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[This corrects the article DOI: 10.3389/fonc.2023.1167625.].

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OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

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Objective: To investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy. Methods: Forty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients. Results: The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006). Conclusion: R/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

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Objective: This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data: NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results: We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions: Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.

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Introduction: For locally advanced, inoperable esophageal cancer, concurrent chemoradiotherapy (CCRT) becomes the norm. Combining immunotherapy with radiotherapy has been shown to improve efficacy. Circulating tumor DNA (ctDNA) is a strong predictor of effectiveness and tumor recurrence and is indicative of minimal residual disease (MRD). Patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC) are enrolled in the ECMRD-001 trial to evaluate changes in MRD status before and after CCRT combined with immunotherapy and adjuvant immunotherapy following neoadjuvant immunochemotherapy. Methods and analysis: The ECMRD-001 trial is a prospective cohort study. Eligible patients will receive radical concurrent chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy, followed by adjuvant immunotherapy for at least one year. Follow-up will be up to three years. MRD-related blood and tissue samples and T-cell immunohistobank related blood and tissue samples collected before, during and after treatment and follow-up will be grouped into sample collection time points. The relationship between MRD status at different time points and treatment efficacy is the primary outcome. Correlation between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence are the secondary outcomes. Examination of ctDNA mutations is the exploratory outcome. Discussion: ctDNA-based MRD may be a potential predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients. Elevated ctDNA-MRD may predict tumor recurrence earlier than imaging. ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment should be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC. Trial registration: The ECMRD-001 study has been registered at ClinicalTrials.gov as NCT05952661 (July 19, 2023), https://classic.clinicaltrials.gov/ct2/show/NCT05952661.

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BACKGROUND: Radioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells. METHODS: Plasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group. RESULTS: The expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX. CONCLUSION: These findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.

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Objective: This study aimed to analyze whether involved field irradiation (IFI) is associated with improving survival outcomes and reducing adverse events compared with elective nodal irradiation (ENI) in patients of esophageal cancer who underwent definitive radiotherapy or chemoradiotherapy. Summary background data: Radiotherapy plays an important role for not surgery patients. However, the role of radiation target size is still uncertain. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Central for English and non-English publications comparing esophageal cancer patients who received radiotherapy with IFI with those with ENI. Primary outcomes included overall survival (OS) and adverse events related to radiotherapy. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality Standard for non-randomized studies. We evaluated the certainty of evidence by Grading of Recommendations, Assessment, Development, and Evaluation. Results: Totally, 23 studies with 4120 patients were included. IFI group demonstrated significant improvement in the OS rates at 5 years, but not at 1, 2, and 3 years, compared with the ENI group (pooled Risk Ratio [RR], 0.78; 95% confidence interval [CI], 0.68-0.90; P = 0.0004; high certainty). In addition, IFI demonstrated a significant decrease in the incidence of grade ≥2 acute esophagitis (AE) (pooled RR, 0.79; 95% CI, 0.69-0.90; P = 0.0005; high certainty) and grade ≥3 AE (pooled RR, 0.51; 95% CI, 0.38-0.69; P < 0.00001; high certainty) compared with ENI, but not in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia. Conclusions: Compared to ENI, IFI demonstrated significant improvement in OS at 5 years. The addition of intensity-modulated radiotherapy (IMRT) to IFI increased the 5-year OS; however, similar results were not observed with the addition of three-dimensional conformal radiotherapy to IFI and ENI. Furthermore, IFI demonstrated a significant decrease in grade ≥2 and grade ≥3 AE, while IMRT demonstrated no difference in the incidence of grade ≥3 AE. IFI and ENI do not differ in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.

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BACKGROUND: To explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway. METHODS AND RESULTS: We observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and RT-qPCR were applied to detect the protein and RNA related to PI3K/Akt/ATM pathway, respectively. In addition, we inhibited the PI3K/Akt pathway with ly294002 and activated it with IGF1, then we explored the invasion, proliferation ability, and apoptosis of esophageal cancer cells in vitro by transwell, CCK8 assay, and flow cytometry respectively. In vivo, xenograft tumor model was established in nude mice to study the effect of HMGB1 on radioresistance via PI3K/AKT/ATM Signaling Pathway. The survival rate in patients with single positive/double negative expression of HMGB1 and p-ATM was significantly higher than in those with both positive expression of HMGB1 and p-ATM, the depletion of HMGB1 combined with ly294002 significantly inhibited cell proliferation and invasion ability, meanwhile, the addition of IGF1 reversed it. Meanwhile, depletion of HMGB1 and ly294002 promoted apoptosis and arrested the cancer cells in G0/G1 cell cycle with the decreased expression of Cyclin D1 and CDK4 and improved P16. We further validated these results in vivo, the application of HMGB1 silencing promoted apoptosis of xenograft tumors after radiation, especially combined with pathway inhibitor ly294002. CONCLUSIONS: Esophageal cancer patients with high expression of HMGB1 and p-ATM have a poor prognosis after chemo-radiotherapy. Down-regulation of HMGB1 may promote the radio-sensitivity of esophageal cancer cells through regulating PI3K/Akt/ATM pathway.

