Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chin...Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.展开更多
Objective:Traditional Chinese medicine(TCM)is a comprehensive system of medical practice.ZHENG(also known as syndrome differentiation)is the essence of TCM;however,its molecular basis remains unknown.This study evalua...Objective:Traditional Chinese medicine(TCM)is a comprehensive system of medical practice.ZHENG(also known as syndrome differentiation)is the essence of TCM;however,its molecular basis remains unknown.This study evaluated the molecular basis of Shi-Re ZHENG in patients with pancreatic cancer.Methods:A total of 144 patients with pathologically-confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma(PDAC)were retrospectively recruited between June 2015 and February 2016.Two cohorts,including the discovery cohort(n=60)and validation cohort(n=84),were included in this study.QPlex multiplex array and an enzyme-linked immunosorbent assay were used to evaluate serum inflammatory cytokine levels of pancreatic cancer patients with different TCM ZHENG.Receiver operating characteristic(ROC)curve analysis was used to evaluate the importance of the systemic inflammation response index(SIRI)in the detection of Shi-Re ZHENG.Results:Shi-Re ZHENG patients exhibited a different expression pattern of cytokines,including interleukin(IL)-6,IL-8,chemokine(C-C motif)ligand 18(CCL18),and C-reactive protein,than patients with other ZHENG diagnoses.M2-like macrophage-related inflammatory cytokines,such as IL-10,CCL17,and CCL22,were increased in Shi-Re ZHENG compared with non-Shi-Re ZHENG patients.The SIRI score was significantly increased in Shi-Re ZHENG compared with non-Shi-Re ZHENG patients(P<0.001).ROC analysis revealed that SIRI had a diagnostic value for Shi-Re ZHENG both in the discovery cohort(area under the curve[AUC]=0.833,95%confidence interval[CI]=0.709–0.957)and validation cohort(AUC=0.810,95%CI=0.716–0.905).Additionally,pancreatic cancer patients with Shi-Re ZHENG had a significantly shorter survival time than non-Shi-Re ZHENG(P=0.002).Conclusion:Shi-Re pancreatic cancer patients are characterized by an increased macrophage inflammation response,which may contribute to a poorer prognosis when compared to those with other ZHENG diagnoses.展开更多
BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndrome...BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.展开更多
基金supported by the National Natural Science Foundation of China(82230122,82025035,82104612)Shanghai Municipal Health Commission program(ZY(2021-2023)-0205-02)the Science Foundation for Young Scholars of Zhongshan Hospital,Fudan University(grant No.2021ZSQN70).
文摘Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.
文摘Objective:Traditional Chinese medicine(TCM)is a comprehensive system of medical practice.ZHENG(also known as syndrome differentiation)is the essence of TCM;however,its molecular basis remains unknown.This study evaluated the molecular basis of Shi-Re ZHENG in patients with pancreatic cancer.Methods:A total of 144 patients with pathologically-confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma(PDAC)were retrospectively recruited between June 2015 and February 2016.Two cohorts,including the discovery cohort(n=60)and validation cohort(n=84),were included in this study.QPlex multiplex array and an enzyme-linked immunosorbent assay were used to evaluate serum inflammatory cytokine levels of pancreatic cancer patients with different TCM ZHENG.Receiver operating characteristic(ROC)curve analysis was used to evaluate the importance of the systemic inflammation response index(SIRI)in the detection of Shi-Re ZHENG.Results:Shi-Re ZHENG patients exhibited a different expression pattern of cytokines,including interleukin(IL)-6,IL-8,chemokine(C-C motif)ligand 18(CCL18),and C-reactive protein,than patients with other ZHENG diagnoses.M2-like macrophage-related inflammatory cytokines,such as IL-10,CCL17,and CCL22,were increased in Shi-Re ZHENG compared with non-Shi-Re ZHENG patients.The SIRI score was significantly increased in Shi-Re ZHENG compared with non-Shi-Re ZHENG patients(P<0.001).ROC analysis revealed that SIRI had a diagnostic value for Shi-Re ZHENG both in the discovery cohort(area under the curve[AUC]=0.833,95%confidence interval[CI]=0.709–0.957)and validation cohort(AUC=0.810,95%CI=0.716–0.905).Additionally,pancreatic cancer patients with Shi-Re ZHENG had a significantly shorter survival time than non-Shi-Re ZHENG(P=0.002).Conclusion:Shi-Re pancreatic cancer patients are characterized by an increased macrophage inflammation response,which may contribute to a poorer prognosis when compared to those with other ZHENG diagnoses.
基金Supported by the National Natural Science Foundation of China,No.81704009,No.81873253,No.81573892,and No.81770571the Project of Shanghai Municipal Health and Family Planning Commission,No.201640122
文摘BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.
