Intraoperative awareness is a very serious complication of general anesthesia. Several studies have evaluated the potential association between bispectral index (BIS) and intraoperative awareness, however, the resul...Intraoperative awareness is a very serious complication of general anesthesia. Several studies have evaluated the potential association between bispectral index (BIS) and intraoperative awareness, however, the results obtained were controversial. Therefore, we performed a metaanalysis to further assess the association between the BIS monitoring and the incidence of intraoperative awareness. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to Feb. 2017. A total of five studies with 17 432 cases and 16 749 controls were included. An odds ratio (OR) and a 95% confidence interval (CI) were calculated to examine the strength of the association. The results showed that in the overall analysis, the association between the BIS monitoring and the incidence of intraoperative awareness was not significant (OR=0.58, 95% CI= 0.22-1.58, P=0.29). A stratified analysis by comparing different anesthesia methods revealed that BIS monitoring group showed a lower incidence of intraoperative awareness in patients with intravenous anesthesia when compared with non-BIS monitoring group (OR=0.20, 95% CI=0.08-0.49, P=-0.0004), whereas there was no statistically significant difference in the incidence of intraoperative awareness between BIS and non-BIS monitoring groups in patients with inhalation anesthesia (OR=1. 13, 95% CI=0.56- 2.26, P=-0.73). In conclusion, our meta-analysis showed that BIS monitoring had no appreciable advantage in the reduction of the intraoperative awareness incidence in inhalation anesthesia, while showed a remarkable superiority in intravenous anesthesia.展开更多
Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also calle...Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.展开更多
Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in ...Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.展开更多
Objective This work explores the impact of electroacupuncture(EA)on acute postoperative pain(APP)and the role of stimulator of interferon genes/type-1 interferon(STING/IFN-1)signaling pathway modulation in the analges...Objective This work explores the impact of electroacupuncture(EA)on acute postoperative pain(APP)and the role of stimulator of interferon genes/type-1 interferon(STING/IFN-1)signaling pathway modulation in the analgesic effect of EA in APP rats.Methods The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36(Zusanli)and SP6(Sanyinjiao)acupoints.Mechanical,thermal and cold sensitivity tests were performed to measure the pain threshold,and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP.Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation.A STING inhibitor(C-176)was administered intrathecally to verify its role in EA.Results APP rats displayed mechanical and thermal hypersensitivities compared to the control group(P<0.05).APP significantly reduced the amplitude ofθ,αandγoscillations compared to their baseline values(P<0.05).Interestingly,expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP(P<0.05).Further,APP increased pro-inflammatory factors,including interleukin-6,tumor necrosis factor-αand inducible nitric oxide synthase,and downregulated anti-inflammatory factors,including interleukin-10 and arginase-1(P<0.05).EA effectively attenuated APP-induced painful hypersensitivities(P<0.05)and restored theθ,αandγpower in APP rats(P<0.05).Meanwhile,EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response(P<0.05).Furthermore,STING/IFN-1 was predominantly expressed in isolectin-B4-or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn.Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP(P<0.05).Conclusion EA can generate robust analgesic and anti-inflammatory effects on APP,and these effects may be linked to activating the STING/IFN-1 pathway,suggesting that STING/IFN-1 may be a target for relieving APP.展开更多
Purpose:Child head injury under impact scenarios(e.g.falls,vehicle crashes,etc.)is an important topic in the field of injury biomechanics.The head of piglet was commonly used as the surrogate to investigate the biomec...Purpose:Child head injury under impact scenarios(e.g.falls,vehicle crashes,etc.)is an important topic in the field of injury biomechanics.The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties.However,up to date,piglet head models with accurate geometry and material properties,which have been validated by impact experiments,are seldom.We aim to develop such a model for future research.Methods:In this study,first,the detailed anatomical structures of the piglet head,including the skull,suture,brain,pia mater,dura mater,cerebrospinal fluid,scalp and soft tissue,were constructed based on CT scans.Then,a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models.Finally,the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model.Results:Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature.The average peak force and duration of the guide drop tower test were similar to that of the simulation,with an error below 10%.The inaccuracy was below 20%.The average peak force and duration reported in the literature were comparable to those of the simulation,with the exception of the duration for an impact energy of 11 J.The results showed that the model was capable to capture the response of the pig head.Conclusion:This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.展开更多
Coronavirus disease 2019(COVID-19)is a newly emerging infectious disease.After its outbreak,researchers started a large number of clinical interventional studies,using a variety of interventions to study the different...Coronavirus disease 2019(COVID-19)is a newly emerging infectious disease.After its outbreak,researchers started a large number of clinical interventional studies,using a variety of interventions to study the different types of COVID-19 cases.In this article,we searched the websites of Chinese Clinical Trial Registry,Clinical Trials.gov,etc.,to study the publicly registered research information.Through the classification and summary of interventional methods,evaluation indicators,research design,etc.,this article provided readers with the outline of clinical research about COVID-19,and looked forward to the scientificity,feasibility,and future evidence of the clinical researches.展开更多
基金Project(U19A2088)supported by the National Natural Science Foundation of ChinaProject(2019RS2058)supported by the Special Fund for Innovative Construction of Hunan Province,China。
基金This work was supported by the Natural Science Foundation of Hubei (No. 2016CFB167, 2017CFB267).
