Epstein-Barr virus positive gastric cancer: the pathological basis of CT findings and radiomics models prediction.

PURPOSE: To analyze the clinicopathologic information and CT imaging features of Epstein-Barr virus (EBV)-positive gastric cancer (GC) and establish CT-based radiomics models to predict the EBV status of GC. METHODS: This retrospective study included 144 GC cases, including 48 EBV-positive cases. Pathological and immunohistochemical information was collected. CT enlarged LN and morphological characteristics were also assessed. Radiomics models were constructed to predict the EBV status, including decision tree (DT), logistic regression (LR), random forest (RF), and support vector machine (SVM). RESULTS: T stage, Lauren classification, histological differentiation, nerve invasion, VEGFR2, E-cadherin, PD-L1, and Ki67 differed significantly between the EBV-positive and -negative groups (p = 0.015, 0.030, 0.006, 0.022, 0.028, 0.030, < 0.001, and < 0.001, respectively). CT enlarged LN and large ulceration differed significantly between the two groups (p = 0.019 and 0.043, respectively). The number of patients in the training and validation cohorts was 100 (with 33 EBV-positive cases) and 44 (with 15 EBV-positive cases). In the training cohort, the radiomics models using DT, LR, RF, and SVM yielded areas under the curve (AUCs) of 0.905, 0.771, 0.836, and 0.886, respectively. In the validation cohort, the diagnostic efficacy of radiomics models using the four classifiers were 0.737, 0.722, 0.751, and 0.713, respectively. CONCLUSION: A significantly higher proportion of CT enlarged LN and a significantly lower proportion of large ulceration were found in EBV-positive GC. The prediction efficiency of radiomics models with different classifiers to predict EBV status in GC was good.

Comparison of outcomes between preoperative and postoperative systemic treatment in patients with hepatocellular carcinoma: a SEER database-based study.

Background: Significant advancements in systemic treatment for hepatocellular carcinoma have been made in recent years. However, the optimal timing of systemic treatment before or after surgery remains unknown. This study aims to evaluate the impact of sequencing systemic treatment and surgical intervention on the long-term prognosis of hepatocellular carcinoma patients. Methods: In our study, we analyzed data from patients diagnosed with primary liver cancer (2004-2015) extracted from the SEER database. Patients who underwent both systemic treatment and surgical intervention were selected, divided into preoperative and postoperative systemic therapy groups. The primary endpoint of the study is overall survival(OS), and the secondary endpoint is cancer-specific survival (CSS). Propensity score matching (PSM) reduced the influence of confounding factors, while Kaplan-Meier curves and a multivariable Cox proportional hazards model accounted for variables during survival analysis. Results: A total of 1918 eligible HCC patients were included, with 1406 cases in the preoperative systemic treatment group and 512 cases in the postoperative systemic treatment group. Survival analysis showed that both the preoperative group demonstrated longer median overall survival (OS) and median cancer-specific survival (CSS) before and after PSM. After conducting multivariate COX regression analysis with stepwise adjustment of input variables, the postoperative systemic treatment group continued to exhibit a higher risk of all-cause mortality (HR: 1.84, 95% CI: 1.55-2.1) and cancer-specific mortality (HR: 2.10, 95% CI: 1.73-2.54). Subgroup analysis indicated consistent results for overall survival (OS) across different subgroups. Conclusions: Hepatocellular carcinoma patients from the SEER database who received preoperative systemic therapy had superior OS and CSS compared to those who received postoperative systemic therapy.

Analysis of the efficacy and influencing factors of preoperative P-SOX neoadjuvant chemotherapy regimen for progressive gastric cancer-construction of a clinical prediction model.

