ABSTRACT
OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.
ABSTRACT
OBJECTIVE:To provide reference for standardized management of skin test of cephalosporin injection in our hos-pital. METHODS:In retrospective analysis,skin test of 8 kinds of cephalosporin [cefotaxime(1.0 g),cefotaxime(0.5 g),cefoti-am (1.0 g),cefotiam (0.5 g),ceftazidime (0.5 g),cefminox (0.5 g),cefminox (1.0 g),ceftriaxone (1.0 g)] and the cost of skin test, related cost of allergic reaction induced by cephalosporin injection were analyzed statistically during Sept. 1st, 2015-Aug. 31th,2016. The cost of skin test of cephalosporin injection was compared with allergic reaction cost reduced by skin test. RESULTS:The positive rate of 100330 patients who used above 8 kinds of cephalosporin injections was 6.27%;the rate of skin test was 82.49%;the direct cost of skin test was 3434411.72 yuan;the indirect cost was 141985.12 yuan;the cost of pa-tient was 3162901.44 yuan;the cost of medical insurance was 259096.28 yuan;the cost of the whole society was 3576396.84 yuan. From the perspective of the whole society,the cost of skin test of cephalosporin injections was(447049.61±247395.07)yuan, and allergic reaction cost reduced by skin test was (316075.48 ± 260600.49)yuan. The cost of skin test was significantly higher than allergic reaction cost reduced by skin test,with statistical significance(P<0.05). CONCLUSIONS:Skin test of cephalosporin injection is low in positive rate,has high expense. The government standardizes the management of skin test of cephalosporin injec-tion and reduces the economic burden of patients under the premise of ensuring the safety of drug use.
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OBJECTIVE:To measure and analysis the related costs of drug-induced liver injury (D1LI) from different decision makers,and to provide reference for reducing related costs of DILI,improving medical insurance system and realizing effective health resource distribution.METHODS:In retrospective study,60 cured or recovered DILI inpatieuts were randomly selected as subjects from medical record management system of 4 hospitals in Henan province during Jun.2014-Jun.2015.Demographic character istic,clinical characteristic and related cost of DILI were analyzed retrospectively and the cost structure was also analyzed from different decison makers (patient,society,medical insurance payer).RESULTS:The total direct medical cost of 60 cases was 584 113.05 yuan,and total direct non-medical cost was 31 093.15 yuan and total indirect cost was 169 379.95 yuan.The total cost of DILI of fered by patients was 616 296.38 yuan;the total cost of DILI offered by society was 784 586.15 yuan;the total cost of DILI offered by medical insurance was 168 289.77 yuan.CONCLUSIONS:DILI results in serious economic damage for patients and society,deserving attracting extensive attention worldwide.The study provide reference for reducing patient's medical burden and improving medical insurance system,and contribute to optimize medical resource distribution.
ABSTRACT
Protein phosphatase 2A(PP2A)is the main serine/threonine protein phosphatase of the brain,and it is involved in many physiological and pathological processes in the cell. Particularly in the pathogenesis of Alzheimer′s disease(AD),PP2A is closely related to the main pathological features of AD. Deregulation of PP2A enzymes correlates with increased tau phosphorylation, the formation of amyloid precursor protein,and the missing of neurons. PP2A as the target of drug development may bring new hope for the treatment of AD. This review introduces the structure and activity regulation of PP2A,and the role of PP2A in AD.