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Purpose: The prognostic effect of postoperative radiotherapy (PORT) on pathological T3N0M0 (pT3N0M0) esophageal squamous cell carcinoma (ESCC) remains inconclusive. This study aimed to retrospectively investigate patterns of failure and whether PORT after R0 resection improves survival in patients with pT3N0M0 ESCC, compared with surgery alone. Patients and methods: The clinical data of 256 patients with pT3N0M0 ESCC from January 2007 to December 2010 were retrospectively reviewed. The included patients were classified into two groups: the surgery-plus-postoperative radiotherapy group (S + R) and the surgery-alone group (S). Propensity score matching (PSM) was used to create comparable groups that were balanced across several covariates (n = 71 in each group). Statistical analyses were performed using the Kaplan-Meier method and Chi-squared test. Results: In the study cohort, the 5- and 10-year overall survival (OS) rates in the S + R group were 53.4% and 38.4%, and those in the S group were 50.3%, 40.9% (p = 0.810), respectively. The 5- and 10-year disease-free survival (DFS) rates in the S + R group were 47.9% and 32.9%, and those in the S group were 43.2%, 24.0% (p = 0.056), respectively. The results were coincident in the matched samples (p = 0.883, 0.081) after PSM. Subgroup analysis showed that patients with upper thoracic lesions in the S + R group had significantly higher OS than patients in the S group (p = 0.013), in addition, patients with upper and middle thoracic lesions in the S + R group had significantly higher DFS than patients in the S group (p = 0.018, 0.049). The results were also confirmed in the matched samples after PSM. The locoregional recurrence between the two groups were significantly different before and after PSM (p = 0.009, 0.002). The locoregional control rate (LCR) in the S + R group was significantly higher than that in the S group before and after PSM (p = 0.015, 0.008). Conclusion: Postoperative radiotherapy may be associated with a survival benefit for patients with pT3N0M0 upper thoracic ESCC. A multicenter, randomized phase III clinical trial is required to confirm the results of this study.

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Objective: To analyze and compare the efficacy and safety of simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic and standardized management for esophageal cancer. Methods: From January 2012 to January 2019, 200 patients with esophageal cancer who received radical chemoradiotherapy in our hospital were treated with lymphatic drainage area radiation prevention combined with systematic and standardized management. According to difference in radiotherapy methods, the patients were divided into local lesion 92 patients treated with simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic standardized management (SIB-IMRT group), and late course boost intensity-modulation radiation therapy (LCB-IMRT) combined with systematic standardized management 108 patients (LCB-IMRT group). The short-term eficacy of the two groups were compared. The dose volume parameters of the organ in danger are evaluated based on the dose volume histogram. The related adverse reactions during chemoradiotherapy were compared between two groups. The local control rate and survival rate were compared between the two groups. Results: The recent total effective rates of rats in the SIB-IMRT group and LCB-IMRT group were 95.65% and 90.74%, respectively, and there was no significant difference between the two groups (p > 0.05). The mean doses to left and right lung, heart and spinal cord in the SIB-IMRT group were significantly lower than that in the LCB-IMRT group (p < 0.05). There was no significant difference in the incidence of adverse reactions such as radiation esophagitis, radiation pneumonitis, radiation tracheitis, gastrointestinal reaction and bone marrow suppression between the SIB-IMRT group and LCB-IMRT groups (p > 0.05). The one-year and three-year overall survival rates in the SIB-IMRT group and LCB-IMRT groups were 82.61%, 42.39% and 77.78%, 34.26%, respectively, and the median survival times were 38 and 29 months, respectively. The local control rates in the SIB-IMRT group and LCB-IMRT group in one and three years were 84.78%, 56.52% and 75.93%, 41.67%, respectively. The 3-year local control rate in the SIB-IMRT group was higher than that in the LCB-IMRT group (p < 0.05), but there was no significant difference in the 1-and 3-year overall survival rates between the two groups (p > 0.05). Conclusion: SIB-IMRT combined with systematic and standardized management in the treatment of esophageal cancer can reduce the amount of some organs at risk and improve the local control rate of the lesion.

