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OBJECTIVE@#To investigate the expression of citrullinated epitopes in articular cartilage protein and whether its expression is sufficient to induce anti-citrullinated protein antibody (ACPA) response in mice.@*METHODS@#The experimental group was treated with different concentrations of lipopolysaccharide (LPS), heat-inactivated bacteria ( and ) or specific monoclonal antibody against type Ⅱ collagen to induce citrullination of articular cartilage protein, with PBS as the control. Immunohistochemistry with the monoclonal antibody ACC4 (IgG1) that specifically binds to the citrullinated epitope of cartilage protein was performed for detecting the expression of citrullinated protein, with ACC1 (IgG2a) as a positive control antibody and L243 (IgG2a) and Hy2.15 (IgG1) as the negative isotype control. In the in vivo experiment, SD rats were subjected to injection of different doses of LPS in the right knee (with PBS as the controls in the left knee), and 3 days later frozen sections were prepared for immunohistochemical detection of the expression of citrullinated protein. Models of collagen-induced arthritis (CIA) established in different mouse strains were observed for incidence and severity of CIA. Serum samples collected from these models and the sera from rheumatoid arthritis patients were examined for anti-citrullinated protein antibody, and immunohistochemistry was performed to detect the expression of citrullinated protein in the cartilage of the mouse.@*RESULTS@#The citrullinated CII epitope-specific antibody ACC4 did not bind to articular cartilage tissues with different treatments as compared with the positive control antibody ACC1. The ACC4 antibody and the antibodies from patients with rheumatoid arthritis with high titers of anti-citrullinated protein antibody were capable of binding to the synovial tissue around the articular cartilage of the CIA. Luminex analysis showed that the anti-citrullinated protein antibody was lowly expressed in mouse serum, but the anti-type Ⅱ collagen triple helix structure peptide antibody exhibited strong reactivity.@*CONCLUSIONS@#Mild acute inflammatory response is not enough to cause citrullination of articular cartilage protein, and the expression of specific epitope requires a high-intensity inflammatory response. Inflammatory articular cartilage protein can express citrullinated epitopes in type Ⅱ collagen-induced arthritis in mice, but the expression of citrullinated epitopes is not sufficient to induce an immune response to anti-citrullinated antibodies. Stronger stimulation signals are required to induce an immune response for producing anti-citrullinated protein antibodies.
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Animals , Humans , Mice , Rats , Arthritis, Experimental , Autoantibodies , Cartilage, Articular , Citrulline , Inflammation , Rats, Sprague-DawleyABSTRACT
Objective To evaluate the changes of hypoxic conditions in non-small cell lung cancer (NSCLC) patients before and after radiotherapy and assess the value of 18F-fluoromisonidzaole (FMISO)PET/CT for radiotherapy efficacy evaluation.Methods A total of 21 NSCLC patients (15 males,6 females,age 30-74 years) from January 2014 to October 2016 were prospectively enrolled.18F-FMISO PET/CT was performed before and after radiotherapy,and all patients underwent 18F-fluorodeoxyglucose (FDG)PET/CT before radiotherapy.Routine chest CT was performed at the 3rd and 6th month after radiotherapy.The maximum standardized uptake value (SUVmax) of tumor and muscle,tumor volume and hypoxic volume (HV) were measured.Tumor-to-muscle (T/M) value of 18F-FMISO was calculated,and T/M ≥ 1.3 was considered as the hypoxia cut-off value.Data were analyzed using Pearson correlation,paired t test,signed rank sum test and Wilcoxon rank sum test.Results Totally 81.0％(17/21) of NSCLC patients had hypoxia.There were significant positive correlations between 18F-FMISO T/M value and tumor volume or 18F-FDG SUVmax(r:0.72,0.60,both P＜0.05).The T/M value after radiotherapy was significantly lower than that before radiotherapy (1.42± 1.12 vs 2.08±0.71;t =3.62,P＜0.05),and median HV was also significantly lower than that before radiotherapy (6.53 vs 12.41 cm3;z =-3.83,P＜0.05).The median T/M values of effective group (n =14) and ineffective group (n =7) before radiotherapy were significantly different (2.14 vs 2.87;z=-2.27,P＜0.05),and the median HV of 2 groups before radiotherapy was also significantly different (6.43 vs 10.20 cm3;z=-2.14,P＜0.05).Conclusions Most NSCLC patients have hypoxia before radiotherapy.The larger tumor volume,the higher degree of hypoxia.Radiotherapy can alleviate the hypoxia of tumors.18F-FMISO PET/CT imaging before radiotherapy can be used to predict the efficacy of patients with NSCLC.
