of all-cause, cardiovascular, and respiratory mortality that were attributed to extreme and moderate cold and heat during 2010-2016 in Nanjing. Our results showed that 12.81%, 19.78%, and 25.33% of all-cause, cardiovascular, and respiratory mortalities, respectively, were attributed to temperature. The highest attributed fractions for three types of mortality were at 4 ℃ and the attributed fractions were high around 4 ℃, which falls within the moderate cold temperatures. Although moderate cold has lower RR than extreme cold, it occurred on more days than did extreme cold. Therefore, health burden caused by moderate cold requires further attention in the future.

Association between Ambient Air Pollution and Hospital Emergency Admissions for Respiratory and Cardiovascular Diseases in Beijing: a Time Series Study.

OBJECTIVE: To investigate the association between ambient air pollution and hospital emergency admissions in Beijing. METHODS: In this study, a semi-parametric generalized additive model (GAM) was used to evaluate the specific influences of air pollutants (PM10, SO2, and NO2) on hospital emergency admissions with different lag structures from 2009 to 2011, the sex and age specific influences of air pollution and the modifying effect of seasons on air pollution to analyze the possible interaction. RESULTS: It was found that a 10 µg/m3 increase in concentration of PM10 at lag 03 day, SO2 and NO2 at lag 0 day were associated with an increase of 0.88%, 0.76%, and 1.82% respectively in overall emergency admissions. A 10 µg/m3 increase in concentration of PM10, SO2 and NO2 at lag 5 day were associated with an increase of 1.39%, 1.56%, and 1.18% respectively in cardiovascular disease emergency admissions. For lag 02, a 10 µg/m3 increase in concentration of PM10, SO2 and NO2 were associated with 1.72%, 1.34%, and 2.57% increases respectively in respiratory disease emergency admissions. CONCLUSION: This study further confirmed that short-term exposure to ambient air pollution was associated with increased risk of hospital emergency admissions in Beijing.

Monocyte-to-lymphocyte ratio affects prognosis in LAA-type stroke patients.

Nowadays, the prognostic prediction of acute ischemic stroke (AIS) patients is still challenging because of the limited predictive properties of existing models. Blood-based biomarkers may provide additional information to the established prognostic factors. Markers of atherosclerosis have been identified as one of the most promising biomarkers for predicting prognosis, and inflammation, in turn, affects atherosclerosis. According to previous studies, the ratio of monocytes to lymphocytes (MLR) has been reported as a novel indicator of inflammation. Thus, our study was the first to conduct more in-depth research on the relationship between MLR and the prognosis of large artery atherosclerosis (LAA)-type AIS patients. A total of 296 patients with LAA-type stroke were recruited. Of these, 202 patients were assigned to the development cohort, and 94 patients were assigned to the validation cohort. In the development cohort, 202 patients were divided into groups A, B, C, and D according to the quartile method of MLR levels. The one-year prognosis of patients was tracked, and the modified Rankin scale (MRS, with a score ranging from 0 to 6) was mainly selected as the measurement result of the function. The relationship between MLR and prognosis was analyzed by building logistics regression models. The models showed that MLR made significant predictions in poor outcomes of LAA-type stroke patients (odds ratio: 4.037; p = 0.048). At the same time, receiver operating characteristics (ROC) curves were used to compare the predictive values between MLR and clinical prediction score (Barthel Index). This study demonstrated that patients with LAA-type stroke and high MLR had a poor prognosis. MLR might be a reliable, inexpensive, and novel predictor of LAA-type stroke prognosis.

[Evaluation of five screening methods for an early detection of cervical cancer and its precancerous lesions in Zhejiang province].

OBJECTIVE: To evaluate five screening methods of cervical cancer so as to popularize an effective screening strategy for cervical cancer in Zhejiang province. METHODS: A total of 1005 women aged 25 - 65 years old were selected from Lishui where cervical cancer was highly prevalent. And 859 subjects were ultimately enrolled between June 2009 and December 2009. Each subject was subjected to five screening methods, including Pap smear, liquid-based cytology (LBC), human papillomavirus DNA with a second-generation hybridization assay (HC2), visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI). CIN (cervical intraepithelial neoplasia) 2+ on biopsy was used as the reference standard for disease positivity. Negative colposcopy was accepted as a negative outcome. RESULTS: The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) were 25%, 90%, 26.7% and 98.6% for Pap smear; 81.3%, 97.3%, 35.1% and 99.6% for LBC; 68.9%, 82.8%, 7.1% and 99.3% for VIA; 81.3%, 84.6%, 9.1% and 99.3% for VILI; 87.5%, 77.3% and 6.8% for HPV-DNA test respectively. CONCLUSIONS: LBC is associated with a better profile of sensitivity, specificity and predictive value for five screening methods. It has the potential of optimizing the effectiveness of primary cervical cancer screening. Due to a low cost and an easy operation, VIA screening is an effective method of screening cervical cancer in the underdeveloped areas.

