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Background: To analysed the short- and long-term outcomes of patients who underwent surgical resection for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) to gain insights into treatment approaches for this rare and heterogeneous entity., Methods: All patients who underwent surgical resection for NF-PNETs at The Second Affiliated Hospital of Guangzhou Medical University, and West China Hospital, Sichuan University, from 2009 to 2019 were retrospectively reviewed. The data of patients was including perioperative management, pathologic analysis and follow-up., Results: A total of 119 cases with histologically or cytologically confirmed NF-PNETs, The mean age of the patients was 52, and 56.3% were female. Twenty-three patients received post-operative adjuvant therapy, and five of nine (55.6%) patients with distant metastasis showed recurrence 14(60.9%) G2/G3 patients without distant metastasis received post-operative therapy with octreotide. Of these 14 patients, 3 (21.4%) revealed recurrence. Univariate analysis indicated that symptoms (P = 0.03), tumour size >4 cm (P = 0.029), ENETS stages III-IV (P < 0.001), positive lymph nodes (P < 0.001), vascular/perineural invasion (P < 0.001), and pathology grade G2 were associated with significantly higher risks of recurrence; age, gender, surgery type, and tumour location were not. Multivariate analysis revealed that positive lymph nodes (P < 0.001), vascular/peripheral invasion (P < 0.001), and pathology grade G3 (P = 0.03) are significant prognostic factors of tumour recurrence., Conclusion: Positive lymph nodes, vascular/peripheral invasion and pathology grade G3 were related to recurrence of NF-PNETs. Lymph node resection is recommend when FNA biopsy indicates pathology grade G3 for patients with NF-PNETs., (© 2021 Royal Australasian College of Surgeons.)

Recently, in-situ surface-enhanced Raman spectroscopy (SERS) is gradually becoming an important method for monitoring photocatalytic reaction processes, in which the quantification potential is a vital factor in determining whether this technology can be truly applied in the future. In order to improve the quantification performance of in-situ SERS and explore a precise operando Raman detection for photocatalytic reactions, an architecture of heterostructural Cu 2 O/ZnO/Ag nano round brush has been designed and discussed in this work. This structure is an integration of sensitive in-situ SERS sensor and high-efficiency photocatalyst, realizing real-time monitoring of photocatalytic reaction in a wide concentration range from 20 to 3 mg l -1 . The coefficient of determination between different detection methods is beyond 0.86 in this range, implying the high-precise quantification of this platform. Comprehensive analysis on structure effect, SERS performance, photocatalytic property, electric filed characteristic, etc were all systematically made and discussed in detail for this platform. This work presents a precise preliminar real-time photocatalytic monitoring using in-situ SERS detection, which is a new attempt and also meaningful reference for other in-situ analytical technology., (© 2022 IOP Publishing Ltd.)

Background: Pancreatic ductal adenocarcinoma (PDAC) prognosis has not improved over the last decades because of the lack of effective diagnostic and therapeutic methods in the early stage of the disease., Methods: Several gene expression profiles were downloaded from the Expression Omnibus (GEO) database. We calculated the differentially expressed mRNAs (DEGs) and miRNAs (DEmiRs). Then, we constructed a miRNA-mRNA regulatory network by using the miRWalk database. For the DEGs regulated by DEmiRs, we introduced GEPIA to confirm these DEGs' expression and effect on overall survival. We used other GEO datasets and mRNA-miRNA target databases to validate these DEGs and their relationship with DEmiRs. All these potential core DEGs regulated by DEmiRs were also analyzed at the single-cell level to confirm their cell type source., Results: CCNB2 and KCNN4, which were regulated by several micro RNAs, showed relatively high expression levels in PDAC patients and significant association with worse overall survival. Furthermore, we identified many DEGs at single-cell level and found that 10 oncogenes were significantly upregulated in type 2 ductal cell type, thereby further demonstrating that type 2 ductal cells might be major sources of malignant cells and are valuable therapeutic targets in PDAC., Conclusions: Our data added some new insights into the molecular mechanism of PDAC and may be helpful for finding potential biomarkers for diagnosis. These discovery at single-cell level may also be useful for developing new therapeutic targets for PDAC patients.

