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Objective:To investigate the effects of pre-treatment Naples prognostic score (NPS), including inflammation-related and nutrition-related indicators, on the treatment efficacy and prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC) receiving chemoradiotherapy.Methods:A retrospective analysis was conducted for 123 patients diagnosed with thoracic ESCC. These patients were treated either with standard curative radiotherapy (RT) alone or with concurrent chemoradiotherapy (CCRT) in the Affiliated Taixing People's Hospital of Yangzhou University between January 2014 and December 2017. The patients were divided into NPS 0 group (18 cases), NPS 1 or 2 group (60 cases), and NPS 3 or 4 group (45 cases). The responsiveness to treatment was analyzed using logistic regression analysis. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the progression-free survival (PFS) and overall survival (OS) rates. Meanwhile, Cox proportional hazards models were used for the multivariate analyses.Results:The overall effective rate across the entire cohort was 65.0%, and the effective rates of the NPS 0 group, NPS 1 or 2 group, and NPS 3 or 4 group were 88.9%, 73.3%, and 44.4%, respectively. As indicated by the univariate logistic analysis, the treatment responses in patients with ESCC were highly associated with TNM stage, treatment method, neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and NPS (1 or 2 group and 3 or 4 group) ( HR =1.633, 0.225, 4.002, 0.320, 2.909, 6.591, P<0.05). Subsequently, multivariate logistic regression analysis showed that treatment strategy alone ( HR =0.214, 95% CI 0.105-0.436, P=0.001), NLR ( HR =2.547, 95% CI 1.248-5.199, P=0.010), and NPS (1 or 2 group: HR=1.193, 95% CI 1.377-9.691, P=0.033; 3 or 4 group: HR =3.349, 95% CI 1.548-10.499, P=0.003) were independent risk factors for tumour response. In addition, the univariate analysis indicates that TNM stage, treatment modality, NLR, LMR, and NPS were significantly associated with PFS and OS( HRPFS=1.480, 0.364, 2.129, 0.635, 3.316, 6.599, P < 0.05; HROS=1.149, 0.308, 2.306, 0.609, 3.316, 6.599, P < 0.05). Furthermore, multivariate Cox proportional hazard regression model analysis showed that TNM stage ( HR =1.408, 95% CI 1.069-1.854, P=0.015), treatment modality ( HR =0.367, 95% CI 0.261-0.516, P=0.015), NLR ( HR =1.518, 95% CI 1.078-2.139, P=0.017), and NPS (1 or 2 group: HR=3.279, 95% CI 1.405-7.653, P=0.006; 3 or 4 group: HR =6.233, 95% CI 2.439-15.875, P < 0.001) were considered independent prognostic factors for PFS. Additionally, these parameters were also independent prognostic factors for OS. Conclusions:Using inflammation-related and nutrition-related biomarkers, this study demonstrated that NPS is promising as a predictive indicator for the therapeutic effects and survival prognosis in patients with ESCC receiving CRT or RT alone.
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Objective:To explore the impact of preoperative Naples prognostic score (NPS) on the survival prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC).Methods:From December 2014 to December 2020, a total of 134 patients who underwent radical esophagectomy in Department of Thoracic Surgery, Affiliated Taixing People′s Hospital of Yangzhou University were retrospectively analyzed. The NPS was calculated by the median values of preoperative serum albumin, total cholesterol, neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR), and then the enrolled patients were divided into NPS 0 group (20 cases), NPS 1 or 2 group (62 cases) and NPS 3 or 4 group (52 cases). Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univa-riate and multivariate Cox models were used to analyze the relationship between NPS and survival prognosis.Results:The 1-, 3- and 5-year progression free survival (PFS) rates were 95.0%, 70.0% and 60.0% in the NPS 0 group, 66.1%, 24.2% and 24.2% in the NPS 1 or 2 group, and 48.1%, 3.8% and 1.9% in the NPS 3 or 4 group respectively, with a statistically significant difference ( χ2=31.27, P<0.001). In the NPS 0 group, the 1-, 3- and 5-year overall survival (OS) rates were 100.0%, 80.0% and 70.0% respectively. In the NPS 1 or 2 group, the 1-, 3- and 5-year OS rates were 96.8%, 36.7% and 32.3% respectively, while in the NPS 3 or 4 group, the 1-, 3- and 5-year OS rates were 90.4%, 32.7% and 5.8% respectively, and there was a statistically significant difference ( χ2=29.70, P<0.001). Univariate analysis found that sex, T stage, N stage, TNM stage and NPS were closely related to PFS and OS of patients with thoracic ESCC (all P<0.05). Furthermore, multivariate Cox regression analysis showed that T stage ( HR=1.46, 95% CI: 1.07-2.00, P=0.019), N stage ( HR=1.34, 95% CI: 1.02-1.76, P=0.037) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.35, 95% CI: 1.58-7.11, P=0.002; NPS 3 or 4 group: HR=6.15, 95% CI: 2.89-13.11, P=0.001) were independent prognostic factors for PFS. Additionally, T stage ( HR=1.67, 95% CI: 1.01-2.77, P=0.046), N stage ( HR=1.44, 95% CI: 1.00-2.20, P=0.048) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.10, 95% CI: 1.31-7.32, P=0.010; NPS 3 or 4 group: HR=5.09, 95% CI: 2.14-12.11, P=0.001) were independent prognostic factors for OS. Conclusion:Preoperative NPS plays an important role in predicting the survival prognosis of patients with thoracic ESCC.
