1.Mechanistic study of endothelial cell division cycle protein 42 in pulmo-nary vascular barrier injury during acute lung injury
Wen XU ; Jiafei LI ; Fang WANG ; Nanlin WU ; Lilong QIN
Chinese Journal of Pathophysiology 2025;41(4):704-713
AIM:This study aims to investigate the potential mechanism of cell division cycle protein 42(Cdc42)in acute lung injury(ALI).METHODS:(1)The levels of Cdc42 and IQ motif-containing GTPase-activating protein 1(IQGAP1)in ALI were analyzed using the Gene Expression Omnibus(GEO)database.(2)The plasma samples were collected from 30 patients diagnosed with ALI and 30 healthy controls between January 2022 and December 2023.The bronchoalveolar lavage fluid(BALF)from ALI patients was also collected.Eighteen male C57BL/6 mice were ran-domly divided into control(CON)group,lipopolysaccharide(LPS)group,and LPS+ML141(Cdc42 inhibitor)group,with 6 mice in each group.After 72 h,the mice were euthanized,and the BALF was collected for analysis,including cell enumeration and protein concentration determination using the bicinchoninic acid method.Enzyme-linked immunosorbent assay was used to measure the levels of Cdc42 and inflammatory cytokines[interleukin-6(IL-6),IL-1β and tumor necro-sis factor α(TNF-α)]in human plasma and mouse BALF.Lung damage in mouse tissue sections was evaluated by HE staining.(3)Mouse pulmonary microvascular endothelial cells(PMVECs)were isolated by magnetic bead-based cell sorting and were divided into CON,LPS and LPS+ML141 groups.Vascular ring formation assay was conducted to assess the an-giogenic potential of PMVECs,and calcium ion imaging technology was employed to measure calcium ion concentrations in PMVECs.The levels of reactive oxygen species(ROS)were assessed using a ROS detection kit.Western blot was uti-lized to analyze the protein levels of Cdc42,VE-cadherin,intercellular adhesion molecule-1(ICAM-1),myosin light chain(MLC),phosphorylated MLC(p-MLC)and IQGAP1 in PMVECs.RESULTS:(1)The GEO database analysis re-vealed significant up-regulation of Cdc42 expression in ALI model(P<0.01).(2)Clinical assessments showed markedly elevated plasma levels of Cdc42 and pro-inflammatory cytokines(IL-6,IL-1β and TNF-α)in ALI patients(P<0.01),with subsequent reductions after treatment(P<0.05).Neutrophil counts in the BALF of ALI patients were significantly in-creased.In ALI animal models,cell count,protein concentration and inflammatory mediator levels in BALF,and lung tis-sue damage scores were significantly elevated(P<0.01),all of which were notably reduced after treatment with Cdc42 in-hibitor ML141(P<0.05).(3)The PMVECs in LPS group exhibited significant increases in Cdc42,ICAM-1,p-MLC,IQGAP1,ROS,and calcium ion concentrations(P<0.01),alongside significant decreases in VE-cadherin expression and angiogenic capacity(P<0.01).All parameters were significantly improved after ML141 treatment(P<0.05).CON-CLUSION:The Cdc42 may influence IQGAP1 by modulating calcium levels in PMVECs,playing a critical role in pulmo-nary vascular barrier injury during ALI.
2.Mechanistic study of endothelial cell division cycle protein 42 in pulmo-nary vascular barrier injury during acute lung injury
Wen XU ; Jiafei LI ; Fang WANG ; Nanlin WU ; Lilong QIN
Chinese Journal of Pathophysiology 2025;41(4):704-713
AIM:This study aims to investigate the potential mechanism of cell division cycle protein 42(Cdc42)in acute lung injury(ALI).METHODS:(1)The levels of Cdc42 and IQ motif-containing GTPase-activating protein 1(IQGAP1)in ALI were analyzed using the Gene Expression Omnibus(GEO)database.(2)The plasma samples were collected from 30 patients diagnosed with ALI and 30 healthy controls between January 2022 and December 2023.The bronchoalveolar lavage fluid(BALF)from ALI patients was also collected.Eighteen male C57BL/6 mice were ran-domly divided into control(CON)group,lipopolysaccharide(LPS)group,and LPS+ML141(Cdc42 inhibitor)group,with 6 mice in each group.After 72 h,the mice were euthanized,and the BALF was collected for analysis,including cell enumeration and protein concentration determination using the bicinchoninic acid method.Enzyme-linked immunosorbent assay was used to measure the levels of Cdc42 and inflammatory cytokines[interleukin-6(IL-6),IL-1β and tumor necro-sis factor α(TNF-α)]in human plasma and mouse BALF.Lung damage in mouse tissue sections was evaluated by HE staining.(3)Mouse pulmonary microvascular endothelial cells(PMVECs)were isolated by magnetic bead-based cell sorting and were divided into CON,LPS and LPS+ML141 groups.Vascular ring formation assay was conducted to assess the an-giogenic potential of PMVECs,and calcium ion imaging technology was employed to measure calcium ion concentrations in PMVECs.The levels of reactive oxygen species(ROS)were assessed using a ROS detection kit.Western blot was uti-lized to analyze the protein levels of Cdc42,VE-cadherin,intercellular adhesion molecule-1(ICAM-1),myosin light chain(MLC),phosphorylated MLC(p-MLC)and IQGAP1 in PMVECs.RESULTS:(1)The GEO database analysis re-vealed significant up-regulation of Cdc42 expression in ALI model(P<0.01).(2)Clinical assessments showed markedly elevated plasma levels of Cdc42 and pro-inflammatory cytokines(IL-6,IL-1β and TNF-α)in ALI patients(P<0.01),with subsequent reductions after treatment(P<0.05).Neutrophil counts in the BALF of ALI patients were significantly in-creased.In ALI animal models,cell count,protein concentration and inflammatory mediator levels in BALF,and lung tis-sue damage scores were significantly elevated(P<0.01),all of which were notably reduced after treatment with Cdc42 in-hibitor ML141(P<0.05).(3)The PMVECs in LPS group exhibited significant increases in Cdc42,ICAM-1,p-MLC,IQGAP1,ROS,and calcium ion concentrations(P<0.01),alongside significant decreases in VE-cadherin expression and angiogenic capacity(P<0.01).All parameters were significantly improved after ML141 treatment(P<0.05).CON-CLUSION:The Cdc42 may influence IQGAP1 by modulating calcium levels in PMVECs,playing a critical role in pulmo-nary vascular barrier injury during ALI.