Surface-enhanced Raman scattering (SERS) is widely considered to be a fingerprint spectrum that can realize molecular identification, and it continues to receive a lot of attention due to its high sensitivity and powerful qualitative analysis capabilities. In recent years, there has been a lot of work and reports on super-sensitive SERS substrates, but often the enhanced ability of the substrate is also effective for impurities and irrelevant molecules. Therefore, a problem that still remains to be solved is how to perform effective trace detection of specific substances in a complex detection environment. Herein, a superhydrophobic Ag nanoparticle/glass microfibre filter (AgNP/GF) substrate was designed to realize the Raman detection of complex multiphase solutions. The hydrophobic three-dimensional net-like structure provides efficient Raman enhancement, making the substrate have extremely high detection limits for dye molecules and even achieving specific detection of the hexane phase component (thiram molecule) in a multiphase solution.

Materials engineering is generally regarded as one of the most effective methods in the construction of photocatalysts, but it still faces many challenges. In this context, we designed and prepared a three-dimensional (3D) heterostructure of nanowires (NWs) formed by C u 2 O core and an Au shell. The C u 2 O - A u NWs not only show fine photocatalytic ability but also proved to have Fenton-like chemical properties and can be used as a hydrogen peroxide sensor. Moreover, this heterostructure realizes an integration of catalytic efficiency, retrievability, and versatility. In further consideration of the facile preparation process and low-cost material source of the structure, the C u 2 O - A u NWs show a promising application prospect in the field of multifunctional photocatalysts.

The surface-enhanced Raman spectroscopy (SERS) has attracted much attention due to the powerful capability of quantificational analysis. Nowadays, most of the enhancement effect by SERS substrate is provided by the 'hot spots' occupying relatively small space. When the amount of analyte is too low, it is difficult to ensure that all the probe molecules can be placed into the 'hot spots', which is a headache in SERS quatification. In order to solve this problem, we have developed a structure of CuO nanowires/Ag nanoparticles with wettability capacity difference, which can aggregate molecules in water and oil simultaneously under two different mechanisms. The limit of detection and enhancement factor of this structure are estimated as 10 -15 M and 1.55 × 10 11 respectively (for rhodamine 6G, R6G). In a proof-in-principle experiment of sewage detection, it successfully achieved the aggregation and additional enhancement of both the R6G molecules in aqueous solution and thiuram molecules in toluene, realizing efficient and accurate Raman detection., (© 2021 IOP Publishing Ltd.)

Background: This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy., Methods: Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks., Results: During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194)., Conclusions: The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

Unstable detection environment is one of the biggest interferences for in situ surface-enhanced Raman spectroscopy (SERS) using in real-time monitoring of toxic pollutants, leading to unreliable results. To address this problem, we have designed and prepared a cavity-based particle-in-quasicavity (PIQC) architecture composed of hierarchical ZnO/Ag nanosheets and nanoprotrusions for improving the in situ SERS performance under a liquid environment. Benefitting from the special cascaded optical field mode, the PIQC ZnO/Ag exhibits excellent in situ SERS detectability, with 10 -18 M of limit of detection for rhodamine 6G and 12.8% of signal relative standard deviation value. Furthermore, by means of a microfluidic chip, this PIQC structure is proved to have the quantitative analysis feasibility and realizes real-time monitoring of the 3,3',4,4'-tetrachlorobiphenyl, a representative global environmental hazard, under the flowing environment. The strategy in this paper provides a brand new idea to promote the application of in situ SERS in contaminant monitoring and is also instructive for light control in other optical fields.

Objective: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1 , has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer., Methods: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer., Results: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = -0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER , through acting as a competing endogenous RNA for miR-182 in colorectal cancer., Conclusion: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER , which may serve as a target for colorectal cancer diagnosis and treatment.