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Objective:To explore the impact of the number of pathological lymph node metastasis areas on the prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC) after radical surgery.Methods:The clinicopathologic data of 153 patients with ESCC treated by radical surgery at the Department of Thoracic Surgery of the Affiliated Taixing People′s Hospital of Yangzhou University from January 2012 to December 2014 were retrospectively analyzed. Among these patients, 76 had no adjuvant therapy, and 77 received adjuvant radiotherapy or chemoradiotherapy after surgery. According to the lymph node classification criteria of American Thoracic Association and the number of pathological lymph node metastasis areas, the patients were divided into non-regional lymph node metastasis group ( n=68), oligo-regional lymph node metastasis group (1-2 regional lymph node metastasis, n=54) and multi-regional lymph node metastasis group (≥3 regional lymph node metastasis, n=31). Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The Cox proportional hazards model was used to analyze prognostic factors, receiver operating characteristic (ROC) curve was used to analyze the predictive value of the number of lymph node metastasis areas. Results:The median overall survival (OS) was 37.0 months for the 153 patients, and the 1-, 3- and 5-year OS rates were 97.4%, 51.0% and 30.7% respectively. In the non-regional lymph node metastasis group, the median OS was 46.0 months, and the 1-, 3- and 5-year OS rates were 97.1%, 58.8% and 39.7% separately. In the oligo-regional lymph node metastasis group, the median OS was 39.0 months, and the 1-, 3- and 5-year OS rates were 94.4%, 55.6% and 35.2% respectively. In the multi-regional lymph node metastasis group, the median OS was 26.0 months, and the 1-, 3- and 5-year OS rates were 98.1%, 25.8% and 3.2% separately. There was a statistically significant difference among the three groups ( χ2=18.257, P<0.001). Among the 76 patients without adjuvant treatment, the 1-, 3- and 5-year OS rates were 94.7%, 50.0% and 34.2% in patients with non-regional lymph node metastasis, 90.9%, 36.4% and 9.1% in patients with oligo-regional lymph node metastasis, 97.4%, 18.8% and 0 in patients with multi-regional lymph node metastasis, and there was a statistically significant difference ( χ2=8.201, P=0.017). Among the 77 patients with adjuvant therapy, the 1-, 3- and 5-year OS rates were 97.7%, 66.7% and 46.7% in patients with non-regional lymph node metastasis, 96.9%, 68.8% and 53.1% in patients with oligo-regional lymph node metastasis, 93.3%, 26.7% and 6.7% in patients with multi-regional lymph node metastasis, and there was a statistically significant difference ( χ2=18.083, P<0.001). Univariate analysis showed that age ( HR=1.534, 95% CI: 1.041-2.260, P=0.030), T stage ( HR=1.757, 95% CI: 1.197-2.579, P=0.004), N stage ( HR=1.548, 95% CI: 1.043-2.297, P=0.030), TNM stage ( HR=1.392, 95% CI: 1.114-2.459, P=0.015), adjuvant therapy ( HR=0.545, 95% CI: 0.370-0.803, P=0.002) and number of lymph node metastasis areas (multi-regional lymph node metastasis versus non-regional lymph node metastasis: HR=0.385, 95% CI: 0.238-0.624, P<0.001; multi-regional lymph node metastasis versus oligo-regional lymph node metastasis: HR=0.442, 95% CI: 0.269-0.726, P=0.001) were closely related to OS in patients with ESCC after operation. Multivariate analysis showed that T stage ( HR=1.699, 95% CI: 1.143-2.525, P=0.009), adjuvant therapy ( HR=0.577, 95% CI: 0.386-0.864, P=0.008) and number of lymph node metastasis areas (multi-regional lymph node metastasis versus non-regional lymph node metastasis: HR=0.553, 95% CI: 0.411-0.996, P=0.011; multi-regional lymph node metastasis versus oligo-regional lymph node metastasis: HR=0.550, 95% CI: 0.328-0.924, P=0.024) were independent prognostic factors for OS. The number of lymph node metastasis areas (AUC=0.648, 95% CI: 0.560-0.735, P=0.004) was better than the number of lymph node metastasis (AUC=0.595, 95% CI: 0.497-0.694, P=0.061) in predicting OS of patients with ESCC after radical surgery. Conclusion:The number of postoperative pathological lymph node metastasis areas in thoracic ESCC has important value in predicting survival prognosis, and adjuvant therapy can significantly improve the OS of patients with oligo-regional lymph node metastasis.
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Objective:To analyze the correlation between the Naples prognostic score (NPS) after preoperative neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC) and evaluate the prognostic value of NPS in LARC.Methods:136 patients with LARC meeting the recruitment criteria from 2015 to 2020 were selected. Serum albumin, total cholesterol (TC) were collected and neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio were calculated. All patients were scored and graded according to the NPS rule. The survival rate was calculated with Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox models. Results:There was no significant correlation between NPS score and tumor regression or pathological complete response (pCR) of LARC patients after neoadjuvant therapy ( P=0.192, P=0.163). However, Cox multivariate analysis showed that NPS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) of LARC ( P=0.009, P=0.003), and hierarchical analysis suggested that LARC patients with lower NPS score obtained better prognosis. Besides NPS, tumor size was also an independent risk factor for OS, and tumor size and N stage were the independent risk factors for DFS. Conclusion:NPS has no correlation with tumor regression or pCR for LARC after neoadjuvant chemoradiotherapy, whereas it could serve as an effective predictor for long-term prognosis of LARC.
