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Objective:To evaluate the relationship between B-cell lymphoma/adenovirus E1B19 kDa-interacting protein 3-like protein (BNIP3L)/adenovirus E1B-interacting protein and mitochondrial dysfunction in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:One hundred and eighty C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=45 each) using a random number table method: control group (C group), sham operation group (Sham group), SAE group, and SAE+ BNIP3L agonist carfilzomib group (SC group). The sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized animals. In SC group, carfilzomib 2 mg/kg was intraperitoneally injected at 2 h after CLP. Twenty mice in each group were selected, and the survival at 7 days after operation was recorded. Eight surviving mice in each group were selected at 1 week after CLP for Morris water maze test. The remaining mice were sacrificed at 24 h after surgery, and the hippocampal tissues were harvested for determination of the expression of BNIP3L (by immunofluorescence) and BNIP3L in mitochondrial protein (by Western blot) and for microscopic examination of the morphological structure of mitochondria. The mitochondrial ATP content was measured by fluorescein-fluorescence enzyme luminescence method, and the mitochondrial membrane potential (MMP) was measured by fluorescence spectrophotometry. Results:Compared with C and Sham groups, the survival rate was significantly decreased, the escape latency was prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform region was decreased, the expression of BNIP3L in the hippocampal mitochondria was down-regulated, the MMP and content of mitochondrial ATP were decreased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was marked in SAE group. Compared with SAE group, the survival rate was significantly increased, the escape latency was shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform region was increased, the expression of BNIP3L in the hippocampal mitochondria was up-regulated, the MMP and content of mitochondrial ATP were increased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was attenuated in SC group. Conclusions:BNIP3L-mediated mitochondrial dysfunction may be involved in the mechanism of SAE developed in mice.
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Objective To explore the drug resistance mechanisms of carbapenem-resistant Citrobacter freundii (C.freundii) and its treatment strategies.Methods Clinical data of 17 strains of carbapenem-resistant C.freundii from this hospital were collected.Carbapenemase resistant genes were amplifies by polymerase chain reaction (PCR).The agar dilution method and the broth dilution method were used to determine the minimal inhibition concentration (MIC) of single antimicrobial drug and drug combination,the partial inhibitory concentration index (Σ FICI) was calculated.Results Eight strains were found to produce blaNDM-1 and 9 strains produced blaIMP,blaKPC,blaSPM and blaoxA-48 were not detected in the study.Furthermore,the synergistic effect and addictive effect of fosfomycin combined imipenem accounted for 75.00％,in which,the synergistic effect was up to 56.25 ％.the synergistic effect and addictive effect of fosfomycin and cefoperazone/sulbactam accounted for 50.00％.Conclusion Fosfomycin combined with imipenem or cefoperazone/sulbactam has good antibacterial activity in vitro,but imipenem combined with fosfomycin may have better effect.
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Objective To explore the drug resistance mechanisms of carbapenem-resistant Citrobacter freundii (C.freundii) and its treatment strategies.Methods Clinical data of 17 strains of carbapenem-resistant C.freundii from this hospital were collected.Carbapenemase resistant genes were amplifies by polymerase chain reaction (PCR).The agar dilution method and the broth dilution method were used to determine the minimal inhibition concentration (MIC) of single antimicrobial drug and drug combination,the partial inhibitory concentration index (Σ FICI) was calculated.Results Eight strains were found to produce blaNDM-1 and 9 strains produced blaIMP,blaKPC,blaSPM and blaoxA-48 were not detected in the study.Furthermore,the synergistic effect and addictive effect of fosfomycin combined imipenem accounted for 75.00％,in which,the synergistic effect was up to 56.25 ％.the synergistic effect and addictive effect of fosfomycin and cefoperazone/sulbactam accounted for 50.00％.Conclusion Fosfomycin combined with imipenem or cefoperazone/sulbactam has good antibacterial activity in vitro,but imipenem combined with fosfomycin may have better effect.
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In educating postgraduate students in aerospace medicine in our country, there are some deficiencies such as the course content lacking forward looking and systematicness, and students' mastery of technology or skills lacking professional characteristics, innovation and divergent thinking. Based on the original foundations, the School of Aerospace Medicine, Fourth Military Medical University, has been con-structing and improving the course system by modifying the course contents, reforming the practical teach-ings, expanding the academic communications, and managing the processes. Finally, they have achieved certain results.
