Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of...Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.展开更多
Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim o...Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone （Dex） on differentiation of marrow stromal cells （MSCs）, and to investigate the pathobiological mechanism of steroid-induced osteonecrosis.Methods MSCs in cultures were treated with increasing concentrations of Dex （0, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L） continuously for 21 days. The cells, which were exposed to 0 mol/L （control） or 10^-7 mol/L Dex for 4-21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan Ⅲ. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase （ALP） of MSCs treated with 0, 10^-8, 10-7, and 10^-6 mol/L Dex for 12 days, and that treated with 0 mol/L and 10^-7 mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10^-7 mol/L Dex were detected. The mRNA expression levels of adipose-specific 422（aP2） gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10^-7 mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student＇s t test and analysis of variance. P values less than 0.05 were considered significant statistically.Results The number of adipocytes in cultures increased with the duration of MSCs＇ exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10^-7 mol/L Dex group on day 12 （t=20.51, P〈0.001）. The level of triglycerides in 10^-7 mol/L Dex group was 3.40 times of that in the control （t=11.00, P〈0.001）. The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10^-7 mol/L Dex g展开更多
The Shikani Optical StyletTM or SOS （Clarus Medical, USA） was developed as an aid to intubation for difficult airways.^1 The-SOS is composed of a J-shaped malleable body and a lens and light source at the tip and an...The Shikani Optical StyletTM or SOS （Clarus Medical, USA） was developed as an aid to intubation for difficult airways.^1 The-SOS is composed of a J-shaped malleable body and a lens and light source at the tip and an eyepiece at the proximal end. It combines the features of a fiberoptic bronchoscope and a lightwand. It can be used alone or combined with a camera or monitor and both adult and pediatric versions are available.^2.3展开更多
Background：Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy,difficult-to-access surgical sites,and the relatively low incidence of such cases.Proper evaluation a...Background：Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy,difficult-to-access surgical sites,and the relatively low incidence of such cases.Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture.The goal of this study was to assess the use of three-dimensional （3D） printing techniques for surgical management of old pelvic fractures.Methods：First,16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data.Next,nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models.The pelvic injuries were all type C,and the average time from injury to reconstruction was 11 weeks （range：8-17 weeks）.The workflow consisted of.：（1） Printing patient-specific bone models based on preoperative computed tomography （CT） scans,（2） virtual fracture reduction using the printed 3D anatomic template,（3） virtual fracture fixation using Kirschner wires,and （4） preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation.These models aided communication between surgical team members during the procedure.This technique was validated by comparing the preoperative planning to the intraoperative procedure.Results：The accuracy of the 3D printed models was within specification.Production of a model from standard CT DICOM data took 7 hours （range：6-9 hours）.Preoperative planning using the 3D printed models was feasible in all cases.Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases.The patients were followed for 3-29 months （median：5 months）.The fracture healing time was 9-17 weeks （mean：l0 weeks）.No delayed incision healing,wound infection,or nonunions occurred.The results were excellent in two cases,g展开更多
AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa a...AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9％ vs89.4％; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 ％ vs 50.4 ％; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.展开更多
AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into ...AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) 展开更多
Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation...Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation and immunity and is activated by toll-like receptor （TLR）. This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-κB activity and concentrations of tumor necrosis factor-alpha （TNF-α）, interleukin-lbeta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein： an initial peak （2-6 hours） and a sustained elevation （12-48 hours）. Immunohistochemical staining showed the inducible expression of TLR4-like immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-κB subunit p65 as well as the production of NF-κB-regulated proinflammatory cytokines （TNF-α, IL-1β and IL-6） were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-κB signaling in early brain injury. Activation of the TLR4/NF-κB signaling may regulate the inflammatory responses after SAH.展开更多
基金supported by the Natural Science Foundation of Shanghai of China,No.17ZR1425800(to KYL)the Shanghai Pudong District Health Bureau of China,No.PDZX2017-25(to KYL)
文摘Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
文摘Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone （Dex） on differentiation of marrow stromal cells （MSCs）, and to investigate the pathobiological mechanism of steroid-induced osteonecrosis.Methods MSCs in cultures were treated with increasing concentrations of Dex （0, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L） continuously for 21 days. The cells, which were exposed to 0 mol/L （control） or 10^-7 mol/L Dex for 4-21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan Ⅲ. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase （ALP） of MSCs treated with 0, 10^-8, 10-7, and 10^-6 mol/L Dex for 12 days, and that treated with 0 mol/L and 10^-7 mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10^-7 mol/L Dex were detected. The mRNA expression levels of adipose-specific 422（aP2） gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10^-7 mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student＇s t test and analysis of variance. P values less than 0.05 were considered significant statistically.Results The number of adipocytes in cultures increased with the duration of MSCs＇ exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10^-7 mol/L Dex group on day 12 （t=20.51, P〈0.001）. The level of triglycerides in 10^-7 mol/L Dex group was 3.40 times of that in the control （t=11.00, P〈0.001）. The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10^-7 mol/L Dex g
文摘The Shikani Optical StyletTM or SOS （Clarus Medical, USA） was developed as an aid to intubation for difficult airways.^1 The-SOS is composed of a J-shaped malleable body and a lens and light source at the tip and an eyepiece at the proximal end. It combines the features of a fiberoptic bronchoscope and a lightwand. It can be used alone or combined with a camera or monitor and both adult and pediatric versions are available.^2.3
基金This study was supported by grants from the National Natural Science Foundation of China，the Beijing Municipal Committee of Science and Technology
文摘Background：Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy,difficult-to-access surgical sites,and the relatively low incidence of such cases.Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture.The goal of this study was to assess the use of three-dimensional （3D） printing techniques for surgical management of old pelvic fractures.Methods：First,16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data.Next,nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models.The pelvic injuries were all type C,and the average time from injury to reconstruction was 11 weeks （range：8-17 weeks）.The workflow consisted of.：（1） Printing patient-specific bone models based on preoperative computed tomography （CT） scans,（2） virtual fracture reduction using the printed 3D anatomic template,（3） virtual fracture fixation using Kirschner wires,and （4） preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation.These models aided communication between surgical team members during the procedure.This technique was validated by comparing the preoperative planning to the intraoperative procedure.Results：The accuracy of the 3D printed models was within specification.Production of a model from standard CT DICOM data took 7 hours （range：6-9 hours）.Preoperative planning using the 3D printed models was feasible in all cases.Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases.The patients were followed for 3-29 months （median：5 months）.The fracture healing time was 9-17 weeks （mean：l0 weeks）.No delayed incision healing,wound infection,or nonunions occurred.The results were excellent in two cases,g
文摘AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9％ vs89.4％; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 ％ vs 50.4 ％; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.
基金Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China),No. 2008ZX10002-007, No. 2012ZX10002-007the Foundation of Shaanxi Provincial Science and Technology Plan Projects,No. 2011K14-09-09
文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL)
文摘Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation and immunity and is activated by toll-like receptor （TLR）. This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-κB activity and concentrations of tumor necrosis factor-alpha （TNF-α）, interleukin-lbeta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein： an initial peak （2-6 hours） and a sustained elevation （12-48 hours）. Immunohistochemical staining showed the inducible expression of TLR4-like immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-κB subunit p65 as well as the production of NF-κB-regulated proinflammatory cytokines （TNF-α, IL-1β and IL-6） were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-κB signaling in early brain injury. Activation of the TLR4/NF-κB signaling may regulate the inflammatory responses after SAH.
