BACKGROUND The current understanding of the magnitude and consequences of multimorbidity in Chinese older adults with coronary heart disease(CHD)is insufficient.We aimed to assess the association and population-attrib...BACKGROUND The current understanding of the magnitude and consequences of multimorbidity in Chinese older adults with coronary heart disease(CHD)is insufficient.We aimed to assess the association and population-attributable fractions(PAFs)between multimorbidity and mortality among hospitalized older patients who were diagnosed with CHD in Shenzhen,China.METHODS We conducted a retrospective cohort study of older Chinese patients(aged≥65 years)who were diagnosed with CHD.Cox proportional hazards models were used to estimate the associations between multimorbidity and all-cause and cardiovascular disease(CVD)mortality.We also calculated the PAFs.RESULTS The study comprised 76,455 older hospitalized patients who were diagnosed with CHD between January 1,2016,and August 31,2022.Among them,70,217(91.9%)had multimorbidity,defined as the presence of at least one of the predefined 14 chronic conditions.Those with cancer,hemorrhagic stroke and chronic liver disease had the worst overall death risk,with adjusted HRs(95%CIs)of 4.05(3.77,4.38),2.22(1.94,2.53),and 1.85(1.63,2.11),respectively.For CVD mortality,the highest risk was observed for hemorrhagic stroke,ischemic stroke,and chronic kidney disease;the corresponding adjusted HRs(95%CIs)were 3.24(2.77,3.79),1.91(1.79,2.04),and 1.81(1.64,1.99),respectively.All-cause mortality was mostly attributable to cancer,heart failure and ischemic stroke,with PAFs of 11.8,10.2,and 9.1,respectively.As for CVD mortality,the leading PAFs were heart failure,ischemic stroke and diabetes;the corresponding PAFs were 18.0,15.7,and 6.1,respectively.CONCLUSIONS Multimorbidity was common and had a significant impact on mortality among older patients with CHD in Shenzhen,China.Cancer,heart failure,ischemic stroke and diabetes are the primary contributors to PAFs.Therefore,prioritizing improved treatment and management of these comorbidities is essential for the survival prognosis of CHD patients from a holistic public health perspective.展开更多
AIM:To investigate the anti-tumor effects of Paris chinensis dioscin(PCD)and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells.METHODS:Cell viability was analyzed by the 3...AIM:To investigate the anti-tumor effects of Paris chinensis dioscin(PCD)and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells.METHODS:Cell viability was analyzed by the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay.Cell apoptosis was evaluated by flow cytometry and laser scanning confocal microscope(LSCM)using Annexin-V/propidium iodide(PI)staining,and the cell cycle was evaluated using PI staining with flow cytom-etry.Intracellular calcium ions were detected under fluorescence microscope.The expression of cell cycle and apoptosis-related proteins cyclin B1,CDK1,cytochrome C and caspase-3 was measured by immunohistochemical staining.RESULTS:PCD had an anti-proliferation effect on human gastric cancer SGC-7901 cells in a dose-and time-de-pendent manner.After treatment of SGC-7901 cells with PCD,apoptosis appeared in SGC-7901 cells.Morpho-logical changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining,and the cell number of the G0/G1 phase was decreased,while the number of cells in the G2/M phase was increased.Cell cycle-related proteins,such as cyclin B1 and CDK1,were all down-regulated,but caspase-3 and cytochrome C were up-regulated.Moreover,intracellular calcium accumulation occurred in PCD-treated cells.CONCLUSION:G2/M phase arrest and apoptosis induced by PCD are associated with the inhibition of CDK-activating kinase activity and the activation of Ca2+-related mitochondrion pathway in SGC-7901 cells.展开更多
AIM: To approach the relationship between alveolar echinococcosis (AE) pathology and level of sIL-2R,TNF-α and IFN-γ in sera and the significance of cytokines in development of AE.METHODS: After 23 patients with AE ...AIM: To approach the relationship between alveolar echinococcosis (AE) pathology and level of sIL-2R,TNF-α and IFN-γ in sera and the significance of cytokines in development of AE.METHODS: After 23 patients with AE were confirmed by ELISA and ultrasound, their sera were collected and the concentrations of sIL-2R,TNF-α and IFN-γ were detected by double antibody sandwich. Twelve healthy adults served as controls. According to the status of livers of AE patients by ultrasound scanning, they were divided into 4 groups: P2,P3, P4 groups and C group (control). Average