Inhibition of astroglial hemichannels ameliorates infrasonic noise induced short-term learning and memory impairment.

As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure.

Optogenetics stimulates nerve reorganization in the contralesional anterolateral primary motor cortex in a mouse model of ischemic stroke.

The anterolateral motor cortex of rodents is an important motor auxiliary area, and its function is similar to that of the premotor area in humans. Activation and inhibition of the contralesional anterolateral motor cortex (cALM) have been shown to have direct effects on motor behavior. However, the significance of cALM activation and inhibition in the treatment of stroke remains unclear. This study investigated the role of optogenetic cALM stimulation in a mouse model of cerebral stroke. The results showed that 21-day optogenetic cALM inhibition, but not activation, improved neurological function. In addition, optogenetic cALM stimulation substantially altered dendritic structural reorganization and dendritic spine plasticity, as optogenetic cALM inhibition resulted in increased dendritic length, number of dendritic spines, and number of perforated synapses, whereas optogenetic activation led to an increase in the number of multiple synapse boutons and the number of dendritic intersections. Furthermore, RNA-seq analysis showed that multiple biological processes regulated by the cALM were upregulated immediately after optogenetic cALM inhibition, and that several immediate-early genes (including cFOS, Erg1, and Sema3f) were expressed at higher levels after optogenetic inhibition than after optogenetic activation. These results were confirmed by quantitative reverse transcription-polymerase chain reaction. Finally, immunofluorescence analysis showed that the c-FOS signal in layer V of the primary motor cortex in the ischemic hemisphere was higher after optogenetic cALM activation than it was after optogenetic cALM inhibition. Taken together, these findings suggest that optogenetic cALM stimulation promotes neural reorganization in the primary motor cortex of the ischemic hemisphere, and that optogenetic cALM inhibition and activation have different effects on neural plasticity. The study was approved by the Experimental Animal Ethics Committee of Fudan University (approval No. 201802173S) on March 3, 2018.

Environmental Enrichment Protects Against Cognition Deficits Caused by Sepsis-Associated Encephalopathy.

BACKGROUND: One of the most serious complications of sepsis is sepsis-associated encephalopathy (SAE), which impairs the cognition ability of survivors. Environmental enrichment (EE) has been demonstrated to alleviate cognition deficits under many kinds of brain injury conditions. However, EE's effects on SAE remain unknown. Therefore, this study aimed to determine EE's effect on cognition disorders under SAE conditions and the underlying mechanism. MATERIALS AND METHODS: Adult male rats, subject to SAE or not, were housed under a standard environment (SE) or EE for 30 days. Subsequently, the rats were subjected to cognitive tests, such as the novel object recognition (NOR) test, the Morris water maze (MWM) test, an Open Field (OF) test, the elevated plus maze (EPM) test, and a sensory neglect (SN) test. Neuroinflammation, apoptosis, and oxidative stress changes in the brain were also detected. RESULTS: The results revealed that SAE impaired somatesthesia, recognition memory, spatial learning and memory, and exploratory activity, which were significantly improved by EE housing. EE also prevented SAE-induced anxiety-like behavior. In addition, EE housing capable induced a decrease in pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines and antioxidant properties in the brain. Moreover, EE housing exerted an anti-apoptosis function by upregulating the level of B-cell lymphoma/leukemia-2 (Bcl-2) level and downregulating the level of p53 level in the hippocampus. CONCLUSIONS: The results of the present study indicated that EE exerts a neuroprotective function on cognitive ability in SAE rats. The effect is achieved by increasing antioxidants, and anti-inflammatory and antiapoptotic capacities. EE can effectively rescue SAE-induced cognitive deficits.

