1.Mechanism of warmed malate ringer's solution in fluid resuscitation in improving the lethal triad of severe trauma
Yinyu WU ; Han SHE ; Yunxia DU ; Yuxi ZHANG ; Xiaowei ZHOU ; Qinghui LI ; Tao LI ; Yi HU ; Qingxiang MAO ; Yaling WANG
Journal of Army Medical University 2025;47(3):216-225
Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200~220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P<0.05),shortened MA and decreased Angle values(P<0.05),extended tail bleeding time(P<0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P<0.05),and continuously increasing K+(P<0.05)and decreasing Na+(P<0.05)and Ca2+levels(P<0.05).Additionally,plasma vWF level(P<0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P<0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P<0.05).MR solution resuscitation shortened tail bleeding time(P<0.05),increased core body temperature(P<0.05),elevated plasma vWF level(P<0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P<0.05),and decreased that of p-Drp1 protein expression(P<0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.
2.Protective effect of remimazolam on intestinal barrier function in septic mice
Weifei WANG ; Haoyue DENG ; Yunxia DU ; Zhongyuan DU ; Liangming LIU ; Tao LI ; Qingxiang MAO
Journal of Army Medical University 2025;47(15):1806-1814
Objective To investigate the protective effects of remimazolam(Remi),a novel benzodiazepine sedative,on intestinal barrier function in septic mice.Methods A mouse model of sepsis was established using cecal ligation and puncture(CLP).A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation(Sham),sepsis(Sepsis),and sepsis with Remi intervention(Sepsis+Remi)groups.Survival rate and survival time were recorded within 72 h after modeling.Intestinal pathological alterations,barrier functional indicators,ZO-1 expression,and macrophage polarization status were observed and detected to evaluate the effects of Remi.Lipopolysaccharide(LPS)was used to treat RAW264.7 cells for 24 h to simulate in vitro sepsis model.The cells were divided into control(Control),LPS,and LPS+Remi groups.Immunofluorescence staining was performed to assess macrophage phenotype,mitochondrial morphology,and mitochondrial reactive oxygen species(MtROS),and Western blotting was applied to detect the protein expression of iNOS and CD206.Results Compared with the sepsis group,Remi intervention significantly improved the survival rate of septic mice from 12.50%to 68.75%and markedly prolonged survival duration(P<0.05).Histopathological analysis demonstrated partial restoration of intestinal villus architecture,accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention.Furthermore,the intervention group demonstrated significant improvement in functional indicators.Both in vivo and in vitro experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages(P<0.05),which were partially reversed after Remi intervention.Furthermore,LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level,whereas Remi intervention ameliorated these conditions(P<0.05).Conclusion Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.
3.Mitochondrial preconditioning of pericytes attenuates pulmonary vascular leakage in sepsis-induced rats
Zhongyuan DU ; Yiyan LIU ; Daiqin BAO ; Yibo ZHAO ; Juncai GUO ; Yuxuan LI ; Liangming LIU ; Tao LI ; Qingxiang MAO
Journal of Army Medical University 2025;47(23):2881-2892
Objective To investigate the protective effects of mitochondrial preconditioning in pericytes(PC)against pulmonary vascular leakage in septic rats.Methods ① 128 specific-pathogen-free SD rats(equal gender,200±20 g)were randomized into:Sham group(postoperative tail vein injection of 0.5 mL saline),Sepsis(Sep)group(CLP+saline),PC group(CLP+untreated PC:106 cells/rat),and Mito-PC group(CLP+PC preconditioned with 2 μg mitochondria/104 cells for 12 h).Assessments included:PC lung colonization(flow cytometry),pulmonary barrier function(Evans blue assay),lung histopathology(HE staining),serum organ injury markers[cTnT(cardiac),urea/creatinine(renal)],and inflammatory cytokines(TNF-α,IL-6).② MSC-derived mitochondria were validated by electron microscopy/flow cytometry;primary retinal PCs from weaned SD rats were purity-verified(confocal microscopy).In vitro groups:Control(PC),Mito-PC,PC+H2O2(0.5 μmol/L,4 h),and Mito-PC+H2O2.Antioxidant capacity was assessed via pentose phosphate pathway(PPP)activity,NADPH levels,G6PD activity,and NADP+/NADPH ratio.Results① Compared with Sham,Sep group showed significant increase in pulmonary leakage(Evans blue P<0.05),severe lung injury,elevated serum markers(TNF-α,IL-6,cTnT,urea,creatinine all P<0.05),0%72 h survival.PC group showed partial improvement(P<0.05).Mito-PC group demonstrated significant reduction in vascular leakage(P<0.05 vs PC group),improved histopathology and organ function(P<0.05),attenuated inflammation(P<0.05),higher 72 h survival rate(P<0.05).