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The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB1R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB1R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB1R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB1R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.
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Animals , Callithrix , Receptors, Cannabinoid , Anxiety , Amygdala , Cannabinoids , PhenotypeABSTRACT
Objective:To summarize the common sites of osteophytes in patients with hand osteoarthritis (OA), and analyze the correlation between the severity of osteophytes and clinical factors.Methods:One hundred and four patients with hand OA were selected and divided into three groups according to the disease duration: <1 year, 1~5 years, >5 years. The first carpometacarpal joint(CMC1), metacarpophalangeal joint(MCP), proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP) were detected by high fre- quency ultrasound. The location of osteophytes and osteophyte semi-quantitative grading scores (OSGS) were recorded. The patients age, disease duration, erythrocyte sedimentation rate (ESR), C-reactionprotein (CRP), the visual analogy score (VAS) and Australian/Canadian osteoarthrits hand index (AUSCAN) were collected. The indicators of different groups were compared, the incidence and location of osteophytes was calculated, and the correlation between osteophytes and clinical factors was analyzed. Data were analyzed by Wilcoxon rank sum test, Kruskal-Wallis test, χ2 test, Spearman correlation analysis. Results:① Osteophytes accounted for 33.56%(1 047/3 120) of the 3 120 joints in hands. There were statistically significant differences in OSGS and AUSCAN in different groups ( H=13.485, P<0.01; H=51.491, P<0.01), while no statistically difference in VAS, ESR and CRP ( H=5.808, P=0.055; H=2.878, P=0.237; H=2.319, P=0.314). ② In different joint areas of hands, PIP accounted for the largest proportion (46.54%, 484/1 040), followed by DIP (46.51%, 387/832), CMC1 (30.77%, 64/208), and MCP accounted for the smallest proportion(10.77%, 112/1 040). There were statistically significant differences in the incidence of osteophytes in different joint areas( χ2=384.194, P<0.01).③ In the interphalangeal joint areas of hands, the largest osteophytes composition ratio was MCP3 (46.43%, 52/112), PIP3 (30.58%, 148/484) and DIP2 (31.01%, 120/387), respectively. ④ OSGS were positively associated with age, disease course, VAS and AUSCAN ( r=0.370, P<0.01; r=0.382, P<0.01; r=0.215, P=0.029; r=0.390; P<0.01), there was no correlation between OSGS and ESR or CRP ( r=0.173, P=0.079; r=0.162, P=0.101). Conclusion:PIP are the most common sites of osteo-phytes in hand OA, followed by DIP. High frequency ultrasound can help the diagnosis and evaluate the severity of hand OA.
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Objective@#To observe any curative effect on dysphagia of freehand respiratory training applied to hemiplegic stroke survivors.@*Methods@#Forty-eight hospitalized, hemiplegic stroke survivors were randomly divided into an observation group and a control group, each of 24. Both groups received routine stroke rehabilitation, including motor function training, exercise training, physical therapy and swallowing training. The observation group was additionally provided with barehanded breathing function training, mainly consisting of cough glottis exercise, lip constriction aspiration exercise, chest movement exercise, abdominal muscle contraction and relaxation exercise, as well as abdominal aspiration training. The intervention lasted for 6 weeks for both groups. Before and after the intervention the maximum breathing time, first and second forced volume (FEV1), forced vital capacity (FVC), maximum inspiratory pressure (PImax), standardized swallowing assessment (SSA), Kubota drinking water test (KDWT) and functional dysphagia scale (FDS) scoring were quantified for both groups.@*Results@#There was no significant difference between the two groups′ averages on any of the measurements before the intervention. Afterward, however, the average maximal breathing time, FEV1, FVC, and PImax of the observation group were all significantly higher than before the intervention and significantly higher than those of the control group. After treatment, the observation group′s average KDWT efficiency was not, however, significantly better than that of the control group. Moreover, after the treatment the average SSA and FDS of the observation group were significantly lower than those of the control group, as well as significantly better than before the treatment.@*Conclusion@#Barehanded breathing function training can supplement routine rehabilitation to significantly improve the breathing of stroke survivors.
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Objective To observe any curative effect on dysphagia of freehand respiratory training applied to hemiplegic stroke survivors. Methods Forty-eight hospitalized, hemiplegic stroke survivors were randomly divid-ed into an observation group and a control group, each of 24. Both groups received routine stroke rehabilitation, in-cluding motor function training, exercise training, physical therapy and swallowing training. The observation group was additionally provided with barehanded breathing function training, mainly consisting of cough glottis exercise, lip constriction aspiration exercise, chest movement exercise, abdominal muscle contraction and relaxation exercise, as well as abdominal aspiration training. The intervention lasted for 6 weeks for both groups. Before and after the inter-vention the maximum breathing time, first and second forced volume ( FEV1 ) , forced vital capacity ( FVC) , maxi-mum inspiratory pressure ( PImax ) , standardized swallowing assessment ( SSA ) , Kubota drinking water test (KDWT) and functional dysphagia scale (FDS) scoring were quantified for both groups. Results There was no significant difference between the two groups' averages on any of the measurements before the intervention. Afterward, however, the average maximal breathing time, FEV1 , FVC, and PImax of the observation group were all significantly higher than before the intervention and significantly higher than those of the control group. After treatment, the obser-vation group's average KDWT efficiency was not, however, significantly better than that of the control group. Moreo-ver, after the treatment the average SSA and FDS of the observation group were significantly lower than those of the control group, as well as significantly better than before the treatment. Conclusion Barehanded breathing function training can supplement routine rehabilitation to significantly improve the breathing of stroke survivors.