文摘Intraoperative awareness is a very serious complication of general anesthesia. Several studies have evaluated the potential association between bispectral index (BIS) and intraoperative awareness, however, the results obtained were controversial. Therefore, we performed a metaanalysis to further assess the association between the BIS monitoring and the incidence of intraoperative awareness. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to Feb. 2017. A total of five studies with 17 432 cases and 16 749 controls were included. An odds ratio (OR) and a 95% confidence interval (CI) were calculated to examine the strength of the association. The results showed that in the overall analysis, the association between the BIS monitoring and the incidence of intraoperative awareness was not significant (OR=0.58, 95% CI= 0.22-1.58, P=0.29). A stratified analysis by comparing different anesthesia methods revealed that BIS monitoring group showed a lower incidence of intraoperative awareness in patients with intravenous anesthesia when compared with non-BIS monitoring group (OR=0.20, 95% CI=0.08-0.49, P=-0.0004), whereas there was no statistically significant difference in the incidence of intraoperative awareness between BIS and non-BIS monitoring groups in patients with inhalation anesthesia (OR=1. 13, 95% CI=0.56- 2.26, P=-0.73). In conclusion, our meta-analysis showed that BIS monitoring had no appreciable advantage in the reduction of the intraoperative awareness incidence in inhalation anesthesia, while showed a remarkable superiority in intravenous anesthesia.
基金supported by the National Natural Science Foundation of China,Nos.81901994(to BZ)and 81571147(to XXX)the Natural Science Foundation of Hubei Province,China,No.2019CFC847(to WWG)the Fundamental Research Funds for the Central Universities,China,No.2042018kf0149(to ML)
文摘Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.
基金financially supported by grants from the Macao Science and Technology Development Fund(0032/2018/AFJ,0003/2019/AKP,and 0010/2020/A1)the Key Program in Emerging Industry of the Hunan Department of Science&Technology(2014GK1058)funded by Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(001/2020/ALC)supported by the Macao Science and Technology Development Fund。
文摘Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.
基金This work was supported by the National Natural Science Foundation of China(Grant No.82071251)National Key Research and Development Program of China(Grant No.2018YFC2001802)Hubei Province Key Research and Development Program(Grant No.2021BCA145).
文摘Objective This work explores the impact of electroacupuncture(EA)on acute postoperative pain(APP)and the role of stimulator of interferon genes/type-1 interferon(STING/IFN-1)signaling pathway modulation in the analgesic effect of EA in APP rats.Methods The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36(Zusanli)and SP6(Sanyinjiao)acupoints.Mechanical,thermal and cold sensitivity tests were performed to measure the pain threshold,and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP.Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation.A STING inhibitor(C-176)was administered intrathecally to verify its role in EA.Results APP rats displayed mechanical and thermal hypersensitivities compared to the control group(P<0.05).APP significantly reduced the amplitude ofθ,αandγoscillations compared to their baseline values(P<0.05).Interestingly,expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP(P<0.05).Further,APP increased pro-inflammatory factors,including interleukin-6,tumor necrosis factor-αand inducible nitric oxide synthase,and downregulated anti-inflammatory factors,including interleukin-10 and arginase-1(P<0.05).EA effectively attenuated APP-induced painful hypersensitivities(P<0.05)and restored theθ,αandγpower in APP rats(P<0.05).Meanwhile,EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response(P<0.05).Furthermore,STING/IFN-1 was predominantly expressed in isolectin-B4-or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn.Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP(P<0.05).Conclusion EA can generate robust analgesic and anti-inflammatory effects on APP,and these effects may be linked to activating the STING/IFN-1 pathway,suggesting that STING/IFN-1 may be a target for relieving APP.
基金National Natural Science Foundation of China(Grant No.51975041No.51505024)Funding of Ministry of Industry and Information Technology for Civil Aircraft(Grant No.MJ-2018-F-18)。
文摘Purpose:Child head injury under impact scenarios(e.g.falls,vehicle crashes,etc.)is an important topic in the field of injury biomechanics.The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties.However,up to date,piglet head models with accurate geometry and material properties,which have been validated by impact experiments,are seldom.We aim to develop such a model for future research.Methods:In this study,first,the detailed anatomical structures of the piglet head,including the skull,suture,brain,pia mater,dura mater,cerebrospinal fluid,scalp and soft tissue,were constructed based on CT scans.Then,a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models.Finally,the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model.Results:Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature.The average peak force and duration of the guide drop tower test were similar to that of the simulation,with an error below 10%.The inaccuracy was below 20%.The average peak force and duration reported in the literature were comparable to those of the simulation,with the exception of the duration for an impact energy of 11 J.The results showed that the model was capable to capture the response of the pig head.Conclusion:This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.
基金supported by the National Major Scientific Research Project(2017ZX10305501)。
文摘Coronavirus disease 2019(COVID-19)is a newly emerging infectious disease.After its outbreak,researchers started a large number of clinical interventional studies,using a variety of interventions to study the different types of COVID-19 cases.In this article,we searched the websites of Chinese Clinical Trial Registry,Clinical Trials.gov,etc.,to study the publicly registered research information.Through the classification and summary of interventional methods,evaluation indicators,research design,etc.,this article provided readers with the outline of clinical research about COVID-19,and looked forward to the scientificity,feasibility,and future evidence of the clinical researches.