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Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.
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Mild hypothermia, as a common means of intraoperative nerve protection, has been used in clinical practice. Compared with the traditional methods such as freezing helmet and nasopharyngeal cooling, hypothermic blood perfusion is considered to be a promising treatment for mild hypothermia, but it lacks experimental and theoretical verification of its cooling effect. In this study, the commercial finite element simulation software COMSOL combined the Pennes equation with the cerebrovascular network model to construct a new simplified human brain model, which was further used to simulate the cooling process of cerebral hypothermic blood perfusion. When the hypothermic blood perfusion was 33 ℃, the human brain could enter the mild hypothermic state within 4 minutes. By comparing with helmet cooling, the feasibility and efficiency of the blood perfusion scheme were verified. By comparing with the calculation results based on Pennes equation, the rationality of the model constructed in this study were verified. This model can non-intrusively predict the changes of brain temperature during surgery, and provide a reference for the setting of treatment parameters such as blood temperature, so as to provide personalized realization of safer and more effective mild hypothermia neuro protection.
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Humans , Hypothermia, Induced/methods , Hypothermia , Hemoperfusion , Brain/physiology , Body TemperatureABSTRACT
Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.
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Infant, Newborn , Humans , Hypothermia, Induced/methods , Hypothermia/therapy , Hyperbaric Oxygenation , Brain , Electroencephalography , Hypoxia-Ischemia, Brain/therapyABSTRACT
Background: Acute myocardial infarction (AMI) complicated with cardiogenic shock is still associated with a significant death rate. Other interventions, including intra-aortic balloon counter pulsation and medical therapy, failed to improve prognosis in large-scale randomised studies, with the exception of early revascularization. Recently, mild therapeutic hypothermia, in which patients are lowered to 33°C over the course of 24 hours, has been proposed as a therapy option for cardiogenic shock patients. The purpose of this study is to determine the impact of mild hypothermia on morbidity and mortality associated with post-AMI cardiogenic shock. Methods: This randomized, controlled, unblinded trial was conducted on 50 patients with AMI complicated by CS. Patients were randomly allocated into two equal groups; group I received MTH to 33°C for 24-36 h and group II (control group) did not receive MTH. Patients were subjected to full history taking, general and clinical examination, laboratory examination, echo, chest ultrasound (US), coronary angiography data and mild therapeutic hypothermia protocol. Results: Stroke until day 30, duration of mechanical ventilation, length of ICU stay, duration of inotropic support, mortality and pulmonary congestion by US were insignificantly different between both groups. Arterial lactate and mean arterial blood pressure (MAP) at 4h, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h were significantly increased in group I than Group II (P value<0.05). and were insignificantly different between both groups at 0h, 2h, 22h, 24h, 26h, 28h, 30h. Serum creatinine at 24h, 48h was significantly increased in group I than Group II (p value <0.05) and was insignificantly different between both groups at 0h. Conclusions: Therapeutic hypothermia (TH) didn’t improve short term outcomes in patients with post AMI cardiogenic shock.
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Hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neonatal morbidity, mortality and disability.Randomized clinical trials have confirmed the safety and effectiveness of mild hypothermia in the treatment of neonatal HIE, and it can significantly reduce the mortality and disability rate of the disease.Although mild hypothermia can improve the prognosis of some neonates with HIE, there is still some controversy about the selection of treatment subjects, the time window and whether it is effective in the resource-limited countries.This article reviews the research progress on controversial parts of mild hypothermia treatment in recent years, so as to provide the corresponding reference basis for clinical decision-making.
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Targeted temperature management mainly affects the progression of sepsis by inhibiting inflammatory response, protecting mitochondrial function and reducing metabolism, which can improve survival, the prognosis and outcome of sepsis to some extent.Targeted temperature management has a positive impact on the occurrence and development of sepsis, which may be an adjuvant treatment method of sepsis.This review summarized the mechanism studies on the impact of targeted temperature management on sepsis in recent years, and summarized the existing problems, so as to provide reference for carrying out practical research on targeted temperature management for patients with sepsis.
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Objective:To study the clinical efficacy, safety and prognosis of systemic hypothermia therapy on neonatal hypoxic-ischemic encephalopathy (HIE)initiated at different times after birth.Method:From January 2013 to August 2018, term neonates (within 12 hours after birth) diagnosed with neonatal moderate to severe HIE and received systemic treatment in the neonatal intensive care unit of our hospital were retrospectively included. According to the starting time of hypothermia therapy, the neonates were assigned into three groups: within 6 h after birth (TH1 group), 6~12 h (TH2 group) and conventional treatment group (control group). Their clinical data during perinatal period, hospitalization period and follow-up at 6-month were reviewed. Their clinical and neurodevelopmental outcomes were compared using SPSS 25.0 statistical software.Result:A total of 147 neonates with moderate to severe HIE were enrolled. 111 received 72-hour hypothermia therapy, including 79 in the TH1 group, 32 in the TH2 group and 36 in the control group. The neurobehavioral test scores at 10-day of life in the TH1 group were significantly higher than the control group ( P<0.05). No significant differences existed among the TH2 group, the TH1 group and the control group ( P>0.05). The brain magnetic resonance imaging (MRI) showed injuries in the TH1 group and the TH2 group were significantly milder than the control group ( P<0.05). No significant differences of brain injuries existed between TH1 group and TH2 group ( P>0.05). 100 patients completed Bailey Infant Intelligence Development Scale at 6-month follow-up. 21 had abnormal scores. No statistically significant differences existed in the psychomotor development index (PDI) scores among the three groups ( P>0.05). TH1 and TH2 groups had significantly fewer cases with mental development index (MDI) <70 points than the control group ( P<0.05). No statistically significant differences existed of MDI scores between the TH1 group and the TH2 group ( P>0.05). No statistically significant differences existed of PDI scores among the 3 groups ( P>0.05). At 6-month, the mortality rate of the control group (32.1%, 9/28) was significantly higher than the TH1 group (6.6%, 4/61) ( P<0.05). No significant differences existed of mortality rate at 6-month among the TH2 group, the TH1 group and the control group ( P>0.05). Conclusion:Systemic hypothermia therapy for neonatal HIE is safe. Starting systemic hypothermia therapy at 6~12-hour after birth may also be effective in reducing mortality rate and improving neurodevelopmental outcome.
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Objective To evaluate the effect of mild hypothermia on the renal ischemia-reperfusion injury (IRI), and the expression profile of RNA-binding motif protein 3(RBM3) and its downstream effector molecules during this process. Methods Eighteen healthy SD male rats were randomly divided into the normal control (NC) group, IRI group and mild hypothermia pretreat (MHP) group, with 6 rats in each group. Serum creatinine level was measured to evaluate the renal function. Hematoxylin-eosin (HE) staining was performed to assess the renal tissue injury. Western blot was used to determine the relative expression levels of RBM3, Yes-associated protein 1(YAP1), nuclear factor E2-related factor 2(Nrf2), B cell-lymphoma-2(Bcl-2) and Bcl-2-associated X protein (Bax) in the kidney tissues. Immunohistochemical staining was employed to further detect the expression levels of RBM3 and YAP1 proteins. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was adopted to detect the cell apoptosis of kidney tissues. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were evaluated to determine the oxidative stress level of kidney tissues. Results Compared with the NC group, the serum creatinine level, the pathological injury score of kidney tissues and the expression levels of RBM3, YAP1 and Nrf2 proteins were significantly up-regulated, the Bcl-2/Bax ratio was considerably lower, the apoptosis rate was remarkably elevated, the MDA content was significantly increased and the SOD activity was dramatically reduced in the IRI and MHP groups (all P < 0.05). Compared with the IRI group, the serum creatinine level and the pathological injury score of kidney tissues were significantly decreased, the expression levels of RBM3, YAP1 and Nrf2 proteins were significantly up-regulated, the Bcl-2/Bax ratio was considerably higher, the apoptosis rate was significantly decreased, the MDA content was significantly decreased and the SOD activity was considerably elevated in the MHP group (all P < 0.05). Conclusions Mild hypothermia may exert protective effect upon renal IRI and it could alleviate cell apoptosis and oxidative stress injury induced by IRI, probably by up-regulating the expression level of RBM3 and its downstream effector molecules of YAP1 and Nrf2.
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OBJECTIVES@#To analyze the differentially expressed genes (DEGs) with radiation-induced rat lung injury, and to reveal the protective mechanism for mild hypothermia in the radiation-induced lung injury in rats at the transcriptome level.@*METHODS@#A total of 10 male SD rats aged 6-8 weeks were randomly divided into 2 groups to establish a rat model of radiation-induced lung injury, and one group was treated with mild hypothermia. RNA was extracted from left lung tissue of each group, and sequenced by BGISEQ-500 platform. Significance analysis of DEGs was carried out by edgeR software. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyze the gene function. Then 5 key DEGs were verified by real-time reverse transcription PCR (real-time RT-PCR).@*RESULTS@#There were 2 790 DEGs (false discovery rate<0.001, |log@*CONCLUSIONS@#The DEGs and pathways related to mild hypothermia protection against radiation-induced lung injury in rats are obtained, which provides an experimental basis for the protection of mild hypothermia against radiation-induced lung injury.
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Animals , Male , Rats , Gene Expression Profiling , Hypothermia , Lung Injury , RNA-Seq , Rats, Sprague-Dawley , TranscriptomeABSTRACT
Cardiac dysfunction (CD) combined with sepsis leads to increase in mortality in intensive care unit (ICU). Currently, the clinical treatment of CD with sepsis is the combination of delaying heart failure and anti-sepsis therapeutics. Mild therapeutic hypothermia (MTH) may decrease the body temperature to 32-35 ℃, improve symptom and decrease mortality in patients with CD and animal with sepsis. MTH has been used in animal models of heart failure and sepsis with pronounced outcomes and reduced mortality. However, it remains controversial if MTH can be used in treating patients with CD and sepsis due to its side effects, although the effectiveness of MTH on CD and sepsis has been testified. The present article reviews the application of MTH on animal researches, clinical use for treatment of patients with CD and sepsis, the effect and possible mechanisms of temperature on heart and sepsis, as well as the effect of MTH onto other organs and coagulation function.
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BACKGROUND: 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) can decrease brain temperature, which is the potential mechanism of its neuroprotection. OBJECTIVE; To investigate the effect of 8-OH-DPAT on hypoxia inducible factor 1 a in the brain tissue of rats with diffuse axonal injury, and to explore the underlying mechanism of 8-OH-DPAT exerting neuroprotection in rats of diffuse axonal injury. METHODS; The study was approved by the Laboratory Animal Ethical Committee of General Hospital of Northern Theater Command. Wistar rats were randomly assigned into four groups: Model group (n=35), constant temperature group (n=35), 8-OH-DPAT group (n-35) and normal group (n=7). Excepting the normal group, rat models of diffuse axonal injury were established according to Marmarou method. Rat models in the constant temperature and 8-OH-DPAT were intraperitoneally injected with 8-OH-DPAT, but those in the model and normal groups were intraperitoneally injected with physiological saline. The body temperature of rats in the constant temperature group was maintained at (37.0±0.5)°C using the blanket. The body temperature of rats was measured every 1 hour. Then, brain injury and hypoxia inducible factor 1a expression level were observed at 6, 12, 24, 72, and 168 hours after diffuse axonal injury in rats. RESULTS AND CONCLUSION: (1) Compared with the constant temperature and model groups, brain temperature was significantly lower in the 8-OH-DPAT group at 1 hour following modeling (P < 0.05), became lowest at 2 hours (P < 0.05), and then gradually increased. (2) Hematoxylin-eosin staining results revealed that brain injury was more serious in the model group, followed by constant temperature group, and lightest in the 8-OH-DPAT group. (3) Results of immunohistochemistry and ELISA showed that the expression level of hypoxia inducible factor 1a in the serum and brain tissue was lowest in the normal group. In the 8-OH-DPAT group, the expression level of hypoxia inducible factor 1a was increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. Compared with the model group, the expression level of hypoxia inducible factor 1a in serum and brain tissue in the constant temperature and 8-OH-DPAT groups was significantly decreased (P < 0.05 or P < 0.01), especially the 8-OH-DPAT group (P < 0.01). (4) These results imply that 8-OH-DPAT decreases hypoxia inducible factor 1a expression in brain tissue of diffuse axonal injury rats by reducing brain temperature, alleviates the degree of nerve injury, and exerts a neuroprotective effect.
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OBJECTIVE@#To explore the effect of mild hypothermia on inflammatory response and angiogenesis in brain tissues of rats with intracerebral hemorrhage (ICH) and its possible mechanism for improving behavioral deficits of the rats After ICH.@*METHODS@#A total of 120 healthy male SD rats were randomly divided into sham operation group, ICH group and mild hypothermia group. Rat models of ICH were established in the latter two groups by stereotactic injection of autogenous blood in the brain, and the rats in the sham operation group received injection of normal saline in the same manner. At 15 min after modeling, the rats in hypothermia group were subjected to mild hypothermia (30-32 ℃) for 8 h followed by rewarming (37-38 ℃); the body temperature was maintained at 37-38 ℃ in the other two groups. At 2, 4, 7, 14 and 21 days after the treatment, Longa scoring, balance beam scoring and Berderson scoring were used to evaluate the behavioral deficits of the rats. Immunohistochemical staining was used to detect the protein expressions of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the brain tissue of the rats, and the mRNA expressions of α subunit of hypoxia-inducible factor 1 (HIF1-α) and vascular endothelial growth factor (VEGF) were detected using RT- PCR.@*RESULTS@#At 2, 4, 7, 14 and 21 days after the treatment, the behavioral scores of the rats were significantly higher in ICH group and mild induced hypothermia group than in the sham operation group ( < 0.05 or 0.01). The protein expressions of TNF-α and NF-κB and mRNA expressions of HIF1-α and VEGF were significantly higher in ICH group and mild hypothermia group than in the sham operation group ( < 0.01). The behavioral scores were significantly lower in mild hypothermia group than in ICH group ( < 0.05), and the protein expressions of TNF-α and NF-κB were lower and the mRNA expressions of HIF1- α and VEGF were higher in mild hypothermia group than in ICH group ( < 0.05 or 0.01).@*CONCLUSIONS@#Mild hypothermia can improve behavioral deficits in rats with ICH possibly by antagonizing brain inflammation and promoting angiogenesis.
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ObjectiveMild hypothermia was an effective way of cerebral resuscitation after cardiac arrest. The expression of cold-induced RNA binding protein (CIRP) was significantly enhanced when the temperature was lowered. This study was to evaluate the effects and the mechanisms of CIRP inhibition on hippocampal neurological and mitochondria function after mild hypothermia in a rat model of cardiac arrest.MethodsFive male Sprague-Dawley rats were injected with AAV9 in the hippocampus, 1 μL on each side, speeding 0.2 μL/min. The expression of GFP was observed by fluorescence microscopy after 2w. Sixty rats were randomly divided into 5 groups (n= 12 for each group): sham operation group, model group, mild hypothermia group, mild hypothermia + CIRP inhibition group and mild hypothermia + normal control group. Injection of AAV9 was performed on mild hypothermia + CIRP inhibition group, same amount of empty vector on mild hypothermia + normal control group, while normal saline on the other groups. Animal models of global cerebral IR were established by transesophageal cardiac pacing inducing cardiac arrest followed by cardiopulmonary resuscitation at 2w after injection. Cooling to 32-34℃ was initiated and the temperature was maintained for 6h on mild hypothermia groups. NDS score, HE staining and pyramidal cell counting on hippocampal CA1 area were performed at 72h after reperfusion. At 24h after reperfusion, mitochondrial structure of pyramidal cells in hippocampal CA1 was observed under electronic microscope and the expressions of CIRP, dynamin-related protein 1 (Drp1) and cytochrome C (Cyt-C) were detected by Western blot.ResultsThe NDS score of model group was decreased, the number of pyramidal cells was reduced, and the mitochondria were severely damaged. The NDS score of mild hypothermia group was increased, and the number of pyramidal cells was increased (all P<0.05), and mitochondrial damage was reduced compared with model group. In mild hypothermia + CIRP inhibition group, the NDS score was no significant difference compared with mild hypothermia + normal control group and model group, and the number of pyramidal cells was lower than that in mild hypothermia + normal control group [(27.2±4.9) vs (50.2±4.4), P<0.05], similar to model group (25.2±3.8), the damage of mitochondria was severe. After 2 weeks of AAV9 injection, GFP was widely expressed in the hippocampus. The expression of CIRP in mild hypothermia + CIRP inhibition group was respectively small compared with sham operation group [(0.14±0.03) vs (0.03±0.01),P<0.05], which was successfully inhibited by injection of AAV9. The expression of CIRP in model group (0.25±0.05) was significantly higher than that in sham operation group. The expression of CIRP in mild hypothermia group (0.37±0.08) and mild hypothermia + normal control group (0.39±0.04) were higher than that in model group (all P<0.05). The trends of Drp1 and Cyt-C expression were the same, in model group was higher than that in sham operation group, in mild hypothermia group was lower than that in model group, in mild hypothermia + CIRP inhibition group was higher than in mild hypothermia + normal control group (all P<0.05); There were no significant differences between model group and mild hypothermia + CIRP inhibition group, and between mild hypothermia group and mild hypothermia + normal control group.ConclusionInhibition of CIRP expression in hippocampus can weaken the protective effects of mild hypothermia on neurons in a rat model of cardiac arrest. The mechanism of those effects might be association with mitochondrial division.
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Objective To explore the effect of continuous renal replacement therapy (CRRT) combined with mild hypothermia (MHT) on acute severe heart failure after cardiovascular surgery. Methods A retrospective analysis was performed of 26 patients who were treated from January 2007 to January 2015 with the combined therapy of CRRT and MHT (CRRT/ MHT). Core temperature was reduced to 34 ℃. The doses of inotropes and vasopressors decreased. Mean arterial pressure (MAP) was maintained at 60-70 mmHg and cardiac index (CI) >1.5 L/(min·m2). When cardiac function was improved core temperature was recovered gradually. The dose of inotropes and the volume load increased, and the CRRT was discontinued. Comparison of outcomes was made with a matched historic ECMO control group. The core body temperature, pulmonary arterial wedge pressure, mean arterial pressure, cardiac index, the doses of inotropes and vasopressors, mean arterial pressure and cardiac index were observed and recorded. The time for supportive treatment, successful off-line rate, ICU time and hospital stay, and the survival rate during the ICU and hospital stay were compared between two groups. Results Core body temperature was maintained at (34.0±0.5) ℃ during the combined therapy; Pulmonary arterial wedge pressure, the doses of inotropes and vasopressors, MAP and CI substantially decreased during the combined therapy (P0.05). There were no major complications in CRRT/MHT group. Conclusions These findings suggest that patients with acute severe heart failure after cardiovascular surgery can benefit from a strategy of CRRT/MHT. The results have given us new insight into the treatment of these patients.
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Objective@#To evaluate the effect of mild hypothermia on the incidence of post-stroke infection and explore the relationship between mild hypothermia and outcome of stroke patients by using propensity score matching.@*Methods@#Patients hospitalized in department of intensive care unit (ICU), neurology and neurosurgery in the First Affiliated Hospital of Guangxi Medical University due to stroke from March 2012 to April 2018 were retrospectively analyzed. According to whether or not mild hypothermia was provided, they were divided into the normal thermic group (NT group) and mild hypothermia treatment group (MHT group). The MHT group patients were matched with the NT group patients by the propensity score matching method at a ratio of 1∶1. The observation period was within the first 7 days after admission. Baseline characteristics including age, gender, type of stroke, comorbidities, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) on admission, surgical operation, dysphagia, invasive procedures and outcomes of these patients had been analyzed. The primary outcome was incidence of post-stroke infection, and the secondary outcomes included the time of initial infection (TII, the duration from stroke to initial infection), hospital mortality, sequential organ failure assessment (SOFA) at discharge, incidence of complications such as arrhythmia, coagulation dysfunction and multiple organ dysfunction syndrome (MODS).@*Results@#201 stroke patients were enrolled, 41.8% (84/201) of whom underwent mild hypothermia. Comparison with NT group before matching, there were more males in MHT group (71.4% vs. 56.4%), the proportion of surgical operation, mechanical ventilation, deep vein catheterization and gastric catheterization were higher (78.6% vs. 54.7%, 84.5% vs. 39.3%, 90.5% vs. 37.6%, 98.8% vs. 70.9%), and so as incidence of infection (90.5% vs. 72.6%), in-hospital mortality (27.4% vs. 12.8%) and TII [hours: 62.00 (35.25, 93.00) vs. 42.00 (28.50, 69.50)]. All the differences were statistically significant (all P < 0.05). Fifty-three patients in the MHT group were matched with 53 patients in the NT group. After matching, there was no significant difference in 15 baseline characteristics between two groups. Significant differences in infection and hospital mortality between the MHT group and NT groups disappeared (92.5% vs. 88.7%, 22.6% vs. 26.4%, both P > 0.05), while TII of MHT group was longer than that of the NT group [hours: 62.00 (40.75, 92.25) vs. 40.00 (28.00, 63.00), P = 0.000]. There were no statistically significant differences in SOFA score or complications between the two groups either before or after matching.@*Conclusion@#Mild hypothermia had no significant effect on the incidence of post-stroke infection and hospital mortality, it could delay the occurrence of infection and provide longer duration of treatment.
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Objective To observe the effect of recombinant human erythropoietin injection (RHEI) assisted with mild hypothermia on the clinical efficacy and safety of children with hypoxic-ischemic encephalopathy (HIE). Methods From January 2015 to December 2017, 110 children with HIE were treated in Shijiazhuang No.1 Hospital. Fifty-five children with routine treatment were taken as Western medicine routine treatment group. In addition, 55 children treated with mild hypothermia combined with RHEI were taken as mild hypothermia+RHEI group. Both groups were treated for 14 days and followed up for 10 months. The neonatal behavioral neurological assessment (NBNA) score, mental development index (MDI), psychomotor development index (PDI), myelin basic protein (MBP), S100B protein and neuron specific enolization enzyme (NSE), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), insulin growth factor-1 (IGF-1), growth hormone (GH), and differences in clinical efficacy in two groups were compared, and the occurrence of adverse reactions was observed. Results The NBNA, MDI, PDI, NGF (μg/L), BDNF (ng/L), IGF-1 (pg/L), and GH (pg/L) of two groups after treatment were higher than those before treatment (the Western medicine routine treatment group: 33.72±3.19 vs. 26.81±2.38, 78.95±5.51 vs. 71.39±4.24, 79.62±4.93 vs. 71.84±4.15, 123.74±22.98 vs. 104.29±15.36, 1 518.35±174.92 vs. 1 197.28±148.43, 38.25±4.96 vs. 23.16±2.87, 39.27±5.24 vs. 20.97±3.15; the mild hypothermia+RHEI group: 39.82±3.36 vs. 26.78±2.53, 84.13±6.29 vs. 71.34±4.27, 85.26±5.74 vs. 71.88±4.13, 145.28±27.52 vs. 104.72±15.41, 1 925.71±204.37 vs. 1 192.61±150.26, 57.94±6.62 vs. 23.13±2.91, 56.43±7.14 vs. 20.94±3.17), NSE (μg/L), MBP (μg/L) and S100B (μg/L) were lower than those before treatment (the Western medicine routine treatment group: 17.05±2.26 vs. 24.96±2.83, 9.71±1.85 vs. 23.14±3.37, 0.93±0.12 vs. 1.49±0.24; the mild hypothermia+RHEI group:12.48±1.94 vs. 25.03±2.81, 5.48±1.42 vs. 23.17±3.35, 0.61±0.07 vs. 1.51±0.25). After treatment, the changes of each index in the mild hypothermia+RHEI group were more significant than those in the control group [NABA:39.82±3.36 vs. 33.72±3.19, MDI: 84.13±6.29 vs. 78.95±5.51, PDI: 85.26±5.74 vs. 79.62±4.93, NSE (μg/L):12.48±1.94 vs. 17.05±2.26, MBP (μg/L): 5.48±1.42 vs. 9.71±1.85, S100B (μg/L): 0.61±0.07 vs. 0.93±0.12, NGF (μg/L): 145.28±27.52 vs. 123.74±22.98, BDNF (ng/L): 1 925.71±204.37 vs. 1 518.35±174.92, IGF-1 (pg/L):57.94±6.62 vs. 38.25±4.96, GH (pg/L): 56.43±7.14 vs. 39.27±5.24, all P < 0.05]. The total effective rate of mild hypothermia+RHEI group was significantly higher than that of Western medicine routine treatment group [94.55% (52/55) vs. 81.82% (45/55), P < 0.05]. There were no serious adverse reactions in the two groups. Conclusion RHEI assisted with mild hypothermia therapy can significantly improve the clinical efficacy and NBNA, MDI, PDI scores of HIE children, reduce the degree of brain injury, and improve the neurological function, with good safety.
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Objective To evaluate the effect of mild hypothermia on the incidence of post-stroke infection and explore the relationship between mild hypothermia and outcome of stroke patients by using propensity score matching. Methods Patients hospitalized in department of intensive care unit (ICU), neurology and neurosurgery in the First Affiliated Hospital of Guangxi Medical University due to stroke from March 2012 to April 2018 were retrospectively analyzed. According to whether or not mild hypothermia was provided, they were divided into the normal thermic group (NT group) and mild hypothermia treatment group (MHT group). The MHT group patients were matched with the NT group patients by the propensity score matching method at a ratio of 1:1. The observation period was within the first 7 days after admission. Baseline characteristics including age, gender, type of stroke, comorbidities, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) on admission, surgical operation, dysphagia, invasive procedures and outcomes of these patients had been analyzed. The primary outcome was incidence of post-stroke infection, and the secondary outcomes included the time of initial infection (TII, the duration from stroke to initial infection), hospital mortality, sequential organ failure assessment (SOFA) at discharge, incidence of complications such as arrhythmia, coagulation dysfunction and multiple organ dysfunction syndrome (MODS). Results 201 stroke patients were enrolled, 41.8％ (84/201) of whom underwent mild hypothermia. Comparison with NT group before matching, there were more males in MHT group (71.4％ vs. 56.4％), the proportion of surgical operation, mechanical ventilation, deep vein catheterization and gastric catheterization were higher (78.6％ vs. 54.7％, 84.5％ vs. 39.3％, 90.5％ vs. 37.6％, 98.8％ vs. 70.9％), and so as incidence of infection (90.5％ vs. 72.6％), in-hospital mortality (27.4％ vs. 12.8％) and TII [hours: 62.00 (35.25, 93.00) vs. 42.00 (28.50, 69.50)]. All the differences were statistically significant (all P < 0.05). Fifty-three patients in the MHT group were matched with 53 patients in the NT group. After matching, there was no significant difference in 15 baseline characteristics between two groups.Significant differences in infection and hospital mortality between the MHT group and NT groups disappeared (92.5％ vs. 88.7％, 22.6％ vs. 26.4％, both P > 0.05), while TII of MHT group was longer than that of the NT group [hours:62.00 (40.75, 92.25) vs. 40.00 (28.00, 63.00), P = 0.000]. There were no statistically significant differences in SOFA score or complications between the two groups either before or after matching. Conclusion Mild hypothermia had no significant effect on the incidence of post-stroke infection and hospital mortality, it could delay the occurrence of infection and provide longer duration of treatment.
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Objective Mild hypothermia (MHT) can effectively protect the brain in traumatic brain injury (TBI). This study was to investigate the effects of MHT on the calmodulin (CAM) expression and brain edema in the rat model of TBI. Methods Ninety adult SD rats were randomly divided into a sham operation, a normal temperature and an MHT group of equal number. Immediately after TBI, the rats of the MHT group maintained at a rectal temperature of (32 ± 0.5) °C for 6 hours. Modified neurological severity scores (mNSS) were obtained from 6 rats in each group at 1, 3, 5 and 7 days after modeling, and the rest of the animals subjected to brain MRI at 6, 12, 24 and 48 hours and then killed for determination of the CAM gene transcription and protein expression in the brain tissue by real-time PCR, immunohistochemistry and Western blot. Results The mNSSs were significantly higher in the MHT and normal temperature groups than in the sham operation control (P < 0.05) at all time points, neurological severity markedly decreased in the MHT group compared with the normal temperature group (P < 0.05). At 6, 12, 24 and 48 hours, the expression of CAM mRNA was remarkably down-regulated in the MHT group (1.83 ± 0.19, 1.72 ± 0.12, 1.59 ± 0.06 and 1.60 ± 0.07) in comparison with the normal temperature group (2.76 ± 0.25, 2.49 ± 0.18, 2.04 ± 0.14 and 1.65 ± 0.09) (P < 0.05), even lower in the MHT than in the normal temperature group (P < 0.05), but higher in both of the two groups than in the sham operation group (P < 0.05). At 6, 12, 24 and 48 hours, the volume of brain edema was significantly reduced in the MHT group ([32.14 ± 4.52], [36.52 ± 4.10], [42.10 ± 4.38] and [46.25 ± 5.02] mm3) as compared with the normal temperature group ([48.56 ± 5.35], [53.13 ± 6.31], [59.23 ± 6.82] and [62.35 ± 7.25] mm3) (P < 0.05). Conclusion Mild hypothermia can improve the neurological function and reduce the CAM expression and brain edema in the brain tissue of rats with traumatic brain injury, which may be related to the neuroprotective effect of mild hypothermia.
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Objective To evaluate the protective effect and mechanism of mild hypothermia on swine kidney after cardiopulmonary resuscitation, and whether changes in body temperature during mild hypothermia weaken the protective effect of mild hypothermia. Methods 18 swines were randomly divided into constant mild hypothermia group (CMH), variable mild hypothermia group (VMH) and control group (CON), with 6 swines in each group. Cardiac arrest model was successfully made. Then ECPR and temperature management was adopted. The target body temperature was 34℃ in the CMH group, and 37℃ in the control group, while the target body temperature of the VMH group fluctuated from 33 to 35 ℃ every two hours. After 24h, the animals were slowly reheated and then sacrificed. The kidneys were taken for real-time quantitative PCR, immunohistochemistry and histopathological examination. Results The expression levels of Bax, GRP78 and CHOP in the CMH group were lower than those in the CON group. Moreover, the expression of GRP78 in the CMH group were lower than those in the VMH group. The expression of Bcl-2 in the CMH group were higher than those in the VMH group and the CON group, and the expression of Bcl-2 in the VMH group were higher than those in the CON group (all P < 0.05). The positive expression of Bax was the most significant in the CON group and the least in the CMH group. The positive expression of Bcl-2 was the most significant in the CMH group and the least in the CON group. The nuclear membrane of porcine kidney cells shrank, nucleoli shrank and mitochondria swelled obviously in the CON group. The morphological injury changes were mild in the CMH group compared with the VMH group, while the CON group showed the severest change. Conclusion Mild hypothermia could attenuate the renal tubular cells apoptosis after cardiopulmonary resuscitation by inhibiting endoplasmic reticulum stress pathway, thus playing a protective role to the kidney. While aAbnormal temperature fluctuation during mild hypothermia maintenance may weaken the protection of kidney by mild hypothermia.
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OBJECTIVE： To investigate the effects of dexmedetomidine combined with mild hypothermia on the levels of High mobility group box 1 protein （HMGB1）， Toll like receptor 4 （TLR4） and Triggering receptor expressed on myeloid cells 1 （Trem-1） in lung tissues of sepsis model rats. METHODS： Totally 100 SD rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， dexmedetomidine group （2 μg/kg）， mild hypothermia group （normal saline+anal temperature 32-35 ℃ caused by whole body spraying of cold water） and combination group （dexmedetomidine 2 μg/kg+anal temperature 32-35 ℃ caused by whole body spraying of cold water）， with 20 rats in each group. Except that sham operation group received sham operation， sepsis model was induced in other groups. After ligation and incision， the corresponding drugs were pumped into the jugular vein and the corresponding body temperature was maintained. Plasma samples were collected 6 h after operation. Interleukin 1 （IL-1）， IL-6， tumor necrosis factor α （TNF-α） were determined by ELISA. The lung wet mass/dry mass ratio （W/D） was calculated by weighing the mass. Lung tissue sections were observed by HE staining， and lung injury scores were scored. The activity of MPO in lung tissue was determined by immunoturbidimetry. The expression of HMGB1，TLR4 and Trem-1 protein was determined by Western blot. RESULTS： Compared with sham operation group， the contents of IL-1， IL-6 and TNF-α， W/D， lung injury score， MPO activity， the protein expression of HMGB1， TLR4 and Trem-1 were increased significantly， with statistical significance （P＜0.05）； lung tissue section showed that alveolar wall was obviously thickened； a large number of inflammatory cells infiltrated； blood vessels were obviously dilated and congested. Compared with model group， above indexes of rats in dexmedetomidine group， mild hypothermia group and combination group were decreased significantly， with statistical significance （P＜0.05）； the degree of pathological changes in lung tissue was significantly reduced. Compared with dexmedetomidine group and mild hypothermia group， above indexes of combination group were decreased more significantly， with statistical significance （P＜0.05）. Alveolar walls were thickened， inflammatory cell infiltration was relieved significantly and no vascular diatation and congestion was found. CONCLUSIONS： Dexmedetomidine combined with mild hypothermia can significantly improve lung injury in sepsis model rats， and down-regulate the protein expression of HMGB1， TLR4 and Trem-1. Therapeutic efficacy of combination therapy is better than single therapy.