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Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.
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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 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 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 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 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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BACKGROUND:Ferroferric oxide (Fe3O4) nanoparticles are a research hotspot in drug delivery system, which can transport antineoplastic drugs to the lesion under external magnetic field. Additional y, its submicrons even can reach the tumor site several centimeters far away from the magnetic source. OBJECTIVE:To investigate the histocompatibility and in vivo distribution of Fe3O4 nanoparticles and to explore its application prospect and limitations as a drug carrier in the chemotherapy of osteosarcoma. METHODS:10.0 mg/kg Fe3O4 nanoparticles were administrated into Wistar rats via tail vein, then the rats were executed at 15, 60 and 120 minutes, respectively, and the rat lung, brain, heart, liver, kidney, hind limb and skeletal muscle were removed. The ferric ion content in each tissue was determined by atomic absorption spectrometer, and the morphological changes of different tissues were observed by hematoxylin-eosin staining at each time point. RESULTS AND CONCLUSION:After administrated for 15 minutes, the concentration of Fe3O4 nanoparticles in the liver and kidney reached peak, fol owed by a decrease at 60 and 120 minutes, but stil remained a high level. The concentration of Fe3O4 nanoparticles at three time points showed significant difference compared with the control group (P0.05), suggesting that the blood-brain barrier can inhibit the nanoparticle penetration. No overt morphological changes were found in each tissue after hematoxylin-eosin staining. In conclusion, the distribution of Fe3O4 nanoparticles conjugate sodium oleate in organism is influenced by the blood perfusion and mononuclear phagocyte system, and they cannot penetrate the blood-brain barrier and make no significant effect on tissues, but maintain a high level in the liver kidney and bone for a long-term, thus providing a theoretical basis for the drug delivery system in the magenetic hyperthermia therapy of malignant tumors.
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Objective To evaluate the efficacy and toxicity of whole brain radiotherapy concurrent with capecitabine for treatment of brain mestastases from breast cancer with post-operative.Methods Fifty patients with brain mestastases from breast cancer with post-operative were randomized into two groups:25 patiens were treatend with whole brain radiotherapy concurrent with capecitabine (treatment group) and the other 25 patients were treated with whole brain radiotherapy alone (control group).Radiation dose was 40 Gy in 20 fractions over 4 weeks.Capecitabine was administered concurrently with radiotherapy in escalatiny dose from the 1st day of RT to the end day (850 mg/m2,twice/day).Results The survival rates at 1-and 2-year were 60.0 % (15/25) and 28.0 % (7/25) in treatment group,44.0 % (11/25) and 16.0 % (4/25) in control group (x2 =1.28,1.05,P > 0.05).Toxicities were tolerable.Conclusion Whole brain radiotherapy concurrent with capecitabine was effective and safe in treatment for patients with breat cancer and well-tolerated toxicity.
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Inorganic/polymer hybrid star polylactic acid (POSS-PLA) was obtained through ring-opening polymerization of lactide by using polyhydroxyl cage silsesquioxane (POSS-OH) as the core and tin (II) octoate as the catalyst. The star polylactic acid (POSS-PLA) was used to modify sodium alginate hydrophobically and a drug carrier was obtained. The drug release behavior was investigated by using ibuprofen as the model drug. The results showed that the drug loading rate could be improved and the release rate was postponed with an increase of POSS-PLA content in the carries. The release mechanism gradually changed from the first-order to the zero-order pattern after the modification.
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This is a study on the biodegradable polymers as gene controlled-released coatings for gene transfer. The PELA (poly (Dl-lactic acid)-co-poly (ethylene glycol), and PLGAE (poly (lactic acid)-co-poly (ethylene glycol)-co-poly (glycolic acid) random copolymer) were synthesized and prepared as the coatings of plasmid pCH110 in the transfection. All kinds of factors affecting the loading efficiency, cytotoxicity, transfection efficiency and the course of the degradation and release in vitro were discussed. The average diameters of microspheres of PELA and PLGAE were 1-3 microm and 0.72 microm respectively. The loading efficiency levels of them were 62% and 70% respectively. The transfection efficiency levels of two kinds of pCH110 delivery system for COS-1 cells were higher and two of them had few cytotoxicity. After transfection, the X-gal assay was performed and reported positive for 96 h. The biodegradable polymeric materials as gene carriers possess their potential superiority.
Sujets)
Matériaux biocompatibles , ADN , Chimie , Vecteurs de médicaments , Chimie , Toxicité , Techniques de transfert de gènes , Lactates , Chimie , Toxicité , Acide lactique , Chimie , Toxicité , Polyéthylène glycols , Chimie , Toxicité , Acide polyglycolique , Chimie , Toxicité , Polymères , Chimie , Toxicité , TransfectionRésumé
Salmonella Typhi capsular polysaccharide vaccines were encapsulated in the Micro-particles made from polyethylene glycol-poly-DL-lactide (PELA). BALB/c mouse were divided into three groups with 20 mice in each. Mouse were immunized respectively with controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines and Salmonella Typhi capsular polysaccharide vaccines by oral and subcutaneous administration. The mice blood and salvia were collected at the 2nd, 4th and 8th weeks respectively for the titrating of IgG and sIgA antibodies by RIA. At the 8th week, live typhoid bacteria were injected into the immunized mice for the calculation of the rate of immunization protection. The IgG titers of the controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines group were higher than those of the other groups(P < 0.05). The IgA titers of the low groups of controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines (oral and subcutaneous) were higher than those of the group of Salmonella Typhi capsular polysaccharide vaccines (P < 0.05). The immunization protection rates of the three groups were 40%, 100% and 60% respectively. The controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines possess the advantages of releasing slowly in vivo and persisting long time immunogenicity.