Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of deat...Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.展开更多
Purpose:This study aims to elucidate the electrotaxis response of alveolar epithelial cells(AECs)in direct-current electric fields(EFs),explore the impact of EFs on the cell fate of AECs,and lay the foundation for fut...Purpose:This study aims to elucidate the electrotaxis response of alveolar epithelial cells(AECs)in direct-current electric fields(EFs),explore the impact of EFs on the cell fate of AECs,and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.Methods:AECs were extracted from rat lung tissues using magnetic-activated cell sorting.To elucidate the electrotaxis responses of AECs,different voltages of EFs(0,50,100,and 200 mV/mm)were applied to two types of AECs,respectively.Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs.Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration.To further demonstrate the impact of EFs on the pulmonary tissue,the human bronchial epithelial cells transformed with Ad12-SV402B(BEAS-2B cells)were obtained and experimented under the same conditions as AECs.To determine the influence on cell fate,cells underwent electric stimulation were collected to perform Western blot analysis.Results:The successful separation and culturing of AECs were confirmed through immunofluorescence staining.Compared with the control,AECs in EFs demonstrated a significant directionality in a voltage-dependent way.In general,type I alveolar epithelial cells migrated faster than type II alveolar epithelial cells,and under EFs,these two types of cells exhibited different response threshold.For type II alveolar epithelial cells,only EFs at 200 mV/mm resulted a significant difference to the velocity,whereas for,EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference.Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.Conclusion:EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects,which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.展开更多
Purpose:To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury.Methods:Twenty female healthy goats were randomly divided ...Purpose:To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury.Methods:Twenty female healthy goats were randomly divided into three groups by different driving pressures:4.0 MPa group(n=4),4.5 MPa group(n=12)and 5.0 MPa group(n=4).The severe blast lung injury model of goats was established using a BST-I bio-shock tube.Vital signs(respiration,heart rate and blood pressure),lung ultrasound score(LUS),PO2/FiO2 and extravascular lung water(EVLW)were measured before injury(0 h)and at 0.5 h,3 h,6 h,9 h,12 h after injury.Computed tomography scan was performed before injury(0 h)and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume.The correlation of LUS with PaO2/FiO2,EVLW,and lung injury ratio(lesion volume/total lung volume*100%)was analyzed.All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination.Statistical analysis was performed by the SPSS 22.0 software.The measurement data were expressed as mean±standard deviation.The means of two samples were compared using independent-sample t-test.Pearson correlation analysis was conducted.Results:(1)At 12 h after injury,the mortality of goats was 0,41.67% and 100%in the 4.0 Mpa,4.5 MPa and 5.0 MPa groups,respectively;the area of pulmonary hemorrhage was 20.00%±13.14% in the 4.0 Mpa group and 42.14%±15.33% in the 4.5 MPa group.A severe lung shock injury model was established under the driving pressure of 4.5 MPa.(2)The respiratory rate,heart rate,LUS and EVLW were significantly increased,while PaO2/FiO2 was significantly reduced immediately after injury,and then they gradually recovered and became stabilized at 3 h after injury.(3)LUS was positively correlated with EVLW(3 h:r=-0.597,6 h:r=-0.698,9 h:r=-0.729;p<0.05)and lung injury ratio(12 h:r=-0.884,p<0.05),negatively correlated with PaO2/FiO2(3 h:r=-0.871,6 h:r=-0.637,9 h:r=-0.658;p<0.05).Conclusion:We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.展开更多
In this work,a comparative study of three frequently employed modification techniques to g-C_(3)N_(4)(CN)nanosheets for the photocatalytic degradation of metribuzin(MET)under visible-light irradiation has been carried...In this work,a comparative study of three frequently employed modification techniques to g-C_(3)N_(4)(CN)nanosheets for the photocatalytic degradation of metribuzin(MET)under visible-light irradiation has been carried out in detail.The modification methods were coupling TiO_(2)nanoparticles(TO)as electron acceptors,nano-sized Fe_(2)O_(3)(FO)to construct a Z-scheme nanocomposite,and phosphate(HP)modification to promote O_(2)adsorption.The steady-state and transient-state surface photovoltage spectra and transient photoluminescence(PL)spectra confirmed that all the three modification techniques enhanced the charge separation with prolonged lifetimes and presented degradation activities in the order of TO/CN[FO/CN[HP/CN.The TO/CN nanocomposite showed the highest photocatalytic activity for MET degradation,with a sixfold higher rate than bulk CN.Liquid chromatography–tandem mass spectrometry and radical trapping experiments indicated that the increased activity was related to the synergetic effect of two radicals(·O^(2-) and ·OH)involved in the photocatalytic degradation pathway,which was different from the·OH radical-dominated pathway of bulk CN.This work reveals the importance of charge separation and the influence of the radical pathway and provides guidance for the design of high-efficiency photocatalysts.展开更多