Modified procedure for prolapse and hemorrhoids: Lower recurrence, higher satisfaction.

BACKGROUND: Hemorrhoidal prolapse is a common benign disease with a high incidence. The treatment procedure for prolapse and hemorrhoids (PPH) remains an operative method used for internal hemorrhoid prolapse. Although it is related to less pos-operative pain, faster recovery and shorter hospital stays, the postoperative recurrence rate is higher than that of the Milligan-Morgan hemorrhoidectomy (MMH). We have considered that recurrence could be due to shortage of the pulling-up effect. This issue may be overcome by using lower purse-string sutures [modified-PPH (M-PPH)]. AIM: To compare the therapeutic effects and the patients' satisfaction after M-PPH, PPH and MMH. METHODS: This retrospective cohort study included 1163 patients (M-PPH, 461; original PPH, 321; MMH, 381) with severe hemorrhoids (stage III/IV) who were admitted to The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from 2012 to 2014. Early postoperative complications, efficacy, postoperative anal dysfunction and patient satisfaction were compared among the three groups. Established criteria were used to assess short- and long-term postoperative complications. A visual analog scale was used to evaluate postoperative pain. Follow-up was conducted 5 years postoperatively. RESULT: Length of hospital stay and operating time were significantly longer in the MMH group (8.05 ± 2.50 d, 19.98 ± 4.21 min; P < 0.0001) than in other groups. The incidence of postoperative anastomotic bleeding was significantly lower after M-PPH than after PPH or MMH (1.9%, 5.1% and 3.7%; n = 9, 16 and 14; respectively). There was a significantly higher rate of sensation of rectal tenesmus after M-PPH than after MMH or PPH (15%, 8% and 10%; n = 69, 30 and 32; respectively). There was a significantly lower rate of recurrence after M-PPH than after PPH (8.7% and 18.8%, n = 40 and 61; P < 0.0001). The incidence of postoperative anal incontinence differed significantly only between the MMH and M-PPH groups (1.3% and 4.3%, n = 5 and 20; P = 0.04). Patient satisfaction was significantly greater after M-PPH than after other surgeries. CONCLUSION: M-PPH has many advantages for severe hemorrhoids (Goligher stage III/IV), with a low rate of anastomotic bleeding and recurrence and a very high rate of patient satisfaction.

[Cervical intraepithelial neoplasia 2+ in low-grade squamous intraepithelial lesion pathologically diagnosed by colposcopy-assisted biopsy].

OBJECTIVE: To assess the accuracy of colposcopy-assisted biopsy for the diagnosis of cervical intraepithelial neoplasia I (CIN(1)) and to reappraise the correlative factors of missed CIN(2+) in low-grade SIL(squamous intraepithelial lesion)pathologically diagnosed by colposcopy-assisted biopsy. METHODS: A total of 274 women with CIN(1) diagnosed by colposcopy-assisted biopsy and missing scheduled follow-up thus elected to undergo loop electrosurgical excisional procedure (LEEP). Epidemiological data and cervical cytology, high risk human papillomavirus (HR-HPV) detection and colposcopy with directed biopsy and endocervical curettage if necessary prior to LEEP were reviewed and correlation of missed CIN(2+) and all the above factors analyzed. RESULTS: Among these patients, 85 cases (31.0%) of CIN(2+) were detected. Univariate analysis showed that poor cervical cytology before colposcopy, unsatisfactory colposcopy and positive HR-HPV detection were risk factors of missed CIN(2+) in low-grade SIL pathologically diagnosed by colposcopy-assisted biopsy. Multivariate logistic analysis showed that whether colposcopic examination was satisfactory or not and cervical cytology before colposcopy were independent risk factors of missed CIN(2+) in low-grade SIL pathologically diagnosed by colposcopy-assisted biopsy (OR: 2.06 and 4.67 respectively). CONCLUSION: The accuracy of colposcopy-assisted biopsy for the diagnosis of CIN(1) remains poor. Whether colposcopic examination is satisfactory or not and cervical cytology before colposcopy are independent risk factors of missed CIN(2+) in low-grade SIL pathologically diagnosed by colposcopy-assisted biopsy.

Metabolic Syndrome, as Defined Based on Parameters Including Visceral Fat Area, Predicts Complications After Surgery for Rectal Cancer.