Preoperative neoadjuvant chemotherapy is one of the most common treatments for patients with advanced gastric cancer that cannot be completely removed by surgery. Nab-paclitaxel is a nano-formulation of paclitaxel that has been shown to be effective in treating stomach cancer. In addition, oxaliplatin + S-1 (SOX) has been a first-line chemotherapy regimen for gastric cancer, and it has the effect of tumor downstaging, improving the R0 resection rate, and reducing the postoperative recurrence rate, but the side effects are significant. During the application of oxaliplatin, obvious gastrointestinal reactions such as nausea and vomiting can be observed. There may also be blood system side effects such as leukopenia and thrombocytopenia, as well as serious adverse reactions such as peripheral neuropathy. Therefore, we reduced the amount of oxaliplatin in SOX and added nab-paclitaxel on the basis of this, in order to increase the efficacy while reducing the side effects of SOX regimen. We selected 192 patients with advanced gastric cancer admitted to the Department of Gastrointestinal Oncology of Qinghai University Hospital from July 2019 to February 2022, and all were treated with nab-paclitaxel plus oxaliplatin + S-1 neoadjuvant chemotherapy regimen, and underwent further surgery after chemotherapy. The tumor regression grade (TRG grade) and response evaluation criteria of solid tumor 1.1 (RECIST1.1) were taken as the dependent variables. According to TRG classification, 120 patients were effective (grade 0, 1, 2 = 62.50%, age: 55.63 ± 9.02 years), 72 patients were ineffective (grade 3 = 37.50%, 55.82 ± 9.21 years), and the effective rate of chemotherapy was 62.50%. According to RECIST1.1, 116 patients were effective (CR + PR = 60.42%, mean age 55.84 ± 9.02 years), 76 patients were ineffective (SD + PD = 39.58%, 55.47 ± 9.19 years), and the effective rate was 60.42%. The factors p < 0.2 in univariate logistic regression analysis were included in multivariate logistic regression analysis, and p < 0.05 was the statistical difference, and statistically significant factors were screened out for modeling and plotted the nomogram. Among them, in the tumor regression grade, the final factors related to effective chemotherapy are the degree of differentiation, cT. stage, tumor diameter, chemotherapy cycle, and the final factors related to effective chemotherapy in the solid tumor response evaluation criteria are the degree of differentiation, cT. stage, tumor diameter. Therefore, we conclude that the regimen of nab-paclitaxel combined with oxaliplatin and S-1 has certain positive significance in the treatment of advanced gastric cancer.

DDX1 is a prognostic biomarker and correlates with immune infiltrations in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading lethal malignant tumors worldwide. DEAD-box (DDX) family helicases are implicated in numerous human cancers. However, the role of DDX1 in HCC has not yet been fully elucidated. We downloaded gene expression data and clinical information data of HCC from The Cancer Genome Atlas and International Cancer Genome Consortium (ICGC) database and conducted subsequent analyses using the R package and online portal. The results revealed that HCC tissues had higher DDX1 expression compared with either paired or unpaired normal tissues. The increased DDX1 expression was closely related to the advanced pathological grade and histologic grade of HCC. Further analysis suggested that patients with high DDX1 expression contributed to poor prognosis The Cox regression analysis revealed that the expression level of DDX1 was an independent prognostic factor for HCC. In addition, an ICGC cohort was used for external validation. The cBio-Portal, MethSurv, and UALCAN database were used for evaluating the genomic mechanism. Moreover, the Tumor Immune Estimation Resource dataset and QUANTISEQ algorithm revealed that DDX1 expression positively correlates with immune infiltrating cells. We also identified the DDX1-related differentially expressed genes (DEGs) and explored their biological functions by GO, KEGG, and GSEA analyses, which indicated that DDX1 may regulate the progression of HCC. In general, increased DDX1 expression predicts a poor prognosis and drives the progression of HCC.

Dual Gas-responsive Fluorescent Diblock Copolymer Synthesized via RAFT Polymerization.

Stimulus-responsive polymers with luminescence properties have a wide range of applications in the fields of controlled drug release, fluorescent probes, and biological stents. In this paper, carbon dioxide (CO2)/oxygen (O2) dual-responsive fluorescent diblock copolymers were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization method with two fluorescent monomers synthesized as its luminescence source, DEAEMA (CO2 responsive monomer) and tFMA (O2 responsive monomer). An experimental study demonstrated that the synthesized stimulus-responsive fluorescent polymer had a high sensitivity to CO2; the double-responsive fluorescent diblock copolymer could form and achieve the reversal of polymer micelles in the aqueous solution when it was sequentially subjected to the introduction of CO2 and O2.