Purpose: In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results., Methods: Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m 2 , fluorouracil 400 mg/m 2 , and fluorouracil 2.4 g/m 2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m 2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS)., Results: In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively., Conclusion: mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

Heterotypic CICs (cell-in-cell structures) have been found between tumor cells and various immune cells in a variety of cancer tissues. The frequency of CICs has been found to correlate with tumor malignancy in some studies but not in others. Herein, we examined in depth the CICs observed in colon cancer to determine their potential significance in disease progression. Heterotypic CICs were observed by histochemistry between epithelial cells and lymphocytes in an expanded spectrum of colon tissue from colitis to cancer and in vitro studies were performed using the colonic tumor cell line HCT8 and human peripheral blood lymphocytes. Our data revealed that the CICs formed by colonic epithelial cells and infiltrated lymphocytes not only positively correlated with tumor malignancy but also were upregulated by the inflammatory cytokine IL-6. In addition, we observed that colon cancer cells could initiate autophagy for survival after cytotoxic lymphocyte internalization and that IL-6 could also be involved in this process to promote the death of lymphocytes in CIC structures. Furthermore, certain changes were observed in tumor cells after experiencing CICs. Our findings suggest that CICs formed by colon cancer cells and lymphocytes contribute to tumor escape from immune surveillance, which could be facilitated by IL-6, and might represent a previously undescribed pathway for tumor cells to adapt and evade host immune defense., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To realize fast detection of trace hazardous chemicals, a SERS substrate with the structure of a blackberry-like silver/graphene oxide nanoparticle cluster (Ag/GO NPC) has been designed and prepared through a quick capillarity-assistant self-assembly technology in this paper. Benefitting from the abundant "hot spots" and active oxygen sites brought by this Ag/GO NPC, the substrate shows good Raman performance for malachite green (MG), a common abusive germicide in aquaculture, with lowest limit of detection below 0.1 µg/L (3.48 × 10 -10 mol/L). Detailed analyses are taken on both the formation process and enhancement mechanism of this SERS substrate, and the finite-difference time-domain simulations are utilized as well to prove our hypotheses. Further constructing this structure on polyethylene terephthalate (PET) film, a translucent flexible SERS substrate can be obtained, realizing a fast in situ detection of trace MG in the fishpond subsequently. In consideration of the facile preparation process, good SERS enhancement and affordable materials (PET, Cu, Ag and GO, etc.), this substrate presents high cost performance and a promising application prospect.

Background: The case-control study aimed to investigate the association between the -31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population., Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene -31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and -31G>C genetic polymorphism was estimated using an unconditional logistic regression model., Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and -31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin -31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m 2 , family cancer history, and premenopausal., Conclusion: Survivin -31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The -31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m 2 , family cancer history, and premenopausal., Competing Interests: None

Aim: The effects of circulating eosinophils and basophils on cancer survival are unclear. Here, we aimed to explore the impacts of eosinophils and basophils on prognosis of stage I-III colorectal cancer (CRC) patients., Methods: From February 2003 to March 2013, 569 stage I-III CRC patients were enrolled in this retrospective study. The associations between pretreatment circulating eosinophils, basophils and CRC overall survival (OS), disease-free survival (DFS) were investigated. Moreover, the prognostic value of combined eosinophils/basophils and neutrophil to lymphocyte ratio (NLR)/platelet to lymphocyte ratio (PLR) was investigated., Results: Kaplan-Meier methods showed the associations of eosinophils < 0.095 × 10 9 /L and shorter OS (P < 0.0001), eosinophils < 0.055 × 10 9 /L and shorter DFS (P < 0.0001), basophils < 0.015 × 10 9 /L and shorter OS (P = 0.001), basophils < 0.015 × 10 9 /L and shorter DFS (P = 0.005). Cox regression model showed that eosinophils < 0.095 × 10 9 /L (hazard ratio [HR], 1.723; 95% confidence intervals [CI] = 1.177-2.523) and basophils < 0.015 × 10 9 /L (HR, 1.714; 95% CI = 1.152-2.548) were independent prognostic factors for OS, and eosinophils < 0.055 × 10 9 /L (HR, 2.309; 95% CI = 1.587-3.361) and basophils < 0.015 × 10 9 /L (HR, 1.397; 95% CI = 1.003-1.945) were independent prognostic factors for DFS, respectively. The combined eosinophil-PLR (HR, 2.611; 95% CI = 1.328-5.130) and basophil-PLR (HR, 2.520; 95% CI = 1.240-5.123) were the independent prognostic factors for OS. The combined eosinophil-NLR (HR, 2.770; 95% CI = 1.528-5.019) and eosinophil-PLR (HR, 4.788; 95% CI = 2.458-9.329) were the independent prognostic factors for DFS., Conclusion: Pretreatment circulating eosinophils < 0.095 × 10 9 /L/0.055 × 10 9 /L and circulating basophils < 0.015 × 10 9 /L have significant impacts on prognosis of stage I-III CRC patients., (© 2018 John Wiley & Sons Australia, Ltd.)

