The sandwich structure is of great interest because of its advantage of combining light weight and high flexural stiffness. Many previous researchers have studied the failure modes in sandwich structures and the effec...The sandwich structure is of great interest because of its advantage of combining light weight and high flexural stiffness. Many previous researchers have studied the failure modes in sandwich structures and the effects on the load capacity caused by the change of the constituent materials’ properties. In this research, by applying Finite Element Analysis (FEA) method, we simulated a cantilever beam composed of a sandwich structure in Abaqus, to find out the preferred design principles that help decrease the stress and displacement in the beam when applied a uniform load. We also determined the effect of the core geometry on decreasing the displacement and the stress in the beam.展开更多
Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.How...Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.展开更多
Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this stud...Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.展开更多
Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the ...Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.展开更多
Recently, low-dose computed tomography （CT） has become highly desirable because of the growing concern for the potential risks of excessive radiation. For low-dose CT imaging, it is a significant challenge to guaran...Recently, low-dose computed tomography （CT） has become highly desirable because of the growing concern for the potential risks of excessive radiation. For low-dose CT imaging, it is a significant challenge to guarantee image quality while reducing radiation dosage. Compared with classical filtered backprojection algorithms, compressed sensing-based iterative re- construction has achieved excellent imaging performance, but its clinical application is hindered due to its computational ineffi- ciency. To promote low-dose CT imaging, we propose a promising reconstruction scheme which combines total-variation mini- mization and sparse dictionary learning to enhance the reconstruction performance, and properly schedule them with an adaptive iteration stopping strategy to boost the reconstruction speed. Experiments conducted on a digital phantom and a physical phantom demonstrate a superior performance of our method over other methods in terms of image quality and computational efficiency, which validates its potential for low-dose CT imaging.展开更多
Oncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer(CRC).Here,we demonstrate a cell-extrinsic role of KRAS,where KRAS engages ...Oncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer(CRC).Here,we demonstrate a cell-extrinsic role of KRAS,where KRAS engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages(TAMs).In human CRC specimens,mutant KRAS positively correlates with the presence of TAMs.Mutationally activated KRAS in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and lactate.In turn,KRAS-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab therapy.Mechanistically,KRAS drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-la(HIF-1a),a transcription factor that controls the expression of CSF2 and glycolytic genes.Mutant KRAS increased the production of reactive oxygen species,an inhibitor of prolyl hydroxylase activity which decreases HIF-1a hydroxylation,leading to enhanced HIF-1a stabilization.This cell-extrinsic mechanism awards KRAS a critical role in engineering a permissive microenvironment to promote tumor malignancy,and may present new insights on potential therapeutic defense strategies against mutant KRAS tumors.展开更多
Objective:The aim of this study was to evaluate the impact of preoperative hypoalbuminemia on the development of intraabdominal septic complications(IASCs)after primary anastomosis for patients with Crohn’s disease(C...Objective:The aim of this study was to evaluate the impact of preoperative hypoalbuminemia on the development of intraabdominal septic complications(IASCs)after primary anastomosis for patients with Crohn’s disease(CD).Methods:All CD patients undergoing bowel resection with a primary anastomosis during the study period from 2007 to 2015 were enrolled.The association of preoperative hypoalbuminemia(<30 g/L)with the risk for IASCs were assessed using both univariate and multivariate analyses.Results:A total of 124 eligible patients were included,117(94.4%)of whom had available preoperative albumin level.Preoperative hypoalbuminemia occurred in 13(11.7%)patients.The duration fromdiagnosis to surgery was longer for patients with preoperative hypoalbuminemia than those without(p=0.012).Patients with preoperative hypoalbuminemia weremore likely to have a history of preoperative use of 5-aminosalicylic acid(p=0.013)and have an intraoperative finding of small bowel obstruction(p=0.015).Of all patients,24(19.4%)developed postoperative IASCs.Univariate analysis showed that patients with preoperative hypoalbuminemia had an increased risk for IASCs(p=0.012).Multivariate analysis confirmed the association between preoperative hypoalbuminemia and IASCs(odds ratio 4.67,95%confidence interval:1.28–17.04,p=0.02).Similar findings were also obtained when preoperative albumin level was analysed as a continuous variable(p=0.019).Conclusions:Preoperative hypoalbuminemia is a significant predictor for the development of postoperative IASCs in CD patients after bowel resection with a primary anastomosis.Favorable preoperative nutrition status might lessen the risk for IASCs.展开更多