Initial Experience With Diffusion-Weighted Magnetic Resonance Imaging for the Evaluation of Endometrial Fibrosis.

OBJECTIVE: This study aimed to determine the feasibility of diffusion-weighted imaging for detecting endometrial fibrosis in patients with intrauterine injury. METHODS: This prospective study included 34 patients with endometrial fibrosis and 34 healthy controls. All participants underwent T2-weighted and diffusion-weighted magnetic resonance imaging with b values of 0 and 1000 s/mm2 during the periovulatory phase with a dominant follicle. The endometrial apparent diffusion coefficient (ADC) and uterine anatomical parameters (endometrial thickness [EMT], length of the uterine cavity [LUC], and junctional zone thickness [JZT]) were measured and compared. Performance of the uterine endometrial ADC and anatomical parameters in diagnosing endometrial fibrosis was evaluated. RESULTS: Patients with endometrial fibrosis showed a lower endometrial ADC, lower EMT, shorter LUC, and higher JZT than did healthy controls (all, P < 0.001). Endometrial ADC value and uterine anatomical parameters showed good performance in diagnosing endometrial fibrosis, with the areas under the receiver operating characteristic curves of 0.976, 0.870, 0.883, and 0.864, respectively. The area under the curve of ADC was significantly higher than those of EMT (z = 1.973, P = 0.0485), LUC (z = 2.059, P = 0.0395), and JZT (z = 2.484, P = 0.0130). Intraobserver and interobserver agreements of endometrial ADC value measurements were excellent for both patients (intraclass correlation coefficient = 0.987 and 0.983, respectively) and healthy women (intraclass correlation coefficient = 0.986 and 0.989, respectively). CONCLUSIONS: Our preliminary results suggest that diffusion-weighted imaging has the potential to be a noninvasive imaging tool for the quantitative assessment of endometrial fibrosis.

NF-κB and neutrophil extracellular traps cooperate to promote breast cancer progression and metastasis.

Aberrant NF-κB activation and neutrophil extracellular traps (NETs) are associated with breast cancer progression. How NF-κB and NETs modulate each other in breast cancer development remains unclear. Here, we found that NETs induced by phorbol 12-myristate 13-acetate promote breast cancer cell progression. In turn, cancer cells-derived factors, such as IL-8 and granulocyte colony-stimulating factor, stimulate neutrophils to form NETs. Mechanistically, NETs increased the interaction of NF-κB essential modifier (NEMO) with IκB kinase (IKK)α/ß and enhanced NF-κB activation. We then employed a cell-permeable peptide corresponding to the NEMO-binding domain (NBD) of IKKα/ß, termed NBD peptide, which disrupts NETs-mediated NEMO interaction with IKKα/ß and abolished NF-κB activation in vitro. NBD peptide also reduced IL-8 level and NETs formation, and suppressed primary tumor growth and/or lung metastasis in human breast cancer mouse xenograft models and mouse spontaneous breast cancer model. Blockade of NET formation using a peptidylarginine deiminase 4 (PAD4) pharmacologic inhibitor decreased NF-κB activation and tumor metastasis. Collectively, these data suggest that NF-κB associates with NETs to form a positive loop facilitating breast tumor progression and metastasis, and that selective inhibition of NF-κB and PAD4-dependent NETs provides an effective therapeutic approach for treating breast cancer.

The role of MYB proto-oncogene like 2 in tamoxifen resistance in breast cancer.