Objective: To examine the association between the genotype (LL, LS and SS) of serotonin transporter promoter gene polymorphism(5-HTTLPR) and clinicopathological factors, and to investigate the effect of 5-HTTLPR on the prognosis of colorectal cancer patients., Methods: Data of peripheral blood samples of 161 colorectal cancer patients at the Second Affiliated Hospital of Guangzhou Medical University from October 2009 to January 2014 were collected retrospectively. The genotyping of 5-HTTLPR was determined by PCR and agarose gel electrophoresis. Coincidence Chi-square test was used to examine the 5-HTTLPR genotype with Hardy-Weinberg law. Chi-square test and Cox multifactor model were used to analyze the association of 5-HTTLPR genotype with clinicopathology and prognosis. All the patients were informed and agreed to participate in the study. This study was approved by the Hospital Ethics Committee (2015056)., Results: Of 161 colorectal cancer patients, 89 were male and 72 were female; the median age was 64 (25-85) years; 86 (53.5%) cases were colon cancer and 75 (46.5%) were rectal cancer. Genotype was LL in 12 cases, LS in 59 cases and SS in 90 cases, which complied with the law of Hardy-Weinberg genetic balance (χ²=0.288, P=0.592). Univariate analysis showed that 5-HTTLPR gene polymorphism was only associated with lymph node metastasis [lymph node metastasis rate: LL and LS genotype 21.1% (15/71);SS genotype 40.0% (36/90), χ²= 6.532, P=0.011]. The 3-year and 5-year overall survival rates of whole patients were 71% and 63% respectively. Multivariate analysis revealed that the SS genotype was an independent risk factor affecting the overall survival of colorectal cancer patients(HR=1.933, 95%CI:1.090-3.428, P=0.024)., Conclusion: Among genotypes of 5-HTTLPR gene, colorectal cancer patients with SS genotype have higher risk of lymph node metastasis and poorer prognosis.

Background and Aim: Hairy enhancer of split-1 (HES1) is a downstream transcriptional factor of Notch signaling pathway, which was found to be related to chemoresistance. This study was aimed to investigate the role of HES1 in chemoresistance of colorectal cancer (CRC). Methods: Tissue microarray was used to analyze the clinical significance of HES1 in radical resected (R0) stage II/III CRC patients that received adjuvant chemotherapy. 5-fluorouracil (5-Fu) chemoresistance was examined in CRC cell lines (RKO and HCT8, LOVO) with stable over-expression and inhibition of HES1 gene by cytotoxicity test. Gene expression microarray was used to investigate the enriched pathways and different expressed of genes in cells with over-expressed HES1. Expression changes of the chemoresistance related genes were confirmed by qPCR and western blot analysis. Results: Stage II CRC patients with higher HES1 expression showed higher recurrence rate after chemotherapy. Colon cancer cell lines which over-expressed HES1 were more resistant to 5-Fu treatment in vitro . Gene expression microarray revealed that HES1 was related to the signaling pathways of epithelial-mesenchymal transition (EMT) and drug metabolism. Immunofluorescence assay showed HES1 over-expression lead to depressed E-cadherin and elevated N-cadherin. QPCR and western blot analysis confirmed that ABCC1, ABCC2 and P-gp1 were induced after HES1 over-expression. Conclusions: HES1 promotes chemoresistance to 5-Fu by prompting EMT and inducing of several ABC transporter genes. HES1 might be a novel therapeutic target in CRC treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Purpose: Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy., Methods: In this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m(2), fluorouracil 400 mg/m(2), and fluorouracil 2.4 g/m(2) over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m(2) on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported., Results: A total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy., Conclusion: mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications., (© 2016 by American Society of Clinical Oncology.)