Purpose:The incidence of acute lung injury(ALI)in severe trauma patients is 48%and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%.Alveolar epithelial type 1 cells(AEC1...Purpose:The incidence of acute lung injury(ALI)in severe trauma patients is 48%and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%.Alveolar epithelial type 1 cells(AEC1 s)and type 2 cells(AEC2s)are the key cells in the repair of injured lungs as well as fetal lung development.Therefore,the purification and culture of AECls and AEC2s play an important role in the research of repair and regeneration of lung tissue.Methods:Sprague-Dawley rats(3-4 weeks,120-150 g)were purchased for experiment.Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells,and then magnetic bead cell sorting was performed to isolate Tla positive cells as AECls from the single-cell suspension by using polyclonal rabbit anti-Tla(a specific AECls membrane protein)antibodies combined with anti-rabbit IgG microbeads.Afterwards,alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining Tla-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads.Cell purity was identified by immunofluorescence staining and flow cytometry.Resii沾••The purity of AECls and AEC2s was 88.3%±3.8%and 92.6%±2.7%,respectively.The cell growth was observed as follows:AECls stretched within the 12-16 h,but the cells proliferated slowly;while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days.Conclusion:AECls and AEC2s sorted by this method have high purity and good viability.Therefore,our method provides a new approach for the isolation and culture of AECls and AEC2s as well as a new strategy for the research of lung repair and regeneration.展开更多
基金supported by the National Natural Science Foundation of China(82222038,82020108021 and 82260372)the Chongqing Special Project for Academicians(cstc2020yszx-jcyjX0004)the Chongqing Outstanding Youth Foundation and Science Foundation for Outstanding Youth of the Army Medical Centre(2019CXJSB004)。
文摘Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
基金National Natural Science Foundation of China(82272908,81672287,82222038)Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX1110)+1 种基金Open Project Program of the State Key Laboratory of Trauma,Burn and Combined Injury(SKLYQ202102,SKLKF2022011)Daping Hospital of Army Medical University(2019CXJSB004,2019CXJSC024)。
文摘Purpose:This study aims to elucidate the electrotaxis response of alveolar epithelial cells(AECs)in direct-current electric fields(EFs),explore the impact of EFs on the cell fate of AECs,and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.Methods:AECs were extracted from rat lung tissues using magnetic-activated cell sorting.To elucidate the electrotaxis responses of AECs,different voltages of EFs(0,50,100,and 200 mV/mm)were applied to two types of AECs,respectively.Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs.Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration.To further demonstrate the impact of EFs on the pulmonary tissue,the human bronchial epithelial cells transformed with Ad12-SV402B(BEAS-2B cells)were obtained and experimented under the same conditions as AECs.To determine the influence on cell fate,cells underwent electric stimulation were collected to perform Western blot analysis.Results:The successful separation and culturing of AECs were confirmed through immunofluorescence staining.Compared with the control,AECs in EFs demonstrated a significant directionality in a voltage-dependent way.In general,type I alveolar epithelial cells migrated faster than type II alveolar epithelial cells,and under EFs,these two types of cells exhibited different response threshold.For type II alveolar epithelial cells,only EFs at 200 mV/mm resulted a significant difference to the velocity,whereas for,EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference.Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.Conclusion:EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects,which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.
基金supported by State Key Laboratory of Trauma,Burns and Combined Injury Project(No.SKLYQ201901,No.SKLKF201801).