Despite the efficacy of tamoxifen in preventing disease relapse, a large portion of breast cancer patients show intrinsic or acquired resistance to tamoxifen, leading to treatment failure and unfavorable clinical outcome. MYB proto-oncogene like 2 (MYBL2) is a transcription factor implicated in the initiation and progression of various human cancers. However, its role in tamoxifen resistance in breast cancer remained largely unknown. In the present study, by analyzing public transcriptome dataset, we found that MYBL2 is overexpressed in breast cancer and is associated with the poor prognosis of breast cancer patients. By establishing tamoxifen-resistant breast cancer cell lines, we also provided evidence that MYBL2 overexpression contributes to tamoxifen resistance by up-regulating its downstream transcriptional effectors involved in cell proliferation (PLK1, PRC1), survival (BIRC5) and metastasis (HMMR). In contrast, inhibiting those genes via MYBL2 depletion suppresses cancer progression, restores tamoxifen and eventually reduces the risk of disease recurrence. All these findings revealed a critical role of MYBL2 in promoting tamoxifen resistance and exacerbating the progression of breast cancer, which may serve as a novel therapeutic target to overcome drug resistance and improve the prognosis of breast cancer patients.

Comparison of autofluorescence and white-light bronchoscopies performed with the Evis Lucera Spectrum for the detection of bronchial cancers: a meta-analysis.

BACKGROUND: Many recent studies have reported that autofluorescence bronchoscopy (AFB) has a superior sensitivity and decreased specificity in the diagnosis of bronchial cancers when compared with white-light bronchoscopy (WLB). We specifically analyzed the diagnostic performances of autofluorescence imaging video bronchoscopy (AFI) performed with the Evis Lucera Spectrum from Olympus, which is a relatively novel approach in detecting and delineating bronchial cancers, and compared it to the older WLB method. METHODS: We searched the PubMed, Embase, Web of Science, and CNKI databases from inception to July 12th, 2018 for trials in which patients were diagnosed with lung cancer via concurrent or combined use of AFI and WLB. The included studies were required to have a histologic diagnosis as the gold standard comparison, and a sufficient amount of data was extracted to assess the diagnostic capacity. A 2×2 table was constructed, and the area under the receiver-operating characteristic curve (AUC) of AFI and WLB was estimated by using a stochastic model for diagnostic meta-analysis using STATA software. RESULTS: A total of 10 articles were eligible for the meta analysis, comprising 1,830 patients with complete data included in the analysis. AFI showed a superior sensitivity of 0.92 (95% CI, 0.88-0.95) over WLB's 0.70 (95% CI, 0.58-0.80) with P<0.01, and a comparable specificity of 0.67 (95% CI, 0.51-0.80) compared with WLB's 0.78 (95% CI, 0.68-0.86) with P=0.056. Egger's test P value (0.225) demonstrated that there was no publication bias. CONCLUSIONS: Our research showed that in the evaluation of bronchial cancers, AFI was superior to conventional WLB. With its higher sensitivity, AFI could be valuable for avoiding misdiagnosis.

Alginate Lyase Guided Silver Nanocomposites for Eradicating Pseudomonas aeruginosa from Lungs.

Pseudomonas aeruginosa (P. aeruginosa) infections lead to a high mortality rate for cystic fibrosis or immunocompromised patients. The alginate of the biofilm was believed to be the key factor disabling immune therapy and antibiotic treatments. A silver nanocomposite consisting of silver nanoparticles and a mesoporous organosilica layer was created to deliver two pharmaceutical compounds (alginate lyase and ceftazidime) to degrade the alginate and eradicate P. aeruginosa from the lungs. The introduction of thioether-bridged mesoporous organosilica into the nanocomposites greatly benefited the conjunction of foreign functional molecules such as alginate lyase and increased their hemocompatibility and drug-loading capacity. Silver nanocomposites with a uniform diameter (∼39 nm) exhibited a high dispersity, good biocompatibility, and high ceftazidime-loading capacity (380.96 mg/g). Notably, the silver nanocomposites displayed a low pH-dependent drug release and degradation profiles (pH 6.4), guaranteeing the targeted release of the drugs in the acidic niches of the P. aeruginosa biofilm. Indeed, particles loaded with alginate lyase and ceftazidime exhibited high inhibitory and degradation effects on the biofilm of P. aeruginosa PAO1 based on the specific catalytic activity of the enzyme to the alginate and antibacterial function of their loaded ceftazidime and silver ions. It should be noted that the enzyme-decorated nanocomposites succeeded in eradicating P. aeruginosa PAO1 from the mouse lungs and decreasing the lung injuries. No deaths or serious side effects were observed during the experiments. We believe that the silver nanocomposites with high biocompatibility and organic group-incorporated framework have the potential to be used to deliver multiple functional molecules for antibacterial therapy in clinical application.