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Objective To investigate the impact on image quality of bone imaging and patients safety when whole body bone imaging was performed on the sme day of renal dynamic imaging.Methods Fifty-three adult patients underwent renal dynamic imaging and whole body bone imaging were selected as observation group.Firstly,99 Tcm-DTPA renal dynamic imaging was performed,and 2 h later,99Tcm-MDP was injected,then whole body bone imaging was performed according to technological process.The other 53 patients received bone imaging only were selected as control group.After injection of 99Tcm-MDP immediately and 30 min,1 h,2 h,4 h,6 h,and 24 h later,physiological response of all patients was observed,and image quality of bone imaging between the two groups was compared.Then the ratio of subjective excellent images of the two groups was calculated.Radioactivity counting of T12,L4,iliac crest,middle humerus,middle femur and soft tissue above 2 cm of ilium on posterior image was measured,and target/non target (T/NT) was calculated.Statistical analysis was performed on the two groups.Results Adverse reaction was not found in all patients in two groups.Subjective excellent rate was 90.57％ (48/53) in observation group,and 92.45％ (49/53) in control group (x2 =0.12,P＞0.05).T/NT of T12,L4,middle humerus and middle femur had no significant differences between two groups (all P＞0.05).The difference of T/NT of iliac crest was statistically significant between two groups (t=3.45,P＜0.05).Conclusion Radionuclide renal dynamic imaging on the same day has no significant impact on the image quality of whole body bone imaging.
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Objective To investigate the early postoperative rehabilitation condition of patients with cervical spondylotic radiculopathy and analyze its correlation with the life style.Methods A retrospective analysis for 164 cases of cervical spondylotic radiculopathy with complete follow-up data were carried out.Using modified MacNab criteria for evaluation of postoperative recovery.The clinical efficacy was evaluated 3 months after operation,and the patients were divided into satisfactory group (excellent/good) and unsatisfactory group (fair/poor).The influencing factors included general information and the lifestyle such as smoking,drinking,sleep time,the height of the pillow,working time and frequency of physical exercise.The chi-square test and Logistic multivariate regression analysis were used to analyze the effects of lifestyle on early postoperative rehabilitation patients with cervical spondylotic radiculopathy.Results Postoperative efficacy satisfaction of patients evaluated by modified MacNab standard was 88.4％ in 3 months.There were differences in age(x2 =5.819),smoking(x2 =5.074) and frequence of physical exercise(x2 =4.430),and the differences were statistically significant (all P＜ 0.05).Logistic analysis showed that age more than 50 years old(OR=3.913,95％ CI =1.321-11.594,P=0.014),smoking(OR=3.217,95％ CI =1.126-9.195,P =0.029) and frequence of physical exercise less than or equal to 3 times a week (OR=3.906,95％ CI =1.026-14.869,P=0.046) were the risk factors affecting the satisfaction of clinical curative effect of early postoperative cervical spondylotic radiculopathy.Conclusion Age,smoking and physical exercise are related to early postoperative rehabilitation of patients with cervical spondylotic radiculopathy,and then more than 50 years old,smoking and exercise less than 3 times a week have adverse effects on the early postoperative rehabilitation.
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Objective: To explore the effects of 17 β-estradiol (E2) and 2-methoxyestradiol (2ME) on endothelium-1/nitric oxide (ET-1/NO) cascade in experimental rats with hypoxic pulmonary hypertension. Methods: A total of 48 female SD rats were randomly divided into 6 groups:①Sham operation group,②Ovariectomy (OVX) group,③Hypoxia group,④OVX+hypoxia group,⑤OVX+hypoxia+E2 group, the rats received subcutaneous E2 at 20μg/(kg?d) and⑥OVX+hypoxia+2ME group, the rats received subcutaneous 2ME at 240μg/(kg?d).n=8 in each group. Blood levels of ET-1, NO, eNOS activity and the expressions of pulmonary tissue endothelium A receptor (ETAR), ETBR and eNOS were compared among different groups. Results: Compared with Sham operation group, Hypoxia and OVX+hypoxia groups showed small pulmonary artery thickening with lumen narrowing, increased mean pulmonary arterial pressure (mPAP), allP<0.01; the above morphological and mPAP changes were reduced by E2 and 2ME intervention. Compared with Sham operation group, OVX and Hypoxia groups had increased blood ET-1 and pulmonary mRNA, protein expressions of ETAR, decreased pulmonary ETBR, all P<0.01; the above changes were more obvious in OVX+hypoxia group; E2 and 2ME intervention reduced blood ET-1 and pulmonary ETAR expression, but they were still higher than Sham operation group, meanwhile, ETBR expression was elevated, but it was still lower than Sham operation group, allP<0.01; blood ET-1 was lower in OVX+hypoxia+2ME group than OVX+hypoxia+E2 group,P<0.05. Compared with Sham operation group, OVX group had decreased pulmonary eNOS protein expression,P<0.01; Hypoxia group had decreased blood NO and pulmonary eNOS protein expression,P<0.05 orP<0.01; OVX+hypoxia group had decreased blood NO, eNOS activity and decreased pulmonary mRNA and protein expressions of eNOS, allP<0.01; E2 and 2ME intervention elevated the above indexes,P<0.05 orP<0.01, but they were still lower than Sham operation group, allP<0.05. Conclusion: E2 and 2ME could decrease blood ET-1 and pulmonary ETAR expression, increase pulmonary ETBR expression; elevate blood NO, eNOS activity and pulmonary eNOS expression. E2 and 2ME may partially reverse pulmonary hypertension via improving ET-1/NO cascade in experimental rats.