② Mitochondrial preconditioning significantly enhanced PPP activation and NADPH-mediated antioxidative capacity,Mito-PC+H2O2 vs PC+H2O2 showed improved cell viability(P<0.05),Mito-PC vs PC showed increased G6PD activity(P<0.05),decreased NADP+/NADPH ratio(P<0.05).Conclusion Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.Mitochondrial preconditioning potentiates pericyte-mediated protection against sepsis-induced pulmonary vascular leakage through enhanced pentose phosphate pathway activity.
4.Effects of dexmedetomidine on activation of mast cells around hematoma and neurological impairment in mouse intracerebral hemorrhage
Chongqing Medicine 2024;53(2):171-175
Objective To explore the effect of dexmedetomidine on the neurological function and mast cells activation in the mouse with intracerebral hemorrhage(ICH).Methods The mouse was intraperitoneal-ly injected with dexmedetomidine at 30 min before intracerebral hemorrhage.After the preparation of intrace-rebral hemorrhage model,the neurological function,brain water content,number of mast cells around hemato-ma and expression levels of tryptase,IL-1β,TNF-α were detected.Results Compared with the control group,the neurological function score in the intracerebral hemorrhage group was significantly elevated(P<0.05),the brain water content was significantly increased(P<0.05),the mast cells number was significantly in-creased(P<0.05),and the tryptase,IL-1β and TNF-α expression levels were sinificantly increased(P<0.05);while the neurological function score in the dexmedetomidine group was significantly decreased(P<0.05),the brain water content was significantly decreased(P<0.05),the number of mast cells was signifi-cantly reduced and the tryptase,IL-1β and TNF-α expression levels were significantly decreased(P<0.05).Conclusion Dexmedetomidine could inhibit the activation of mast cells around hematoma and reduce the dam-age of neurological function after mouse intracerebral hemorrhage.
5.Impact of changes in cognitive load of anesthesia residents on the effectiveness of high-fidelity scenario simulation teaching
Haoyu PEI ; Yi HU ; Li WANG ; Juan DAI ; Qi SUN ; Xing ZHU ; Xiaoli RAN ; Qiuping WU ; Qingxiang MAO
Chinese Journal of Medical Education Research 2024;23(4):548-555
Objective:To investigate the influence of changes in the cognitive load of anesthesia residents on the teaching effectiveness of high-fidelity scenario simulation.Methods:Eighty-seven anesthesia residents in a grade-A tertiary hospital from February to November 2022 were divided into groups A, B, and C according to the random number method. Three cases were selected from the anesthesia crisis resource teaching case library for high-fidelity simulation training for the three groups, respectively, using the crossover design to control the order of the cases. Each round of training consisted of pre-training instruction, simulation teaching, and post-training summarization and analysis. After three rounds of simulation teaching, cognitive load, anxiety status, test scores, and non-technical skills were evaluated for all the study participants. SPSS 20.0 was used to perform analysis of variance with repeated measures and Pearson's correlation analysis.Results:All the three groups showed significantly higher cognitive load and anxiety scores during the first-round simulation training than during the second-round and third-round simulation trianing. The test scores were significantly lower in the first round [(87.07±5.66), (88.38±5.41), (89.07±6.17)] than in the second round [(95.69±2.29), (96.10±2.08), (96.07±2.60)] and the third round [(96.34±1.45), (96.38±1.50), (96.17±1.73); all P<0.05]. The non-technical skill scores were also significantly lower in the first round [(37.24±7.58), (38.69±7.27), (39.24±8.74)] than in the second round [(46.17±5.55), (47.07±5.59), (47.59±6.74)] and the third round [(47.17±5.21), (48.48±5.38), (48.24±6.83); all P<0.05]. For simulations with the same cases, the trainees showed significantly higher cognitive load and anxiety scores and significantly lower test scores and non-technical skill scores in the first round than in the second and third rounds ( P<0.05). Conclusions:Anesthesia residents have higher levels of cognitive load and anxiety in the first scenario simulation training, which can reduce learning outcomes, and repeated simulation training can reduce trainees' cognitive load and anxiety.
