Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemothe...Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.展开更多
Frequent occurrence of land expropriation disputes in rural areas of China has attracted attention of scholars to study causes. Most existing studies discuss causes from " structure- institution" level. In o...Frequent occurrence of land expropriation disputes in rural areas of China has attracted attention of scholars to study causes. Most existing studies discuss causes from " structure- institution" level. In other words,land expropriation disputes are caused by existing imperfect institutions,regulations,and policies. Such analysis model points institutional causes,but pays little attention to policy implementation process,especially the subjective initiative of parties concerned. This paper described a decade-long land expropriation dispute case in detail.Through description of event and process and survey of reasons of actors,it revealed factors resulting in occurrence and upgrade of dispute,and analyzed factors and their interactions with the aid of Smith Process Model.展开更多
A minor new diterpenoid alkaloid, soulidine, was isolated from the roots of DelphiniumSouliei Franch, its structure was established on the basis of spectral evidences.
Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric cancer.Methods: This retrospective st...Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric cancer.Methods: This retrospective study included 134 patients with gastric cancer(HER2-negative: n=87;HER2-positive: n=47) from April 2013 to March 2018, who were then randomly divided into training(n=94) and validation(n=40) cohorts. Radiomics features were obtained from the CT images showing gastric cancer. Least absolute shrinkage and selection operator(LASSO) regression analysis was utilized for building the radiomics signature. A multivariable logistic regression method was applied to develop a prediction model incorporating the radiomics signature and independent clinicopathologic risk predictors, which were then visualized as a radiomics nomogram. The predictive performance of the nomogram was assessed in the training and validation cohorts.Results: The radiomics signature was significantly associated with HER2 status in both training(P<0.001) and validation(P=0.023) cohorts. The prediction model that incorporated the radiomics signature and carcinoembryonic antigen(CEA) level demonstrated good discriminative performance for HER2 status prediction,with an area under the curve(AUC) of 0.799 [95% confidence interval(95% CI): 0.704-0.894] in the training cohort and 0.771(95% CI: 0.607-0.934) in the validation cohort. The calibration curve of the radiomics nomogram also showed good calibration. Decision curve analysis showed that the radiomics nomogram was useful.Conclusions: We built and validated a radiomics nomogram with good performance for HER2 status prediction in gastric cancer. This radiomics nomogram could serve as a non-invasive tool to predict HER2 status and guide clinical treatment.展开更多
Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retro...Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography(CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration,discrimination, and clinical usefulness.Results: The radiomics-based classifier was constructed, which consisted of 13 selected radiomics features.Multivariate models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable,patients with RPRSs of 0-3, 4-5, 6, 7-8, and 9 had distinctly very low(0%-20%), low(21%-40%), intermediate(41%-60%), high(61%-80%), and very high(81%-100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration (C-index: 0.785, 95% confidence interval(95% CI):0.780-0.790)Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index(NRI) of 0.711(95% CI: 0.555-0.867).Conclusions: The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.展开更多
Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologic...Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.展开更多
Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ...Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.展开更多
Objective: To develop and validate a radiomics prediction model for individualized prediction of perineural invasion(PNI) in colorectal cancer(CRC).Methods: After computed tomography(CT) radiomics features ext...Objective: To develop and validate a radiomics prediction model for individualized prediction of perineural invasion(PNI) in colorectal cancer(CRC).Methods: After computed tomography(CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort(346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen(CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation(separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results: The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index(c-index): 0.817; 95% confidence interval(95% CI): 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination(c-index: 0.803; 95% CI: 0.794–0.812).Conclusions: Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.展开更多
Continuing investigation of Delphinium souliei Franch yielded two minor new diterpenoid alkaloids--souline E(1) and souline F(2), their structures were determined on the basis of spectroscopic evidences.
The phytochemical investigation of Delphinium tongolense Franch. yielded two new diterpenoid alkaloids tongolenine C and tongolenine D. Their structures were elucidated by spectroscopical methods.
Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into grou...Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into groups. Control group were treated with DMEM without drugs, DEX group were treated with DMEM containing 5μmol/L dexamethasone, and NT-3 group were treated with DMEM containing 5μmol/L dexamethasone and 100ng/mL NT-3. Apoptosis rate, proliferation viability, osteogenesis marker contents as well as apoptosis gene and PI3K/AKT/mTOR signaling pathway molecule expression were detected.Results: The apoptosis rate as well as bax and caspase-3 expression in the cells of DEX group was significantly higher than those of control group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly lower than those of control group (P<0.05);the apoptosis rate as well as bax and caspase-3 expression in the cells of NT-3 group was significantly lower than those of DEX group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly higher than those of DEX group (P<0.05).Conclusion:NT-3 has inhibiting effect on the dexamethasone-induced mouse MC3T3-E1 osteoblast apoptosis, and the possible mechanism of this effect is to activate the PI3K/AKT/mTOR signaling pathway.展开更多
This study aims to analyze the coking process and propose an effective method for the reutilization of fluid catalytic cracking(FCC)coke block.Herein,we analyzed the basic characteristics and chemical composition of F...This study aims to analyze the coking process and propose an effective method for the reutilization of fluid catalytic cracking(FCC)coke block.Herein,we analyzed the basic characteristics and chemical composition of FCC coke blocks.The results showed that the main components were carbon,oxygen,and aluminum,accounting for 60.8%,26.6%,and 11.5%,respectively.Under the conventional catalytic cracking reaction temperature from 500℃ to 600℃,the formation of the first aromatic hydrocarbon was particularly important for the formation of coke.The condensation of oil-gas-entrained catalyst particles and their heavy components was the physical cause of coking,while the dehydrogenation condensation reaction of oil-gas heavy components was the chemical factor.In addition,the membrane prepared by powdered coke had excellent photothermal conversion ability,which could be heated to more than 110℃ within 360 s under two fixed light intensities.The evaporation rate of photothermal water was 5.89 kg m^(2) h^(−1),which has great industrial application potential.These works provide a novel and effective method of separation membrane for the reutilization of FCC coke blocks.展开更多
Background: Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this s...Background: Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in patients with benign and malignant hydrothorax. Methods: The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion (n = 35) and benign pleural effusion (n = 30) were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization (FISH). The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion. Results: The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were (384.91 ± 120.18), and (129.62 ±46.35) ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax (207.97 ± 64.04), (63.49 ± 24.58) ng/L (P 〈 0.01 ). The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% (the boundary value was 297.06 ng/L), respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively (the boundary value was 99.21 ng/L) for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax (P 〈 0.01 ). Conclusions: VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It is feasible to detect the gene copy number of the pleural effusion cell mass EGFR by FISH technique. Joint detection can improve the diagnostic sensitivity.展开更多
Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain (NOD)-Iike receptors (NLRs). We elucidated the NOD1 and NOD2-mediated ...Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain (NOD)-Iike receptors (NLRs). We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and NOD2 ligand muramyl dipeptide (MDP). However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule (ICAM)-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system (all P〈0.05). Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 (Th2) cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice (all P〈0.05). This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.展开更多
Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine research.The study of bNAbs arising in natural infection is ...Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine research.The study of bNAbs arising in natural infection is essential in this endeavor.We generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient.This antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2.We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization.We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6.This motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding model.Next,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization activity.Interestingly,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs.Overall,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains.展开更多
基金supported by the National Key Research and Development Plan of China(No.2017YFC1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Scientific Foundation of China(No.81771912,81901910,82072090,and 82001986)。
文摘Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.
基金Supported by Youth Foundation for Humanities and Social Science Research from the Ministry of Education(10YJC840078)the Fundamental Research Funds for the Central Universities(SWU1209363&SWU1409319)
文摘Frequent occurrence of land expropriation disputes in rural areas of China has attracted attention of scholars to study causes. Most existing studies discuss causes from " structure- institution" level. In other words,land expropriation disputes are caused by existing imperfect institutions,regulations,and policies. Such analysis model points institutional causes,but pays little attention to policy implementation process,especially the subjective initiative of parties concerned. This paper described a decade-long land expropriation dispute case in detail.Through description of event and process and survey of reasons of actors,it revealed factors resulting in occurrence and upgrade of dispute,and analyzed factors and their interactions with the aid of Smith Process Model.