of concentrations of sIL-2R, TNF-α and IFN-yin homologous group was statistically analyzed by both ANOV and Newman-Keuls, respectively.RESULTS: The mean of sIL-2R in P2 group was 97±29, P3:226±80, P4:194±23 and control group (111±30)×10^3 u/L(P<0.01). The mean of TNF-α in P2 group was 1.12±0.20, P3:3.67±1.96, P4:1.30±0.25 and control group 0.40±0.19 μg/L(P<0.01). The mean of IFN-γ in P2 group was 360±20, P3:486±15, P4:259±19 and control group: 16±2 ng/L (P<0.01).Judged by ANOV and Newman-Keuls, the mean concentrations of sIL-2R, TNF-α and IFN-γ had a significant difference among groups. Except for P2group, the mean sIL-2R between other groups of AE patients had a significant difference (P<0.05). The mean of TNF-α concentration in P3 group was the highest (P<0.01). The mean of IFN-γ concentration in all patients was higher than that in control group (P<0.01),but there was no difference between AE groups (P>0.05).CONCLUSION: Low sIL-2R level indicates an early stage of AE or stable status, per contra, a progression stage. Higher level of TNF-α might be related to the lesion of liver. The role of single IFN-γ is limited in immunological defense against AE and it can not fully block pathological progression.展开更多
Lung cancer is the leading cause of cancer mortality worldwide.Dendritic cells(DCs)are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in l...Lung cancer is the leading cause of cancer mortality worldwide.Dendritic cells(DCs)are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in lung cancer patients.It is evident that the immunoregulatory network may play a key role in the failure of the immune response to terminate tumors.Lung tumors likely employ numerous strategies to suppress DC-based anti-tumor immunity.Here,we summarize the recent advances in our understanding on lung tumor-induced immunosuppression in DCs,which affects the initiation and development of T-cell responses.We also describe which existing measures to restore DC function may be useful for clinical treatment of lung tumors.Furthering our knowledge of how lung cancer cells alter DC function to generate a tumor-supportive environment will be essential in order to guide the design of new immunotherapy strategies for clinical use.展开更多
As a typical plant virus which has biocompatibility and high transfection efficiency,tobacco mosaic virus(TMV)has shown broad application potential in drug or gene delivery field.Elucidating its intracellular traffick...As a typical plant virus which has biocompatibility and high transfection efficiency,tobacco mosaic virus(TMV)has shown broad application potential in drug or gene delivery field.Elucidating its intracellular trafficking is of great importance in investigation of its cytotoxicity,targeting site,and delivery efficiency,and is advantageous to designing new TMV-based drug delivery systems with different targets.By taking advantage of the regulated pH value of different organelles in a mammalian cell,we exploit a pH detection strategy to investigate the intracellular trafficking pathway of TMV.Here,we report a single-wavelength excited ratiometric fluorescent pH probe.This probe is constructed by simultaneously coupling pH-sensitive fluorescein isothiocyanate(FITC)and pH-insensitive rhodamine B isothiocyanate(RBIRC)onto the inner surface of TMV.The fluorescence intensity ratio of FITC to RBITC excited at 488 nm responds specifically towards pH value over other interferential agents.By taking use of this single-wavelength excited ratiometric pH probe and confocal laser scanning microscopy,it is shown that the endocytosed TMV is located in a pH decreasing microenvironment and eventually enters lysosomes.This work may provide important guidance on construction of TMV-based nano carriers.展开更多
Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have show...Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivoby transplanting MSCs into normal and diabetic rats viathe tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting mutes and microenvironments can lead to divergent immunogenicity of MSCs.展开更多
基金supported by the National Natural Science Foundation of China(Grants 12126602)the R&D project of Pazhou Lab(Huangpu)under Grant 2023K0610+5 种基金the National Natural Science Foundation of China(Grants 82030102)the Shenzhen Medical Academy of Research and Translation(Grants C2302001)the Shenzhen Science and Technology Innovation Committee(No.ZDSYS20200810171403013)the Chinese Postdoctoral Science Foundation(No.2022M721463)the SUSTech Presidential Postdoctoral Fellowshipthe Ministry of Science and Technology of China(Grants 2022YFC3702703).