6.Effects of dexmedetomidine on oxidative stress brain injury and NOX4 expression after mouse intracerebral hemorrhage
Chongqing Medicine 2024;53(14):2099-2103,2109
Objective To explore the effects of dexmedetomidine on oxidative stress brain injury and nicotinamide adenine dinucleotide phosphate oxidase (NOX)4 expression after intracerebral hemorrhage in mouse.Methods The mouse intracerebral hemorrhage model was prepared after 30 min intraperitoneal injec-tion of dexmedetomidine. The neurological motor function,brain water content,NOX4 mRNA content,NOX4 protein expression level and oxidative stress levels were detected.Results Compared with the control group,the neurological motor function score in the intracerebral hemorrhage group was significantly increased (P<0.05),the brain water content was increased (P<0.05),the NOX4 mRNA and NOX4 protein expression levels were significantly increased (P<0.05),the oxidative stress level was increased;but the neurological motor function score in the dexmedetomidine group was significantly decreased (P<0.05),the brain water content was significantly decreased,the NOX4 mRNA and NOX4 protein expression levels were significantly decreased (P<0.05) and the oxidative stress level was decreased.Conclusion Dexmedetomidine could inhibit the NOX4 expression after intracerebral hemorrhage and alleviate the oxidative stress brain injury in mice.
7.Mechanism of inhibiting acetyl CoA carboxylase 2 to improve cardiac dysfunction in septic mice
Yunxia DU ; Han SHE ; Yinyu WU ; Yi WANG ; Yuanqun ZHOU ; Weifei WANG ; Tao LI ; Yi HU ; Qingxiang MAO
Journal of Army Medical University 2024;46(24):2689-2697
Objective To observe the ameliorative effect of inhibiting acetyl-CoA carboxylase 2(ACC2)on cardiac dysfunction in septic mice and investigate its underlying mechanism.Methods Mouse model of sepsis was established by cecal ligation and perforation.A total of 24 male C57BL/6 mice(aged 8 weeks,weighing 20~25 g)were divided into sham operation group,sepsis group and ND-630+sepsis group.The cardiac specific ACC2 knockout(ACC2△CM)mice were constructed by Cre-LoxP recombinase system,and ACC2flox/flox Myh6-Cre-(ACC2fl/fl)mice were used as control.Several genetically engineered mice(8 weeks old,20~25 g,male)were divided into ACC2fl/fl+sham operation group,ACC2fl/fl+sepsis group,ACC2△CM+sepsis group,ACC2△CM+Mal-CoA+sepsis group,and ACC2△CM+sham operation group according to the random number table method.The contractile function and myofilament calcium sensitivity of cardiomyocytes were measured by a cell microtensiometer.Western blotting was used to detect the expression level of ACC2,and ELISA was employed to measure the level of malonyl-CoA(Mal-CoA)in myocardial tissue.The