Objective: To analyze the impact of platelet count on the prognosis of stage II-III colorectal cancer receiving adjuvant chemotherapy., Methods: Clinical and follow-up data of 286 patients with stage II-III colorectal cancer receiving adjuvant FOLFOX chemotherapy from March 2003 to October 2011 were analyzed retrospectively. Associations of baseline blood platelet count before chemotherapy and nadir blood platelet count during chemotherapy with relapse and death after adjuvant chemotherapy were analyzed by ROC curve and the optimal cutoff was selected. The association of the blood platelet count and the prognosis was analyzed by Kaplan-Meier and Cox regression model., Results: ROC curve showed the baseline blood platelet count was associated with recurrence (AUC=0.588, P=0.034). The optimal cutoff affecting recurrence was 276×10(9)/L. Kaplan-Meier showed those with baseline platelet count >276×10(9)/L receiving adjuvant chemotherapy had worse disease free survival (DFS) than those with baseline platelet count ≤276×10(9)/L, whose 5-year disease free survival(DFS) was 66% and 80% respectively (P=0.013). Cox regression analysis revealed baseline platelet count >276×10(9)/L was an independent unfavorable factor for DFS of adjuvant chemotherapy in colorectal cancer (HR=1.865, 95% CI: 1.108-3.141, P=0.019)., Conclusion: Colorectal cancer patients receiving adjuvant chemotherapy with baseline platelet count >276×10(9)/L have worse prognosis.

Purpose: Down-regulated expression of the putative tumor suppressor gene spleen tyrosine kinase (SYK) is strongly associated with the development of various cancers, including colorectal cancer (CRC). SYK gene promoter polymorphisms have been shown to be involved in the pathogenesis of multiple malignant tumors. In this study, we investigated associations of SYK gene promoter polymorphisms with the susceptibility to colorectal cancer development in a Southern Han Chinese population., Methods: SNPs in the promoter region of the human SYK gene were identified using in silico analysis tools, linkage disequilibrium analysis, and a search for likely transcription factor binding sites via TFSEARCH in the NCBI SNP database (gene ID: 6850). Based on this information, -803A>T and -534T>C were selected as candidates for further analysis. TaqMan-MGB probe analyses were performed in 567 CRC patients and 569 age- and gender-matched healthy controls for SYK gene promoter genotyping. Associations between CRC risk and SNPs were estimated using an unconditional logistic regression model, and environmental risk factors were included in a multivariate logistic regression model for correction., Results: The frequencies of the TA and TT genotypes and the T allele of the -803A>T SNP were found to be significantly higher in the CRC patients compared to the healthy individuals of the control group (P=0.020, 0.023, and 0.013, respectively). Synergistic effects between -803A>T genotypes (i.e., TA+TT) and age (≤60 years; P=0.039), male gender (P=0.011), smoking (P=0.005), drinking alcohol (P=0.002), and high BMI (≥24.0 kg/m2; P=0.009) were found to increase the risk to develop CRC by stratified analyses., Conclusions: The SYK -803 A>T genotypes TA and TT are independent risk factors for CRC development in Han Chinese in Southern China, and an association with TA+TT genotypes appears predominant among younger patients, male patients, patients with a high BMI, and patients who smoke or drink alcohol.