Background:Tumor heterogeneity is contributed by tumor cells and the microenvironment.Dynamics of tumor heterogeneity during colorectal cancer(CRC)progression have not been elucidated.Methods:Eight single-cell RNA seq...Background:Tumor heterogeneity is contributed by tumor cells and the microenvironment.Dynamics of tumor heterogeneity during colorectal cancer(CRC)progression have not been elucidated.Methods:Eight single-cell RNA sequencing(scRNA-seq)data sets of CRC were included.Milo was utilized to reveal the differential abundance of cell clusters during progression.The differentiation trajectory was imputed by using the Palantir algorithm and metabolic states were assessed by using scMetabolism.Three spatial transcription sequencing(ST-seq)data sets of CRC were used to validate cell-type abundances and colocalization.Cancer-associated regulatory hubs were defined as communication networks affecting tumor biological behaviors.Finally,quantitative reverse transcription polymerase chain reaction and immunohistochemistry staining were performed for validation.Results:TM4SF1t,SOX4t,and MKI67t tumor cells;CXCL12t cancer-associated fibroblasts;CD4t resident memory T cells;Treg;IgAt plasma cells;and several myeloid subsets were enriched in stage IV CRC,most of which were associated with overall survival of patients.Trajectory analysis indicated that tumor cells from patients with advanced-stage CRC were less differentiated,when metabolic heterogeneity showed a highest metabolic signature in terminal states of stromal cells,T cells,and myeloid cells.Moreover,ST-seq validated cell-type abundance in a spatial context and also revealed the correlation of immune infiltration between tertiary lymphoid structures and tumors followed by validation in our cohort.Importantly,analysis of cancer-associated regulatory hubs revealed a cascade of activated pathways including leukocyte apoptotic process,MAPK pathway,myeloid leukocyte differentiation,and angiogenesis during CRC progression.Conclusions:Tumor heterogeneity was dynamic during progression,with the enrichment of immunosuppressive Treg,myeloid cells,and fibrotic cells.The differential state of tumor cells was associated with cancer staging.Assessment of cancer-associated regulatory hubs suggested impaired antitumor immunity and increased metastatic ability during CRC progression.展开更多
Background:Patients with Crohn’s disease(CD)are often reported to be at a high risk for incisional surgical site infection(SSI).The aim of this study was to identify the risk factors associated with post-operative in...Background:Patients with Crohn’s disease(CD)are often reported to be at a high risk for incisional surgical site infection(SSI).The aim of this study was to identify the risk factors associated with post-operative incisional SSI in CD patients after bowel resection.Method:CD patients undergoing bowel resection between 2007 and 2015 were enrolled.Demographic and clinical features related to post-operative incisional SSI were analysed using both univariate and multivariate logistical analyses.Results:Of all eligible patients(n=159),123(77.4%)were male,with a mean age at surgery of 33.4611.8 years.A total of 35(22.0%)CD patients developed post-operative incisional SSI.Post-operative incisional SSI was more likely to happen in patients who had penetrating type of disease(P=0.018),underwent bowel resection for the indication of chronic fistula(P=0.005)and had an intra-operative finding of fistula(P=0.001).A greater proportion of patients with post-operative incisional SSI were found to have anemia(P=0.019)but elevated levels of white blood cells(P=0.027),neutrophils(P=0.006)as well as an elevated percentage of neutrophils(P=0.005).Multivariate logistic regression analysis showed that anemia(odds ratio[OR]:3.31,95%confidence interval[CI]:1.05-10.46,P=0.041),an elevated percentage of neutrophils(OR:2.85,95%CI:1.23-6.59,P=0.014)and an intra-operative finding of fistula(OR:3.76,95%CI:1.53-9.21,P=0.004)were significantly associated with the risk for post-operative incisional SSI.Conclusions:Anemia,elevated percentage of neutrophils and intra-operative finding of fistula are predictors for the development of post-operative incisional SSI in CD patients undergoing bowel resection.Favorable pre-operative nutrition status and low inflammatory status may lessen the incidence of post-operative incisional SSI.展开更多
Objective To investigate the risk factors for death in patients with corona virus disease 2019(COVID-19).Methods The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan Universit...Objective To investigate the risk factors for death in patients with corona virus disease 2019(COVID-19).Methods The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan University from February 1 to February 26,2020,were included in this retrospective analysis.The gender,age,time of hospitalization after the onset,clinical manifestations,underlying diseases.展开更多
文摘The sandwich structure is of great interest because of its advantage of combining light weight and high flexural stiffness. Many previous researchers have studied the failure modes in sandwich structures and the effects on the load capacity caused by the change of the constituent materials’ properties. In this research, by applying Finite Element Analysis (FEA) method, we simulated a cantilever beam composed of a sandwich structure in Abaqus, to find out the preferred design principles that help decrease the stress and displacement in the beam when applied a uniform load. We also determined the effect of the core geometry on decreasing the displacement and the stress in the beam.
