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Background The prognostic values of preoperative tumor markers (TMs) remain elusive in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy treatment (NACT). This study aimed to assess and establish a novel scoring system incorporating carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4) to enhance prognostic accuracy for progression-free survival (PFS) and pathological response (pCR). Methods Patients' data were retrospectively analyzed from December 2006 to December 2017 in our center. The cutoff value of TMs was determined using the time-dependent receiver operating test characteristics method. These three TMs were allocated 1 point each for the post neoadjuvant chemotherapy combination of tumor markers (post-NACT CTM) scores. The training group comprised 533 patients, responsible for full analysis, and the validation group comprised 137 patients based on the selection protocol. Results Of 533 enrolled patients, 138, 233, 117, and 45 patients scored 0, 1, 2, 3 respectively. The 3-year PFS rate Multivariate analysis revealed that post-NACT CTM score was an independent predictor of PFS (0 vs. 1, HR: 1.34, 95% CI: 0.92–1.96, P = 0.128; 0 vs. 2, HR: 2.03, 95% CI: 1.35–3.05, P = 0.001; 0 vs. 3, HR: 2.98, 95% CI: 1.83–4.86, P P = 0.077; 2/3 vs. 0, OR: 4.33, 95% CI: 1.38–13.61, P = 0.012). A nomogram was formed with both internal and external validation. Conclusions The post-NACT CTM score system served as a strong independent predictor for PFS and pCR in LAGC patients who received NACT. Further population-based studies are required to confirm our results.

Fuji apple (Malus × domestica Borkh.) is a popular fruit cultivar and occupies an important position in the fruit market due to its excellent flavor and storage quality. Ethylene emission can induce respiration, which would reduce postharvest quality and increase storage losses. In order to maintain fruit quality and extend shelf life, apples are usually stored in a low-temperature environment after harvest to reduce the formation of ethylene. Volatile aroma components are regarded as one of the most important aspects of flavor quality and a key factor for apple quality grading and customer satisfaction. Ethylene emission and its relationship with volatile aromas during low temperature, however, have not been determined. In this study, the dynamic changes of volatile aroma compounds of Fuji apples stored at 4 °C were detected and analyzed for 42 days. The variation of ethylene released from Fuji apple was studied correspondingly. The results showed that ethyl butyrate, ethyl caproate, ethyl 2-methylbutyrate and 2-methylbutyl acetate were the main aroma components of Fuji apple. The change in ethylene emission and the normalized peak area of volatile aroma compounds exhibited a similar tendency that increased significantly from the 3rd day to the peak on the 14th day and then decreased; there was a positive linear correlation between them with a correlation coefficient of 0.79 (P < 0.05). Therefore, ethylene release can be used as a potential indicator for evaluation of volatile aroma compounds in apples. Using ethylene emission as an indicator could reduce the difficulty and complexity of volatile aroma evaluation, which could be a new non-destructive inspection choice for apple flavor quality assessment.

1′,4′-trans-diol-ABA is a key precursor of the biosynthesis of abscisic acid (ABA) biosynthesis in fungi. We successfully obtained the pure compound from a mutant of Botrytis cinerea and explored its function and possible mechanism on plants by spraying 2 mg/L 1′,4′-trans-diol-ABA on tobacco leaves. Our results showed that this compound enhanced the drought tolerance of tobacco seedlings. A comparative transcriptome analysis showed that a large number of genes responded to the compound, exhibiting 1523 genes that were differentially expressed at 12 h, which increased to 1993 at 24 h and 3074 at 48 h, respectively. The enrichment analysis demonstrated that the differentially expressed genes (DEGs) were primarily enriched in pathways related to hormones and resistance. The DEGs of transcription factors were generally up-regulated and included the bHLH, bZIP, ERF, MYB, NAC, WRKY and HSF families. Moreover, the levels of expression of PYL/PYR, PP2C, SnRK2, and ABF at the ABA signaling pathway responded positively to exogenous 1′,4′-trans-diol-ABA. Among them, seven ABF transcripts that were detected were significantly up-regulated. In addition, the genes involved in salicylic acid, ethylene and jasmonic acid pathways, reactive oxygen species scavenging system, and other resistance related genes were primarily induced by 1′,4′-trans-diol-ABA. These findings indicated that treatment with 1′,4′-trans-diol-ABA could improve tolerance to plant abiotic stress and potential biotic resistance by regulating gene expression, similar to the effects of exogenous ABA.

