Objective To investigate the effects of different concentration and inhalation duration time of isoflurane on cognitive performance and the expression of GABAR1 and NMDAR2B in aged SD rat cerebral temporal lopes.Methods Aged male SD rats (9 months) were randomly divided into control group (n=10) and test group (n=80).The control group received air at room tempreture.Test groups were divided into four groups: group S1 (1.5%-2 h),group S2 (2.5%-2 h),group S3 (1.5%-4 h),group S4 (2.5%-4 h)according to isoflurane concentration and inhalation duration time.Every group was equally divided into two groups and Morris water maze test was performed day 1 and day 7 after isoflurane inhalation.Then the right temporal lobe was gathered and the mRNA transcription and protein expression of GABAR1 and NMDAR2B were detected by RT-PCR and Immunofluorescence technique.Results One day after isoflurane inhalation, accompanied with increased isoflurane concentration and inhalation duration, the spatial memory ability of every test group decreased continually, and the mRNA transcription and protein expression of GABAR1 increased and the mRNA transcription and protein expression of NMDAR2B decreased compared with control group (P<0.01).Seven days after isoflurane inhalation, the spatial memory ability of group S4 decreased, the mRNA transcription and protein expression of both GABAR1 increased, the mRNA transcription and protein expression of NMDAR2B decreased compared with control group and the other test groups (P<0.01).There was no significant difference between the control group and groups S1, S2, S3.Conclusion Continuous inhalation of isoflurane has great effects on spatial memory ability.And impaired spatial memory by isoflurane inhalation of high concentration with long duration is present in a long time.Thoses are related with the mRNA transcription and protein expressions of GABAR1 and NMDAR2B in cerebral temporal lope.

Objective To observe the changes of learning and memory ability and the expression of GRP8,ATF4 and CHOP in the frontal lobe neurons of rats after isoflurane anesthesia.Methods Male SD aged rats were randomly divided into 4 groups with 15 in each group.Rats in ISO group received 1.5% isoflurane 2 h,SAL group received intraperitoneal injection Salubrinal(1 mg/kg),ISO+SAL group received 1.5% 2 h after intraperitoneal injection Salubrinal(1 mg/kg),C group only inhaled 30% air and oxygen mixture.Morris water maze (MWM) test was performed 24 hours after isoflurane anesthesia,and then the left frontal lobe of rats was collected,gene transcription and protein expression changes of 78-kDa glucose-regulated protein(GRP78),activating transcription factor 4(ATF4),C/EBP homologous protein(CHOP) were evaluated by real-time fluorescence quantitative PCR and immunofluorescence.Results Compared with the C group,the latent time of ISO group was significantly prolonged(ISO group(19.10±2.98)s vs C group (10.54±2.05)s,P<0.05);the number of times passing through the target platform of ISO group was decreased significantly(ISO group (6.78±1.47) vs Cgroup (9.03±1.69),P<0.05);protein expression level of GRP78 was significantly increased in group ISO (ISO group (965.8±86.5) vs C group(247.5±46.3),P<0.05);protein expression level of ATF4 was significantly increased in group ISO(ISO group (470±69.4) vs C group (275.4±56.3),P<0.05) protein expression level of CHOP was significantly increased in group ISO(ISO group (618.7±83.3) vs C group(174.5±71.2),P<0.05).The transcription trends of GRP78,ATF4,CHOP were consistent with their protein expression.Conclusion The decrease of short-term memory ability after isoflurane anesthesia may be related to the activation of endoplasmic reticulum stress pathway in frontal lobe neurons.

Objective:To investigate the clinical characteristics and prognosis of idiopathic inflammatory myopathy (IIM) patients with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:A total of 194 hospitalized IIM patients who were tested for myositis-specific autoantibodies (MSAs) in the Departments of Rheumatology and Immunology of Tianjin Medical University General Hospital from January 2015 to September 2020 were collected, including 29 cases with positive anti-MDA5 antibody and 165 cases with negative anti-MDA5 antibody. Their clinical data were analyzed retrospectively. T test was used for measurement data with normal distribution. Measurement data with non-normal distribution were tested by Mann-Whitney U rank sum test. χ2 test was used for counting data. Risk factors were analyzed by binary Logistic regression, survival analysis by Kaplan-Meier method and