基金This work is supported by grants from the National Key Clinical Discipline,National Natural Science Foundation of China(No.81300367 and No.81400604)Guangdong Natural Science Foundation(No.2015A030313108)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.
基金supported by the National Key R&D Program of China[no.2017YFC1308800]the National Natural Science Foundation of China[no.81870383]+1 种基金the Clinical Innovation Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)[no.2018GZR0201005]the Science and Technology Planning Project of Guangzhou City[no.201804010014].
文摘Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.
基金supported by National Natural Science Foundation of China(No.81400603)Guangdong Natural Science Foundation(No.2015A030310190)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.
基金Project supported by the National High-Tech R＆D Program （863） of China （No. 2015AA016704e） and the Zhejiang Provincial Natural Science Foundation, China （No. LY14F020028）
文摘Recently, low-dose computed tomography （CT） has become highly desirable because of the growing concern for the potential risks of excessive radiation. For low-dose CT imaging, it is a significant challenge to guarantee image quality while reducing radiation dosage. Compared with classical filtered backprojection algorithms, compressed sensing-based iterative re- construction has achieved excellent imaging performance, but its clinical application is hindered due to its computational ineffi- ciency. To promote low-dose CT imaging, we propose a promising reconstruction scheme which combines total-variation mini- mization and sparse dictionary learning to enhance the reconstruction performance, and properly schedule them with an adaptive iteration stopping strategy to boost the reconstruction speed. Experiments conducted on a digital phantom and a physical phantom demonstrate a superior performance of our method over other methods in terms of image quality and computational efficiency, which validates its potential for low-dose CT imaging.
基金This work was supported by the National Natural Science Foundation of China(81870383)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201005)+1 种基金Science and Technology Planning Project of Guangzhou City(201804010014)the National Key R&D Program of China(2017YFC1308800).
文摘Oncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer(CRC).Here,we demonstrate a cell-extrinsic role of KRAS,where KRAS engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages(TAMs).In human CRC specimens,mutant KRAS positively correlates with the presence of TAMs.Mutationally activated KRAS in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and lactate.In turn,KRAS-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab therapy.Mechanistically,KRAS drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-la(HIF-1a),a transcription factor that controls the expression of CSF2 and glycolytic genes.Mutant KRAS increased the production of reactive oxygen species,an inhibitor of prolyl hydroxylase activity which decreases HIF-1a hydroxylation,leading to enhanced HIF-1a stabilization.This cell-extrinsic mechanism awards KRAS a critical role in engineering a permissive microenvironment to promote tumor malignancy,and may present new insights on potential therapeutic defense strategies against mutant KRAS tumors.
基金This work was supported by the National Natural Science Foundation of China(No.81400603)Guangdong Natural Science Foundation(No.2015A030310190)the Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Objective:The aim of this study was to evaluate the impact of preoperative hypoalbuminemia on the development of intraabdominal septic complications(IASCs)after primary anastomosis for patients with Crohn’s disease(CD).Methods:All CD patients undergoing bowel resection with a primary anastomosis during the study period from 2007 to 2015 were enrolled.The association of preoperative hypoalbuminemia(<30 g/L)with the risk for IASCs were assessed using both univariate and multivariate analyses.Results:A total of 124 eligible patients were included,117(94.4%)of whom had available preoperative albumin level.Preoperative hypoalbuminemia occurred in 13(11.7%)patients.The duration fromdiagnosis to surgery was longer for patients with preoperative hypoalbuminemia than those without(p=0.012).Patients with preoperative hypoalbuminemia weremore likely to have a history of preoperative use of 5-aminosalicylic acid(p=0.013)and have an intraoperative finding of small bowel obstruction(p=0.015).Of all patients,24(19.4%)developed postoperative IASCs.Univariate analysis showed that patients with preoperative hypoalbuminemia had an increased risk for IASCs(p=0.012).Multivariate analysis confirmed the association between preoperative hypoalbuminemia and IASCs(odds ratio 4.67,95%confidence interval:1.28–17.04,p=0.02).Similar findings were also obtained when preoperative albumin level was analysed as a continuous variable(p=0.019).Conclusions:Preoperative hypoalbuminemia is a significant predictor for the development of postoperative IASCs in CD patients after bowel resection with a primary anastomosis.Favorable preoperative nutrition status might lessen the risk for IASCs.