Background Among locally advanced gastric cancer (LAGC) patients, poor response to initial neoadjuvant chemotherapy (NAC) is associated with unfavorable outcomes; however, changing the postoperative therapy regimen in this group of patients is unclear. We compared the poor responders who continued the original protocols with that of patients who switched treatment after NAC plus D2 gastrectomy. Methods Our study included LAGC patients who achieved tumor regression grade 3 according to the American Joint Committee on Cancer/College of American Pathologists system, after NAC, between December 2006 and December 2017 at our institution. Outcomes were overall survival (OS), progression-free survival (PFS), and adverse events during postoperative treatment. The propensity score matching method was used to match patients. Results Overall, 160 patients were enrolled in the final analysis set, including 21 switched cases and 139 non-switched cases. A 1:2 matched cohort (21 switching vs. 42 non-switching) was generated to eliminate all confounding factors. No statistical differences were observed in OS and PFS, either in the whole patients (OS: log-rank p = 0.804; PFS: log-rank p = 0.943) or in the matched cohort (OS: log-rank p = 0.907; PFS: log-rank p = 0.670) between the two groups. Patients with changed regimens had a significantly higher rate of peripheral neurotoxicity (p = 0.045). Contrarily, a lower rate of overall adverse events was observed in the non-switching group with marginal significance (p = 0.069). Conclusion Adjusting to a non-cross-resistant regimen only by post-NAC pathological evaluation may not be sufficient for designing an effective treatment route for LAGC poor responders. Treatment change required a more scrutinized clinical track, which involved a multifaceted assessment.

BackgroundEpstein–Barr virus-associated gastric cancer(EBVaGC)has a unique tumor immune microenvironment. We performed a comprehensive analysis of the tumor-infiltrating immune cells in a cohort of EBVaGC in a Chinese population.MethodsEpstein–Barr encoding region (EBER) in situ hybridization was performed in 1,328 consecutive cases of surgically resected GC. Densities of immune cells, including T cells, B cells, natural killer cells, and macrophages from the patients were calculated after immunohistochemical staining with CD3, CD20, CD57, and CD68 antibodies in tissue microarrays, respectively.ResultsEBVaGC patients accounted for 4.1% (55 of 1,328) cases in the overall population. The average age of patients with EBVaGC was lower than that of non-EBVaGC patients. Histologically, EBVaGC patients exhibited poorly differentiated adenocarcinoma (P = 0.004) and lower frequency of vascular invasion (P = 0.034). The density of CD3+ T lymphocytes (CD3, 23.84 ± 14.49 vs. 12.76 ± 8.93, P < 0.001) and CD68+ macrophages (CD68, 9.73 ± 5.25 vs. 5.44 ± 4.18, P < 0.001) was significantly higher in EBVaGC patients. CD3+ T cell density predicted better 5-year overall survival of EBVaGC patients (P = 0.022).ConclusionsEBVaGC patients were younger with low-differentiated adenocarcinoma and less vascular invasion. Increased infiltration of multiple immune cells affected the prognosis of patients, especially EBVaGC patients with more CD3+ T lymphocytes, who survived longer.

The effects of background speech or noise on visually based cognitive tasks has been widely investigated; however, little is known about how the brain works during such cognitive tasks when music, having a powerful function of evoking emotions, is used as the background sound. The present study used event-related potentials to examine the effects of background music on neural responses during reading comprehension and their modulation by musical arousal. Thirty-nine postgraduates judged the correctness of sentences about world knowledge without or with background music (high-arousal music and low-arousal music). The participants’ arousal levels were reported during the experiment. The results showed that the N400 effect, elicited by world knowledge violations versus correct controls, was significantly smaller for silence than those for high- and low-arousal music backgrounds, with no significant difference between the two musical backgrounds. This outcome might have occurred because the arousal levels of the participants were not affected by the high- and low-arousal music throughout the experiment. These findings suggest that background music affects neural responses during reading comprehension by increasing the difficulty of semantic integration, and thus extend the irrelevant sound effect to suggest that the neural processing of visually based cognitive tasks can also be affected by music.

