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Keel bone damage (KBD) is more prevalent in alternative laying hen housing systems than in conventional cages, and its incidence differs from strain to strain. However, the information of KBD in Lindian chickens, a native Chinese strain, is limited. To investigate the effect of KBD on fearfulness and physiological indicators of stress in Lindian chickens and commercial laying hens, a total of two hundred 25-wk-old chickens (100 Hy-line Brown and 100 Lindian chickens) were studied for 7 wk. The birds were housed in furnished cages with 10 birds per cage for each strain. At 32-wk of age, the birds in each strain were divided into normal (NK), deviated (DK), and fractured (FK) hens according to the keel bone status. Ten birds in each keel bone status per strain were subsequently selected to collect blood for the determination of stress and fear-related indicators, including corticosterone, serotonin, interleukin-1β, and interleukin-6, and measure fear responses, including novel object test (NOT), human approach test (HAT), and tonic immobility (TI) test. The results showed that egg production was lower and the incidence of keel bone fractures was higher in Lindian chickens than in Hy-line Brown hens (P < 0.05). Lindian chickens showed a significantly increased whole blood serotonin content, NOT-latency, HAT-score, and TI induction times (P < 0.05) and decreased serum interleukin-6 content and TI-duration (P < 0.05) compared with Hy-line Brown hens. Additionally, FK hens had significantly elevated whole blood corticosterone, serum interleukin-1β and interleukin-6 levels, TI-duration, and NOT-latency (P < 0.05), and a reduced whole blood serotonin content (P < 0.05) compared with NK and DK hens. Our results indicated that KBD affected stress and fear responses, and this impact was mainly reflected by FK hens compared with NK and DK hens. We suggest that keel bone fractures are the main factor impairing hen welfare. Besides, the incidence of keel bone fractures and stress and fear responses of Lindian chickens are more severe than Hy-line Brown laying hens, indicating that the strain type can affect the health and welfare of laying hens. [ABSTRACT FROM AUTHOR]

Purpose The aim of the present study was to evaluate the prognostic value of magnetic resonance imaging (MRI)!determined lymph nodal necrosis (LNN) in nasopharyngeal carcinoma (NPC) and explore the feasibility of an N-classification system based on the 8th edition of the American Joint Committee on Cancer (AJCC) system. Materials and Methods The MRI scans of 616 patients with newly diagnosed stage T1-4N1-3M0 NPC who were treated with definitive intensity-modulated radiotherapy were reviewed. Results Multivariate analysis showed that LNN was an independent negative prognostic predictor of distant metastasis free survival (hazard ratio, 1.634; 95% confidence interval, 1.023 to 2.609; p=0.040) and overall survival (hazard ratio, 2.154; 95% confidence interval, 1.282 to 3.620; p=0.004). Patients of classification N1 disease with LNN were reclassified as classification N2, and classification N2 disease with LNN as classification N3 in the proposed N-classification system. Correlation with death and distant failure was significant, and the total difference between N1 and N3 was wider with the proposed system. Conclusion MRI-determined LNN is an independent negative prognostic factor for NPC. The proposed N classification system is powerfully predictive. [ABSTRACT FROM AUTHOR]

Purpose Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT). Materials and Methods Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model. Results The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013, and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥ 2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival time of rectal cancer. Conclusion These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment. [ABSTRACT FROM AUTHOR]

