Developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent p...Developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell detection.The probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic cells.In the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor cells.Our study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.展开更多
The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfo...The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,...Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,the ecophysiology of P.globosa has been investigated by numerous studies.However,the proteomic response of P.globosa to nitrogen depletion remains largely unknown.We compared four protein preparation methods of P.globosa for two-dimensional electrophoresis(2-DE)(Urea/Triton X-100 with trichloroacetic acid(TCA)/acetone precipitation;TCA/acetone precipitation;Radio Immuno Precipitation Assay(RIPA)with TCA/acetone precipitation;and Tris buffer).Results show that the combination of RIPA with TCA/acetone precipitation had a clear gel background and showed the best protein spot separation effect,based on which the proteomic response to nitrogen depletion was studied using 2-DE.In addition,we identified six differentially expressed proteins whose relative abundance increased or decreased more than 1.5-fold(P<0.05).Most proteins could not be identified,which might be attributed to the lack of genomic sequences of P.globosa.Under nitrogen limitation,replication protein-like,RNA ligase,and sn-glycerol-3-phosphate dehydrogenase were reduced,which may decrease the DNA replication level and ATP production in P.globosa cells.The increase of endonucleaseⅢand transcriptional regulator enzyme may affect the metabolic and antioxidant function of P.globosa cells and induce cell apoptosis.These findings provide a basis for further proteomic study of P.globosa and the optimization of protein preparation methods of marine microalgae.展开更多
A coupled numerical calculation method combining smooth particle hydrodynamics(SPH)and the finite element method(FEM)was implemented to investigate the seismic response of horizontal storage tanks.Anumericalmodel of a...A coupled numerical calculation method combining smooth particle hydrodynamics(SPH)and the finite element method(FEM)was implemented to investigate the seismic response of horizontal storage tanks.Anumericalmodel of a horizontal storage tank featuring a free liquid surface under seismic action was constructed using the SPH–FEM coupling method.The stored liquid was discretized using SPH particles,while the tank and supports were discretized using the FEM.The interaction between the stored liquid and the tank was simulated by using the meshless particle contact method.Then,the numerical simulation results were compared and analyzed against seismic simulation shaking table test data to validate the method.Subsequently,a series of numerical models,considering different liquid storage volumes and seismic effects,were constructed to obtain time history data of base shear and top center displacement,which revealed the seismic performance of horizontal storage tanks.Numerical simulation results and experimental data showed good agreement,with an error rate of less than 18.85%.And this conformity signifies the rationality of the SPH-FEM coupling method.The base shear and top center displacement values obtained by the coupled SPH-FEM method were only 53.3% to 69.1% of those calculated by the equivalent mass method employed in the current code.As the stored liquid volume increased,the seismic response of the horizontal storage tank exhibited a gradual upward trend,with the seismic response increasing from 73% to 388% for every 35% increase in stored liquid volume.The maximum von Mises stress of the tank and the supports remained below the steel yield strength during the earthquake.The coupled SPH-FEM method holds certain advantages in studying the seismic problems of tanks with complex structural forms,particularly due to the representation of the flow field distribution during earthquakes by involving reservoir fluid participation.展开更多
BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,al...BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.展开更多
BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on ba...BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.展开更多
建立一种基于美国官方分析化学师协会(Association of Official Analytical Chemists,AOAC)方法检测黑果枸杞及其制品中花青素含量的改进pH示差法。考察了黑果枸杞及其制品中花青素的最佳提取和检测条件,通过液相色谱-三重四级杆串联质...建立一种基于美国官方分析化学师协会(Association of Official Analytical Chemists,AOAC)方法检测黑果枸杞及其制品中花青素含量的改进pH示差法。考察了黑果枸杞及其制品中花青素的最佳提取和检测条件,通过液相色谱-三重四级杆串联质谱法鉴别出黑果枸杞中花青素的具体化学结构,并计算出混合花青素的平均摩尔质量。通过分光光度法测得混合花青素的平均摩尔消光系数,对改进后的pH示差法进行方法学验证和花青素的含量测定。结果显示,最佳提取和检测条件如下:黑果枸杞花青素提取溶剂为盐酸-80%(体积分数)乙醇(3∶97,体积比),料液比为1∶100(g∶mL),提取温度为50℃,提取时间为30 min,缓冲溶液稀释5倍后静置平衡20 min。液相色谱-三重四级杆串联质谱法鉴别黑果枸杞中主要以矮牵牛素类花青素为主(占97.96%),黑果枸杞特有的混合花青素平均摩尔质量为912.7 g/mol,平均摩尔消光系数为29591 L/(mol·cm)。pH示差法改进后能够满足方法学验证要求,固体样品和液体样品最低检出限分别为28.2 mg/100 g、0.282 mg/100 mL。方法改进后花青素提取增长率均大于20%,静置平衡20 min后单次检测结果精密度小于0.3%。以矮牵牛素类花青素代替矢车菊素-3-O-葡萄糖苷计算花青素含量平均提高了2.41倍,能真实地反映黑果枸杞及其制品中花青素的含量。展开更多
基金financially supported by the National Key Research and Development Plan(No.2018AAA0100301)National Science Foundation of China(No.21925802)+1 种基金Research Funds for the Central Universities(No.DUT22LAB601)the Basic Research Project of Free Exploration(No.2021Szvup019)。
文摘Developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell detection.The probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic cells.In the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor cells.Our study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.
