Objective:To evaluate the role of nuclear factor erythroid 2-related factor/ heme oxygenase-1 (Nrf2/HO-1) signaling pathway in dexmedetomidine-induced reduction of oxygen-glucose deprivation and restoration (OGD/R) injury to microglia.Methods:BV-2 microglia were cultured in high-glucose DMEM culture medium supplemented with 10% fetal bovine serum in an normal culture incubator at 37 ℃ (5%CO 2-21%O 2-74 %N 2). The cells were seeded in 96-well plates at a density of 1.5×10 4 cells/ml (200 μl/well) or 6-well plates at a density of 2×10 5 cells/ml (2 ml/well) and divided into 5 groups ( n=30 each) using a random number table method: control group (group C), dexmedetomidine group (group D), group OGD/R, OGD/R+ dexmedetomidine group (group OGD/R+ D) and OGD/R+ dexmedetomidine+ ML385 group (group OGD/R+ D+ ML). The cells in group C were continuously cultured in a normal culture incubator for 26 h. In group D, dexmedetomidine at the final concentration of 10 μmol/L was added, cells were incubated for 2 h, and then were continuously incubated in a normal culture incubator for 26 h. In OGD/R, OGD/R+ D and OGD/R+ D+ ML groups, the culture medium was replaced with glucose-free DMEM culture medium, cells were cultured for 2 h in an incubator at 37 ℃ (5%CO 2-1%O 2-94 %N 2), the culture medium was replaced with high-glucose DMEM culture medium containing 10% fetal bovine serum and then the cells were cultured for 24 h in a normal incubator.Dexmedetomidine at the final concentration of 10 μmol/L was added at 2 h before OGD in OGD/R+ D and OGD/R+ D+ ML groups.Nrf-2 inhibitor ML385 at the final concentration of 4 μmol/L was added at 30 min before dexmedetomidine was added in group OGD/R+ D+ ML.Cells in 6 wells in each group were selected randomly for assessment of cell viability (by methyl thiazolyl tetrazolium assay) and apoptosis (using flow cytometry), and for determination of the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the supernatant (using enzyme-linked immunosorbent assay), the expression of Nrf2 in nucleus, Nrf2 and HO-1(by Western blot ) and the expression of HO-1 mRNA (by real-time polymerase chain reaction). Results:Compared with group C, the cell viability was significantly decreased, cell apoptosis rate and concentrations of TNF-α, IL-6 and IL-10 in the supernatant were increased, and the expression of Nrf2 in nucleus, Nrf2, HO-1 and its mRNA was up-regulated in OGD/R and OGD/R+ D groups ( P<0.05), and no significant change was found in each parameter mentioned above in group D ( P>0.05). Compared with group OGD/R, the cell viability and IL-10 in the supernatant concentration were significantly increased, cell apoptosis rate and concentrations of TNF-α and IL-6 in the supernatant were decreased and the expression of Nrf2 in nucleus, Nrf2, HO-1 and its mRNA was up-regulated in group OGD/R+ D ( P<0.05), and no significant changes were found in the parameters mentioned above in group OGD/R+ D+ ML ( P>0.05). Compared with group OGD/R+ D, the cell viability and concentration of IL-10 in the supernatant were significantly decreased, cell apoptosis rate and concentrations of TNF-α and IL-6 in the supernatant were increased and the expression of Nrf2 in nucleus, Nrf2, HO-1 and its mRNA was down-regulated in group OGD/R+ D+ ML ( P<0.05). Conclusion:The mechanism by which dexmedetomidine alleviates OGD/R injury to microglia may be related to promoting the activation of Nrf2/HO-1 signaling pathway and inhibition of inflammatory responses.

Adult ; Aged ; Bone Screws ; Female ; Femoral Neck Fractures ; pathology ; physiopathology ; surgery ; therapy ; Follow-Up Studies ; Fracture Fixation, Internal ; instrumentation ; Humans ; Male ; Middle Aged ; Pressure ; Recovery of Function

Objective To observe the changes of TNF-α and NF-κB after different doses of nalmefene hydrochloride (NAL) therapy for traumatic brain injury (TBI) in an effort to identify the effect of NAL on TBI-induced inflammatory response and the possible mechanism.Methods A model of TBI in the rat was produced using the improved Feeney' s free-fall impact method.The animals were randomly divided into sham group,TBI group,TBI + large dose of NAL (ip,0.2 mg/kg) group (TBI + NAL1group),TBI + medial dose of NAL (ip,0.14 mg/kg) group (TBI + NAL2 group),TBI + small dose of NAL (ip,0.07 mg/kg) group (TBI + NAL3 group).Form of brain tissues in each group was observed and mRNA levels of TNF-α and NF-κB were measured by real-time quantitative PCR assay.Results HE staining revealed severe injury and inflammatory infiltration of brain parenchyma in TBI group ;on the contrary,the situation ameliorated in TBI + NAL1 group,TBI + NAL2 group and TBI + NAL3group,with especially obvious improvement in TBI + NAL2 group.In PCR assay,significant expression of NF-κB and TNF-α was observed at post-TBI days 1,3,5 and 7 (P ＜ 0.05),followed by great reverse after NAL therapy (P ＜ 0.05),particularly in TBI + NAL2 group.Conclusions NAL can reduce the inflammation response to TBI and promote post-injury recovery.Moreover,there exists a NAL concentration window.