Association between skin advanced glycation end products and carotid atherosclerosis in population with normal glucose regulation / 中华健康管理学杂志

Objective:To investigate the association between skin advanced glycation end products (AGEs) and carotid atherosclerosis (AS) in subjects with normal glucose regulation (NGR).Methods:This was a cross-sectional study. Data from the Health Management Center of the First Affiliated Hospital of University of Science and Technology between January 2019 to June 2019 were collected. A total of 902 NGR subjects aged 40-79 were enrolled and categorized into control group (530 cases), carotid intima-media thickness (IMT) thickening group (150 cases), and carotid atherosclerosis plaque group (222 cases) based on the carotid ultrasound results. Data as follows were collected, gender, age, blood pressure, body mass index (BMI), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), glycosylated hemoglobin (HbA 1c) and skin AGEs. Comparison via ANOVA analysis were carried out among the 3 groups. Logistic regression analysis was used to screen the independent influencing factors of carotid atherosclerosis plaque. Spearman correlation analysis was used to evaluate the correlation between AGEs and other parameters, and receiver operating characteristic (ROC) curve was used to evaluate the efficiency of skin AGEs in predicting carotid atherosclerosis plaque in NGR subjects. Results:Among the control group, IMT thickening group and carotid atherosclerosis plaque group, gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, LDL-C, FPG, HbA 1c, AGEs were significantly different (all P<0.05). Compared with IMT thickening group, the age, SBP and AGEs of carotid atherosclerotic plaque group were higher [55 (50, 60) vs 53 (49, 56) year; 132 (122, 141) vs 126 (115, 142) mmHg(1 mmHg=0.133 kPa); 74 (67, 81) vs 72 (67, 78) AU] (all P<0.001); compared with the control group, age, LDL-C, HbA 1c and AGEs of IMT thickening group were higher [53 (49, 56) vs 48 (45, 52) year; (2.8±0.7) vs (2.7±0.7) mmol/L; 5.4% (5.2, 5.6)% vs 5.4% (5.1, 5.6)%; 72 (67, 78) vs 70 (66, 76)] (all P<0.05). Age ( OR=1.179, 95% CI: 1.107-1.255), SBP ( OR=1.045, 95% CI: 1.013-1.077), LDL-C ( OR=2.028, 95% CI: 1.036-3.969), AGEs ( OR=1.049, 95% CI: 1.000-1.100) were independent influencing factors of carotid atherosclerotic plaque in population with normal glucose regulated (all P<0.05). AGEs was positively correlated with age, HbA 1c and carotid atherosclerosis plaque ( r=0.407, 0.092, 0.172) (all P<0.01). The area under the ROC curve of skin AGEs for identifying carotid atherosclerotic plaque in NGR population was 0.650 (95% CI 0.601-0.698), the best cutoff value was 70.5, the sensitivity was 65.8%, and the specificity was 56.9%. Conclusion:Skin AGEs level is closely associated with the occurrence of carotid atherosclerosis in NGR subjects.

Constraint-induced movement therapy enhances AMPA receptor-dependent synaptic plasticity in the ipsilateral hemisphere following ischemic stroke.

Constraint-induced movement therapy (CIMT) can promote the recovery of motor function in injured upper limbs following stroke, which may be associated with upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) at synapses in the ipsilateral sensorimotor cortex in our previous study. However, AMPAR distribution is tightly regulated, and only AMPARs on the postsynaptic membrane can mediate synaptic transmission. We speculated that synaptic remodeling induced by movement-associated synaptic activity can promote functional recovery from stroke. To test this hypothesis, we compared AMPAR expression on the postsynaptic membrane surface in a rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) with versus without CIMT, which consisted of daily running wheel training for 2 weeks starting on day 7 after MCAO. The results showed that CIMT increased the number of glutamate receptor (GluR)2-containing functional synapses in the ipsilateral sensorimotor cortex, and reduced non-GluR2 AMPARs in the ipsilateral sensorimotor cortex and hippocampal CA3 region. In addition, CIMT enhanced AMPAR expression on the surface of post-synaptic membrane in the ipsilateral sensorimotor cortex and hippocampus. Thus, CIMT promotes the recovery of motor function of injured upper limbs following stroke by enhancing AMPAR-mediated synaptic transmission in the ischemic hemisphere. These findings provide supporting evidence for the clinical value of CIMT for restoring limb movement in stroke patients. All experimental procedures and protocols were approved by the Department of Laboratory Animal Science of Fudan University, China (approval No. 201802173S) on March 3, 2018.