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<p><b>BACKGROUND</b>Lead exposure during pregnancy contributes to fetal abortion and/or teratogenesis. Endoplasmic reticulum (ER) apoptosis can be induced by various pathological conditions when ER function is disturbed. However, it is unclear whether ER stress and apoptosis play a role in the etiology of lead-exposed disease status. We aimed to investigate whether lead induced placental apoptosis and subsequent toxicity is initiated by ER apoptosis via caspase-12.</p><p><b>METHODS</b>Sixty-three female Wistar rats were exposed to lead in drinking water during various gestational periods. Blood lead level was determined by atomic absorption spectrophotometry. Placental cytoplasmic organelles were examined by electronic microscopy. Placental caspase-12 mRNA expression was evaluated by qRT-PCR. TUNEL assay was used to determine the placental apoptosis.</p><p><b>RESULTS</b>Lead exposure significant induced ER apoptosis compared to that of the controls (P < 0.05), accompanied with increased caspase-12 mRNA expression. Significant differences of caspase-12 mRNA expression levels were observed among the four groups (F = 13.78, P < 0.05). Apoptotic index (AI) was significantly increased in experimental groups compared to that of the controls (F = 96.15, P < 0.05). In lead-exposed groups, trophoblast cells underwent degeneration and fibrin deposition; Mitochondria were swollen and decreased in number; ER swelling, expansion, and vacuolization were observed.</p><p><b>CONCLUSION</b>Lead exposure contributes to placental apoptosis, as well as increased caspase-12 mRNA expression, which in turn promoted ER stress.</p>
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Animals , Female , Pregnancy , Rats , Apoptosis , Endoplasmic Reticulum Stress , Lead , Toxicity , Placenta , Cell Biology , Rats, WistarABSTRACT
Objective To investigate the distribution and resistance of clinical isolates obtained from the second affiliated hospi-tal of Chongqing medical university in 2012 .Methods The bacteria strains isolated from clinics were collected .Identification and drug susceptibility test were performed by automatic analysis system and API manual identification system .The date was analyzed according with software WHONET 5 .6 .Results A total of 3 454 bacterial isolates were obtained ,which included 36% gram-posi-tive strains ,64% gram-negative strains and 1% Anaerobic bacteria .The detection rates of methicillin-resistant S .aures was 33% , the detection rate of vancomycin -resistant enterococci was 1 .6% .In enterobacteriaceae ,ESBLs producing strains accounted for 60 .6% and 35 .8% in E .coil and K .pneumonia respectively .The drug resistance of A .baumannii and P .aeruginosa was increased . Conclusion Drug resistance of bacterial isolated from our hospital is universal .Drug monitoring data is important for clinical treat-ment .
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Objective To investigate the relationship of S100B protein expression and the pathogenesis of early-onset and late-onset preeclampsia.Methods Sixty patients with preeclampsia who received caesarean section at Qingdao Municipal Hospital from October 2010 to September 2011 were enrolled in this study.Thirty cases were early-onset preeclampsia( referred as early-onset preeclampsia group,＜ 34 weeks),and the other 30 cases were late-onset preeclampsia (referred as late-onset preeclampsia group,≥34 weeks).Thirty women who received caesarean section because of pelvic structural deformities,breech presentation,macrosomia and social factors were included as the control group.The expression of S100B mRNA in the placenta was detected by reverse transcription ( RT)-PCR.The expression of S100B protein in the placenta was detected by immunohistochemistry.Results ( 1 ) S100B mRNA was expressed in the trophoblasts of preeclampsia and control groups.The expression of S100B mRNA in early-onset preeclampsia group (0.73 ±0.11 ) was significantly higher than the control group (0.58 ±0.08) and lateonset preeclampsia group (0.64 ±0.10,P ＜0.05 ).There was no significant difference between late-onset preeclampsia group and the control group ( P ＞ 0.05 ).(2) S100B protein was expressed in the plasma membrane and cytoplasm of the trophoblasts,correlated positively with the brownish yellow and brown particles inside the cells.It was expressed in all the three groups.Immunohistochemistry revealed that the expression of S100B protein in the placenta of early-onset preeclampsia group was 100％ (30/30),significantly higher than those of late-onset preeclampsia group and the control group,in which the positive rate were 70％ (21/30) and 63％ (19/30) respectively (P ＜0.05).There was no difference between late onset preeclampsia group and the control group (P ＞0.05).Conclusion Early-onset and late-onset preeclampsia may have different etiology and pathogenesis.S100B may be a factor in the pathogenesis of early-onset preeclampsia.