Background Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. Patients and methods A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients’ PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. Results RS1, RS2, and Lauren type were significant predictors of occult PM (all P

Objective Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. Methods Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer (cT≥2M0). We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination (P) and cytology results (CY). Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic (ROC) analysis were performed in training set to find out risk factors of intra-abdominal metastasis, and then validate it in testing set. Results Out of 249 cM0 patients, 51 (20.5%) patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 (8.0%) P1CY1, 17 (6.8%) P0CY1 and 14 (5.6%) P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography (CT) scan ≥21 mm and tumor-occupied ≥2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. Conclusions According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis.

// Ziyu Li 1, * , Xiaofang Xing 2, * , Fei Shan 1 , Shuangxi Li 1 , Zhongwu Li 3 , Aitang Xiao 1 , Zhaodong Xing 1 , Kan Xue 1 , Zhemin Li 1 , Ying Hu 4 , Yongning Jia 1 , Rulin Miao 1 , Lianhai Zhang 1 , Zhaode Bu 1 , Aiwen Wu 1 , Jiafu Ji 1, 2, 3 1 Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China 2 Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China 3 Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China 4 Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China * These authors contributed equally to this work Correspondence to: Jiafu Ji, email: jiafuj@hotmail.com Keywords: ABCC2, rs717620, gastric cancer, neoadjuvant chemotherapy, overall survival Received: February 03, 2016 Accepted: June 29, 2016 Published: July 30, 2016 ABSTRACT Several studies have evaluated the efficacy of neoadjuvant treatment using oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However, preoperative biomarkers predictive of clinical outcome remain lacking. We examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from peripheral blood cells, and the genotypes were analyzed using a SNaPShot TM assay, polymerase chain reaction amplification, and sequencing. The ABCC2 -24C > T (rs717620) genotype was associated with pathologic response to neoadjuvant chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27–11.32). Patients with the CC genotype also had poorer outcomes than those with other genotypes. Thus, ABCC2 -24C > T polymorphism may help to predict the response to preoperative chemotherapy in GC patients.

Background Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. Methods Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. Results In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). Conclusions Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.

Abscisic acid (ABA) is one of the five classical phytohormones involved in increasing the tolerance of plants for various kinds of stresses caused by abiotic or biotic factors, and it also plays important roles in regulating the activation of innate immune cells and glucose homeostasis in mammals. For these reasons, as a "stress hormone," ABA has recently received attention as a candidate drug for agriculture and biomedical applications, prompting significant development of ABA synthesis. Some plant-pathogenic fungi can synthesize natural ABA. The fungus Botrytis cinerea has been used for biotechnological production of ABA. Identification of the transcription factors (TFs) involved in regulation of ABA biosynthesis in B. cinerea would provide new clues to understand how ABA is synthesized and regulated. In this study, we defined a novel Cys2His2 TF, BcabaR1, that regulates the transcriptional levels of ABA synthase genes (bcaba1, bcaba2, bcaba3, and bcaba4) in an ABA-overproducing mutant, B. cinerea TBC-A. Electrophoretic mobility shift assays revealed that recombinant BcabaR1 can bind specifically to both a 14-nucleotide sequence motif and a 39-nucleotide sequence motif in the promoter region of bcaba1 to -4 genes in vitro A decreased transcriptional level of the bcabaR1 gene in B. cinerea led to significantly decreased ABA production and downregulated transcription of bcaba1 to -4 When bcabaR1 was overexpressed in B. cinerea, ABA production was significantly increased, with upregulated transcription of bcaba1 to -4 Thus, in this study, we found that BcabaR1 acts as a positive regulator of ABA biosynthesis in B. cinereaIMPORTANCE Abscisic acid (ABA) could make a potentially important contribution to theoretical research and applications in agriculture and medicine. Botrytis cinerea is a plant-pathogenic fungus that was found to produce ABA. There has been a view that ABA is related to the interaction between pathogenic fungi and plants. Identification of regulatory genes involved in ABA biosynthesis may facilitate an understanding of the underlying molecular mechanisms of ABA biosynthesis and the pathogenesis of B. cinerea Here, we present a positive regulator, BcabaR1, of ABA biosynthesis in B. cinerea that can affect the transcriptional level of the ABA biosynthesis gene cluster, bcaba1 to -4, by directly binding to the conserved sequence elements in the promoter of the bcaba1 to -4 genes. This TF was found to be specifically involved in regulation of ABA biosynthesis. This work provides new clues for finding other ABA biosynthesis genes and improving ABA yield in B. cinerea.