Objective: To investigate the protective factors and risk factors of nosocomial infection of severe acute respiratory syndrome (SARS) among health care workers (HCWs) , and thus provide the scientific basis for prevention and control of nosocomial infection. Methods: With the case-control study,a standardized questionnaire was used for data collection in three general hospitals where nosocomial infection had occurred. Univariate analysis was done at first. All concerned factors about SARS infection were scanned by using Chi-square test and Fisher' s exact test one by one, and determined as to whether they were risk factors or protective factors according to odd ratio (OR) score. Then, multivariate unconditional logistic regression analysis was used to re-analyze the picked-out factors for finding out which factors played independent roles. Results: Twenty-two factors (nineteen protective factors and three risk factors), among the total fifty-six factors, were significantly associated with SARS infection. Multivariate unconditional logistic regression revealed that factors such as double exposure suits ( OR = 0.053 ), education ( OR =0.072), gloves ( OR =0.102), hands sterilized by iodine ( OR =0.231 ), room air ventilation (OR = 0.32), were significantly protective; conversely, tracheal intubation ( OR = 30.793 ) was a significant risk factor. Conclusion: Strict defense and antisepsis measures were pivotal in preventing SARS infection among high-risk medical personnel. Education about associated knowledge and effective air ventilation were also important factors.

Objective:To see the influence of different antiplatelet therapies on stroke patients’ readmission by performing a deep data-mining into Beijing Healthcare Insuring Database,based on a large sample size.Methods:Aretrospective cohort study,was adopted to extract patients primarily diag-nosed as ischemic stroke from healthcare database.The first hospital records were considered as the pa-tient’s baseline in this study,who were divided into MAPT (aspirin)and DAPT (aspirin and clopi-dogrel)according to the patient’s baseline medications.A follow-up was conducted to see whether the patients would have rehospitalization record because of major result events after medication.The major re-sult events,included:(1 )recurrence of ischemic stroke;(2)hemorrhagic transformation of ischemic stroke;(3)myocardial infarction;(4)the digestive hemorrhage.The Kaplan-Meier figure was used to compare the survival situations between these two groups,the log-rank test was used to test the difference of the survival curve,and 1 ∶1 propensity score matching was calculated from the patients’baseline da-ta.Cox proportional hazards model was used to calculate the hazard ratio (HR).Results:A total of 27 695 patients From January 201 0 to September 201 3 were included,4 047 with DAPT,and 23 648 with MAPT.Because the baseline characteristics of the patients was disequilibrium,so we used 1 ∶1 pro-pensity score matching,after which,the number of the two groups was 4 046 each.Adjusted for the gen-eral demographic characteristics such as age,sex,nationality,complication and drug combination,no statistical significance was observed between the survival curves of the two groups (P =0.06).HR value of major result events between the groups was 0.91 (0.82 -1 .01 ,P =0.07),which was not statistically significant.The covariate gender HR =1 .36 (1 .20 -1 .55,P <0.05),accompanied by diabetes HR =1 .36 (1 .20 -1 .54,P <0.05 ),dyslipidemia HR =1 .1 3 (1 .00 -1 .27,P =1 .1 3),heart disease HR =1 .39 (1 .22 -1 .58,P <0.05)was statistically significant.Drug combination with other antiplate-let agents HR =1 .05 (0.95 -1 .1 7,P >1 .05)did not increase the risk of readmission.Conclusion:There was no difference in prevention of readmission between patients with DAPT and MAPT.Patients with complications should actively treat the complications at the same time as they prevent recurrence after first attack.

Aim To observe the protective effect of quercetin on rat cardiomyocyte apoptosis induced by adriamycin and explore its possible mechanism.Methods Cultured neonatal rat cardiomyocytes were randomly divided into six groups:normal control group, adriamycin group,quercetin control group, adriamycin+quercetin(25,50,100 ?mol?L-1)groups. The activity of LDH was detected by chromatometry, the cardiomyocyte viability was measured by MTT, the ultrastructure of cardiomyocyte was observed by electron microscope, the expression of protein Bcl-2 and Bax was analyzed by immunocytochemical, and the mRNA and protein of caspase-3 were detected by RT-PCR and Western blot respectively.Results Compared with the control group, the activity of LDH was increased but the viability of cardiomyocyte was decreased; the expression of Bax and caspase-3 was up-regulated while Bcl-2 was down-regulated in ADR group.Compared with ADR group, the above changes were lightened in adriamycin+quercetin groups. But the quercetin control group, in which cultured myocardial cells only exposed to quercetin without ADR, had no obvious changes.Conclusions Quercetin significantly inhibits the apoptosis induced by ADR in the cultured myocardial cells. Its mechanism is involved in the apoptosis-related pathways, including caspase-3, Bax and Bcl-2.