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Objective To investigate the effects of lead exposure on rat placental apoptosis during different periods of pregnancy. Methods All Wistar rats were randomly divided into four groups with 27 for each group with the sex ratio of 2 : 1 (female : male).The groups with lead exposure consumed water with 0. 025％ lead acetate during the entire, early or late period of pregnancy. Controls were given distilled water without lead.Blood lead levels were determined by atomic absorption spectrophotometry at the end of pregnancy. Placental apoptosis were assessed by both Hoechst staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Data were assessed by one-way analysis of variance, and differences between groups were compared by q-test. ResultsBlood lead levels at the end of pregnancy of the groups with lead exposure (entire, early or late pregnancy) and the control group were (1. 74±0. 19) μmol/L,(1.27±0.26) μmol/L, (0.60±0. 11) μmol/L and (0.04±0.01) μmol/L respectively(F= 12. 10,P＜0.01).In the groups with lead exposure, Hoechst staining showed hyperchromatic nuclei in placental trophoblast apoptotic cells and compact fluorescent particles in some nucleus； TUNEL assay showed brown-staining apoptotic cells nuclei with some nuclei particles staining brown. Two assays showed the same results: the apoptotic index of the groups with lead exposure were higher than that of the control group; the apoptosis index of the group with lead exposure during entire pregnancy was higher than that of the group with lead exposure during early and late pregnancy (P ＜ 0. 05).ConclusionsLead exposure during pregnancy could elevate the blood levels of lead and the degree of placental apoptosis.
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@#ObjectiveTo investigate the relation between erectile dysfunction and myocardial infarction in recurrent myocardial infarction, sudden cardiac death and heart failure.Methods53 male patients with myocardial infarction were randomly divided into erectile dysfunction group and erectile normal group through International Index of Erectile Function-5(IIEF-5) subject test. Then the incidence of recurrent myocardial infarction, sudden cardiac death and heart failure were observed.ResultsThe incidence of recurrent myocardial infarction, sudden cardiac death and heart failure was higher in erectile dysfunction group than in erectile normal group.ConclusionThe prognosis of the patients with myocardial infarction following erectile dysfunction is unfavourable.
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One hundred and five patients with non-ST segment elevation acute coronary syndrome were followed up for 1 year.They were assigned to the event group or non-event group according to the presence of endpoint events(cardiac death and nonfatM myocardial infarction).B-type natriuretic peptide level was measured at 30 days and 1 year and compared between the two groups.The results showed that the level of B-type natriuretic peptide was higher in the event group[(235±107)μg/L vs(154±49)μg/L at 30 days;(259±100)μg/L vs(143±57)μg/L at 1 year].Thus,B-type natriuretic peptide is an important prognostic factor for patients with non-ST segment elevation acute coronary syndrome.
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OBJECTIVE:To study curative effect of the combination of cyclosporine A,mycophenolate mofetil,anti-thymocyte globulin,interleukin-11 and short-term methotrexate as acute graft-versus-host disease(aGVHD) prophylaxis on HLA-matched unrelated donor or HLA-mismatched related donor allogenic peripheral blood stem cell transplantation(Allo-PBSCT).METHODS:Thirteen patients with haematological malignancies who underwent HLA-matched unrelated donor or HLA-mismatched related donor Allo-PBSCT with the combination of cyclosporine A as aGVHD prophylaxis at Haikou Municipal People's Hospital from September to November 2008 were selected,including 7 of unrelated donor,3 of haplotype transplantation,and 3 of 1-locus mismatched.The conditioning regimen was performed at 7 days prior to transplantation,with cyclosporine A 5-10 mg/(kg?d),12 hours per time with twice per day.From day 7 prior to transplantation,mycophenolic acid was intravenous drip once per day,then 2.5 mg/(kg?d) antithymocyte globulin at days 5-2 prior to transplantation,1.5 mg/d interleukin 11 was subcutaneous injected at day 2 prior to and 10 days after transplantation,followed by intravenous drip 15 mg/m2 amethopterin at day 1 and 10 mg/m2 at days 3,6,11 after transplantation.The drug doge was reduced and stopped gradually after 3-6 months,which could be prolonged for haplotype grafter.Recombinant human granulocyte colony-stimulating factor was injected subcutaneously at day 3 prior to transplantation,and PBSCT was collected at days 4 and 5 after medication,which was infused to patients with subclavian vein at the same day.In total(7.82-9.11)?108/kg mononuclearcell and(2.9-7.7)?106/kg CD34+ cells were infused.RESULTS:Hematopoiesis was rebuilt in all patients with 46.15%(6/13) aGVHD incidence rate,including 8 %(1/13) of Ⅲ-Ⅳ aGVHD.Up to April of 2009,all patients live and work as normal except one patient who can not visit public places.CONCLUSION:The combination of cyclosporine A,mycophenolate mofetil,anti-thymocyte globulin,interleukin-11 and short-term methotrexate is effective in the prevention of aGVHD.