文摘Purpose:To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury.Methods:Twenty female healthy goats were randomly divided into three groups by different driving pressures:4.0 MPa group(n=4),4.5 MPa group(n=12)and 5.0 MPa group(n=4).The severe blast lung injury model of goats was established using a BST-I bio-shock tube.Vital signs(respiration,heart rate and blood pressure),lung ultrasound score(LUS),PO2/FiO2 and extravascular lung water(EVLW)were measured before injury(0 h)and at 0.5 h,3 h,6 h,9 h,12 h after injury.Computed tomography scan was performed before injury(0 h)and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume.The correlation of LUS with PaO2/FiO2,EVLW,and lung injury ratio(lesion volume/total lung volume*100%)was analyzed.All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination.Statistical analysis was performed by the SPSS 22.0 software.The measurement data were expressed as mean±standard deviation.The means of two samples were compared using independent-sample t-test.Pearson correlation analysis was conducted.Results:(1)At 12 h after injury,the mortality of goats was 0,41.67% and 100%in the 4.0 Mpa,4.5 MPa and 5.0 MPa groups,respectively;the area of pulmonary hemorrhage was 20.00%±13.14% in the 4.0 Mpa group and 42.14%±15.33% in the 4.5 MPa group.A severe lung shock injury model was established under the driving pressure of 4.5 MPa.(2)The respiratory rate,heart rate,LUS and EVLW were significantly increased,while PaO2/FiO2 was significantly reduced immediately after injury,and then they gradually recovered and became stabilized at 3 h after injury.(3)LUS was positively correlated with EVLW(3 h:r=-0.597,6 h:r=-0.698,9 h:r=-0.729;p<0.05)and lung injury ratio(12 h:r=-0.884,p<0.05),negatively correlated with PaO2/FiO2(3 h:r=-0.871,6 h:r=-0.637,9 h:r=-0.658;p<0.05).Conclusion:We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21971057 and U1805255)the Natural Science Foundation of Heilongjiang Province(Nos.YQ2019B006 and LH2020B012)+2 种基金the Postdoctoral Research Foundation of Heilongjiang Province(No.LBH-Q19052)the Outstanding Youth Fund of Heilongjiang University(No.JCL201901)the Basic Scientific Research Expenses of Colleges and Universities in Heilongjiang Province(No.2020-KYYWF-1008).
文摘In this work,a comparative study of three frequently employed modification techniques to g-C_(3)N_(4)(CN)nanosheets for the photocatalytic degradation of metribuzin(MET)under visible-light irradiation has been carried out in detail.The modification methods were coupling TiO_(2)nanoparticles(TO)as electron acceptors,nano-sized Fe_(2)O_(3)(FO)to construct a Z-scheme nanocomposite,and phosphate(HP)modification to promote O_(2)adsorption.The steady-state and transient-state surface photovoltage spectra and transient photoluminescence(PL)spectra confirmed that all the three modification techniques enhanced the charge separation with prolonged lifetimes and presented degradation activities in the order of TO/CN[FO/CN[HP/CN.The TO/CN nanocomposite showed the highest photocatalytic activity for MET degradation,with a sixfold higher rate than bulk CN.Liquid chromatography–tandem mass spectrometry and radical trapping experiments indicated that the increased activity was related to the synergetic effect of two radicals(·O^(2-) and ·OH)involved in the photocatalytic degradation pathway,which was different from the·OH radical-dominated pathway of bulk CN.This work reveals the importance of charge separation and the influence of the radical pathway and provides guidance for the design of high-efficiency photocatalysts.
基金the National Natural Science Foundation of China(82020108021 and 81530063)the Projects of the State Key Laboratory of Trauma,Burns and Combined Injury(SKLYQ201901)+1 种基金the Chongqing Science and Technology Talents,Chongqing Special Project for Academicians(cstc2020yszx-jcyjX0004)the Training Plan for Innovation Ability on the Frontiers of Military Medical Research(2019CXJSB014).
文摘Purpose:The incidence of acute lung injury(ALI)in severe trauma patients is 48%and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%.Alveolar epithelial type 1 cells(AEC1 s)and type 2 cells(AEC2s)are the key cells in the repair of injured lungs as well as fetal lung development.Therefore,the purification and culture of AECls and AEC2s play an important role in the research of repair and regeneration of lung tissue.Methods:Sprague-Dawley rats(3-4 weeks,120-150 g)were purchased for experiment.Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells,and then magnetic bead cell sorting was performed to isolate Tla positive cells as AECls from the single-cell suspension by using polyclonal rabbit anti-Tla(a specific AECls membrane protein)antibodies combined with anti-rabbit IgG microbeads.Afterwards,alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining Tla-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads.Cell purity was identified by immunofluorescence staining and flow cytometry.Resii沾••The purity of AECls and AEC2s was 88.3%±3.8%and 92.6%±2.7%,respectively.The cell growth was observed as follows:AECls stretched within the 12-16 h,but the cells proliferated slowly;while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days.Conclusion:AECls and AEC2s sorted by this method have high purity and good viability.Therefore,our method provides a new approach for the isolation and culture of AECls and AEC2s as well as a new strategy for the research of lung repair and regeneration.