Objective: The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). Methods: The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. Results: We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. Conclusions: Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR), which is common in colorectal cancer (CRC), induces high mortality in patients. Due to its robust and selective apoptosis induction in some CRC cells with MDR, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is attractive as a novel tool for CRC therapy. However, TRAIL is limited by its poor tumor-homing ability and inefficient apoptosis induction in CRC cells expressing low levels of death receptor (DR). Here, the tumor-homing RGR peptide (CRGRRST) was fused to TRAIL to produce RGR-TRAIL. Compared with TRAIL, RGR-TRAIL showed greater cell binding and cytotoxicity in CRC cells. In addition, RGR-TRAIL exerted significantly enhanced tumor uptake and growth suppression in mice bearing CRC tumor xenografts. Notably, RGR-TRAIL eradicated all tumor xenografts of DR-overexpressing COLO205 cells. However, TRAIL only showed mild tumor growth suppression under the same conditions, indicating that RGR fusion significantly increased the antitumor effect of TRAIL in DR-overexpressing CRC cells by improving tumor homing. Nevertheless, RGR fusion did not significantly enhance the antitumor effect of TRAIL in HT29 cells expressing low levels of DR. We found that DR expression in HT29 cells was enhanced by epidermal growth factor receptor (EGFR)-targeted photodynamic therapy (PDT). Moreover, both the in vitro and in vivo antitumor effects of RGR-TRAIL were significantly improved by combination with PDT. HT29 tumor xenografts (-20%) were even eradicated by combination therapy. These results indicate that it is valuable to further evaluate the combination therapy of RGR-TRAIL and tumor-targeted PDT for clinical therapy of CRC with MDR. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to spare hematopoietical bone marrow (BM) identified by magnetic resonance (MR) radiation in order to alleviate acute hematologic toxicity (HT) for gastric cancer patients treated with postoperative chemoradiotherapy (CRT). Methods: A prospective, open-label, single-arm Phase II study (Clinicaltrials.gov; NCT 01863420) was conducted in 25 patients with gastric cancer who were eligible for postoperative concurrent CRT. The MR images of vertebral body T8-L4 were fused with images of simulating computed tomography. Hematopoietical BM was contoured according to the MR and spared in radiotherapy plan. The CRT regimen consisted of daily capecitabine (1600 mg/m2/d) and 45 Gy of radiation at 1.8 Gy per day. Primary endpoints were grade ≥3 HT that occurred within 2 months of initiation of CRT. The relationship between HT and dose-volume of BM was estimated by multivariable linear regression model. Results: Twenty four patients (96%) had T3-4 disease and 22 (88%) had disease with node positive. The median age was 53 years (range, 28-73 years). Before concurrent CRT, adjuvant chemotherapy was administered with a mean cycle of 4.3±0.5. Only five patients (20%) developed grade 3-4 HT during treatment, among whom two (8.0%) patients experienced grade 3-4 leucopenia, two (8.0%) experienced neutropenia, and two (8.0%) experienced thrombocytopenia, respectively. None of the patients showed grade 3-4 anemia. Multivariable linear regression revealed increased BM-V5 (P=0.03) and BM-V20 (P=0.002) were found to be significantly associated with decreased white blood cells nadirs in multivariable regression; increased BM-V20 (P<0.001) with decreased absolute neutrophil count nadirs, increased BM-V30 (P=0.002) and volume of BM (P=0.001) with decreased platelet count nadirs. Conclusion: Irradiation of active BM identified by MR is associated with HTs. Techniques to limit low-dose radiation, especially V20, to BM could reduce HT in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Noise is a potential but not negligible environmental factor in animal husbandry. To investigate the effects of farm noise on intestinal barrier function of pullets, 336 Hailanhe pullets aged 1 day were randomly divided into 3 groups: control group (CON), low noise group (LN), high noise group (HN). LN group and HN group were exposed to noise respectively at 65-75 dB and 85-95 dB, the average and the range of the highest loudness of noise in laying hens' farms for 6h every day (7:00-19:00, hourly intervals for one hour) and lasted 4 weeks. Non additional noise addition in CON group, noise loudness of which was less than 40dB. 6 birds were randomly chosen form each group after every week of noise stimulation for ileum tissue samples. Hematoxylin-eosin stain (HE stain), immunofluorescence, and real-time quantitative PCR (qRT-PCR) were used to determine changes in ileum structure, expression of intestinal barrier related proteins and mRNAs and HSPs. Results shown that 1 week and 2 weeks after noise exposed inflammatory cell infiltration reduced, the expression of intestinal barrier related proteins (Occludin, Mucin2 and ZO-1) and mRNAs (Claudin-1, Claudin-4, E-cadherin, Occludin, Mucin2, ZO-1 and ZO-2) were significantly increased (P < 0.05), the mRNA expression of HSPs decreased (P < 0.05) or have no significate changes (P > 0.05). After 4 weeks of noise treatment, the expression of mRNAs of intestinal tight junction protein and mucin, HSPs were significantly decreased (P < 0.05). There was no difference between the LN and HN groups on those indicators (P > 0.05). The study indicates that noise at 65-75dB and 85-95dB does not cause stress to ileum of pullets while promote the development of intestinal barrier of chicks within 2 weeks maybe by mild stimulation and birds restored to balance due to habitualization after 4 weeks of noise treatment. [ABSTRACT FROM AUTHOR]