[Effect of Modified Constraint-induced Movement Therapy on Neurotransmitter Levels of Motor Cortex in Cerebral Ischemia-Reperfusion Injured Rats].

OBJECTIVE: To study the effect and mechanism of modified constraint-induced movement therapy (mCIMT) on motor function recovery in cerebral ischemia-reperfusion rats. METHODS: The rats were randomly divided into the control group and the mCIMT group, with 12 rats in each group. The left middle cerebral artery occlusion (MCAO) model was established by the Longa suture method. In the mCIMT group, the rats started continuous training for 14 d on the 7 th day after modeling. The unaffected limb was tied to the chest with elastic bandages, and the affected limb was trained in the compulsory runner equipment. In the control group, rats moved freely in the cage. The body mass of rats was recorded within 20 d after modeling, and behavior was assessed by the foot-fault test. Some of the rats were euthanized 18 d after modeling, and high performance liquid chromatography (HPLC) was used to detect monoamine neurotransmitters (5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIVV), homovanillic acid (HVA) ), and amino acid neurotransmitters (glutamic acid (Glu), asparaginic acid (ASP), glutamine (Gln), glycine (Gly), taurine (Tau), gamma aminobutyric acid (GABA) ) in the motor cortex and striatum, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of total P70 ribosomal protein S6 kinase (p70s6k) and p70s6k phosphorylated protein (p-p70s6k) in motor cortex and striatum, respectively. RESULTS: Compared with the control group, the body mass of rats in the mCIMT group was comparable (P >0.05) within 21 d after modeling, foot-fault rate of the mCIMT group was significantly lower at 17 d after modeling (P<0.05). At 18 d after modeling, compared with the control group, the level of 5-HIVV in the motor cortex increased significantly (P<0.05), and the relative content of amino acid neurotransmitters (the ratio of Glu) in the motor cortex including Gln, Gly, Tau and GABA to Glu increased significantly (P<0.05 or P<0.01) except for decreased ASP/Glu (P<0.05). Moreover, compared with the control group, the expression of p-p70s6k in the motor cortex of the mCIMT was significantly decreased (P<0.05). There were no significant differences in monoamine neurotransmitters and amino acid neurotransmitters in the striatum between two groups (P>0.05). CONCLUSION: mCIMT improved the motor function of MCAO rats, and the mechanism might be related to the increase of amino acid neurotransmitters and 5-HIVV and decrease of p-p70s6k expression in the motor cortex.

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke.

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model (MCAO) and paired associated magnetic stimulation (PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments-the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the foot-fault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion.

Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb. However, the molecular mechanism underlying its efficacy remains unclear. In this study, a middle cerebral artery occlusion (MCAO) rat model was produced by the suture method. Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days, starting from the 7th day after middle cerebral artery occlusion. Day 1 of treatment lasted for 10 minutes at 2 r/min, day 2 for 20 minutes at 2 r/min, and from day 3 onward for 20 minutes at 4 r/min. CatWalk gait analysis, adhesive removal test, and Y-maze test were used to investigate motor function, sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21st day after MCAO. On the 21st day after MCAO, the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay. The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography. The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats, but had no effect on cognitive function. The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3 (Gria3) in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1A, Avpr1a in the middle cerebral artery-occluded rats. In the ipsilateral hippocampus, only Adra2a was downregulated, and there was no significant change in Gria3. Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3, which is an α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor, within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region. The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged. Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion, but had no effect on Synapsin I levels. Besides, we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus. This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats, and suggests that these positive effects occur via the upregulation of the postsynaptic membrane α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Fluoxetine adjunct to therapeutic exercise promotes motor recovery in rats with cerebral ischemia: Roles of nucleus accumbens.