文摘A minor new diterpenoid alkaloid, soulidine, was isolated from the roots of DelphiniumSouliei Franch, its structure was established on the basis of spectral evidences.
基金supported by the National Key Research and Development Program of China (No. 2017YFC1309100)National Natural Scientific Foundation of China (No. 81771912, 81601469, and 81701782)+1 种基金the Science and Technology Planning Project of Guangdong Province (No. 2017B020227012)the Science and Technology Planning Project of Guangzhou (No. 20191A011002).
文摘Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric cancer.Methods: This retrospective study included 134 patients with gastric cancer(HER2-negative: n=87;HER2-positive: n=47) from April 2013 to March 2018, who were then randomly divided into training(n=94) and validation(n=40) cohorts. Radiomics features were obtained from the CT images showing gastric cancer. Least absolute shrinkage and selection operator(LASSO) regression analysis was utilized for building the radiomics signature. A multivariable logistic regression method was applied to develop a prediction model incorporating the radiomics signature and independent clinicopathologic risk predictors, which were then visualized as a radiomics nomogram. The predictive performance of the nomogram was assessed in the training and validation cohorts.Results: The radiomics signature was significantly associated with HER2 status in both training(P<0.001) and validation(P=0.023) cohorts. The prediction model that incorporated the radiomics signature and carcinoembryonic antigen(CEA) level demonstrated good discriminative performance for HER2 status prediction,with an area under the curve(AUC) of 0.799 [95% confidence interval(95% CI): 0.704-0.894] in the training cohort and 0.771(95% CI: 0.607-0.934) in the validation cohort. The calibration curve of the radiomics nomogram also showed good calibration. Decision curve analysis showed that the radiomics nomogram was useful.Conclusions: We built and validated a radiomics nomogram with good performance for HER2 status prediction in gastric cancer. This radiomics nomogram could serve as a non-invasive tool to predict HER2 status and guide clinical treatment.
基金supported by the National Key Research and Development Plan of China (No. 2017YFC1309100)the National Natural Scientific Foundation of China (No. 81771912, 81901910, and 81701782)the Provincial Science and Technology Plan Project of Guangdong Province (No. 2017B020227012)
文摘Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography(CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration,discrimination, and clinical usefulness.Results: The radiomics-based classifier was constructed, which consisted of 13 selected radiomics features.Multivariate models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable,patients with RPRSs of 0-3, 4-5, 6, 7-8, and 9 had distinctly very low(0%-20%), low(21%-40%), intermediate(41%-60%), high(61%-80%), and very high(81%-100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration (C-index: 0.785, 95% confidence interval(95% CI):0.780-0.790)Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index(NRI) of 0.711(95% CI: 0.555-0.867).Conclusions: The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.
基金supported by the National Key Research and Development Program of China(No.2017YFC 1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Science Foundation of China(No.82071892,81771912,81901910)。
文摘Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.
基金supported by the National Key R&D Program of China (No. 2021YFF1201003)the Key R&D Program of Guangdong Province, China (No. 2021B0101420006)+2 种基金the National Science Fund for Distinguished Young Scholars (No. 81925023 and 82071892)the National Natural Science Foundation of China (No. 81771912 and 82071892)the National Natural Science Foundation for Young Scientists of China (No. 81701782 and 81901910).
文摘Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.
基金supported by the National Key Research and Development Program of China (No. 2017YFC1309100)the National Natural Scientific Foundation of China (No. 81771912, 81701782 and 81601469)
文摘Objective: To develop and validate a radiomics prediction model for individualized prediction of perineural invasion(PNI) in colorectal cancer(CRC).Methods: After computed tomography(CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort(346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen(CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation(separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results: The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index(c-index): 0.817; 95% confidence interval(95% CI): 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination(c-index: 0.803; 95% CI: 0.794–0.812).Conclusions: Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.
文摘Continuing investigation of Delphinium souliei Franch yielded two minor new diterpenoid alkaloids--souline E(1) and souline F(2), their structures were determined on the basis of spectroscopic evidences.