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β-Amyrin synthase (β-AS) genes of Glycyrrhiza uralensis from 6 different regions were analyzed by PCR-SSCP and sequenced, then the correlationship between β-AS SNP and regions of Glycyrrhiza uralensis were determined. According to the 1 coding single nucleotide polymorphism on the first exon of β-AS gene at 94 bp site, Glycyrrhiza uralensis could be divided into 3 genotypes. In these genotypes, the percentage of 94A type in genuine regions was much higher, and it had significant differences with the percentage in non-genuine regions (P < 0.001). The results of the experiment proved that different β-AS genotypes at 94 bp site from different regions may be one of the important reasons to result in the genuineness of Glycyrrhiza uralensis.
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Objective To evaluate the value of 18F-FDG and 18F-FLT PET/CT for the detection of primary and regional lymph node metastasis of gastric cancer.Methods Thirty-seven patients with gastric cancer underwent preoperative 18F-FLT and 18F-FDG PET/CT within one week from March 2011 to April 2013.Postoperative histopathology confirmation was obtained in all patients.The PET/CT images were assessed visually and semi-quantitatively.Two-sample t and x2 tests were analyzed using SPSS 13.0.Results For the detection of primary gastric cancer,the sensitivities of 18 F-FLT and 18 F-FDG PET were 89.2％ (33/ 37) vs 91.9％(34/37),respectively (x2=0.158,P＞0.05).The 18F-FLT SUVmax of 16/37 cases with diffuse-type gastric cancer was significantly higher than that of 21/37 cases with intestinal-type gastric cancer (6.89±1.38 vs 3.79±2.45,t=4.533,P＜0.05) ; while 18F-FDG SUVmaxwas not significantly different between the two subgroups (7.13± 1.97 vs 6.36±2.32,t =1.066,P＞0.05).For the detection of regional lymph node metastasis,the sensitivity,specificity and accuracy of 18F-FLT and 18F-FDG were 64.8％(35/54) vs 88.9％(48/54),97.6％(246/252) vs 82.9％(209/252),91.8％(281/306) vs 84.0％(257/306),respectively (x2 =8.796,30.948,8.854,all P＜0.05).The overall sensitivity,specificity and accuracy by both tracers were 92.6％(50/54),98.8％(249/252) and 97.7％(299/306).Conclusions 18F-FLT might be a better or complementary tracer to 18F-FDG for the detection of diffuse-type gastric cancer.Compared with 18FFDG PET/CT,18F-FLT PET/CT may be less sensitive but more specific and accurate for the detection of regional lymph node metastasis.The overall diagnostic accuracy can be improved by using both tracers.