文摘BACKGROUND The current understanding of the magnitude and consequences of multimorbidity in Chinese older adults with coronary heart disease(CHD)is insufficient.We aimed to assess the association and population-attributable fractions(PAFs)between multimorbidity and mortality among hospitalized older patients who were diagnosed with CHD in Shenzhen,China.METHODS We conducted a retrospective cohort study of older Chinese patients(aged≥65 years)who were diagnosed with CHD.Cox proportional hazards models were used to estimate the associations between multimorbidity and all-cause and cardiovascular disease(CVD)mortality.We also calculated the PAFs.RESULTS The study comprised 76,455 older hospitalized patients who were diagnosed with CHD between January 1,2016,and August 31,2022.Among them,70,217(91.9%)had multimorbidity,defined as the presence of at least one of the predefined 14 chronic conditions.Those with cancer,hemorrhagic stroke and chronic liver disease had the worst overall death risk,with adjusted HRs(95%CIs)of 4.05(3.77,4.38),2.22(1.94,2.53),and 1.85(1.63,2.11),respectively.For CVD mortality,the highest risk was observed for hemorrhagic stroke,ischemic stroke,and chronic kidney disease;the corresponding adjusted HRs(95%CIs)were 3.24(2.77,3.79),1.91(1.79,2.04),and 1.81(1.64,1.99),respectively.All-cause mortality was mostly attributable to cancer,heart failure and ischemic stroke,with PAFs of 11.8,10.2,and 9.1,respectively.As for CVD mortality,the leading PAFs were heart failure,ischemic stroke and diabetes;the corresponding PAFs were 18.0,15.7,and 6.1,respectively.CONCLUSIONS Multimorbidity was common and had a significant impact on mortality among older patients with CHD in Shenzhen,China.Cancer,heart failure,ischemic stroke and diabetes are the primary contributors to PAFs.Therefore,prioritizing improved treatment and management of these comorbidities is essential for the survival prognosis of CHD patients from a holistic public health perspective.
基金Supported by The grant from the Department of Education of Shandong Province,China,No.J10LF18
文摘AIM:To investigate the anti-tumor effects of Paris chinensis dioscin(PCD)and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells.METHODS:Cell viability was analyzed by the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay.Cell apoptosis was evaluated by flow cytometry and laser scanning confocal microscope(LSCM)using Annexin-V/propidium iodide(PI)staining,and the cell cycle was evaluated using PI staining with flow cytom-etry.Intracellular calcium ions were detected under fluorescence microscope.The expression of cell cycle and apoptosis-related proteins cyclin B1,CDK1,cytochrome C and caspase-3 was measured by immunohistochemical staining.RESULTS:PCD had an anti-proliferation effect on human gastric cancer SGC-7901 cells in a dose-and time-de-pendent manner.After treatment of SGC-7901 cells with PCD,apoptosis appeared in SGC-7901 cells.Morpho-logical changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining,and the cell number of the G0/G1 phase was decreased,while the number of cells in the G2/M phase was increased.Cell cycle-related proteins,such as cyclin B1 and CDK1,were all down-regulated,but caspase-3 and cytochrome C were up-regulated.Moreover,intracellular calcium accumulation occurred in PCD-treated cells.CONCLUSION:G2/M phase arrest and apoptosis induced by PCD are associated with the inhibition of CDK-activating kinase activity and the activation of Ca2+-related mitochondrion pathway in SGC-7901 cells.