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Objective:To explore the changes of dendritic spine morphology and structure in dentate gyrus(DG) and CA1 areas of hippocampus of young rats, so as to provide a direct morphological basis for studying the molecular mechanism of radiation cognitive impairment.Methods:21-day-old Sprague-Dawley (SD) rats were given a single dose of 10 Gy whole brain irradiation. The changes of cognitive function, dendritic spine density and morphological changes in DG and CA1 areas of hippocampus were observed 1 and 3 months after irradiation, and the expression of postsynaptic density protein (PSD95) was detected by Western blot.Results:The cognitive impairment was observed in young rats 3 months after irradiation. The density of dendritic spines in DG area of hippocampus was decreased significantly by 39.06% and 29.27% at 1 and 3 months after irradiation ( t=14.96, 12.35, P<0.05), respectively. The density of dendritic spines in the basal dendrites of hippocampal CA1 area was decreased by 33.40% ( t=10.39, P<0.05) 1 month after irradiation, but had no significant change at 3 months after irradiation. While the density of dendritic spines in the apical dendrites of CA1 region did not change significantly at 1 and 3 months after irradiation. In addition, the morphology of dendritic spines in DG and CA1 regions of hippocampus was dynamically changed after irradiation. The expression of PSD95 protein was decreased by 24.6% and 50.5% ( t=2.97, 9.27, P<0.05) at 1 and 3 months after irradiation, respectively. Conclusions:This study reported the density and morphological changes of dendritic spines in different brain regions of hippocampus of young rats after ionizing radiation, suggesting that PSD95 may participate in the occurrence of radiation-induced cognitive impairment by affecting the structure and morphology of dendritic spines and reducing synaptic plasticity.
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Objective:To investigate whether TNM staging combined with systemic immune inflammation index (SII) has a high predictive value for the clinical prognosis of elderly patients with esophageal cancer.Methods:Clinical data of 118 elderly patients with esophageal cancer who received radiotherapy and chemotherapy were retrospectively analyzed, and the SII was calculated. SII and clinicopathological features were included in the Cox proportional risk model, and the prognostic index (PI) equation was obtained. Kaplan- Meier survival analysis was adopted. According to PI, the survival of patients was predicted and the predictive values of PI and TNM were statistically compared. Results:Univariate analysis showed that SII, N staging and TNM staging were closely correlated with the overall survival (all P<0.01). Cox multivariate analysis revealed that SII and N staging were the independent risk factors for overall survival. According to the results of Cox analysis, the equation of PI=0.961 × SII grouping+ 0.523 × N staging was obtained. The receiver operating characteristic (ROC) curve was drawn according to PI and overall survival, and the critical value was obtained and divided into different groups. The 1-, 2-and 3-year survival rates in the low-risk group were significantly higher than those in the high-risk group ( HR=0.365, 95% CI: 0.221-0.604, P<0.001). The prediction of overall survival by SII-N[area under curve (AUC)=0.707] was significantly better than that by TNM staging (AUC=0.560, P<0.001). Conclusion:This study preliminarily proves that the SII-N prognosis score model is better than the traditional TNM staging, which may have guiding significance for the selection of therapeutic strategies for elderly patients with esophageal cancer, and is worthy of further study.
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Objective:To explore the influence of clinicopathological factors besides TNM stage, including preoperative tumor volume, length and maximum diameter, on survival prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC), and to evaluate the predictive survival rate of clinicopathological variables with statistical significance by nomogram.Methods:A total of 296 patients with ESCC treated by radical resection at the Department of Thoracic Surgery of Affiliated Taixing People′s Hospital of Yangzhou University from 2011 to 2014 were retrospectively analyzed. These patients were grouped for further analysis according to the optimal threshold of preoperative tumor volume, length and maximum diameter. Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univariate and multivariate Cox models were used to analyze the relationships between clinical variables and survival prognosis. Finally, nomogram model was established by integrating statistically significant clinicopathological parameters, and the predictive value of this model was further verified by calibration curve, concordance index (C-index) and decision curve.Results:The optimal thresholds of preoperative tumor volume were 32 cm 3 and 72 cm 3 by X-tile analysis, and among the patients whose tumor volume was <32 cm 3 ( n=94), the 1-, 3- and 5-year survival rates were 100%, 84.0% and 68.1%; in the 32-72 cm 3 group ( n=118), the 1-, 3- and 5-year survival rates were 98.3%, 42.4% and 24.6%; in the >72 cm 3 group ( n=84), the 1-, 3- and 5-year survival rates were 94.1%, 25.0 and 7.1% ( χ2=86.639, P<0.001). The optimal cutoff values of tumor length were 3.0 cm and 5.0 cm, and among the patients with tumor length <3.0 cm ( n=62), the 1-, 3-, and 5-year survival rates were 99.5%, 87.1% and 69.4%; in the 3.0-5.0 cm group ( n=146), the 1-, 3-, and 5-year survival rates were 98.6%, 47.9% and 30.1%; in the >5.0 cm group ( n=88), the 1-, 3-, and 5-year survival rates were 94.3%, 29.6%, 13.6%, respectively ( χ2=53.607, P<0.001). The thresholds of tumor maximum diameter were 2.5 cm and 3.5 cm, and among these, the 1-, 3- and 5-year survival rates were 99.5%, 84.3% and 74.5% in the maximum diameter <2.5 cm group ( n=51); 98.3%, 57.0% and 36.4% in the 2.5-3.5 cm group (n=121); and 96.0%, 29.0% and 13.7% in the maximum diameter >3.5 cm group ( n=124, χ2=62.109, P<0.001). In univariate analysis, the following factors were significantly associated with overall survival (OS): tumor location, differentiation grade, T stage, N stage, TNM stage, adjuvant therapy, preoperative tumor volume, length and maximum diameter (all P<0.05). Furthermore, multivariate Cox regression analysis showed that differentiation grade ( HR=0.514, 95% CI: 0.366-0.723, P=0.019), TNM stage ( HR=1.757, 95% CI: 1.267-2.612, P=0.015), adjuvant therapy ( HR=0.669, 95% CI: 0.503-0.889, P=0.006), preoperative tumor volume (set <32 cm 3 as the dummy variable, 32-72 cm 3: HR=3.689, 95% CI: 2.415-5.637, P<0.001; >72 cm 3: HR=5.720, 95% CI: 3.606-9.075, P<0.001) were independent risk factors for OS. Finally, the C-index of OS by nomogram incorporated the statistically significant clinicopathological parameters was predicted to be 0.722 (95% CI: 0.687-0.757), which was significantly higher than the 7th AJCC TNM stage, the C-index 0.633 (95% CI: 0.595-0.671). In addition, the calibration curve of nomogram model was highly consistent with actual observation for the five-year OS rate, and the decision curve analysis also showed that nomogram model had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic ESCC after surgery. Conclusion:The nomogram incorporated preoperative tumor volume is of great value in predicting survival prognosis of patients with thoracic ESCC.