survival of the mice in 36 h after sepsis was observed.Results Compared with the sham operation group,the contraction amplitude of cardiomyocytes in sepsis group was decreased markedly,and the calcium sensitivity decreased significantly as well(P<0.05).Based on the ACC2fl/fl+sham operation group,the ACC2△CM+sepsis group showed significant improvement in myocardial contraction compared with the ACC2fl/fl+sepsis group,with the contraction amplitude of cardiomyocytes recovered by 48.1%,and significantly restored calcium sensitivity(P<0.05).ACC2△CM+Mal-CoA+sepsis group showed a notable decrease in myocardial cell contraction amplitude and a significant decrease in calcium sensitivity when compared to the ACC2△CM+sepsis group(P<0.05).Compared with the sepsis group,the contraction amplitude of cardiomyocytes in the ND-630+sepsis group increased significantly,and the calcium sensitivity of myofilament also increased(P<0.05).The expression level of ACC2 protein in the myocardial tissue of mice in the sepsis group increased compared to the sham operation group(P<0.05).The level of myocardial Mal-CoA in the sepsis group was higher than that in the sham operation group(P<0.05);Mal-CoA level in the myocardium of ACC2△CM+sepsis group mice was lower than that of sepsis group(P<0.05).The 36-hour survival rate of the ACC2△CM+sepsis group.mice was 37.5%higher than that of the ACC2fl/fl+sepsis group mice.(P<0.05).Conclusion Inhibition of ACC2 exerts a protective effect on myocardial contractility and calcium sensitivity in septic mice by reducing Mal-CoA.
8.Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023)
Yang LI ; Yuchang WANG ; Haiwen PENG ; Xijie DONG ; Guodong LIU ; Wei WANG ; Hong YAN ; Fan YANG ; Ding LIU ; Huidan JING ; Yu XIE ; Manli TANG ; Xian CHEN ; Wei GAO ; Qingshan GUO ; Zhaohui TANG ; Hao TANG ; Bingling HE ; Qingxiang MAO ; Zhen WANG ; Xiangjun BAI ; Daqing CHEN ; Haiming CHEN ; Min DAO ; Dingyuan DU ; Haoyu FENG ; Ke FENG ; Xiang GAO ; Wubing HE ; Peiyang HU ; Xi HU ; Gang HUANG ; Guangbin HUANG ; Wei JIANG ; Hongxu JIN ; Laifa KONG ; He LI ; Lianxin LI ; Xiangmin LI ; Xinzhi LI ; Yifei LI ; Zilong LI ; Huimin LIU ; Changjian LIU ; Xiaogang MA ; Chunqiu PAN ; Xiaohua PAN ; Lei PENG ; Jifu QU ; Qiangui REN ; Xiguang SANG ; Biao SHAO ; Yin SHEN ; Mingwei SUN ; Fang WANG ; Juan WANG ; Jun WANG ; Wenlou WANG ; Zhihua WANG ; Xu WU ; Renju XIAO ; Yang XIE ; Feng XU ; Xinwen YANG ; Yuetao YANG ; Yongkun YAO ; Changlin YIN ; Yigang YU ; Ke ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Gang ZHAO ; Xiaogang ZHAO ; Xiaosong ZHU ; Yan′an ZHU ; Changju ZHU ; Zhanfei LI ; Lianyang ZHANG
Chinese Journal of Trauma 2023;39(2):97-106
During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.