The study aimed to explore the molecular mechanism of fluoxetine as an adjunct to therapeutic exercise to improve motor recovery using a rat cerebral ischemic model with middle cerebral artery occlusion (MCAO). We hypothesized that the nucleus accumbens (NAc) may be one of the responding areas to fluoxetine where relevant elevations in 5-hydroxytryptamine (5-HT) and ΔFosB were associated with motor behavioral recovery. Male Sprague-Dawley rats were randomly divided into five groups: rats without intervention; rats that underwent MCAO without exercise or fluoxetine; rats that underwent MCAO treated only with fluoxetine; rats that underwent MCAO treated only with exercise; and rats that underwent MCAO treated with both exercise and fluoxetine. Motor function and motivation were assessed by the fault footsteps test and the forced swimming test. 5-HT level in the bilateral NAc and the expression of 5-HT2C receptor (5-HT2CR) and ΔFosB in the ipsilesional (left) NAc were measured. Correlation was explored by Pearson correlation analysis. Our results indicated that either treatment helped improve the grasp dexterity of the affected limb, motor motivation, and resilience to adverse environment in MCAO rats. The dual treatment with fluoxetine and exercise may hasten the recovery process. The dual treatment helped restore the balance of 5-HT level between the bilateral NAc by significantly increasing its level in the ipsilesional side. Either treatment could resume the expression of 5-HT2CR in the ipsilesional side of the NAc close to the normal level, which was correlated with motor recovery. The dual treatment significantly increased the expression of ΔFosB in the ipsilesional side of the NAc, which was correlated with the balance of 5-HT in the bilateral NAc, but not directly with motor recovery. In conclusion, the NAc may play an important role in driving physical motivation, which was possibly related to motor recovery after stroke. Fluoxetine may hasten the effectiveness of therapeutic exercise, possibly via regulating 5-HT and its receptors in the NAc.

Constrained-induced movement therapy promotes motor function recovery by enhancing the remodeling of ipsilesional corticospinal tract in rats after stroke.

Constraint-induced movement therapy (CIMT), which forces the use of the impaired limb by restraining the unaffected limb, has been used extensively for the recovery of limb motor function after stroke. However, the underlying mechanism of CIMT remains unclear. Diffusion tensor imaging (DTI) is a well-known neuroimaging technique that reflects the microstructure of white matter tracts and potential changes associated with different treatments. The aim of this study is to use DTI imaging to determine how corticospinal tract (CST) fibers remodel in ischemic rats with CIMT. In the present study, rats were randomly divided into three groups: a middle cerebral artery occlusion group (MCAO), a therapeutic group (MCAO + CIMT), and a sham-operated group (sham). A plaster cast was used to restrict the unaffected limb of the rats in the MCAO + CIMT group for 14 days. The Catwalk system was used to assess the limb motor function of rats. Fractional anisotropy (FA) and the average diffusion coefficient (ADC) of the CST were quantified through DTI. The expression of the c-Jun-N-terminal kinase signaling pathway (JNK) was examined after 14 days of CIMT. We found that CIMT could accelerate and enhance motor function recovery, and the MCAO + CIMT group showed significantly increased FA values in the ipsilesional posterior limb of internal capsule (PLIC) compared with the MCAO group. In addition, we found no significant difference in the ratio of phosphorylated-JNK/total-JNK among the three groups, whereas the expression of P-JNK decreased significantly in the chronic phase of stroke. In conclusion, CIMT-induced functional recovery following ischemic stroke through facilitation of the remodeling of ipsilesional CST, and restoration after ischemic stroke may be associated with the declining value of the ratio of P-JNK/JNK.

Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up-regulation of endogenous tissue kallikrein.