Geranylgeranyl diphosphate synthase 1 knockout ameliorates ventilator-induced lung injury via regulation of TLR2/4-AP-1 signaling.

OBJECTIVE: To investigate the role of geranylgeranyl diphosphate synthase 1 (GGPPS1) in ventilator-induced lung injury along with the underlying mechanism. METHODS: A murine VILI model was induced by high-tidal volume ventilation in both wild-type and GGPPS1 knockout mice. GGPPS1 expression was detected in the bronchoalveolar lavage fluid (BALF) supernatants of acute respiratory distress syndrome (ARDS) patients and healthy volunteers, as well as in lung tissues and BALF supernatants of the VILI mice using enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western bolt and immunohistochemical (IHC). The wet/dry ratio, total BALF proteins, and lung injury score were analyzed. The percentage of neutrophils was detected by flow cytometry and IHC. Inflammatory cytokine levels were measured by ELISA and qRT-PCR. The related expression of Toll-like receptor (TLR)2/4 and its downstream proteins was evaluated by western blot. RESULTS: GGPPS1 in BALF supernatants was upregulated in ARDS patients and the VILI mice. Depletion of GGPPS1 significantly alleviated the severity of ventilator induced lung injury in mice. Total cell count, neutrophils and inflammatory cytokines (interleukin [IL]-6, IL-1ß, IL-18 and tumor necrosis factor-α) levels in BALF were reduced after GGPPS1 depletion. Moreover, addition of exogenous GGPP in GGPPS-deficient mice significantly exacerbated the severity of ventilator induced lung injury as compared to the PBS treated controls. Mechanistically, the expression of TLR2/4, as well as downstream proteins including activator protein-1 (AP-1) was suppressed in lung tissues of GGPPS1-deficient mice. CONCLUSION: GGPPS1 promoted the pathogenesis of VILI by modulating the TLR2/4-AP-1 signaling pathway, and GGPPS1 knockout significantly alleviated the lung injury and inflammation in the VILI mice.

A rapid and sensitive method for quantification of ibrutinib in rat plasma by UPLC-ESI-MS/MS: validation and application to pharmacokinetic studies of a novel ibrutinib nanocrystalline.

Ibrutinib has an excellent effect in the treatment of mantle cell lymphoma so it has attracted much attention. A novel ibrutinib nanocrystalline was exploited in our study to improve the bioavailability. A fast and reliable UPLC-MS/MS method was established for the accurate quantification of ibrutinib in rat plasma. The chromatographic separation was achieved by an Agilent zorbax SB-C18 rapid solution HD column (2.1 × 50 mm, 1.8 µm). The mobile phase consisted of deionized water (containing 10 mm ammonium acetate and 0.1% formic acid) and pure acetonitrile. Isocratic elution (water-acetonitrile 10:90, v/v) was adopted and the flow rate was 0.4 mL/min. Column temperature was set to 40°C. Vilazodone was used as the internal standard in this analytical method. Multiple reaction monitoring mode with positive electrospray ionization was selected to detect ibrutinib and vilazodone. Acetonitrile was used to precipitate protein to extract plasma samples. There was no endogenous interference for both ibrutinib and vilazodone and the linear range of this method was 1-2000 ng/mL. The recoveries were 98.4, 97.4 and 102.7% at low, medium and high concentrations. Accordingly, the matrix effect was 96.6, 111.1 and 99.6%. The pharmacokinetic difference between ibrutinib crude and a novel ibrutinib nanocrystalline in rats was investigated by this validated method successfully. The peak concentration and area under the concentration-time curve showed significant differences in gender and the bioavailability was improved after oral administration of ibrutinib nanocrystalline.

Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice.

The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

An Elevated Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Colorectal Cancer: A Meta-Analysis.

Background. The aims of this study were to evaluate the clinicopathological and prognostic values of platelet-to-lymphocyte ratio (PLR) in colorectal cancer (CRC). Methods. The PubMed and Embase databases and the references of relevant studies were systematically searched. This study was performed with hazard ratios (HRs) and odd ratios (ORs) with corresponding 95% confidence intervals (CIs) as effect measures. Results. Our results indicated that elevated PLR was associated with poor overall survival (HR = 1.46, 95% CI = 1.23-1.73), disease-free survival (HR = 1.64, 95% CI = 1.17-2.30), cancer-specific survival (HR = 1.30, 95% CI = 1.12-1.51), and recurrence-free survival (HR = 1.38, 95% CI = 1.09-1.74) in CRC. For the clinicopathological characteristics, our results indicated that there were differences in the rate of elevated PLR between stages III/IV and I/II groups (OR = 1.38, 95% CI = 1.01-1.88), pT3/T4 and pT1/T2 groups (OR = 1.82, 95% CI = 1.03-3.20), and poor differentiation and moderate/well differentiation (OR = 2.59, 95% CI = 1.38-4.84). Conclusions. Our results indicated that elevated PLR predicted poor prognosis and clinicopathological characteristics in CRC and PLR is a convenient and low-cost blood-derived prognostic marker for CRC.

Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis.

BACKGROUND: There are no consistent agreements on whether radiotherapy after breast-conserving surgery (BCS) could provide local control and survival benefit for older patients with early breast cancer or breast ductal carcinoma in situ (DCIS). The present study aimed to evaluate the efficacy of radiotherapy after BCS in older patients with early breast cancer or DCIS. RESULTS: Radiotherapy could reduce the risk of local relapse in older patients with early breast cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non-radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25. The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non-radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20. However, radiotherapy could not improve survival benefits, including overall survival, cancer-specific survival, breast-cancer-specific survival, and distant relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast events in older patients with DCIS. MATERIALS AND METHODS: PubMed and Embase database were searched for relevant studies. Hazard ratios (HRs), risk ratios (RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy in older patients. CONCLUSIONS: Our study indicates that radiotherapy could slightly reduce the risk of local relapse in older patients with favorable early breast cancer. However, radiotherapy cannot translate into significant survival benefits.

Aspirin and non-steroidal anti-inflammatory drugs use reduce gastric cancer risk: A dose-response meta-analysis.

BACKGROUND: The association between non-steroidal anti-inflammatory drugs (NSAIDs) and gastric cancer (GC) risk is controversial. The aim of this study is to evaluate the chemopreventive effect of NSAIDs for GC. METHODS: A literature search was performed for relevant studies using the PubMed and Embase database (up to March 2016). Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the effect measures. The dose-response analysis and subgroup analysis were also performed. RESULTS: Twenty-four studies were included. Our results indicated that NSAIDs could reduce GC risk (any NSAIDs: RR=0.78, 96%CI=0.72-0.85; aspirin: RR=0.70, 95%CI=0.62-0.80; non-aspirin NSAIDs: RR=0.86, 95%CI=0.80-0.94), especially for non-cardia GC risk. Moreover, the dose-response analysis indicated the risk of GC decreased by 11% and 5% for 2 years increment of any NSAIDs and aspirin use, respectively. There were nonlinear relationships between the frequency of any NSAIDs use and aspirin use and GC risk (P for non-linearity<0.01), with a threshold effect of 5 times/week. A monotonically decreasing trend was observed only for the frequency of less than 5 times/week. CONCLUSIONS: Our results indicate that NSAIDs is inversely associated with GC risk, especially for non-cardia GC risk. NSAIDs use may become a feasible approach to prevent GC.