基金supported by grants from the National Institutes of Health,No.NS105689(to WL)the Department of Defense through the Multiple Sclerosis Research Program,No.W81XWH-22-1-0757(to WL).
文摘The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
基金the National Natural Science Foundation of China(Nos.42176142,41906111,41806127)the Marine Economic Development Project of Guangdong Province(No.2023B1111050011)+1 种基金the Basic and Applied Basic Research Project of Guangzhou(Nos.2023A04J1548,2023A04J1549)the Outstanding Innovative Talents Cultivation Funded Programs for Doctoral Students of Jinan University(No.2021CXB010)。
文摘Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,the ecophysiology of P.globosa has been investigated by numerous studies.However,the proteomic response of P.globosa to nitrogen depletion remains largely unknown.We compared four protein preparation methods of P.globosa for two-dimensional electrophoresis(2-DE)(Urea/Triton X-100 with trichloroacetic acid(TCA)/acetone precipitation;TCA/acetone precipitation;Radio Immuno Precipitation Assay(RIPA)with TCA/acetone precipitation;and Tris buffer).Results show that the combination of RIPA with TCA/acetone precipitation had a clear gel background and showed the best protein spot separation effect,based on which the proteomic response to nitrogen depletion was studied using 2-DE.In addition,we identified six differentially expressed proteins whose relative abundance increased or decreased more than 1.5-fold(P<0.05).Most proteins could not be identified,which might be attributed to the lack of genomic sequences of P.globosa.Under nitrogen limitation,replication protein-like,RNA ligase,and sn-glycerol-3-phosphate dehydrogenase were reduced,which may decrease the DNA replication level and ATP production in P.globosa cells.The increase of endonucleaseⅢand transcriptional regulator enzyme may affect the metabolic and antioxidant function of P.globosa cells and induce cell apoptosis.These findings provide a basis for further proteomic study of P.globosa and the optimization of protein preparation methods of marine microalgae.
基金supported by Scientific Research Fund of Institute of Engineering Mechanics,China Earthquake Administration(Grant Nos.2021B06,2021C05)Heilongjiang Natural Science Foundation Joint Guidance Project(Grant No.LH2021E122).
文摘A coupled numerical calculation method combining smooth particle hydrodynamics(SPH)and the finite element method(FEM)was implemented to investigate the seismic response of horizontal storage tanks.Anumericalmodel of a horizontal storage tank featuring a free liquid surface under seismic action was constructed using the SPH–FEM coupling method.The stored liquid was discretized using SPH particles,while the tank and supports were discretized using the FEM.The interaction between the stored liquid and the tank was simulated by using the meshless particle contact method.Then,the numerical simulation results were compared and analyzed against seismic simulation shaking table test data to validate the method.Subsequently,a series of numerical models,considering different liquid storage volumes and seismic effects,were constructed to obtain time history data of base shear and top center displacement,which revealed the seismic performance of horizontal storage tanks.Numerical simulation results and experimental data showed good agreement,with an error rate of less than 18.85%.And this conformity signifies the rationality of the SPH-FEM coupling method.The base shear and top center displacement values obtained by the coupled SPH-FEM method were only 53.3% to 69.1% of those calculated by the equivalent mass method employed in the current code.As the stored liquid volume increased,the seismic response of the horizontal storage tank exhibited a gradual upward trend,with the seismic response increasing from 73% to 388% for every 35% increase in stored liquid volume.The maximum von Mises stress of the tank and the supports remained below the steel yield strength during the earthquake.The coupled SPH-FEM method holds certain advantages in studying the seismic problems of tanks with complex structural forms,particularly due to the representation of the flow field distribution during earthquakes by involving reservoir fluid participation.
基金Supported by the Scientific and Technological Research Council of Turkiye/TUBİTAK,No.118S260Turkish Society of Gastroenterology,No.797-TGD-2021.
文摘BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.
文摘BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.