AIMS: Remote ischemic conditionings, such as pre- and per-conditioning, are known to provide cardioprotection in animal models of ischemia. However, little is known about the neuroprotection effect of postconditioning after cerebral ischemia. In this study, we aim to evaluate the motor function rescuing effect of remote limb ischemic postconditioning (RIPostC) in a rat model of acute cerebral stroke. METHODS: Left middle cerebral artery occlusion (MCAO) was performed to generate the rat model of ischemic stroke, followed by daily RIPostC treatment for maximum 21 days. The motor function after RIPostC was assessed with foot fault test and balance beam test. Local infarct volume was measured through MRI scanning. Neuronal status was evaluated with Nissl's, HE, and MAP2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area. RESULTS: Daily RIPostC for more than 21 days promoted motor function recovery and provided long-lasting neuroprotection after MCAO. Reduced infarct volume, rescued neuronal loss, and enhanced microvessel density and size in the injured areas were observed. In addition, the RIPostC effect was associated with the up-regulation of endogenous tissue kallikrein (TK) level in circulating blood and local ischemic brain regions. A TK receptor antagonist HOE-140 partially reversed RIPostC-induced improvements, indicating the specificity of endogenous TK mediating the neuroprotection effect of RIPostC. CONCLUSION: Our study demonstrates RIPostC treatment as an effective rehabilitation therapy to provide motor function recovery and alleviate brain impairment in a rat model of acute cerebral ischemia. We also for the first time provide evidence showing that the up-regulation of endogenous TK from remote conditioning regions underlies the observed effects of RIPostC.

Therapeutic effect and mechanism of Chaizhixiaji Decoction on bile reflux gastritis rats / 药物评价研究

Objective To investigate the therapeutic effect and mechanism of Chaizhixiaji Decoction on experimental bile reflux gastritis (BRG) rats.Methods Wistar rats were randomly divided into five groups by random according to weight and sex:control group,model group,Chaizhixiaji Decoction low and high dose groups,and Hydrotalcite Tablets group.Rats were given self-made reflux liquid orally to induce experimental bile reflux gastritis.The diet,stool and urine,hair color and body weight of rats in control group and model group were observed.The histopathological changes of gastric antrum mucosa were observed by naked eyeand light microscope after HE staining.ELISA method was used for detection of serum GAS,PGE2 content in gastric antrum mucosa.Result Compared with control group,rats in model group show thin boicing stool containing red yellow mucus,slow reaction,and body weight decreased significantly (P ＜ 0.05).There were patchy erosions of the gastric antrum with yellow green bile and more yellow mucus of model group in the naked eye.Model control group had a significant rise of inflammatory cells infiltration and intestinal metaplasia,and scores of inflammation and intestinal metaplasia increased significantly (P ＜ 0.01).GAS and PGE2 contents obviously decreased compared with that in control group (P ＜ 0.01).Compare with model group,Chaizhixiaji Decoction of high dosesignificantly improved gastric mucosal tissue damage morphology;reduced the infiltration of inflammatory cells and intestinal metaplasia,which score decreased significantly (P ＜ 0.05,0.01);and increasedlevels of GAS and PGE2 significantly (P ＜ 0.01).Conclusion Chaizhixiaji Decoction has obvious protective effect on gastric mucosa,and its mechanism may be related with the regulation of GAS,PGE2 contents.

Therapeutic effect and mechanism of Chaizhixiaji Decoction on bile reflux gastritis rats / 药物评价研究

Objective To investigate the therapeutic effect and mechanism of Chaizhixiaji Decoction on experimental bile reflux gastritis (BRG) rats.Methods Wistar rats were randomly divided into five groups by random according to weight and sex:control group,model group,Chaizhixiaji Decoction low and high dose groups,and Hydrotalcite Tablets group.Rats were given self-made reflux liquid orally to induce experimental bile reflux gastritis.The diet,stool and urine,hair color and body weight of rats in control group and model group were observed.The histopathological changes of gastric antrum mucosa were observed by naked eyeand light microscope after HE staining.ELISA method was used for detection of serum GAS,PGE2 content in gastric antrum mucosa.Result Compared with control group,rats in model group show thin boicing stool containing red yellow mucus,slow reaction,and body weight decreased significantly (P ＜ 0.05).There were patchy erosions of the gastric antrum with yellow green bile and more yellow mucus of model group in the naked eye.Model control group had a significant rise of inflammatory cells infiltration and intestinal metaplasia,and scores of inflammation and intestinal metaplasia increased significantly (P ＜ 0.01).GAS and PGE2 contents obviously decreased compared with that in control group (P ＜ 0.01).Compare with model group,Chaizhixiaji Decoction of high dosesignificantly improved gastric mucosal tissue damage morphology;reduced the infiltration of inflammatory cells and intestinal metaplasia,which score decreased significantly (P ＜ 0.05,0.01);and increasedlevels of GAS and PGE2 significantly (P ＜ 0.01).Conclusion Chaizhixiaji Decoction has obvious protective effect on gastric mucosa,and its mechanism may be related with the regulation of GAS,PGE2 contents.