BACKGROUND/OBJECTIVES: Metabolic syndrome (MetS) has become a major public health problem. However, few studies have examined the impact of MetS on the postoperative complications of colorectal cancer and the conclusions remain controversial. The present study aimed to investigate whether MetS, as defined based on visceral fat area (VFA) instead of BMI or waist circumference, would predict complications after surgery for rectal cancer. SUBJECTS/METHODS: We conducted a retrospective study of patients who underwent surgery for rectal cancer at our department between January 2013 and August 2018. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. A receiver operating characteristic curve analysis was used to determine the gender-specific cut-off values for VFA. RESULTS: A total of 381 patients were included in the study. The optimal cut-off values for VFA were 117.9 cm2 for men and 76.9 cm2 for women, and 153 patients were diagnosed as having MetS. The rate of postoperative complication was significantly higher in the MetS group than that in the non-MetS group (34.6% versus 15.8%, P < 0.001). The multivariate logistic regression analysis demonstrated that MetS (OR 3.712, P < 0.001), NRS 2002 scores ≥ 3 (OR 2.563, P = 0.001), and tumor located at the lower 1/3 (OR 3.290, P = 0.001) were independent risk factors for complications after surgery for rectal cancer. CONCLUSION: Metabolic syndrome, as defined based on parameters including visceral fat area, was an independent risk factor for complications after surgery for rectal cancer.

Mean Platelet Volume-To-Lymphocyte Ratio Predicts Poor Functional Outcomes Among Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: According to previous studies, the mean platelet volume-to-lymphocyte ratio (MPVLR) represents a novel marker of a poor short-term prognosis in patients with a myocardial infarction who underwent primary percutaneous coronary intervention. We aimed to evaluate the association between MPVLR and clinical outcomes of patients with acute ischemic stroke who were treated with intravenous thrombolysis. Methods: Two hundred forty-one patients with ischemic stroke receiving intravenous thrombolysis were prospectively enrolled in this study. Blood samples for MPVLR were obtained at admission and at 18-24 h after treatment with intravenous thrombolysis. A poor functional outcome was defined as a modified Rankin scale score of 3-6 at 3 months after stroke. Results: At admission, the area under the curve of MPVLR to predict poor functional outcomes at 3 months was 0.613 [95% confidence interval (CI), 0.541-0.686; P = 0.003), and the best predictive MPVLR value was 5.8. Patients with an MPVLR ≥5.8 had a 3.141-fold increased risk of a poor outcome at 3 months (95% CI, 1.491-6.615; P = 0.003) compared to patients with an MPVLR <5.8. At 18-24 h after treatment with intravenous thrombolysis, the area under the curve of MPVLR to predict a poor outcome at 3 months was 0.697 (95% CI, 0.630-0.765, P < 0.001), and the best predictive MPVLR value was 6.9. The inclusion of MPVLR as a continuous (odds ratio, 1.145; 95% CI, 1.044-1.256, P = 0.004) and categorical variable (odds ratio, 6.555; 95% CI, 2.986-14.393, P < 0.001) was independently associated with poor outcomes at 3 months. Conclusions: Both the values of MPVLR at admission and 18-24 h after intravenous thrombolysis were independently associated with poor functional outcomes. MPVLR may serve as an activity marker for a poor prognosis in patients with acute ischemic stroke receiving intravenous thrombolysis.

Prognostic value of human papillomavirus 16/18 genotyping in low-grade cervical lesions preceded by mildly abnormal cytology.

Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432-5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.

Human papillomavirus (HPV) E6/E7 mRNA detection in cervical exfoliated cells: a potential triage for HPV-positive women.

Cytology triage has been generally recommended for human papillomavirus (HPV)-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou (Pap) test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus® HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson's Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion (HSIL) cases was higher than that in low-grade squamous intraepithelial lesion (LSIL) or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity (89.52% vs. 86.67%, P=0.671), specificity (48.96% vs. 48.96%, P=1.000), positive predictive value (39.00% vs. 38.24%, P=1.000), and negative predictive value (92.76% vs. 90.97%, P=0.678) for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women.

[Inhibition of HPV16 E6 oncogene in cervical cancer by RNA interference].