文摘The phytochemical investigation of Delphinium tongolense Franch. yielded two new diterpenoid alkaloids tongolenine C and tongolenine D. Their structures were elucidated by spectroscopical methods.
基金National Natural Science Foundation of China(81900800)Natural Science Basic Research Plan in Shaanxi Province(2019JM-560).
文摘Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into groups. Control group were treated with DMEM without drugs, DEX group were treated with DMEM containing 5μmol/L dexamethasone, and NT-3 group were treated with DMEM containing 5μmol/L dexamethasone and 100ng/mL NT-3. Apoptosis rate, proliferation viability, osteogenesis marker contents as well as apoptosis gene and PI3K/AKT/mTOR signaling pathway molecule expression were detected.Results: The apoptosis rate as well as bax and caspase-3 expression in the cells of DEX group was significantly higher than those of control group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly lower than those of control group (P<0.05);the apoptosis rate as well as bax and caspase-3 expression in the cells of NT-3 group was significantly lower than those of DEX group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly higher than those of DEX group (P<0.05).Conclusion:NT-3 has inhibiting effect on the dexamethasone-induced mouse MC3T3-E1 osteoblast apoptosis, and the possible mechanism of this effect is to activate the PI3K/AKT/mTOR signaling pathway.
基金support from the National Natural Science Foundation of China(grant No.12202127)the Scientific Research Staring Foundation of Hainan University(grant No.KYQD(ZR)20042)+1 种基金Young Talents’Science and Technology Innovation Project of Hainan Association for Science and Technology(grant No.QCXM202027)Hainan Provincial Natural Science Foundation(grant Nos.520QN228 and 323MS009).
文摘This study aims to analyze the coking process and propose an effective method for the reutilization of fluid catalytic cracking(FCC)coke block.Herein,we analyzed the basic characteristics and chemical composition of FCC coke blocks.The results showed that the main components were carbon,oxygen,and aluminum,accounting for 60.8%,26.6%,and 11.5%,respectively.Under the conventional catalytic cracking reaction temperature from 500℃ to 600℃,the formation of the first aromatic hydrocarbon was particularly important for the formation of coke.The condensation of oil-gas-entrained catalyst particles and their heavy components was the physical cause of coking,while the dehydrogenation condensation reaction of oil-gas heavy components was the chemical factor.In addition,the membrane prepared by powdered coke had excellent photothermal conversion ability,which could be heated to more than 110℃ within 360 s under two fixed light intensities.The evaporation rate of photothermal water was 5.89 kg m^(2) h^(−1),which has great industrial application potential.These works provide a novel and effective method of separation membrane for the reutilization of FCC coke blocks.
文摘Background: Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in patients with benign and malignant hydrothorax. Methods: The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion (n = 35) and benign pleural effusion (n = 30) were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization (FISH). The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion. Results: The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were (384.91 ± 120.18), and (129.62 ±46.35) ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax (207.97 ± 64.04), (63.49 ± 24.58) ng/L (P 〈 0.01 ). The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% (the boundary value was 297.06 ng/L), respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively (the boundary value was 99.21 ng/L) for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax (P 〈 0.01 ). Conclusions: VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It is feasible to detect the gene copy number of the pleural effusion cell mass EGFR by FISH technique. Joint detection can improve the diagnostic sensitivity.
文摘Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain (NOD)-Iike receptors (NLRs). We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and NOD2 ligand muramyl dipeptide (MDP). However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule (ICAM)-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system (all P〈0.05). Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 (Th2) cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice (all P〈0.05). This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.
基金supported by grants from the Chinese National 973 Program(2015CB554302)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)to B.S.+4 种基金the Chinese National 973 Program(2015CB554300)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010205)to M.the National Natural Science Foundation of China(31670172)Shanghai Science and Technology Innovation Action(16DZ1910100)to B.S.Nanjing Galaxy Biopharma C.O.
文摘Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine research.The study of bNAbs arising in natural infection is essential in this endeavor.We generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient.This antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2.We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization.We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6.This motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding model.Next,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization activity.Interestingly,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs.Overall,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains.