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【Objective】 To explore the expression and role of stimulator of interferon gene (STING)-TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) signaling pathway in the brain of chronic stress mice. 【Methods】 Mice were divided into control (CON) group and chronic restraint stress (RST) group. Mice in the RST group were given chronic restraint stress stimulation (6 hours per day, 14 days). After 14 days, the mRNA expressions of pro-inflammatory cytokines CCL2, CXCL10, IL-1β, IL-6, IL-10, and TNFα in the brain were detected and analyzed by qRT-PCR; protein expression of STING, TBK1, p-TBK1, IRF3, and p-IRF3 were detected and analyzed by immunofluorescence staining and Western blotting. 【Results】 Compared to the CON group, the mRNA expressions of pro-inflammatory cytokines in the RST group were significantly increased (P<0.05). STING and microglia marker Iba-1 were highly co-located and the expression of STING was decreased as detected by immunofluorescence staining. Moreover, the protein expressions of STING, p-TBK1, and p-IRF3 were significantly decreased (all P<0.01). 【Conclusion】 Chronic restraint stress triggers a neuroinflammatory response and the STING-TBK1-IRF3 pathway in the brain of the RST mice is significantly inhibited.
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Objective:To evaluate the relationship between cannabinoid receptor 1 (CB1R) and the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) during the reduction of cerebral ischemia-reperfusion (I/R) injury by electroacupuncture (EA) preconditioning in rats.Methods:Forty SPF healthy male Sprague-Dawley rats, aged 7-9 weeks, weighing 250-280 g, were divided into 5 groups ( n=8 each) according to the random number table method: sham operation group (Sham group), cerebral I/R group (I/R group), EA preconditioning group (EA group), CB1R antagonist AM251+ EA preconditioning group (AM251+ EA group), and CB1R agonist WIN 55, 212-2 group (WIN group). Cerebral I/R was induced by middle cerebral artery occlusion (MCAO) in anesthetized animals. In EA group, EA preconditioning was performed, and the acupoint Baihui (GV20) was stimulated for 30 min with disperse-dense waves, the intensity of 1 mA and frequency of 2/15 Hz once a day for 5 consecutive days, and the model of cerebral I/R injury was developed at 24 h after the last EA. In AM251+ EA group, CB1R antagonist AM251 1 mg/kg was intraperitoneally injected at 30 min before each stimulation, and the remaining operations were the same as those previously described in EA group. CB1R agonist WIN 55, 212-2 1.5 mg/kg was intraperitoneally injected for 5 consecutive days, and the model of cerebral I/R injury was prepared at 24 h after the last injection in WIN group. Neurological behavior was assessed and scored at 3 days of reperfusion. Then the rats were sacrificed, and brains were removed, and the infarct volume was measured by TTC staining, and the tissues in the ischemic penumbra were extracted for determination of the expression of NLRP3, caspase-1 and interleukin-1bata (IL-1β) by Western blot. Results:Compared with Sham group, the percentage of cerebral infarct volume was significantly increased, the neurobehavioral score was decreased, and the expression of NLRP3, caspase-1 and IL-1β was up-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of cerebral infarct volume was significantly decreased, the neurobehavioral score was increased, and the expression of NLRP3, caspase-1 and IL-1β was down-regulated in EA and WIN groups ( P<0.05). Compared with EA group, the percentage of cerebral infarct volume was significantly increased, the neurobehavioral score was decreased, and the expression of NLRP3, caspase-1 and IL-1β was up-regulated in AM251+ EA group ( P<0.05). Conclusions:EA preconditioning may inhibit the activation of NLRP3 inflammasomes by activating CB1R, thus alleviating cerebral I/R injury in rats.
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To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.
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Objective:To explore effects and mechanism of resveratrol on apoptosis of vascular smooth muscle cell in diabetic rats. Methods: The mRNA level of monocyte chemoattractant protein 1 (MCP1),macrophage migration inhibitory factor (MIF) and in-terleukin 18 (IL-18) was detected by quantitative real-time reverse transcription PCR (qRT-PCR). Myocardial fibrosis was analyzed by hematoxylin-eosin (HE) staining and Masson staining. Apoptosis was tested by flow cytometry. The expression of Cleaved caspase-3, Cleaved caspase-9,B cell lymphoma 2 (Bcl-2),Bcl-2-associated X protein (Bax),PI3K,p-PI3K,AKT and p-AKT was measured by Western blot. Results: The mRNA levels of MCP1,MIF and IL-18 in STZ-induced diabetic were reduced by resveratrol (P＜0. 05). The aggravation of myocardial fibrosis in STZ-induced diabetic rats was ameliorated by resveratrol. Apoptosis of vascular smooth muscle cell in STZ-induced diabetic rat group was higher than control group (P＜0. 05 ) . Compared with STZ-induced diabetic rat group, apoptosis of vascular smooth muscle cell in STZ+ resveratrol group was decreased (P＜0. 05). What′s more,the expression of Cleaved caspase-3,Cleaved caspase-9 and Bax in STZ-induced diabetic rats were inhibited by resveratrol(P＜0. 05). And the expression of Bcl-2 in STZ-induced diabetic rats was elevated by resveratrol(P＜0. 05). Compared with control group,the rate of p-PI3K/PI3K and p-AKT/AKT in STZ-induced diabetic rat group was decreased (P＜0. 05). The rate of p-PI3K/PI3K and p-AKT/AKT in STZ+ resveratrol group was higher than STZ-induced diabetic rat group ( P＜0. 05). Conclusion: Resveratrol represses apoptosis of vascular smooth muscle cell in STZ-induced diabetic rats through activating of PI3K/AKT signal pathway.
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Objective To establish a new method for the rapid and sensitive determination of biapenem. Methods A simple, rapid and sensitive flow injection chemiluminescence(CL) method for the determination of biapenem was developed based on the fact that biapenem could enhance the CL of the luminol (LMN)-potassium ferricyanide reaction system under an alkaline condition. Results Under the optimal experimental conditions, we obtained a linear relationship between the CL intensity and the concentration of biapenem in the range of 0.02%0.6 mg/L with a detection limit of 7.3 x10-3 mg/L. The relative standard deviation was 1.76% for the eleven-time determination of 0.2 mg/L biapenem. Conclusion The method shows high sensitivity, low detection limit and good repeatability. It has been successfully applied to the determination of biapenem for injection and the results are satisfactory.
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Objective To establish a new method for the rapid and sensitive determination of biapenem. Methods A simple, rapid and sensitive flow injection chemiluminescence(CL) method for the determination of biapenem was developed based on the fact that biapenem could enhance the CL of the luminol (LMN)-potassium ferricyanide reaction system under an alkaline condition. Results Under the optimal experimental conditions, we obtained a linear relationship between the CL intensity and the concentration of biapenem in the range of 0.02~0.6 mg/L with a detection limit of 7.3×10-3 mg/L. The relative standard deviation was 1.76% for the eleven-time determination of 0.2 mg/L biapenem. Conclusion The method shows high sensitivity, low detection limit and good repeatability. It has been successfully applied to the determination of biapenem for injection and the results are satisfactory.
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Objective To study the pathogenesis, clinical characteristics, laboratory tests, treatments and prognosis of con-genital factorⅦdeficiency. Methods The clinical data of two cases of congenital factorⅦdeficiency diagnosed at the Chil-dren’s Hospital of Fudan University and 9 cases reported in the past 10 years retrieved from Pubmed, Web of Knowledge and CNKI, Wangfang database by using the factorⅦdeficiency , congenital, newborn and case report as keyword were reviewed and analyzed. Results All cases were full term birth with normal birth weight (>2 500 g), including 4 females and 7 males. Pa-rental consanguinity was found in 3 cases, and a family history was found in 3 cases. The laboratory tests were characterized by significantly prolonged prothrombin time, normal partial thromboplastin time, and decreased coagulation factorⅦactivity. The coagulation factorⅦactivity of 10 cases were less than 5%. Five cases (45.5%) were treated with human recombinant activated factorⅦ. Four cases (36.4%) treated with plasma or human recombinant activated factorⅦare currently in normal growth and development. Four cases (36.4%) died during the hospitalization. Conclusions A diagnosis of congenital factorⅦdeficiency should be considered in the neonates with severe bleeding, prolonged prothrombin time, normal partial thromboplastin time, and being intractable to vitamin K treatment. Human recombinant activated factorⅦis the first choice of the treatment of congenital factorⅦdeficiency. The further study of gene mutation type will be of great significance for disease screening, diagnosis, treat-ment and prognosis prediction.
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Objective To investigate the neurodevelopmental outcomes and its risk factors of very low birth weight infant (VLBWI) and extremely low birth weight infants (ELBWI).Methods Data of 85 VLBWI and ELBWI hospitalized in Children's Hospital of Fudan University from October 2005 to November 2009 who had finished infant development test of Baley Scales of Infant Development Ⅱ (Bayley Ⅱ) for neurological development at corrected gestational age between 18 to 42 months were retrospectively reviewed.Twelve infants who accepted treatment in other hospital over 10 days were excluded; the rest 73 infants were divided into normal (neurodevelopment) group or abnormal group according to the definition of neurodevelopmental impairment reported by National Institute of Child Health and Human Development (NICHD) Neonatal Network.Potential risk factors of neurodevelopmental impairment were analyzed with Logistic stepwise regression.Results The mean gestational age of 73 infants was (30.4±2.3) weeks; among which 13 were smaller than 28 weeks,42 between 28 and 32 weeks,and 18 older than 32 weeks.The mean birth weight was (1208.0±208.5) g; among which 15 (20.6％) ＜1000 g,and 58 (79.4％) were between 1000 g and 1500 g.Four babies (5.5％) were diagnosed as movement retardation,and neurodevelopmental impairment occurred in 16 cases (21.9 ％),psychomotor developmental index ＜70 occurred in 6 cases (8.2％,one case complicating with cerebral palsy); mental developmental index ＜70 occurred in 2 cases (2.7％); both psychomotor developmental index and mental developmental index ＜70 occurred in 7 cases (9.6 ％,two cases complicating with cerebral palsy),and one case (1.4 ％) was cerebral palsy only.Blind in either eyes and hearing impairment requiring deaf-aid were not found in any of the 73 babies.Logistic stepwise regression showed that use of mechanical ventilation was related to neurodevelopmental impairment (OR =6.183,95％ CI:1.664-22.983,P =0.003).Psychomotor developmental index of infants who needed mechanical ventilation (77.5±15.1) was lower than that of infants did not need (87.3±15.1)(t=2.646,P=0.010).Conclusions VLBWI and ELBWI are in high risk of neurodevelopmental impairment,especially those who need mechanical ventilation.
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Objective To explore the predisposing factors in the development of acute respiratory failure after abdominal surgery and the factors affecting the therapeutic effect of mechanical ventilation. Methods A (retrospective) study was undertaken for acute respiratory failure after abdominal surgery in 91 patients. The (underline) diseases, introducing causes and efficacy of mechanical ventilation were retrospectively analysed. (Results) Postoperative pneumonia was the cause of acute respiratory failure in 53 cases and ARDS caused by severe abdominal infection and severe acute pancreatitis in 38 cases. Of the 91 cases, complicated with COPD in 38 cases, severe malnutrion 32 cases, and hypokalemia 14 cases. Respiratory failure occurred at(4.08?2.45)days after operation. The duration of mechanical ventilation was(21.66?21.42)days; 33 cases died, and 58 cases were successfully recovered with mechanical ventilation.Conclusions The (management) of acute respiratory failure after abdominal asurgery should be rational use of mechanical (ventilation), adjustment of weaning strategy and avoidance of dependance on mechanical ventilation. Timely treatment of the primary disease, effective control of abdominal infection and aggressive symptomatic and (supportive) treatment are factors that affect the success or failure of mechanical ventilation.