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BACKGROUND: The preoperative prognostic nutritional index (PNI) is associated with postoperative complications and long-term survival of various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting survival in ESCC patients undergoing radical radiotherapy. METHODS: We retrospectively reviewed 354 ESCC patients undergoing radical radiotherapy. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value. The association between PNI and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching was applied to balance the baseline characteristics. RESULTS: PNI was positively correlated with hemoglobin (P < 0.001) and prealbumin (P < 0.001). The optimal cutoff value of PNI was set at 50.5. The 5-year overall survival (OS) in low PNI group and high PNI group were 20.8% and 34.0%, respectively (P < 0.001). The 5-year progression free survival in patients with low PNI and high PNI were 15.2% and 28.5%, respectively (P = 0.001). Multivariate analysis showed that PNI was a significant predictor for OS (P = 0.038). In the PSM analysis, PNI still remained an independent predictor for OS (P = 0.015). CONCLUSIONS: The PNI is a significant and independent predictor for OS of ESCC patients undergoing radical radiotherapy.

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Forward osmosis (FO) has drawn wide attention as a promising method to address world-wide water crisis due to the advantages of low-energy consumption and easy separation operation. Unfortunately, the trade-off between permeability and selectivity as well as membrane fouling hindered the application of forward osmosis. Surface modification is a feasible method to address these issues. However, there is a lack of systematic evaluation about the effect of modification position on FO performance due to the asymmetric structure of thin film composite (TFC) FO membrane. To provide new insights into the design of FO membrane with satisfied permeability and fouling resistance, novel TFC FO membranes were fabricated by introducing polydopamine (PDA) on the support layer (TFC-I) or active layer (TFC-S), respectively. The surface morphology, chemical composition and wettability of the fabricated membrane were studied. It was found that the surface wettability of the modified membrane was improved greatly compared to pristine TFC membrane (TFC-C). Moreover, TFC-S membrane displayed a rougher surface than that of TFC-I membrane. As a result, a superior TFC-S membrane with a water flux of 60.95 ± 3.15 L m-2h-1 in AL-DS mode was obtained, which was 72.61% and 17.87% higher than that of TFC-C and TFC-I membrane, respectively. In addition, the TFC-S membrane also presented an excellent fouling resistance and membrane regeneration performance during the three organic fouling cycle experiments. The results indicated that the introduction of PDA as a surface coating for TFC membranes modification guaranteed the high-performance and fouling resistance. Especially, the PDA coating on the support layer surface resulted in an enhancement in permeability, while both the permeability and anti-fouling performance were significantly improved with the PDA coating on the polyamide active layer surface. This study provides new insights into the development of modification TFC-FO membranes for practical applications in water treatment.

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Patients with familial hypercholesterolemia (FH) are susceptible to premature coronary artery disease. We generated a human iPSC line CIBi009-A from a patient with FH who carried variants of LDLR c.T1241G and APOB c.G1618T. This line will be a valuable resource for investigating novel therapeutic approaches to FH.

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The protein expression levels of Ring finger protein 2 (RNF2) and phosphor-protein kinase B (P-AKT) were determined in esophageal squamous cell carcinoma (ESCC) tissues, and the association between patient clinicopathological characteristics and survival time following definitive intensity-modulated radiotherapy was assessed. Cancerous biopsy tissues were collected from patients with ESCC at The Fourth Affiliated Hospital of Hebei Medical University between January 2010 and December 2013. Of these 99 cases, 83 were used to analyze the protein expression level of RNF2 (89.2% positive), 85 for P-AKT (65.9% positive) and 80 for RNF2+P-AKT protein expression levels (62.5% both positive). The expression levels of RNF2 protein in ESCC were associated with tumor volume (P=0.024), whilst those of P-AKT and RNF2+PAKT were associated with sex (P=0.041 and P=0.003, respectively). There were no significant differences in overall survival (OS) or progression-free survival (PFS) rate between the RNF2- and the RNF2+-+++ groups (P=0.134 and P=0.366, respectively), or between the P-AKT- group and P-AKT+-+++ group (P=0.468; P=0.580, respectively). The 1-, 3- and 5-year OS rates were 68.0, 28.0, and 20.0%, and 86.7, 53.3, and 31.1%, in the RNF2/P-AKT+ group and Other group, respectively (χ2=4.205; P=0.040). Multivariate analysis revealed that age, T stage and RNF2+P-AKT expression were independent prognostic factors for ESCC (P=0.010, P=0.008 and P=0.010, respectively). The expression of RNF2+P-AKT combined was an independent prognostic factor affecting survival rate, and therefore presents a potential prognostic indicator for patients with ESCC, treated with definitive radiotherapy.