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Allotransplantation of peripheral blood-derived hemopoietic stem cells is the best therapy for acute leukemia. With increases of only-child families, sibling donors are decreasing. Moreover, the probability is low and time consuming is long to search a matched hemopoietic stem cell donor from the Chinese Marrow Donor Program. Haploidentical stem cell transplantation would bring a hope for donor resource. However, difficult transplantation and high incidence of graft versus host disease are two risks. Based on modified regimen and cyclosporine A+short-term amethopterin, mycophenolic acid, interleukin-11, anti-lymphocyte immunoglobulin and hemopoietic stem cells mobilized by recombinant human granulocyte colony-stimulating factor can prevent graft versus host disease. This therapy succeeded in two cases with no severe graft versus host disease.
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AIM: The aim of this study was to observe the cardiac performance in 2-week or 4-week levothyroxine(T4)-induced cardiac hypertrophy and to elucidate the possible underlying mechanism of cardiac hypertrophy transition to heart failure in T4 treatment rats.METHODS: The blood pressure and pulse rate were measured by tail-cuff technique.The cardiac output and the preload-cardiac output were measured in working heart mode.The shortening of unloading contraction in cardiomyocytes was observed by an edge-detector system.RESULTS: Resting heart rate in T4 treatment rats increased significantly and the width of cardiomyocytes widened in T4 rats,but the length of cardiomyocytes had no difference compared with control values.The cardiac output in 2-week T4 group was higher than that in control group.The cardiac output increased when the preload increased from 5 mmHg to 15 mmHg.The unloading shortening amplitude at 1 Hz and 2 Hz increased in 2-week T4 group.No difference between 2-week T4 group and control group at 4 Hz was observed.When the stimulating frequency increased from 1 Hz to 4 Hz,the shortening amplitude also increased in control cardiomyocytes,but decreased in 2-week or 4-week T4 group.The shortening amplitude increased further in 4-week T4 group as compared with that in control.The time to peak shortening and time from peak shortening to 75% relaxation reduced at each frequency in 2-week and 4-week T4 group.The shortening and relaxation rates in 2-week or 4-week T4 group were higher than those in control group at 1 Hz and 2 Hz.The shortening and relaxation rate kept higher at 4 Hz in 2-week T4 group,but showed no difference with control at 4 Hz in 4-week T4 group.CONCLUSION: These above results suggest that shortening amplitude-frequency relationship of cardiomyocytes in 4-week T4 rats is earlier to be altered than cardiac performance in working heart.
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Objective:To explore the change of membrane protein composition of red blood cells after the blood being filtered by leukocyte filter.Methods:A total of 400ml blood from 20 healthy donors were equally divided into control group and filtered group according to the paired design.SDS-PAGE electrophoresis was done for the red blood cell membrane protein of both groups.Bandscan protein analysis software was used to analyze the composition of membrane protein.Fluorescence degree of polarization was detected by fluorescence polarization method and membrane flowability was counted.Plasma concentration of free hemoglobin(FHb) was detected weekly.Results:The band Ⅰ,Ⅱ and Ⅶ parotein of membrane skeleton of the filtered group decreased significantly compared with those of the control group(P﹤0.01),and the fluorescence degree of polarization and microviscosity of the filtered group was higher(P﹤0.01).There was significant difference of plasma FHb between filtered group and control group at each week except week 0,and that of the filted group was higher(P﹤0.01).Conclusion: Leukocyte filter can bring damage to erythrocyte membrane protein composition.Membrane microviscosity and plasma concentration of free hemoglobin increase and membrane flowability decreases.