Aims: To explore the etiology of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) abnormalities in colorectal cancer., Methods: In total, 230 patients with histopathologically confirmed colorectal cancer from August 2009 to August 2011 were recruited to our study. The associations between lifestyles (smoking, alcohol and pickled food consumption) and pretreatment NLR and PLR were estimated using the Kruskal-Wallis tests and linear regression model., Results: The Kruskal-Wallis test showed a significant association between pickled food intake and pretreatment NLR but not PLR (P = 0.002, 0.057, respectively). Pairwise comparisons showed that, compared with those with a moderately frequent (2-3 times/week) and an infrequent (≤ once a week) intake of pickled food, high frequency (≥ four times/week) consumption of pickled food had a higher pretreatment NLR (P = 0.01, 0.007, respectively). Multivariate linear regression analysis showed pretreatment NLR increased significantly in high frequency (≥ four times/week) consumption of pickled food (P < 0.0001). No association between other lifestyle factors and pretreatment PLR was found., Conclusions: A higher frequency intake of pickled food possibly contributes to higher NLR, which may reflect a systemic inflammatory response in colorectal cancer., (© 2013 Wiley Publishing Asia Pty Ltd.)

p38 plays a critical role in the proliferation, survival, migration and metastasis of colorectal cancer (CRC) cells. The present study assessed the correlation between a single nucleotide polymorphism (SNP) in the p38β promoter region (rs2235356, -1628A>G) and the predisposition of individuals to sporadic CRC in a case-control study. A genotyping method was developed to detect this SNP, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A logistic regression analysis was used to determine the odds ratio (OR) and 95% confidence interval (CI). It was revealed that the -1628G variant allele was correlated with an increased risk of CRC (OR, 1.99; 95% CI, 1.60-2.47; P<0.0001). An in silico analysis revealed several transcription factors that either acquired or lost the ability to bind to -1628AA in the p38β promoter region due to the SNP. Therefore, this allelic variant may be a genetic modifier for CRC susceptibility.

Objective: Evaluate the prognostic value of lymph node ratio (LNR) in patients undergoing resection of stage III colorectal cancer., Methods: The clinicopathological and follow-up data were collected from 174 surgical patients with stage III colorectal cancer. The 5-year disease-free survival (DFS) and overall survival (OS) were evaluated using Kaplan-Meier method. The impact of LNR and clinicopathological factors on DFS and OS were evaluated using univariate and multivariate analysis., Results: After a median follow-up of 62.5 months, the 5-year DFS and OS of the patients were 51.8% and 56.3%, respectively. The median number of lymph nodes harvested and the median number of positive lymph nodes examined were 10 and 3, respectively. The patients were stratified into 4 groups according to LNR quartiles (LNR1, LNR≤0.125; LNR2, 0.1250.500), whose 5-year DFS and OS were 64.2%, 53.5%, 41.8%, and 25.7% (P<0.05) and 68.1%, 60.8%, 49.2%, and 32.7% (P<0.05), respectively. Multivariate analysis identified age, T stage and LNR as the independent predictors of both DFS and OS. Subgroup analysis showed that LNR had an independent prognostic value on DFS and OS irrespective of the number of lymph nodes harvested., Conclusion: LNR is an independent prognostic factor for survival in patients with stage III colorectal cancer and is superior to the pN category in TNM staging.

Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a network of mitogen-activated protein kinase pathways, play a pivotal role in carcinogenesis. The purpose of this study was to investigate whether variants in the MEK5 gene promoter were involved in susceptivity of individuals to sporadic colorectal cancer (CRC). In the present hospital-based case-control study of 737 patients with sporadic CRC and 703 healthy control subjects in a southern Chinese population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C>T and rs3743354T>C) were genotyped by TaqMan assay. There were significant differences between cases and controls in the genotype and allele distribution of the MEK5 gene rs3743354T>C polymorphism. The rs3743354 CC genotype was associated with a significantly decreased risk of CRC when compared with the TT genotype (adjusted odds ratios [ORs]=0.43; 95% confidence interval [CI], 0.24-0.77). Compared to the T allele, a significant correlation was detected between the presence of the C allele and decreased risk of CRC (adjusted OR=0.79; 95% CI, 0.61-0.94). The decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT+CC) was found in the smoker subgroup (adjusted OR=0.63; 95% CI=0.45-0.88). Further, environmental factors, including smoking and drinking, interacted with rs3743354C variant genotypes to reduce CRC risk. Western blot analysis showed that the levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal colorectal epithelium tissues were lower in the carriers of rs3743354 CC genotypes than that in those with rs3743354 TT genotypes or those with rs3743354 TC genotypes. However, no significant association was found between the rs7172582C>T polymorphism and risk of CRC. These data indicate that the rs3743354 polymorphism in the MEK5 promoter may affect the risk of developing CRC.