OBJECTIVE: The efficiency of HPV16 E6 gene silenced by RNA interference in vitro and in vivo was assessed. METHODS: The specific siRNA of HPV16 E6 was designed and transfected into CaSki cells by liposome. Cell apoptotic rates and the changes in HPV16 E6 mRNA and protein before and after transfection were measured. Cervical cancer nude mice models were set up, siRNA was injected directly into subcutaneous tumor. The function of siRNA was evaluated by the changes in tumor volume, HPV16 E6 protein expression and apoptosis of tumor cells. RESULTS: In vitro research, the cell apoptotic rates were 7.7%, 11.8%, 37.4% and 12.6% respectively at 24 h, 48 h, 5th day and 9th day after transfection. The HPV16 E6 mRNA was reduced by 77%, 83%, 59% and 41% at 24 h, 48 h, 5th day and 9th day after transfection. The inhibition rates of E6 protein measured by Flow cytometry were 79.7%, 80.4%, 71.3% and 57.4% at 24 h, 48 h, 5th day and 9th day after transfection, which were confirmed by the results of Western blot. In vivo research, E6 siRNA administration groups had great power in inhibiting tumor growth, restraining E6 protein expression, increasing tumor necrosis and apoptosis. The result of repeated injections of siRNA was better than that of single injection. CONCLUSION: RNA interference with HPV16 E6 is specific and highly efficient in vitro and in vivo.

[Tissue microarray and in situ hybridization study on hypoxia inducible factor 1alpha mRNA expression in epithelial ovarian tumor].

OBJECTIVE: To study the expression and significance of hypoxia inducible factor 1alpha (HIF-1alpha) in epithelial ovarian tumors. METHODS: The expression of HIF-1alpha mRNA in 295 patients with epithelial ovarian tumor was analyzed retrospectively by high-throughput tissue microarray and in situ hybridization, which was compared with 13 normal ovarian tissue samples. RESULTS: The expression rates of HIF-1alpha mRNA were 0, 13.2%, 42.1% and 81.9% in normal ovarian tissue, benign, borderline and malignant ovarian tumors. Expression rate of HIF-1alpha mRNA in borderline and invasive tumor was significantly higher than those in normal ovarian tissue and benign tumor (P < 0.001). Statistical analysis revealed that the expression of HIF-1alpha mRNA was not related to FIGO stages or histological subtypes. Close negative relation was observed between the expression of HIF-1alpha mRNA and tumor histological differentiation (P < 0.001). CONCLUSION: The overexpression of HIF-1alpha may play an important role in oncogenesis of epithelial ovarian tumor. Tissue microarray is an efficient technique of molecular biology.

Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers.

CONTEXT: The biologic effects of Notch1 and Notch2 vary with cancer types and their potential role(s) in gastric cancers (GCs) remains largely unknown. OBJECTIVES: This study aimed to address the previously mentioned issue by checking the expression of Notch1, Notch2, and Notch target gene Hes1 in GCs, premalignant gastric lesions, and noncancerous endoscopic gastric mucosa and by inhibiting Notch signal transduction in GC cells. DESIGN: The status of Notch1, Notch2, and Hes1 expression in 74 GC surgical specimens, 10 endoscopic samples, and 4 human GC cell lines was evaluated by tissue microarray-based immunohistochemical staining, Western blotting, and reverse transcription-polymerase chain reaction, and the importance of Notch signaling was elucidated by treating 2 GC cell lines with 2 γ-secretase inhibitors. RESULTS: Notch1 was undetectable in noncancerous gastric mucosa but was expressed with nuclear translocation in 16.7% (4 of 24) of chronic gastritis, 50.0% (9 of 18) of intestinal metaplasia, 54.2% (26 of 48) of intestinal GC, and 23.1% (6 of 26) of diffuse GC, showing distinct differences of Notch1 detection rates between either intestinal metaplasia and chronic gastritis or intestinal GCs and diffuse GCs (P  =  .03; P  =  .005, respectively). Notch2 nuclear translocation frequencies were 10.0% (1 of 10) in noncancerous endoscopic mucosa, 71.4% (30 of 42) in premalignant lesions, and 97.3% (72 of 74) in GC tissues, demonstrating a correlation of Notch2 expression with both intestinal GC and diffuse GC formation (P < .001). The rates of nuclear-Hes1 labeling were 1 of 10 among noncancerous, 42.9% premalignant, and 81.1% cancer tissues, which were closely correlated with Notch2 (P < .001) rather than Notch1 (P  =  .42) nuclear translocation. Only Notch2 was expressed accompanied with Hes1 nuclear labeling in the 4 GC cell lines established from diffuse GC cases. Inhibition of Notch signaling with γ-secretase inhibitors, L-685,458 and DAPT, prevented Hes1 nuclear translocation but neither suppressed growth nor induced cell death. CONCLUSIONS: This study demonstrated a close correlation of Notch2 expression with GC formation and the potential link of Notch1 upregulation with intestinal-like phenotypes of gastric lesions. Although inhibition of Notch activity failed to achieve anti-GC effects, the activated Notch signaling may reflect a potential GC risk.