9.Study on protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats
Daiqin BAO ; Yiyan LIU ; Zisen ZHANG ; Han SHE ; Lei TAN ; Tao LI ; Qingxiang MAO ; Liangming LIU
China Pharmacy 2023;34(5):537-543
OBJECTIVE To investigate the protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats based on network pharmacology, and conduct experimental verification. METHODS The network pharmacology was used to predict the potential target of ziyuglycoside Ⅰ in the treatment of acute lung injury following sepsis. The rat model of sepsis was reproduced by cecum ligation and puncture for experimental verification. Totally 192 SD rats were randomly divided into the sham operation group (Sham group), sepsis group (Sep group), conventional therapy group (CT group) and ziyuglycoside Ⅰ group (Zg Ⅰ group), respectively. Sham group and Sep group were given sterile normal saline, and CT group and ZgⅠ group were given relevant volume of Ringer’s solution and ziyuglycoside Ⅰ. The arterial blood gas, serum inflammatory factors, lung wet/dry mass ratio, pathological changes of lung tissue, pulmonary vascular permeability, the expressions of pulmonary vein tight junction protein 1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) protein and 72-hour survival were observed in each group. RESULTS Results of network pharmacology showed that there were 47 potential targets of ziyuglycoside Ⅰ in the treatment of sepsis. The results of gene ontology function enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the mechanism could 598486924@qq.com be correlated with biological processes such as positive regulation of reactive oxygen species metabolism, wound healing, regulation of endothelial cell proliferation, cell activation, blood vessel development, response to oxidative stress, etc., and with signaling pathway such as apoptosis, tight junction, HIF-1 signaling pathway, etc. The results of experimental verification showed that compared with Sham group, pH value and the level of partial arterial oxygen pressure were decreased significantly in Sep group (P<0.05), while the level of partial pressure of carbon dioxide, serum levels of tumor necrosis factor α, interleukin 6 were increased significantly (P<0.05); the ratio of lung wet/dry mass was increased significantly (P<0.05); the protein expressions of ZO-1 and VE-cadherin were decreased significantly (P<0.05); 72 h survival rate decreased,the survival time was significantly shortened (P<0.05); the results of pathological observation of lung tissue showed that the rats’ alveoli were extensively ruptured, the alveolar wall was thickened and accompanied with edema, and there was obvious inflammatory cell infiltration; the results of pulmonary vascular permeability observation showed that the lung surface of rats was dark, with a large amount of Evans blue exudation, and the left lower lung was obviously dark blue. Compared with Sep group, the levels of above indexes almost were reversed significantly in CT group and ZgⅠ group (P<0.05); the lung histopathology and pulmonary vascular permeability were significantly improved, and the recovery degree of ZgⅠ group was greater than that of CT group, which was close to the results of Sham group. CONCLUSIONS Ziyuglycoside Ⅰ can significantly reduce inflammatory reaction and acute lung injury in septic rats, which is related to vascular function and tight junction signal pathway.
10. Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel coronavirus pneumonia
Yang LI ; Zhanfei LI ; Qingxiang MAO ; Ding LIU ; Letian ZHANG ; Fan YANG ; Yu XIE ; Siru ZHOU ; Huayu ZHANG ; Shanmu AI ; Hao TANG ; Qiu ZHONG ; Qingshan GUO ; Yaoli WANG ; Weiguo ZHANG ; Liyong CHEN ; Xiangjun BAI ; Lianyang ZHANG
Chinese Journal of Trauma 2020;36(2):1-7
A novel coronavirus pneumonia (NCP) epidemic has occurred in Wuhan, Hubei Province since December 2019, caused by a novel coronavirus (2019-nCoV) never been seen previously in human. China has imposed the strictest quarantine and closed management measures in history to control the spreading of the disease. However, severe trauma can still occur in the NCP patients. In order to standardize the emergency treatment and the infection prevention and control of severe trauma patients with hidden infection, suspected or confirmed infection of 2019-nCoV, Trauma Surgery Branch of Chinese Medical Doctors' Association organized this expert consensus. The consensus illustrated the classification of the NCP patients, severe trauma patients in need of emergency surgery, emergency surgery type, hierarchical protection for medical personnel and treatment places. Meanwhile, the consensus standardized the screening, injury severity evaluation, emergency surgical treatment strategy and postoperative management strategy of severe trauma patients during the epidemic period of NCP, providing a basis for the clinical treatment of such kind of patients.

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