基金supported by the National Key Research and Development Program of China[grant number 2022YFA1304000]the National Natural Science Foundation of China Key Joint Project[grant number U21A20344]+5 种基金the National Natural Science Foundation of China[grant number 81970452]the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases[grant number 2020B1111170004]the Science and Technology Program of Shenzhen,China[grant number JCYJ20190807161807867]the Starting Funding of Faculty from Sun Yat-sen University[grant number 2021276]the Regional Joint Project for Basic and Applied Basic Research Fund of Guangdong Province[grant number 2022A1515111043]the Science and Technology Planning Project of Guangzhou City[grant number 2023A04J01601],and National Key Clinical Discipline.
文摘Background:Tumor heterogeneity is contributed by tumor cells and the microenvironment.Dynamics of tumor heterogeneity during colorectal cancer(CRC)progression have not been elucidated.Methods:Eight single-cell RNA sequencing(scRNA-seq)data sets of CRC were included.Milo was utilized to reveal the differential abundance of cell clusters during progression.The differentiation trajectory was imputed by using the Palantir algorithm and metabolic states were assessed by using scMetabolism.Three spatial transcription sequencing(ST-seq)data sets of CRC were used to validate cell-type abundances and colocalization.Cancer-associated regulatory hubs were defined as communication networks affecting tumor biological behaviors.Finally,quantitative reverse transcription polymerase chain reaction and immunohistochemistry staining were performed for validation.Results:TM4SF1t,SOX4t,and MKI67t tumor cells;CXCL12t cancer-associated fibroblasts;CD4t resident memory T cells;Treg;IgAt plasma cells;and several myeloid subsets were enriched in stage IV CRC,most of which were associated with overall survival of patients.Trajectory analysis indicated that tumor cells from patients with advanced-stage CRC were less differentiated,when metabolic heterogeneity showed a highest metabolic signature in terminal states of stromal cells,T cells,and myeloid cells.Moreover,ST-seq validated cell-type abundance in a spatial context and also revealed the correlation of immune infiltration between tertiary lymphoid structures and tumors followed by validation in our cohort.Importantly,analysis of cancer-associated regulatory hubs revealed a cascade of activated pathways including leukocyte apoptotic process,MAPK pathway,myeloid leukocyte differentiation,and angiogenesis during CRC progression.Conclusions:Tumor heterogeneity was dynamic during progression,with the enrichment of immunosuppressive Treg,myeloid cells,and fibrotic cells.The differential state of tumor cells was associated with cancer staging.Assessment of cancer-associated regulatory hubs suggested impaired antitumor immunity and increased metastatic ability during CRC progression.
基金supported by the National Natural Science Foundation of China(No.81400603)the Guangdong Natural Science Foundation(No.2015A030310190)the Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background:Patients with Crohn’s disease(CD)are often reported to be at a high risk for incisional surgical site infection(SSI).The aim of this study was to identify the risk factors associated with post-operative incisional SSI in CD patients after bowel resection.Method:CD patients undergoing bowel resection between 2007 and 2015 were enrolled.Demographic and clinical features related to post-operative incisional SSI were analysed using both univariate and multivariate logistical analyses.Results:Of all eligible patients(n=159),123(77.4%)were male,with a mean age at surgery of 33.4611.8 years.A total of 35(22.0%)CD patients developed post-operative incisional SSI.Post-operative incisional SSI was more likely to happen in patients who had penetrating type of disease(P=0.018),underwent bowel resection for the indication of chronic fistula(P=0.005)and had an intra-operative finding of fistula(P=0.001).A greater proportion of patients with post-operative incisional SSI were found to have anemia(P=0.019)but elevated levels of white blood cells(P=0.027),neutrophils(P=0.006)as well as an elevated percentage of neutrophils(P=0.005).Multivariate logistic regression analysis showed that anemia(odds ratio[OR]:3.31,95%confidence interval[CI]:1.05-10.46,P=0.041),an elevated percentage of neutrophils(OR:2.85,95%CI:1.23-6.59,P=0.014)and an intra-operative finding of fistula(OR:3.76,95%CI:1.53-9.21,P=0.004)were significantly associated with the risk for post-operative incisional SSI.Conclusions:Anemia,elevated percentage of neutrophils and intra-operative finding of fistula are predictors for the development of post-operative incisional SSI in CD patients undergoing bowel resection.Favorable pre-operative nutrition status and low inflammatory status may lessen the incidence of post-operative incisional SSI.
文摘Objective To investigate the risk factors for death in patients with corona virus disease 2019(COVID-19).Methods The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan University from February 1 to February 26,2020,were included in this retrospective analysis.The gender,age,time of hospitalization after the onset,clinical manifestations,underlying diseases.