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Objective The purpose of this study was to investigate the influence of pre-treatment inflammatory markers on the therapeutic effect and survival outcome in patients with esophageal squamous cell carcinoma (ESCC) who received chemoradiotherapy (CRT) or radiotherapy (RT) alone.Methods A total of 107 patients who were diagnosed with ESCC were retrospectively analysed.They were treated with radical radiotherapy alone or concurrent chemoradiotherapy in the Affiliated Taixing People's Hospital of Yangzhou University between January 2013 and December 2014.According to the median values of neutrophil-lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR) and CRP/Alb ratio before treatment,the patients were divided into NLR＜3.06 group (54 cases) and NLR≥3.06 group (53 cases),PLR＜145.26 group (54 cases) and PLR≥ 145.26 (53 cases),CRP/Alb＜0.13 group (52 cases) and CRP/Alb≥0.13 (55 cases),respectively.The relationships between the response to treatment and these markers were analysed by univariate and multivariate logistic analyses.The Kaplan-Meier method and logrank test were adopted to calculate and compare associations of the progression-free survival (PFS) rates with these blood markers.Cox proportional hazards models were used for the univariate and multivariate analyses.Results The therapeutic effects of chemoradiotherapy,NLR＜3.06,PLR＜ 145.26 and CRP/ Alb＜ 0.13 were better than those of radiotherapy alone,NLR≥ 3.06,PLR≥ 145.26 and CRP/Alb ≥ 0.13,respectively,and the differences were statistically significant (HR=2.118,4.138,2.297,3.784,P＜0.05).Further analysis showed that chemoradiotherapy (HR =1.342,95％ CI 1.023 ～ 2.467,P＜ 0.05) and CRP/Alb ratio＜ 0.13 (HR =7.004,95％ CI 2.088 ～ 23.496,P＜0.05) were independent risk factors for good tumour response.In addition,TNM stage,treatment modality,NLR,PLR and CRP/Alb ratio were significantly associated with PFS by the univariate analysis (P＜0.05 for all).Furthermore,the multivariate Cox proportional hazard regression model analysis showed that only TNM stage (HR =1.326,95％ CI 1.070-1.833 P＜0.05),treatment modality (HR =0.400,95％ CI 0.230-0.694,P＜0.05) and CRP/Alb ratio (HR=3.518,95％ CI 1.975-6.266,P＜ 0.05) were considered independent prognostic factors for PFS.And according to TNM staging and treatment subgroup analysis,CRP/Alb＜0.13 had better progression-free survival time than CRP/Alb≥ 0.13 ESCC patients.Finally,the ROC curve also confirmed that CRP/Alb was superior to NLR and PLR in predicting short-term efficacy and progression-free survival in ESCC patients receiving chemoradiotherapy.Conclusions Our study demonstrated that CRP/Alb ratio was promising as a predictive marker for the therapeutic effect and survival outcome in ESCC patients receiving CRT or RT alone.
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Objective@#To evaluate preoperative nutritional status and inflammatory status by Nutritional Risk Screening-2002 (NRS-2002) and hematologic inflammatory markers in patients with thoracic esophageal squamous cell carcinoma (ESCC), and to explore their effects on long-term survival prognosis.@*Methods@#A total of 113 patients with thoracic ESCC treated by radical resection were grouped for further analysis according to preoperative NRS-2002 score, systemic inflammation score (SIS) and the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (CNP) score. The progression free survival (PFS) and overall survival (OS) between groups were compared. Multivariate Cox regression analysis was used to determine the independent prognostic factors of patients with thoracic esophageal squamous cell carcinoma, and the interaction analysis of statistically significant factors was carried out.@*Results@#The median PFS was 21 months for all the patients. The 1-year, 3-year and 5-year PFS rates were 69.0%, 25.7% and 23.1%, respectively. Correspondingly, the median OS was 36 months, and the 1-year, 3-year and 5-year OS rates were 95.6%, 46.2% and 29.2%, respectively. Cox univariate analysis showed that T stage, N stage, TNM stage, SIS, CNP score and NRS-2002 score were significantly associated with PFS and OS (all P<0.05), and sex was associated with PFS (P=0.032) in patients with thoracic ESCC. Furthermore, cox multivariate analysis showed that TNM stage (HR=1.570, P=0.039), NRS-2002 score (HR=2.706, P<0.001) and CNP score (HR=1.463, P=0.011) were independent prognosis factors of PFS in patients with thoracic ESCC. In cox model interaction analysis, there was a positive interaction between NRS-2002 score and CNP score (RR=2.789, P<0.001).@*Conclusion@#Preoperative NRS-2002 score combined with CNP score are risk factors for prognosis of patients with thoracic ESCC, which can be used as prognostic indicators.