Objective To improve the accuracy with magnetic resonance imaging (MRI) diagnosis of spontaneous intraocular hemorrhage. Design Retrospective case series. Participants 6 patients with spontaneous intraocular hemorrhage. Methods The image findings were retrospectively analyzed in 6 patients confirmed by surgery with or without pathology. All of them were examined with ultrasonography and 5 cases with color ultrasonography. MRI was performed in 6 cases,and enhanced MRI in 5 cases. Main Outcome Measures Configuration,signal intense,characteristics of enhancement signal and ultrasonograph. Results 1 case was crescent shape on MRI of spontaneous intraocular hemorrhage,2 cases were lenticular shape,3 cases were hump shape. 2 cases showed high signal intensity on T1WI,and low signal on T2WI. 2 cases showed high signal on both T1 and T2WI. 2 cases showed low signal on T1WI,and high signal intensity on T2WI. 2 cases presented a ring with hypointensity on T2WI. No enhancement was revealed within the lesions in 5 cases. Liner enhancement was showed in 2 cases; ring enhancement was showed in 1 case. 2 cases were corrected diagnosed by MRI,2 cases were misdiagnosed as melanoma,and 2 cases were misdiagnosed as tumor concomitant hemorrhage,and all cases were diagnosed as tumor with ultrasonography. With color Doppler imaging 4 cases were correctly diagnosed as hemorrhage based on without blood-flow signal,and 1 case was diagnosed as tumor. Conclusions The MRI signal characteristic of spontaneous ocular hemorrhage is variable,and the main feature is no enhancement within the lesion. MRI combined with ultrasonography can make the diagnosis more correctly.

Objective:To discuss the etiology, clinical manifestations and renal pathological features of acute interstitial nephritis (AIN) in children.Methods:The etiology, clinical manifestations, pathological characteristics, clinical effects and outcome of the children with AIN diagnosed by renal biopsy from January 2010 to December 2019 in Nanjing Jinling Hospital were analyzed retrospectively. The Kaplan-Meier method was used to evaluate the kidney survival rate. Cox regression model was built to analyze the risk factors for developing end-stage renal disease (ESRD) at baseline in AIN children.Results:A total of 51 children with AIN were diagnosed by renal biopsy, including 36 males and 15 females. The age was (12.94±2.55) years old (2-17 years old). The clinical manifestations of AIN in children were various and lack of specificity. Only 2 cases (3.92%) had triad. All of the 51 children with AIN showed acute renal injury (AKI), accompanied by increased serum creatinine and decreased estimated glomerular filtration rate. The stage of AKI was mainly stageⅢ(33 cases, 64.71%). Infection was the main cause (38 cases, 74.51%) and drug factor was the second cause (27 cases, 52.94%) in children with AIN. Nonsteroidal antiinflammatory drugs (NSAIDs) were the main inducers of drug-induced AIN (18 cases, 35.29%). The interstitial inflammatory cell infiltration or interstitial edema was found in 51 children. The infiltration of inflammatory cells was mainly mononuclear cells (46 cases, 90.20%). After 4 weeks of treatment, 32 cases (62.75%), 11 cases (21.57%) and 8 cases (15.69%) showed complete, partial and no recovery of renal function, respectively. After 12 weeks of treatment, 49 cases (96.08%), 0 cases (0) and 2 cases (3.92%) showed complete, partial and no recovery of renal function, respectively. After an average follow-up of 4.0(2.0-15.0) months, 2 case (3.92%) patients developed ESRD. The cumulative survival rates of ESRD at 1 year and 2 years after renal biopsy both were 100%, and renal survival rates at 5 years and 10 years were 96.55% and 72.41%, respectively. Multivariate Cox regression analysis results showed that N-acetyl-β-D-glucosidase (NAG) enzyme level>17.6 U/g·cr ( HR=15.729, 95% CI 1.045-15.977, P=0.042) and IgM deposition in renal tissue ( HR=7.523, 95% CI 1.142-9.541, P=0.033) were independent risk factors for developing ESRD in AIN children. Conclusions:AKI is the main clinical manifestation of AIN in children. The characteritic of renal pathology in AIN is tubulointerstitial lesions. After active treatment, most of the patients have a good prognosis. Prevention of infection and rational use of drugs are the key to reduce the incidence rate of AIN in children. The N-acetyl-β-D-glucosidase enzyme level>17.6 U/g·cr and IgM deposition in renal tissue are independent risk factors for developing ESRD in AIN children.