基金Supported by the STD3 Programme of the EC,No.TS3-CT94-0270
文摘AIM: To approach the relationship between alveolar echinococcosis (AE) pathology and level of sIL-2R,TNF-α and IFN-γ in sera and the significance of cytokines in development of AE.METHODS: After 23 patients with AE were confirmed by ELISA and ultrasound, their sera were collected and the concentrations of sIL-2R,TNF-α and IFN-γ were detected by double antibody sandwich. Twelve healthy adults served as controls. According to the status of livers of AE patients by ultrasound scanning, they were divided into 4 groups: P2,P3, P4 groups and C group (control). Average of concentrations of sIL-2R, TNF-α and IFN-yin homologous group was statistically analyzed by both ANOV and Newman-Keuls, respectively.RESULTS: The mean of sIL-2R in P2 group was 97±29, P3:226±80, P4:194±23 and control group (111±30)×10^3 u/L(P<0.01). The mean of TNF-α in P2 group was 1.12±0.20, P3:3.67±1.96, P4:1.30±0.25 and control group 0.40±0.19 μg/L(P<0.01). The mean of IFN-γ in P2 group was 360±20, P3:486±15, P4:259±19 and control group: 16±2 ng/L (P<0.01).Judged by ANOV and Newman-Keuls, the mean concentrations of sIL-2R, TNF-α and IFN-γ had a significant difference among groups. Except for P2group, the mean sIL-2R between other groups of AE patients had a significant difference (P<0.05). The mean of TNF-α concentration in P3 group was the highest (P<0.01). The mean of IFN-γ concentration in all patients was higher than that in control group (P<0.01),but there was no difference between AE groups (P>0.05).CONCLUSION: Low sIL-2R level indicates an early stage of AE or stable status, per contra, a progression stage. Higher level of TNF-α might be related to the lesion of liver. The role of single IFN-γ is limited in immunological defense against AE and it can not fully block pathological progression.
基金This work was supported by the National Natural Science Foundation of China(No.81502589)the Natural Science Foundation of Guangdong(No.408140352062 and 2014A030310481)+1 种基金the Science and Technology Project of Shenzhen(CXZZ20130515092016300 and JCYJ20160422142707177)the China Postdoctoral Science Foundation(No.2018M631046).
文摘Lung cancer is the leading cause of cancer mortality worldwide.Dendritic cells(DCs)are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in lung cancer patients.It is evident that the immunoregulatory network may play a key role in the failure of the immune response to terminate tumors.Lung tumors likely employ numerous strategies to suppress DC-based anti-tumor immunity.Here,we summarize the recent advances in our understanding on lung tumor-induced immunosuppression in DCs,which affects the initiation and development of T-cell responses.We also describe which existing measures to restore DC function may be useful for clinical treatment of lung tumors.Furthering our knowledge of how lung cancer cells alter DC function to generate a tumor-supportive environment will be essential in order to guide the design of new immunotherapy strategies for clinical use.
基金the National Key R&D Program of China(No.2018YFC1105300)the National Natural Science Foundation of China(Nos.51703230 and 21776021)+3 种基金the Bejjing Natural Science Foundation(No.7182110)the Cross Training Plan for High Level Talents in Beiingthe Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2017039)the Presidential Foundation of Technical Institute of Physics and Chemistry.
文摘As a typical plant virus which has biocompatibility and high transfection efficiency,tobacco mosaic virus(TMV)has shown broad application potential in drug or gene delivery field.Elucidating its intracellular trafficking is of great importance in investigation of its cytotoxicity,targeting site,and delivery efficiency,and is advantageous to designing new TMV-based drug delivery systems with different targets.By taking advantage of the regulated pH value of different organelles in a mammalian cell,we exploit a pH detection strategy to investigate the intracellular trafficking pathway of TMV.Here,we report a single-wavelength excited ratiometric fluorescent pH probe.This probe is constructed by simultaneously coupling pH-sensitive fluorescein isothiocyanate(FITC)and pH-insensitive rhodamine B isothiocyanate(RBIRC)onto the inner surface of TMV.The fluorescence intensity ratio of FITC to RBITC excited at 488 nm responds specifically towards pH value over other interferential agents.By taking use of this single-wavelength excited ratiometric pH probe and confocal laser scanning microscopy,it is shown that the endocytosed TMV is located in a pH decreasing microenvironment and eventually enters lysosomes.This work may provide important guidance on construction of TMV-based nano carriers.
基金We thank our colleagues Ya-Ying Zhou, Chun-Yan Deng and Li-Li Ren for their technical assistance. This work was supported by the National Natural Science Foundation of China (No. 81270857), the Natural Science Foundation of Guangdong (No. $2013010014832), and the Science and Technology Project of Shenzhen (JCYJ20120618153743791, GJHZ20120618153934353).
文摘Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivoby transplanting MSCs into normal and diabetic rats viathe tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting mutes and microenvironments can lead to divergent immunogenicity of MSCs.