3.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.
4.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.
5.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.
6.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.
7.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.
8.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.
9.Study of the types of mutations of Thalassemia in Shanghai area
Yanying GU ; Beiying WU ; Yiyi LU ; Mingmin GU ; Jiafei LIN
Chinese Journal of Medical Genetics 2024;41(4):385-392
Objective:To analyze the mutations of globin genes among patients suspected for thalassemia from the Shanghai area.Methods:A total of 4 644 patients diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between June 2016 and December 2019 were selected as the study subjects. The patients were tested for common mutations associated with thalassemia gene by Gap-PCR and reverse dot blotting (RDB). Patients were suspected to harbor rare mutations based on the inconsistency between hematological phenotypes and results of common mutation detection, and were further analyzed by Gap-PCR and Sanger sequencing.Results:Among the 4 644 patients, 2 194 (47.24%) were found to carry common thalassemia mutations, among which 701 (15.09%) were α-thalassemia, 1 448 (31.18%) were β-thalassemia, and 45 (0.97%) were both α- and β-thalassemia. Forty six samples were found to harbor rare mutations, which included 17 α-globin gene and 29 β-globin gene mutations. CD77(CCC>ACC) ( HBA2: c. 232C>A) of the α-globin gene, NG_000007.3: g. 70567_71015del449, codon 102(-A) ( HBB: c. 308_308delA) and IVS-Ⅱ-636 (A>G) ( HBB: c. 316-215A>G) of the β-globin gene were previously unreported new types of globin gene mutations. Conclusion:Among the 4 644 patients, the detection rate for common thalassemia mutations was 47.24%, whilst 46 samples were detected with rare gene mutations. The type of gene mutation types were diverse in the Shanghai area. The study has provided more accurate results for genetic diagnosis and counseling.
10.Epidemiological characteristics of traumatic spinal cord injuries in the intensive care unit from 2018 to 2023:a retrospective hospital-based study
Chen WEITING ; Wu HAOPENG ; Yu JIAFEI ; Cao LANXING ; Zhang GENSHENG
World Journal of Emergency Medicine 2024;15(6):455-464
BACKGROUND:The objective of this retrospective hospital-based study was to describe the epidemiological features of traumatic spinal cord injury(TSCI)in the intensive care unit(ICU)and assess the incidence and possible risk factors for venous thromboembolism(VTE)following TSCI. METHODS:We retrospectively reviewed the medical records of 370 patients with TSCI who were admitted between January 2018 and March 2023.The following parameters were collected:age,sex,body mass index,occupation,underlying diseases,smoking history,education level,etiology of injury,injury segments,American Spinal Injury Association(ASIA)Impairment Scale score,severity of injury,injury severity score(ISS),VTE risk score(Caprini score),treatment,VTE prophylaxis,ICU length of stay,length of hospital stay,concomitant injuries,and complications.Descriptive statistics were used to summarize the demographic and clinical characteristics of the study participants.Logistic regression analysis was used to determine the risk factors for VTE. RESULTS:The mean age of patients with TSCI was 55.5±13.4 years,with a male-to-female ratio of 6.5:1.The leading cause of TSCI was falls from height(46.5%),followed by traffic accidents(36.5%).The cervical spinal cord was the most affected segment,followed by the thoracolumbar region.Among all the patients,362(97.8%)had concomitant injuries.Complications were observed in 255 patients(68.9%)during hospitalization.The incidence rate of VTE was 25.1%.Logistic regression analysis revealed that age(OR=1.721,95%CI:1.207-2.454,P=0.003),mechanical ventilation(OR=3.427,95%CI:1.873-6.271,P<0.001),and non-use of chemical prophylaxis(OR=2.986,95%CI:1.749-5.099,P<0.001)were risk factors for VTE. CONCLUSION:Falls from height and traffic accidents were the main causes of TSCIs in the ICU,especially for male patients with cervical spinal cord injuries.VTE is a frequent complication in patients with TSCI in the ICU.Age,mechanical ventilation,and non-use of chemical prophylaxis were found to be independent risk factors for VTE following TSCI.

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