Distribution characteristics and antimicrobial resistance of pathogens about hospital infection from patients in single hematology center during 2011 and 2013 / 北京大学学报(医学版)

Objective:To analyze the characteristics of hospital infection of hematological disease, so as to provide reference for clinical therapy. Methods: Bacterial strains and antimicrobial resistance of pa-tients with hospital infection in Department of Hematology, Peking University Third Hospital from Jan. 2011 to Dec. 2013 were identified and analyzed retrospectively. The specimens were from their blood, urine, sputum, throat swabs and etc. Results:Among the total of 168 isolates of bacteria,the majority of the bacteria strains were from sputum (42. 9%);114(67. 9%) bacteria strains were gram negative and 54(32. 1%) bacteria strains were gram positive;the pathogen testing showed that 20. 8% were Pseudo-monas aeruginosa,18. 5% Escherichia coli,17. 9% Staphylococcus aureus, 9. 5% Klebsiellar pneumonia, 5. 9% Staphylococcus epidermis and 27. 4% other bacteria ;The gram negative bacilli to cefepime, ami-kacin and carbapenems showed the lowest antimicrobial resistance rates, and S. aureus showed the lowest antimicrobial resistance rates to vancomycin and linezolid. Conclusion:Patients with hemopathy are the main population of hospital infections, the gram negative bacteria are the most common pathogens. It is very important to promptly know the change in distribution of the pathogens in order to rationally select antibiotics and reduce the incidence of bacterial infections.

Intrahospital dissemination of carbapenem-resistant Acinetobacter baumannii and analysis of the infected patients' prognosis / 北京大学学报(医学版)

Objective:To assess the genetic relationship of clinical isolates of carbapenem-resistant A.baumannii (resistant to both imipenem and meropenem) from January 2007 to March 2008 in Peking University Third Hospital for measures to decrease the isolates; to investigate the characteristics of patients with carbapenem-resistant A. baumannii colonization or infection and to evaluate antibiotic treatment for health care-associated infections caused by carbapenem-resistant A. baumannii. Methods: The medical records of patients with carbapenem-resistant A. baumannii colonization or infection were reviewed. Antibiotic susceptibilities of the isolates were determined by the standardized disk-diffusion method and the clonal relationship of the isolates was analyzed by pulsed-field gel electrophoresis. Results: A total of 49 carbapenem-resistant A. baumannii strains were isolated from the 49 patients hospitalized during the study period and pulsed-field gel electrophoresis typing yielded 7 different patterns. A total of 45 (91.8%)genotyped strains showed clonal relationship. The most frequently identified predisposing factors were intensive care unit stay, invasive procedures, and hypoalbuminemia. Chronic obstructive pulmonary disease (12 cases) and cerebrovascular disease (10 cases) were the most common comorbid conditions.The mortality of patients with carbapenem-resistant A. baumannii infection was 38. 1% (8 of 21 patients), and the acute physiology and chronic health evaluation Ⅱ score, initial antibiotic therapy failure rate and the presence of hypoalbuminemia were significantly increased in the death group. Combination therapy regimens had higher success rates than monotherapy regimens (11/13, 84. 6% vs. 3/17,17.6%). Conclusion: There has been clonal spread of carbapenem-resistant A. baumannii strains among patients in our hospital since 2007. Intensive care unit stay, invasive procedures, hypoalbuminemia, chronic obstructive pulmonary disease and cerebrovascular disease were common in patients with carbapenem-resistant A. baumannii colonization or infection. Antibiotic combination therapy may be effective for carbapenem-resistant A. baumannii infection.