IntroductionCurrent guidelines recommend open gastrectomy with D2 lymph node dissection and adjuvant chemotherapy as the standard treatment for advanced gastric cancer. However, the prognosis is not satisfactory. Perioperative chemotherapy has been proposed to improve survival. Although still in debate, the efficacy of laparoscopic distal gastrectomy (LDG) in patients with advanced gastric cancer has been demonstrated in a few trials. Therefore, LDG after neoadjuvant chemotherapy can be a candidate for future standard treatment on advanced distal gastric cancer. We propose a randomised phase II trial to compare LDG and open distal gastrectomy (ODG) after neoadjuvant chemotherapy for advanced gastric cancer.Methods and analysisTo test the efficacy and safety, a randomised, open-label, single-centre, phase II trial was designed to evaluate the non-inferiority of LDG compared with ODG after neoadjuvant chemotherapy, with 3-year recurrence-free survival as the primary endpoint. The chosen critical value of a non-inferiority margin was an increase of Ethics and disseminationThis study was approved by the Peking University Cancer Hospital Ethics Committee. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT02404753; Pre-results.

The dietary patterns determine the nutrition structure and suitable nutrition benefits for health. In order to measure the relationship between nutrition and health, this article focuses on the relationship between Dietary patterns and health expenditure. We collected 547 household samples from six counties in rural Hainan Province of China. The authors applied Seemingly Unrelated Regression (SUR) model to estimate the empirical model. The results are: (1) some animal food have significant effect to health expenditure; (2) based on the current analysis, consuming more pork and eggs, health expenditure would significantly increase; while consuming more chicken and fish, health expenditure would significantly decrease. We could conclude that appropriate dietary pattern benefits health; livestock meat consuming, primarily pork, may cause more health care expenditure, while fish-dominant diet could reduce health expenditure

Background Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer. Methods We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration’s Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS. Results A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25–0.98; p = 0.04), 0.34 (95% CI, 0.21–0.55; p

Purpose Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of anti-angiogenic agents in gastric cancer. Design A systematic search of PubMed, Embase and conference databases is performed to identify clinical trials with specific anti-angiogenic agents in gastric cancer treatment Results The risk of disease progression (37–52%) and death (19–22%) with ramucirumab as second-line treatment decreases in phase III trials in advanced gastric cancer. No significant improvement in overall survival (OS) with the addition of bevacizumab to chemotherapy is shown. Bevacizumab or ramucirumab combined with traditional chemotherapy is associated with higher adverse event rate compared to chemotherapy alone. Except for apatinib, phase II trials of other tyrosine kinase inhibitors (TKIs) may improve overall response rate, but there are no significant improvements in OS and progression-free survival (PFS) when combined with chemotherapy. Conclusion Phase III trials in advanced gastric cancer have demonstrated improved outcome with ramucirumab as second-line treatment. Most of the other studies on anti-angiogenic agents in gastric cancer have reported improvement in response rate but not in OS compared to chemotherapy alone. Future research is expected in optimizing the anti-angiogenic therapy combined with traditional treatment.