OBJECTlVE To study the Iong term toxicity of vinoreIbine tartrate(NVB)on rat immune and hematopoietic systems pathoIogicaIIy. METHODS SD Rats were randomIy divided into 4 groups:normaI controI group and NVB 5.0,10.0,and 20.0 mg·m-2 groups,each group containing 6 maIe and femaIe rats. The rats in NBV groups were administered different concentrations of NVB by intravenous drip on the 1st and 8th days,21 da cycIe,for 4 cycIes. On the 14th day after the Iast administration, white bIood ceIIs(WBC),neutrophiI(Neut),Iymphocytes(Lym),red bIood ceIIs(RBC)and reticuIo-cyte‰(RET‰)were detected by ADVIA2120 hematoIogy anaIyzer. Thymus,sternum marrow,spIeen and mesenteric Iymph nodes were observed by histopathoIogicaI examination. The thymus and spIeen were preciseIy weighed to obtain the reIative organ coefficients. Bone marrow smears were made for counting and cIassification. RESULTS Compared with normaI controI group,WBC,Neut,Lym,RBC and RET% of peripheraI bIood of NVB 5,10 and 20 mg·m-2 groups were decreased(P﹤0.05,P﹤0.01). The Neut vaIue of maIe rats was(2.35±0.56)×109·L-1 in normaI controI group,but was reduced to (1.66±0.44),(0.67±0.22)and(0.20±0.02)×109·L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The Neut vaIue of femaIe rats was(1.26± 0.27)× 109 L-1 in normaI controI group,but was reduced to(1.14±0.56),(0.47±0.13)and(0.21±0.08)×109 L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The resuIts of counting and cIassification of bone marrow smears showed that the myeIoid ceII ratio decreased(P﹤0.05,P﹤0.01). The myeIoid ceII ratio of maIe rats was(42.7±6.1)% in normaI controI group,but was reduced to(28.8±5.3)%,(22.0±3.2)% and(18.9±3.9)% in NVB 5,10 and 20 mg·m-2 groups. The myeIoid ceII ratio of femaIe rats in normaI controI group was(35.4±3.0)%, but was reduced to(31.2±4.7)%,(22.9±6.7)% and(20.8±4.2)% in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient was reduced(P﹤0.05,P﹤0.01). The thymus coefficient of maIe rats in normaI controI group was 0.36±0.04,but was reduced to 0.31±0.06,0.18±0.03 and 0.08±0.01 in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient of femaIe rats in normaI controI group was 0.29±0.06,but was reduced to 0.25±0.06,0.19±0.06 and 0.07±0.01 in NVB 5,10 and 20 mg·m-2 groups. Histopatho-IogicaI examination showed that thymus was atrophiedand bone marrow was suppressed. SpIeen com-pensatory extrameduIIary hematopoietic ceIIs were increased in NVB 5.0,10.0 and 20.0 mg·m-2 groups (maIe and femaIe)to different degrees,but the mesenteric Iymph nodes of NVB groups showed no sig-nificant pathoIogicaI changes. CONCLUSlON NVB has immune and hematopoietic toxicity on SD rats, as is showed by thymic atrophy and bone marrow suppression.

OBJECTIVETo evaluate the effect of autologous bone marrow stem cell transplantation in the treatment of severe liver damage.

METHODSAutologous bone marrow (50 ml) was harvested from 6 patients aged 44 to 69 years admitted for severe liver damage. Human bone marrow stem cells (HMSCs) were isolated and transplanted in to the patients' liver. At l, 4, 8, and 12 weeks after the transplantation, the changes in ALT, ALB, Cr, TB, PT and the clinical symptoms of the patients were observed.

RESULTSThe transplantation of autologous bone marrow stem cells resulted in obvious improvement of the liver function. At 12 weeks after the transplantation, ALT was reduced from 98.4 IU/L to 41.5 IU/L, TB from 136.5 µmol/L to 78.4 µmol/L, Cr from 112.3 µmol/L to 72.1 µmol/L, and ALB rose from 23.3 g/L to 32.6 g/L. The survival of the patients was 100% at 12 weeks, but one patient died at 7 months after the transplantation. The symptoms of the patients were also alleviated after the transplantation. At 12 weeks after transplantation, 3 patients reported improved appetite, 3 showed recovery of physical strength, and 2 showed lessened abdominal swelling. No serious adverse complications in association with the transplantation were found in the in 4 patients available to the follow-up.

CONCLUSIONAutologous bone marrow stem cell transplantation can improve the liver function of patients with severe liver damage without causing serious complications.