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Objective@#To evaluate the role of prognostic nutritional index (PNI) in the radiotherapy for elderly patients with esophageal squamous cell carcinoma.@*Methods@#Clinical data of 108 elderly patients (aged>65 years) with esophageal squamous cell carcinoma who underwent radical radiotherapy were retrospectively analyzed. The PNI value of each patient was calculated, and the optimal cutoff value of PNI before treatment was determined by establishing the receiver operating characteristic curve (ROC curve). All patients were divided into the low and high PNI value groups. The overall survival rate was calculated by Kaplan-Meier method. Log-rank test, univariate and Cox’s multivariate prognosis analyses were performed.@*Results@#The ROC curve demonstrated that the optimal cutoff value of PNI was 50.1(n=52 in high PNI group and n=56 in low PNI group). Age, gender and treatment did not significantly differ between two groups, whereas the TNM staging significantly differed (P=0.022). The effective rate of radiotherapy in the high PNI group was 96%, significantly higher than 73% in the low PNI group (P=0.001). In the high PNI group, the 1-, 2-, and 3-year overall survival rates were 94%, 69%, and 62%, significantly higher compared with 70%, 32% and 27% in the low PNI group (all P<0.001). Univariate analysis showed that PNI, T staging, N staging and TNM staging were significantly correlated the overall survival of patients (all P<0.01). Cox’s multivariate analysis revealed that N staging (RR=1.94, 95%CI=1.29-2.94, P=0.002) and PNI (RR=0.83, 95%CI=0.77-0.90, P<0.001) were independent risk factors affecting overall survival.@*Conclusions@#PNI before treatment has a good correlation with the prognosis and radiotherapy efficacy of patients, which can be used as a pivotal index to predict the clinical benefit of radiotherapy for elderly patients with esophageal squamous cell carcinoma.
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OBJECTIVE： To screen and characterize effective components of immunopotentiating activity in Senecionis cannabifolii Herba. METHODS： The polysaccharide components were obtained by water extraction and alcohol precipitation method to yield 50％ alcohol precipitation sample （SCHE-1） and 80％ alcohol precipitation sample （SCHE-2）. The cells from mice mononuclear macrophage line RAW264.7 were divided into blank group （medium without serum）， negative control group （medium with serum）， lipopolysaccharide group （LPS， positive control drug， 1 μg/mL）， SCHE-1 and SCHE-2 low-dose and high-dose groups （0.5， 1 mg/mL）. The cell viability of RAW264.7 cells was detected by MTT assay. The levels of IL-1β， IL-6 and TNF-α in RAW264.7 were detected by ELISA. These were used to investigate the effects of SCHE-1 and SCHE-2 on the immunological enhancing activity of RAW264.7 cells. The molecular weight and distribution of SCHE-1 were determined by size exclusion chromatography； the monosaccharide composition of SCHE-1 was determined by HPLC pre-column derivatization. Methylation analysis of SCHE-1 was conducted by NaOH method. RESULTS： Compared with negative control group， the activity of RAW264.7 cells was enhanced significantly in SCHE-1 groups and LPS group， which also significantly increased the levels of IL-1β， IL-6 and TNF-α in cell culture fluids （P＜0.01）. SCHE-1 was an effective component with immunopotentiating activity. The neutral sugar content of SCHE-1 was 40.05％， the uronic acid was 35.62％， and the protein was 8.89％. SCHE-1 was a mixture， molecular weight of which was 62-6 119 Da； monosaccharide was mainly composed of galacturonic acid， arabinose （Ara） and galactose （Gal）. The results of methylation analysis showed that the backbone was composed of 1→3， 1→4 and 1→6 linked Gal， and branches were on the O-6 position of the 1→3 linked Gal， and the non-reducing terminals were Ara. CONCLUSIONS： SCHE-1 may be the effective component of immuno potentiating activity， and main component of SCHE-1 is polysaccharide. SCHE-1 may regulate the immune function by activating macrophages to release IL-1β， IL-6 and TNF-α.
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Objective To evaluate the role of prognostic nutritional index (PNI) in the radiotherapy for elderly patients with esophageal squamous cell carcinoma.Methods Clinical data of 108 elderly patients (aged ＞ 65 years) with esophageal squamous cell carcinoma who underwent radical radiotherapy were retrospectively analyzed.The PNI value of each patient was calculated,and the optimal cutoff value of PNI before treatment was determined by establishing the receiver operating characteristic curve (ROC curve).All patients were divided into the low and high PNI value groups.The overall survival rate was calculated by Kaplan-Meier method.Log-rank test,univariate and Cox's multivariate prognosis analyses were performed.Results The ROC curve demonstrated that the optimal cutoff value of PNI was 50.1 (n =52 in high PNI group and n=56 in low PNI group).Age,gender and treatment did not significantly differ between two groups,whereas the TNM staging significantly differed (P=0.022).The effective rate of radiotherapy in the high PNI group was 96％,significantly higher than 73％ in the low PNI group (P=0.001).In the high PNI group,the 1-,2-,and 3-year overall survival rates were 94％,69％,and 62％,significantly higher compared with 70％,32％ and 27％ in the low PNI group (all P＜0.001).Univariate analysis showed that PNI,T staging,N staging and TNM staging were significantly correlated the overall survival of patients (all P＜ 0.01).Cox's multivariate analysis revealed that N staging (RR =1.94,95％CI=1.29-2.94,P=0.002) and PNI (RR=0.83,95％CI=0.77-0.90,P＜0.001) were independent risk factors affecting overall survival.Conclusions PNI before treatment has a good correlation with the prognosis and radiotherapy efficacy of patients,which can be used as a pivotal index to predict the clinical benefit of radiotherapy for elderly patients with esophageal squamous cell carcinoma.
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Objective To investigate the prognostic values of systemic inflammatory markers,including preoperative neutrophil-to-lymphocyte ratio (NLR),platelet-to-lymphocyte ratio (PLR) and the lymphocyte-to-monocyte ratio (LMR),in patients with esophageal squamous cell carcinoma (ESCC) by curative esophagectomy.Methods A total of 117 patients with ESCC from January 2010 to December 2012 in Affiliated Taixing People's Hospital of Yangzhou University were retrospectively analyzed.They were treated with standard curative esophagectomy.These patients were divided into NLR≥2.8 group and NLR ＜2.8 group,PLR≥127.3 group and PLR ＜127.3 group,LMR≥3.8 group and LMR ＜3.8 group for comparing the patients' general survival conditions and analyzing the influence on the progression-free survival (PFS) and overall survival (OS) rates according to the median values 2.8,127.3,3.8 of NLR,PLR and LMR,respectively.The COX proportional hazards models of NLR,PLR and LMR were used to carry out univariate and multivariate analyses for PFS and OS.The evaluation of prognostic values of NLR,PLR and LMR were carried by receiver operating characteristic (ROC) curve.Results For 117 patients,the median PFS time was 17 months,and the PFS rates at the 1-,3-and 5-year period were 66.7％,21.4％ and 17.9％,respectively;the median OS time was 36 months,and the OS rates at the 1-,3-and 5-year time were 94.9％,46.2％ and 28.2％,separately.In addition,a close relationship was identified between high NLR,high PLR,low LMR and tumor relapse (all P ＜0.05).Furthermore,in the NLR ＜2.8 group,the median PFS time was 24 months (95％ CI:19.788-28.212),and the 1-,3-,5-year PFS rates were 78.9％,35.1％ and 31.6％ separately,while in the NLR≥2.8 group,the median PFS time was 13 months (95％CI:10.153-15.847),and the 1-,3-,5-year PFS rates were 55.0％,8.3％ and 5.0％,respectively (x2 =15.601,P ＜ 0.001).In the PLR ＜ 127.3 group,the median PFS time was 24 months (95％ CI:19.891-28.109),and the 1-,3-,5-year PFS rates were 78.0％,30.5％ and 27.1％.In the PLR≥ 127.3 group,the median PFS time was 15 months (95％CI:11.832-18.168),and the 1-,3-,5-year PFS rates were 55.2％,12.1％ and 8.6％ (x2 =7.621,P =0.006).In the LMR ＜3.8 group,the median PFS time was 14 months (95％ CI:11.534-16.466),and the 1-,3-,5-year PFS rates were 57.9％,8.8％ and 5.3％,whilein the LMR≥3.8 group,the median PFS time was 21 months (95％ CI:16.783-25.217),and the 1-,3-,5-year PFS rates were 75.0％,33.3％ and 30.0％ (x2 =10.201,P =0.001).Correspondingly,the median OS time was 42 months (95％ CI:29.188-48.282) and the 1-,3-,5-year OS rates were 98.2％,56.1％ and 47.4％ in the NLR ＜2.8 group.While the median OS time was 27 months (95％ CI:20.358-33.642) and the 1-,3-,5-year OS rates were 91.7％,36.7％ and 10.0％ in the NLR ≥2.8 group (x2 =19.161,P ＜ 0.001).Themedian OS time was 38 months (95％ CI:31.310-44.690) and the 1-,3-,5-year OS rates were 94.9％,54.2％ and 37.3 ％ in the PLR ＜ 127.3 group and the median OS time was 27 months (95 ％ CI:19.537-34.463) and the 1-,3-,5-year OS rates were 93.1％,37.9％ and 19.6％ in the PLR≥127.3 group (x2 =7.019,P =0.008).The median OS time was 30 months (95％ CI:23.659-36.341) and the 1-,3-,5-year OS rates were 91.2％,36.8％ and 12.3％ in the LMR ＜ 3.8 group.While the median OS time was 38 months (95％ CI:27.878-48.121) and the 1-,3-,5-year OS rates were 95.0％,55.3％ and 43.3％ in the LMR≥3.8 group (x2 =10.201,P=0.001).In univariate analysis,the following factors were significantly associated with poor PFS:T stage (HR =1.292,95％ CI:1.077-2.211,P =0.048),N stage(HR =1.773,95％ CI:1.186-2.651,P =0.005),TNM stage (HR =1.768,95 ％ CI:1.181-2.645,P =0.006),NLR (HR =2.193,95 ％ CI:1.450-3.316,P＜0.001),PLR(HR =1.722,95％CI:1.149-2.581,P =0.009) and LMR (HR =0.531,95％CI:0.353-0.799,P =0.002).The univariate analysis further revealed that T stage (HR =1.982,95％ CI:1.162-3.383,P=0.012),N stage (HR =1.910,95％ CI:1.243-2.934,P =0.003),TNM stage (HR =2.115,95％ CI:1.375-3.252,P =0.001),NLR (HR =2.599,95％ CI:1.657-4.078,P ＜ 0.001),PLR (HR =1.764,95％CI:1.145-2.717,P =0.010) and LMR (HR =0.470,95％ CI:0.303-0.728,P =0.001) were also significantly associated with poor OS.Furthermore,multivariate COX regression analysis showed that TNM stage (HR=1.608,95％CI:1.057-2.445,P =0.026) and NLR (HR =1.886,95％CI:1.133-3.138,P=0.015) were independent prognostic factors for PFS in patients with ESCC after surgery.Correspondingly,TNM stage (HR =1.867,95 ％ CI:1.190-2.928,P =0.007) and NLR (HR =2.226,95 ％ CI:1.292-3.835,P =0.004) were also independent prognostic factors for OS in ESCC patients following surgery.Finally,ROC curves of NLR,PLR and LMR for PFS predictive values were as follows:the area under the curve (AUC) for NLR,PLR and LMR were 0.725 (95％ CI:0.615-0.835,P =0.001),0.657 (95％ CI:0.533-0.781,P =0.025) and 0.290 (95％ CI:0.178-0.402,P =0.003),respectively.ROC curve analysis of NLR,PLR and LMR in diagnostic value of OS indicated that the AUC was 0.731 (95％ CI:0.632-0.829,P ＜ 0.001) for NLR,0.613 (95％ CI:0.501-0.726,P =0.057) for PLR and 0.308 (95％ CI:0.205-0.412,P =0.053) for LMR.Conclusion NLR is superior to PLR.and LMR in predicting the survival outcome of patients with ESCC,and NLR is of great value in predicting the survival and prognosis of patients with thoracic ESCC after operation.
