BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of li...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.展开更多
Ganglioside and sulfatide are primary components of acidic glycosphingolipids(AGSLs),which are abundant in the brain tissue.AGSLs are potential tumor markers.In this paper,we use ultra-high performance liquid chromato...Ganglioside and sulfatide are primary components of acidic glycosphingolipids(AGSLs),which are abundant in the brain tissue.AGSLs are potential tumor markers.In this paper,we use ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry to generate a first-ever comprehensive profile of AGSLs in brain and plasma of C6 glioma rats treated with temozolomide(TMZ).The AGSLs detected consisted mainly of C18-/C20-sphingosine.12,20,19,14 and 12 species were identified in GM1,GD1a,GD1b,GM3 and GT1b ganglioside groups which were abundant in rat brain,respectively.These five groups accounted for 88-89%of total ganglioside content.However,no AGSLs were detected in rat plasma.Possible biomarkers for abnormal changes in the glioma model and the protective effect of TMZ were mainly found in these ganglioside groups and sulfatide.The main lipid component of central and peripheral nervous system myelin sheathes is sulfatide,which is upregulated in many tumors.Antitumor properties of TMZ are due to modulation of sulfatide levels in tumor tissues.展开更多
To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell le...To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.展开更多
To the Editor: The issue of patient safety has been making headlines continuously. China is facing the same patient safety problem. According to the statistical report of 2014 to 2015 medical disputes, in many large c...To the Editor: The issue of patient safety has been making headlines continuously. China is facing the same patient safety problem. According to the statistical report of 2014 to 2015 medical disputes, in many large cities of China, for example, Beijing and Shanghai, patient death is mainly caused by lack of standards in the medical treatment and operational procedures.[1] Implementation of simulation-based healthcare training could be a potential solution to standardize the medical procedures. However, healthcare simulation in China is still facing great challenges for the moment.展开更多
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.
基金The Ministry of Science and Technology of the People’s Republic of China[2016ZX09101017]supported this project.
文摘Ganglioside and sulfatide are primary components of acidic glycosphingolipids(AGSLs),which are abundant in the brain tissue.AGSLs are potential tumor markers.In this paper,we use ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry to generate a first-ever comprehensive profile of AGSLs in brain and plasma of C6 glioma rats treated with temozolomide(TMZ).The AGSLs detected consisted mainly of C18-/C20-sphingosine.12,20,19,14 and 12 species were identified in GM1,GD1a,GD1b,GM3 and GT1b ganglioside groups which were abundant in rat brain,respectively.These five groups accounted for 88-89%of total ganglioside content.However,no AGSLs were detected in rat plasma.Possible biomarkers for abnormal changes in the glioma model and the protective effect of TMZ were mainly found in these ganglioside groups and sulfatide.The main lipid component of central and peripheral nervous system myelin sheathes is sulfatide,which is upregulated in many tumors.Antitumor properties of TMZ are due to modulation of sulfatide levels in tumor tissues.
基金supported by the National Natural Science Foundation of China(82230004,81970113,82300149)the National Key Research and Development Program of China(2021YFC2500304)+1 种基金Capital Health Research and Development of Special(2022-1-4082)Peking University Medicine Fund for world's leading discipline or discipline cluster development(71003Y3035).
文摘To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.
基金grants from the Special fund for clinical research of Wu Jieping Medical Foundation(No.320.6750.18338)the National Science Foundation for Youth(No.81701318).
文摘To the Editor: The issue of patient safety has been making headlines continuously. China is facing the same patient safety problem. According to the statistical report of 2014 to 2015 medical disputes, in many large cities of China, for example, Beijing and Shanghai, patient death is mainly caused by lack of standards in the medical treatment and operational procedures.[1] Implementation of simulation-based healthcare training could be a potential solution to standardize the medical procedures. However, healthcare simulation in China is still facing great challenges for the moment.