C-Jun plays important roles in the development of multiple cancers, but no well-designed association studies have been conducted to assess the roles of its genetic polymorphisms in cancer risk. In a cohort of 1016 pairs of colorectal cancer (CRC) patients and matched cancer-free controls, we investigated two genetic polymorphisms in the promoter regions of the c-Jun (rs4646999, -673C > T and rs2760501, -1318T > G) via the Taqman assay and evaluated the association between two polymorphisms and risk of CRC. We found that both the -1318G and -673C variant genotypes were associated with an increased risk of CRC [-1318TG: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.04-1.54; -1318GG: OR = 1.63, 95% CI = 1.03-2.60; -673CT: OR = 1.60, 95% CI = 1.23-2.07; -673CC: OR = 1.80, 95% CI = 1.36-2.37]. Haplotype association analysis showed that compared with the carriers of -1318T-673T haplotype, carriers of the -1318T-673C, -1318G-673T, and -1318G-673C haplotypes all had a significantly increased risk of CRC (P < 0.05 for all). The combined genotypes incorporating both polymorphisms obtained a more significantly additive risk of CRC (one variant genotype: OR = 1.81, 95% CI = 1.30-2.51; two variant genotype: OR = 2.42, 95% CI = 1.70-3.44). Moreover, we found that the change of the -1318T to G allele interact with the -673T to C allele elevated the transcription activity of the c-Jun, and we confirmed the same trends by analyzing c-Jun protein expression in the CRC tissues from patients carrying different number of variant genotypes. This study suggests that -673C > T and -1318T > G genetic variants in c-Jun promoter regions contribute to an increased risk of CRC, possibly by elevating the transcription activity and protein expression levels that appeared to upregulate activity of c-Jun thus tumorigenesis.

Background: Nuclear factor κB (NFκB) plays a key role in the regulation of apoptosis. The function of NFκB is inhibited by binding to NFκB inhibitor (IκB), and disruption of the balance of NFκB and IκB is related to the development of many diseases, including tumors. Therefore, we hypothesized that the NFκB1 (-94del/insATTG) and NFκBIA (2758 A>G) polymorphisms were associated with colorectal cancer (CRC) susceptibility., Methods: In a hospital-based case-control study of 1001 CRC patients and 1005 cancer-free controls frequency matched by age and sex, we genotyped polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and performed luciferase assays and Western blotting analysis to identify whether genetic variants in NFκBIA alter its gene expressions and functions and thus cancer risk., Results: We found that both NFκB1-94 ins/delATTG and NFκBIA 2758 A>G polymorphisms were correlated with CRC risk (OR = 1.47; 95%CI = 1.14-1.86, and OR = 1.38; 95% CI = 1.14-1.66, respectively). Furthermore, when evaluated these two polymorphisms together, the combined genotypes with 2 variant (risk) alleles (2758GG and -94ins/ins+del/ins) were associated with an increased risk of CRC (OR = 1.71; 95% CI = 1.23-2.38) compared to 0 variant, and the significant trend for 2 variant (risk) alleles were more pronounced among subgroups of aged <60 years, women, never drinkers, never smokers, persons with a normal BMI and those with a family history of cancer(P(trend)<0.01). Moreover, luciferase assays showed that the G allele in the 3'UTR significantly decreased NFκBIA mRNA stability and the A allele regulation by miRNA449a in vitro and that the NFκBIA protein expression levels of the AA+AG variant carriers were significantly higher in peritumoral tissues than those of the 2758GG genotype., Conclusion: NFκB1 and NFκBIA polymorphisms appear to jointly contribute to risk of CRC. These two variants may be a genetic modifier for CRC susceptibility in this southern Chinese population.

Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its expression and thus cancer risk. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we genotyped two common polymorphisms in the MKK4 promoter region (-1304T>G and -1044A>T) with the Taqman assay, and we found that compared with the most common -1304TT genotype, carriers of -1304G variant genotypes had a decreased risk of lung cancer [odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.61-0.90 for TG, and OR = 0.62; 95% CI = 0.41-0.94 for GG] in an allele dose-response manner (adjusted P(trend) = 0.0005). Further stratification analysis showed that the protective role of the -1304G variant allele was more evident in low or normal body mass index (BMI) but restrained in the overweighters and that the -1304G variant genotypes interacted with BMI in reducing cancer risk (adjusted P(interaction) = 0.003). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 protein expression levels of the G variant carriers was significantly higher in tumor tissues than those of the -1304TT genotype. However, no significant association was observed between the -1044A>T polymorphism and risk of lung cancer. Our data suggest that the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer.

MKK4 (mitogen-activated protein kinase kinase 4, NM&#95;003010.2), which belongs to the mitogen-activated protein kinase pathways, possesses functions in tumorigenesis. We hypothesized the genetic variants in MKK4 gene may alter its functions and thus cancer risk. In current hospital-based case-control study of 706 patients with sporadic colorectal cancer (CRC) and 723 sex-age-frequency-matched control subjects in a southern Chinese population, we genotyped two polymorphisms of MKK4 promoter (i.e., -1304T>G, rs3826392 and -1044A>T, rs3809728) and assessed their associations with the risk of sporadic CRC. Compared with -1304TT genotypes, -1304TG had a significantly decreased risk of CRC (adjusted odds ratios [OR] = 0.56; 95% CI = 0.44-0.72; p = 3.53 x 10(-6)), the -1304GG carriers had a further decreased risk of CRC (OR = 0.40; 95% CI = 0.23-0.70; p = 1.32 x 10(-3)), and there was a significant trend for an allele dose effect on risk of CRC (p(trend) = 2.64 x 10(-7)). The decreased risk associated with -1304G variant genotypes (i.e., TG+GG) was more pronounced in the subjects older than 60 years (adjusted OR = 0.41; 95% CI = 0.29-0.57; p = 2.25 x 10(-7)), in ever drinkers (adjusted OR = 0.41; 95% CI = 0.28-0.59; p = 2.42 x 10(-6)). The age and alcohol drinking status interacted with -1304G variant genotypes on reducing cancer risk (p values for interaction were 0.015 and 0.043, respectively). Western blotting analysis showed that the levels of Mkk4 protein in sporadic CRC neoplastic tissues were significantly higher in the carriers of -1304G variant genotypes than that in those with -1304TT genotypes. However, no significant association was observed between -1044A>T polymorphism and risk of CRC. To the best of our knowledge, this is the first study of genetic variants in MKK4 and cancer susceptibility. Larger studies are needed to validate our findings.

The objective of the present study was to evaluate the effect of batroxobin agents on perioperative hemorrhage in thoracic surgery.We systematically searched Cochrane Library, Pubmed, EMBASE and the China Biological Medicine CD-ROM Databases up to August 2007. Reference lists of all included studies and of reviews related to the topic of the present systematic review were manually searched. Two reviewers independently identified the eligible studies, assessed their methodological quality and extracted data. Results of relevant outcomes were pooled together whenever possible, using RevMan software.Five randomized controlled trials involving 678 patients were included. Three trials were for pneumonectomy and two for cardiac surgery with cardiopulmonary bypass. The quality of the identified studies was generally poor. All the trials claimed randomized allocation, but allocation concealment was unclear. Blinding was not mentioned. Two trials found that batroxobin agents decreased intraoperative blood loss for pneumonectomy. Mean differences between the batroxobin agents group and the no-treatment group were -182.20 ml [95% confidence interval (CI), -207.48 to -156.92] and -131.32 ml (95% CI, -142.95 to -119.69), respectively, for these two trials. All included trials reported less drainage volume favoring the batroxobin agents group. Mean differences at different time points after operation ranged from -15 ml (95% CI, -31.77 to 1.77) to -150.60 ml (95% CI, -179.26 to -121.94). Although most of the differences between the batroxobin agents group and the no treatment group were statistically significant, clinical value was limited.There is not enough evidence supporting any benefit of batroxobin agents for hemorrhage during thoracic surgery.