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Objective To evaluate the effects of the size of lymph node metastasis (LNM) on the chemoradiotherapy efficacy and prognosis for the patients after resection of thoracic esophageal squamous cell carcinoma (ESCC).Methods Between 2011 and 2014,a total of 75 esophageal squamous carcinoma patients with secondary LNM after resection of ESCC were recruited in this retrospective study.They were treated with curative radiotherapy only or concurrent chemoradiotherapy in the Affiliated Taixing People's Hospital of Yangzhou University.Thc LNM volume and maximum diameters were measured by the Monaco treatment planning system.The enrolled patients were grouped according to the median values of LNM volume and maximum diameters.The relationship between the responsiveness to treatment and these markers was analyzed by univariate and multivariate logistic analysis.The Kaplan-Meier method and Log-rank test were adopted to calculate and compare the overall survival (OS) rates with these markers.The Cox proportional hazards model was used to carry out univariate and multivariate analyses.Results The overall effective rate was 69.3％ for all enrolled patients.The response rates were 81.6％ with LNM volume ＜57 cm3 and 56.8％ with LNM volume ≥57 cm3.The response rates were 83.8％ with LNM maximum diameter ＜ 5 cm and 55.3％ with LNM maximum diameter ≥5 cm.The responses to treatment were highly associated with treatment method (OR =1.825,95％ CI:1.134-3.658,P =0.017),LNM volume (OR =4.183,95％ CI:1.416-12.354,P =0.010) and maximum diameter (OR =3.374,95％ CI:1.185-9.611,P =0.023) by univariate logistic regression analysis.Multivariate logistic regression analysis showed that therapeutic method (OR =1.225,95％ CI:1.085-2.837,P =0.038) and LNM volume (OR =1.614,95％ CI:1.003-3.025,P =0.048) were independent risk factors for tumor response.The median OS time of this cohort was 14 months,and the 1,2 and 3 year OS rates were 60.7％,25.3％ and 20.1％,respectively.Kaplan-Meier survival analysis revealed that TNM stage (HR =2.039,95 ％ CI:1.234-3.370,P =0.005),treatment methods (HR =1.858,95 ％ CI:1.385-2.958,P =0.013),LNM volume (HR =2.642,95％ CI:1.552-4.497,P ＜ 0.001) and LNM maximum diameter (HR =3.399,95 ％ CI:1.939-5.958,P ＜ 0.001) were significantly associated with OS.Furthermore,multivariate Cox proportional hazard regression model analysis for OS was performed and the results showed that TNM stage (HR =2.023,95 ％ CI:1.149-3.560,P =0.015),LNM volume (HR =2.055,95 ％ CI:1.041-4.055,P =0.038) and maximum diameter (HR =1.910,95％ CI:1.137-3.895,P =0.045) were considered as independent prognostic risk factors for OS.Conclusion LNM volume in ESCC patients with secondary LNM after esophagectomy has great values for predictive therapeutic effects and survival outcomes,and LNM maximum diameter has significant value for survival outcomes.
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Objective@#To apply Nutritional Risk Screening-2002(NRS-2002) to perform nutritional status score for the patients with thoracic esophageal squamous cell carcinoma (ESCC) receiving surgery, and to explore the prognostic impact of long-term survival.@*Methods@#A total of 117 patients who were diagnosed with ESCC from 2010 to 2012 were retrospectively analyzed. They recieved standard curative esophagectomy in the Yangzhou University Affiliated Taixing People′s Hospital. The nutritional status and risk score for recruited patients were assessed according to the standard of NRS-2002 tool prior to surgery, and these patients were grouped for further analysis according to the median values of NRS-2002 score. Finally, the relationship between NRS-2002 score and prognosis was analyzed.@*Results@#Patients were classified into two groups, with 45 in the NRS-2002<2.0 group, and 72 cases in the NRS-2002≥2.0, respectively. In the NRS-2002<2.0 group, the 1-, 3-, and 5-year progression-free survival (PFS) rates were 75.6%, 44.4% and 40.0% separately, while in the NRS-2002≥2.0 group, the PFS rates were 61.1%, 6.9% and 4.2% respectively, and the differences were statistically significant (P<0.001). Correspondingly, in the NRS-2002< 2.0 group, the 1-, 3-, and 5-year overall survival (OS) rates were 97.8%, 66.7% and 57.8% separately, while in the NRS-2002≥2.0 group, the OS rates were 91.7%, 33.3% and 16.7% respectively, and the differences were also statistically significant (P<0.001). Univariate analysis showed that N stage, TNM stage and NRS-2002 score were closely related to PFS and OS (P<0.05), and T stage was only associated with OS in patients with thoracic esophageal squamous cell carcinoma (P<0.05). Furthermore, multivariate Cox regression analysis showed that N stage (RR=1.640, 95% CI 1.049-2.565, P=0.030) and NRS-2002 (RR=3.154, 95% CI 1.946-5.113, P<0.001) were independent prognostic factors for PFS in patients with ESCC after surgery. Additionally, pathological differentiation (RR=1.556, 95% CI 1.004-2.440, P=0.041), N stage (RR=1.624, 95% CI 1.017-2.593, P=0.042) and NRS-2002 (RR=3.906, 95% CI2.245-6.795, P<0.001) were independent prognostic factors for OS in ESCC patients following surgery.@*Conclusion@#Preoperative nutritional risk screening NRS-2002 score is an independent prognostic factor in patients with ESCC receiving surgery and could be used as a tool for primary screening for nutritional risk.