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Transketolase-like-1 (TKTL1), which is a rate-limiting enzyme in the non-oxidative part of the pentose-phosphate pathway, has been demonstrated to promote carcinogenesis through enhanced aerobic glycolysis. Dysregulation of TKTL1 expression also leads to poor prognosis in patients with urothelial and colorectal cancer. However, the expression pattern and underlying cellular functions in human esophageal squamous cell carcinoma (ESCC) remain largely unexplored. In this study, we measured TKTL1 expression in ESCC cell lines and paraffin-embedded ESCC tumor tissues. Our results revealed that TKTL1 expression was upregulated in all of the four ESCC cell lines and in 61.25% (98/160) of ESCC specimens detected, while only 27.5% (11/40) in normal epithelium. Silencing of TKTL1 expression decreased cell proliferation through inhibiting the expression of MKI67 and cyclins including Ccna2, Ccnb1, Ccnd1 and Ccne1. Meanwhile, down-regulation of TKTL1 also associated with increased apoptotic ratio and altered protein expression of Bcl-2 family in ESCC cells. Furthermore, knockdown of TKTL1 significantly reduced the invasive potential of ESCC cells through up-regulation of anti-metastasis genes (MTSS1, TIMP2 and CTSK) and down-regulation of pr-metastasis genes (MMP2, MMP9, MMP10 and MMP13). Taken together, our results indicate that TKTL1 is associated with a more aggressive behavior in ESCC cells and suppresses its expression or enzyme activity might represents a potential target for developing novel therapies in human ESCCs.

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Immunological stress is the status of animal in active immune when they are challenged by bacterial, virus and endocrine. It is associated with immunological, neurological, and endocrinological response. An immunological stress model was established in this study using Chinese indigenous breed (Laiwu), crossbred (Lulai), and exotic breed (Yorkshire), to explore the capacity of immunological stress resistance among different breeds. The study was also to reveal the effect of chromium yeast to immunological stress. 48 post-weaning piglets were taken from three breeds, 16 piglets of each breed from Laiwu, Lulai and Yorkshire. The experiment was designed as 2 × 2 factors, immunological stress (Saline, LPS) and Chromium (with Cr, without Cr). There were four treatments: control, LPS, Cr, and Cr+LPS. Blood parameters related to immunological stress, such as IL-1ß, TNF-α, GH, and cortisol, were examined after blood sample were taken at 0, 2, 5, and 7 h of post-injection. The results showed that IL-1ß, TNF-α, and cortisol increased in group of LPS treatment while GH declined at 2 h of post-injection in comparison to the control (p < 0.01). However, IL-1ß, TNF-α, and cortisol in group of Cr+LPS were lower than that in group of LPS while GH were higher (p < 0.05). Total RNA was extractedfrom blood lymphocytes separation samples at 2 h of post-injection. Q-PCR was applied to determine the gene expression of IL-1ß, IL-6 and TNF-α. The results showed that LPS injection increased the gene expression of IL-1ß, IL-6 and TNF-α. Among three breeds, the expression of IL-1ß, IL-6 and TNF-α in Yorkshire were significantly higher than in Laiwu and Lulai (p < 0.05), but there was no difference between Laiwu and Lulai. Among four treatments, the expression of three genes in group of LPS was the highest, compared to the group of Cr+LPS (p < 0.05) and control (p < 0.01). This study concluded that Laiwu had stronger capacity of immunological stress resistance and next was Lulai among three breeds. Chromium yeast helped piglets relieve immunological stress.

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The score is a symbolic encoding that describes a piece of music, written according to the conventions of music theory, which must be rendered as sound (e.g., by a performer) before it may be perceived as music by the listener. In this paper we provide a step towards unifying music theory with music perception in terms of the relationship between notated rhythm (i.e., the score) and perceived syncopation. In our experiments we evaluated this relationship by manipulating the score, rendering it as sound and eliciting subjective judgments of syncopation. We used a metronome to provide explicit cues to the prevailing rhythmic structure (as defined in the time signature). Three-bar scores with time signatures of 4/4 and 6/8 were constructed using repeated one-bar rhythm-patterns, with each pattern built from basic half-bar rhythm-components. Our manipulations gave rise to various rhythmic structures, including polyrhythms and rhythms with missing strong- and/or down-beats. Listeners (N = 10) were asked to rate the degree of syncopation they perceived in response to a rendering of each score. We observed higher degrees of syncopation in time signatures of 6/8, for polyrhythms, and for rhythms featuring a missing down-beat. We also found that the location of a rhythm-component within the bar has a significant effect on perceived syncopation. Our findings provide new insight into models of syncopation and point the way towards areas in which the models may be improved.

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