Cox regression analysis. Results:IIM patients with positive anti-MDA5 antibody had a high incidence of dermatomyositis specific skin rash, and the skin rash was the most common presenting symptom. In the positive anti-MDA5 antibody group, muscle symptoms were mild; and the patients were prone to have fever, arthritis, oral ulcer and weight loss. All patients were complicated with interstitial lung disease (ILD). In patients with negative anti-MDA5 antibody, white blood cell (WBC) count [7.59(5.61, 9.89)×10 9/L vs 4.07(3.17, 5.50×10 9/L, Z=-5.05, P<0.001], platelet (PLT) [249.00 (200.00, 302.00)×10 9/L vs 205.00 (178.00, 244.00)×10 9/L, Z=-2.59, P=0.010], lymphocyte (LY) [1.34(0.85, 1.94)×10 9/L vs 0.64(0.40, 0.83)×10 9/L, Z=-5.78, P<0.001), serum creatine kinase (CK) [558.00 (72.00, 2 959.00) U/L vs 64.00 (35.00, 149.50) U/L, Z=-3.97, P<0.001], creatine kinase isoenzymes (CK-MB) [38.00 (17.00, 127.00) U/L vs 16.00 (14.00, 25.00) U/L, Z=-3.84, P<0.001], myoglobin (MYO) [243.65 (60.50, 829.83) ng/ml vs 34.55(21.00, 104.23) ng/ml, Z=-3.98, P<0.001], troponin T (TnT) [0.09(0.03, 0.44) ng/ml vs 0.02(0.01, 0.04) ng/ml, Z=-4.17, P<0.001], albumin (ALB) [34.00(30.00, 38.00) g/L vs 31.00 (26.50, 36.00) g/L, Z=-2.68, P=0.007], cluster of differentiation 4 (CD4) + T cells [498.00(276.00, 752.00) cells/μl vs 259.50 (179.00, 498.25) cells/μl, Z=-2.79, P=0.005], partial pressure of carbon dioxide (PaCO 2) [39.00(36.13, 42.00) mmHg vs 35.35 (31.30, 38.88) mmHg, Z=-3.75, P<0.001], partial pressure of oxygen (PaO 2) [82.00(71.90, 90.20) mmHg vs 73.25(64.30, 84.05) mmHg, Z=-2.08, P=0.037], arterial oxygen saturation (SaO 2) [96.50% (95.05%, 97.30)% vs 95.80%(93.70%, 96.55%), Z=-2.11, P=0.035], diffusion capacity for carbon monoxide of the Lung (DLco) [(63±21) % vs (52±14)%, t=0.96, P=0.006] were significantly reduced, while UTP [260.50 (172.25, 401.25) g vs 331.00 (252.75, 666.25) g, Z=-2.18, P=0.029], alanine aminotransferase (ALT) [40.00 (21.00, 83.00) U/L vs 56.00(40.00, 107.50), Z=-2.27, P=0.023], glutamyltranspeptidas (GGT) [22.50(15.00, 42.00) U/L vs 57.00 (38.00, 101.50) U/L, Z=-4.98, P<0.001], D-Dimer [850.00 (485.00, 1 799.50) ng/ml vs 1 346.00 (896.50, 2 527.00) ng/ml, Z=-2.55, P=0.011], immunoglobulin (Ig)E [60.00 (25.60, 147.50) U/ml vs 173.00(68.25, 471.50) U/ml, Z=-3.06, P=0.002], C4[20.25(16.68, 25.03) mg/L vs 23.60(20.20, 28.35) mg/L, Z=-2.38, P=0.017], Fer [228.01 (115.40, 513.36) ng/ml vs 1 636.39 (851.80, 3 888.82) ng/ml, Z=-6.01, P<0.001], krebsvondenlungen-6 (KL-6) [365.00 (180.25, 1 018.75) U/ml vs 788.00 (406.00, 1 364.00) U/ml, Z=-2.10, P=0.035] were higher when compared to patients with positive anti-MDA5 antibody. In the anti-MDA5 antibody positive group, patients had high mortality rate [8.5%(14/165) vs 34.5%(10/29), χ2=13.07, P<0.001], and the use of intravenous immunoglobulin [32.7%(54/165) vs 65.5%(19/29), χ2=11.30, P=0.001] and steroid pulse therapy [4.8%(86/165) vs 27.6%(8/29), χ2=13.98, P<0.001] were more frequent. Patients in the positive anti-MDA5 antibody group were classified into two sub groups based on lung features: the rapidly progressive interstitial lung disease (RP-ILD) group (48.28%, 14/29) and the chronic interstitial lung disease (C-ILD) group (51.72%, 15/29). RP-ILD patients had significantly elder disease onset age, higher C-reaction protein (CRP), Fer, IgE levels and the positive rate of anti-Ro52 antibody, while ALT was lower. The difference was statistically significant. Regression analysis suggested that older onset age [ HR (95% CI)=1.154 (1.069, 1.246), P<0.001], male [ HR(95% CI)=6.383(1.038, 39.242), P=0.045], positive anti-MDA5 antibody [ HR(95% CI)=17.180 (2.900, 101.766), P=0.002], LY decrease [ HR (95% CI)=0.083 (0.008, 0.817), P=0.033], high serum Fer level [ HR (95% CI)=1.001(1.000, 1.001), P=0.016], increased D-Dimer [ HR(95% CI)=1.000(1.000, 1.001), P=0.004] and compicated with carcinoma [ HR (95% CI)=11.849 (1.978, 70.970), P=0.007] were independent risk factors for death in IIM patients. Binary logistic regression analysis suggested that late onset age [ OR(95% CI)=1.090 (1.005, 1.183), P=0.038], high Fer level [ OR (95% CI)=1.001 (1.000, 1.001), P=0.022] and decreased ALB [ OR (95% CI)=0.818 (0.696, 0.963), P=0.016] might be risk factors for RP-ILD in patients with positive anti-MDA5 antibody. Conclusion:In patients with positive anti-MDA5 antibody group, typical skin damage, mild muscle symptoms, high proportion of ILD and poor prognosis are chardcteristic when compared to patients without this autoantibody. It is necessary to monitor the disease activity closely and explore the treatment strategy.