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Objective@#To investigate the role of p75 neurotrophin receptor (p75NTR) in the irradiation-induced hippocampal neurogenesis impairment.@*Methods@#Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation, the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluorescence confocal laser microscopy was performed to observe the variations in the hippocampal neurogenesis. The stereotatic method was adopted for intra-hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR.The relationship between p75NTR and hippocampal neurogenesis was analyzed.@*Results@#Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation (P<0.05). Immunofluorescent staining showed that the quantity of BrdU+ NeuN+ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group (P<0.01). After the specific knockout of p75NTR, hippocampal neurogenesis was obviously protected.@*Conclusion@#p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.
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Objective To investigate the roles of TrkA and TrkB in radiation-induced hippocampal neurogenesis impairment.Methods Fifty-six rats were randomized into radiation group and sham control group.Radiation group received whole brain irradiation at a single dose of 10 Gy.The hippocampus were separated from rats in day 1,day 3,day 14 and 1 month after irradiation.Western blot and RT-PCR were applied to detect the protein levels and mRNA levels.Golgi staining was used to observe the dendritic spine of hippocampus.Immunofluorescence was performed to detect neural precursor's proliferation.Results Compared with control group,the numbers of dendritic spine significantly decreased after irradiation and its shape change obviously.Immunofluorescence showed a significant decrease in neural precursor's proliferation comparing with control group (t =6.49,P ＜ 0.05).Protein level of TrkA expression increased (t =2.64,3.06,4.80,2.64,P ＜ 0.05),while the levels of TrkB protein expression decreased significantly (t =4.59,3.06,2.81,2.57,P ＜ 0.05).The mRNA level of TrkA expressions increased (t =4.57,3.06,5.39,5.86,P ＜ 0.05),while the mRNA level of TrkB decreased (t =14.87,11.69,4.98,P ＜ 0.05).Conclusions As a signaling pathways downstream of NGF and BDNF,TrkA and TrkB may play an important role in radiation-induced neurogenesis impairment.
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Objective To explore the role of p16 gene methylation in fibroblasts in the occurrence and development of keloid.Methods Skin tissue specimens were resected from the lesions of patients with keloid and normal skin of healthy human controls.Fibroblasts were isolated from these tissue specimens and subjected a primary culture.An immunohistochemical analysis was performed to measure the expression of p16 protein in tissue specimens,real-time fluorescence-based quantitative PCR to determine the mRNA expression level (expressed as 2-△△Ct) of p 16 and DNA methyltransferases (DNMTs) in fibmblasts,and bisulfite sequencing PCR (BSP) to estimate the methylation status of p16 gene in the tissue specimens and primary fibroblasts.Results The keloid fibroblasts (KFbs) showed significandy lower mRNA expression of p16 gene (0.64 ± 0.18 vs.1.92 ± 0.23,t =10.54,P＜ 0.05),but significantly higher mRNA expressions of 3 DNMTs (DNMT1:2.58 ± 0.23 vs.1.13 ± 0.21,t =11.22,P ＜ 0.05; DNMT3A:4.87 ± 0.46 vs.2.38 ± 0.32,t =10.81,P＜ 0.05; DNMT3B:1.57 ± 0.12 vs.0.57 ± 0.16,t =12.45,P＜ 0.05) compared with the normal fibmblasts (NFbs).The DNA methylation rate in the p16 gene promoter region was significantly increased in keloid tissue (1.81％ ± 0.46％) and KFbs (3.15％ ± 0.94％) compared with normal skin tissue (0.90％ ± 0.35％,F =14.23,P＜ 0.01) and NFbs (0.17％ ± 0.29％,F=37.62,P＜ 0.01).Conclusions The methylation and low expression of p16 gene in KFbs may be associated with the uncontrolled growth of keloid,and DNMTs may play a role in the pathogenesis of keloid.
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Objective To evaluated the inhibitory effect of garcinia glycosides on growth of 8 kinds of human tumor cells in vi-vo by hollow fiber assay and confirm the reliability of hollow fiber assay in anticancer effect by the nude mice xenograft test .Methods Hollow fibers containing tumor cells were inserted underneath the skin of the NOD /SCID mice.The fibers were collected from the mice on the day after the administration and subjected to the stable endpoint MTT assay .The tumor cells of HL-60 and B16 were subcutane-ously implanted into the right flank of BALb /c nude mice.The positive control group was treated with cyclophosphamide .Each group was administered for 10 days.24 hours after the last administration , the mice were sacrificed and the tumors were excised and weigh-ted, the inhibition rate of tumor growth was calculated .Results The high-dose group of 8 mg/( kg· d) , middle dose group of 4 mg/( kg· d) of garcinia glycosides were measured by hollow fiber assay and nude mice test significantly inhibited the in vivo growth of HL -60 and B16 comparing with those in the solvent control group (P<0.01).Conclusion As a new model by hollow fiber assay to evalu-ate the inhibitory effect of garcinia glycosides , the test results were basically the same with nude mice test results .It made the experi-ment more rapidly , accurately and economically .An instruction and reliable evidence for follow-up study of garcinia glycosides was provided in this study .
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ObjectiveTo investigate the relationship between 10 cGy whole brain radiation and cognitive dystunction.MethodsThirty-two male Sprague-Dawley rats at age one month were randomized into irradiation and sham exposed groups.Behavioral and histopathological tests were performed 3 months after irradiation in the order of open field,Morris water maze,passive avoidance,and histopathological test.Comparison between the two groups was conducted using independent samples t-test.ResultsIn the place navigation test of Morris water maze,irradiation group showed significantly longer latency than sham exposed group on day 3 and 4 ( t =2.91 and 2.65,all P ＜ 0.05 ).In the total latency of the place navigation,irradiation group also presented longer latency comparing with sham exposed group ( t =2.63,P ＜ 0.05 ).In the spatial probe test of Morris water maze,the open field test and the passive avoidance test showed no significant difference between the two groups ( t =0.92,0.59,0.83,all P ＞ 0.05 ).The histopathological examination had no significant difference either.ConclusionWhole brain radiation of 10 cGy could partly injury the cognitive function of the rat.