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Objective To study the effects of sleep inertia (SI) of different time course sleeps on sleep stages and cognitions in healthy men after 30 h sleep deprivation,and also to investigate the mechanism of cognitive functions impairment in sleep inertia stages and the influential factors of sleep inertia.Methods Ten healthy men (age,(20.8 ±2.1) years) participated in the program.The program was divided into 2 stages.First,participants attended a series of tests after 20 min nap(20 min nap group)after 30 h sleep deprivation.The testing series included 3 parts:the continuous performance task,the Stroop Tests,and the Addition Tests.The series of tests were done 3 times immediately after the volunteers were awoken and each lasted about 15 minutes with an interval of 10 minutes between each test.The polysomnogram (PSG) was recorded during the nap.The following 7 days was set as washing-out period to ensure a complete recovery.Participants repeated the similar processes with 2 h nap(2 h nap group) instead of 20 min nap.The cognitive performance of each group was compared with each other along with the best cognitive performance in awakening to estimate whether or not the cognitive abilities regained the normal condition.Results ( 1 ) Sleep latency became shortened in both groups after 30 h sleep deprivation.There were no slow wave sleep (SWS) and rapid eye movement sleep (REM) sleep stages in the 20 min naps,while the percentage of SWS was increased and percentage of REM declined in 2 h naps.(2)In the early of SI (5 min after awaking),cognitive tasks showed that the abilities of continuous attention,selected attention and addition ability were all impaired (continuous performance task:(371.8 ± 21.3 ) times/3 min vs (334.4 ± 22.4) times/3 min,( 373.2 ± 19.0) times/3 min vs ( 323.7 ± 23.8) times/3 min,t =10.443,7.774,both P＜0.01; Stroop tests:(20.3 ±1.5) points vs(17.3 ± 1.0) points,(21.5 ±0.8)points vs( 16.1 ± 1.4 ) points,t =8.478,4.934,both P ＜ 0.05 ; Addition Tests:( 222.2 ± 13.2 ) s vs ( 266.6 ±23.7 ) s,( 226.3 ± 10.9) s vs ( 267.6 ± 23.4 ) s,t =5.748,6.685,both P ＜ 0.01 ).The cognitive functions impairments of 2 h nap group were more severe at the initiation of sleep inertia,but regained the normal condition more quickly.Different cognitive tasks recovered at different speeds.The dispersion of SI needed 30 min.Conclusions ( 1 ) There are difference in the sleep construction and awaked sleep stage between 20 min nap and 2 h nap groups.(2) SI exerts negative influences on cognitive performances of continuous attention,selected attention and addition after sleep deprivation.Many factors may influence the dispersion of SI,including sleep debt,compensation of sleep debt and others.(3) Fragments of sleep are unfavorable to the recovery of body.
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Objective To establish an animal model of rapid eye movement (REM) sleep deprivation (SD) and an animal model for perifornical nucleus microdialysis and investigate the change of cognition, hypocretinergic system and GABAergic system in rats' hypothalamus after various degrees of REM sleep deprivation and sleep revival and two GABAergic drugs intervention. Methods The modified multiple platform method (MMPM)was used to establish sleep deprivation model and the cognitive function was assessed by Morris' water maze. Immunofluorescence technique was used to analyze the number of Hypocretin (Hcrt) immunoreactive neurons, total Fos immunoreactive neurons, Hcrt and Fos colabeled neurons, and the integrated optical density ( IA ) of GABAA Rαl immunoreactive area in rats' hypothalamus.High performance liquid chromatograph (HPLC) was used to quantitatively analyze the level of GABA and Gluin in the rats' hypothalamus. Two GABAergic drugs, a selective GABAA R antagonist, SR-95531, and a selective blocker of type 1 GABA transporter (uptake blocker), NO-711, were used for perifornical nucleus microdialysis. Results There was no statistically significant difference in tests between CC and TC ( Define CC and TC). There was a significant decrease (P ＜ 0. 05 ) of cognitive function measured by Morris maze test in SD 3 d, SD 5 d and RS 6 h of SD groups compared with CC and TC groups. Number of Fos immunoreactive, F+ &H+ immunoreactive neuronsand IA of GABAA Rαl immunoreactive area were all significantly increased ( P ＜ 0. 05 ). Content of GABA measured by HPLC was also increased ( P ＜ 0. 05 ). However, all these changes were partly reversed by sleep revival SR-95531 and NO-711 had different effect on these changes. Conclusions Sleep deprivation, no matter mild or severe, has adverse effects on cognitive function. Activities of both GABAergic and Hcrtergic system are increased during REMSD. These two neurons system could be regulated by each other and the relationship between them is positive correlation. GABAergic system also had self-regulation during REMSD, but microdialysision of either SR-95531 or NO-711 acquired adverse effects on cognitive function of rats. So GABAergic system is not an optimal therapeutic target. Because GABAergic and Hcrtergic system has inhibitory effect on each other,suppressing activity of Hcrtergic system might be a promising therapeutic target.
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Efficiency, one of the key principles of economic assessment in the health service sector, has three implications: technical efficiency, cost efficiency and allocation efficiency. The paper gives an account of the various interpretations of some relevant concepts and different assessment methods. The following methods are frequently used to measure technical efficiency: ratio analysis, CPD, comprehensive index, DEA, etc. Economic efficiency is measured by production function while CEA, CUA and CBA are used to assess cost result. The major indexes for assessing allocation efficiency include the proportion between medical and preventive services, the proportion between basic and non basic medical services and the flow direction of total health expenses.