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Objective To compare the effect of GammaTM wet wipes and 75% alcohol on the disinfection of X-ray protective clothing,and provide reference for choosing rational disinfection methods.Methods 62 pieces of X-ray protective clothing were selected,30 were from operating rooms,32 from catheterization room.Protective clothing were randomly divided into trial group and control group,each had 31 pieces.Trial group disinfected clothing with GammaTM wet wipes,control group disinfected clothing with 75% alcohol,disinfection effect,drying time,and cost between both groups were compared.Results Average bacterial colony counts in trial group and control group before disinfection were 2.38 CFU/cm2 and 2.36 CFU/cm2 respectively,qualified rates were 80.64% and 83.87%respectively.Bacteria were not detected in both groups after disinfection.The average drying time in trial group was shorter than control group([352.35±9.93]s vs[676.13±10.62]s,t=123.98,P <0.01).The cost of disinfecting X-ray protective clothing in trial group was 29.60% less than control group.Conclusion Effect of GammaTM wet wipes and 75% alcohol on disinfecting X-ray protective clothing are both reliable,compared with 75% alcohol, GammaTM wet wipes are without corrosion,have shorter drying time,and save more cost.
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Objective:To analyse the role of Bcl-6/Blimp-1/IL-21 in pathogenesis of primary Sj?gren′s syndrome(PSS),the relationship between Bcl-6/Blimp-1/IL-21 expression and labial gland biopsy grading.Methods:Immunohistochemical(IHC) method was used to detect the expression of Bcl-6/Blimp-1 in salivary gland between 30 cases pations with PSS in disease group and 11 cases patients with mucous cyst,lower lip trauma in control group,and the serum IL-21 levels between disease group of 40 cases patients with PSS and 30 cases healthy volunteers were measured by enzyme-linked immunosorbent assay( ELISA) ,relations among 15 patients with IL-21 expression levels with labial gland biopsy grading.Results:The expression levels of Bcl-6/Blimp-1/IL-21 in disease group were higher than control group;in disease group,with pathological grades increased,the expression levels of Bcl-6/Blimp-1/IL-21 were also raised.Conclusion:①Bcl-6/Blimp-1/IL-21 may participate in the pathogenesis of PSS;Bcl-6/Blimp-1/IL-21 is associated with infiltration lymphocytes of salivary gland.
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Objective To explore the role of Th17 cells in systemic lupus erythematosus (SLE)with cardiovascular disease (CVD).Methods 61 patients of SLE were collected from September 2011 to March 2013 in the Second Hospital of Hebei Medical University by revised SLE classification standards of ACR in 1997.These patients were divided two groups:22patients of SLE with CVD and 39 patients of SLE without CVD;the control group include 20 healthy.Th17 cells were measured by flow cytometry,IL-1 7 was detected by enzyme-linked immunosorbent assay.The correlation among them and the disease active index were analyzed.Results ①The percent of Th1 7 cells in the group of SLE with CVD,that in the group of SLE without CVD and that in control group were (2.09±0.98)%,(1.75±0.75)% and (0.89±0.44)%,respec-tively.The percent of Th1 7 cells in healthy group were lower than that in SLE with CVD and SLE without CVD group (t=4.717~5.030,P0.05;t=1.513,P>0.05).②The level of IL-17 were correlated positively with SLEDAI and the anti-double strand DNA (r=0.393,P=0.008;r=0.558,P<0.001),were correlated negatively with complement C3 (r=-0.423,P=0.005).The percent of Th17 cells in CD4+T cells were correlated positively with SLEDAIand the anti-double strand DNA (r=0.681,P<0.001;r=0.492,P=0.015)were correlated negatively with complement C3 (r=-0.534,P=0.027).Con-clusion The level of Th1 7 cells and IL-1 7 were high in SLE,and they were related with the disease activity.The cardiovas-cular factor had not affect the expression of Th1 7 cells and IL-1 7 in SLE.
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Objective To investigate the effects of valproic acid ( VPA ) on SD rats with experimental autoimmune encephalomyelitis ( EAE) and its possible immunomodulatory mechanism .Meth-ods Fifty female Sprague-Dawley ( SD) rats were randomly divided into five groups by random digit table , including control group (n=10), EAE group(n=10), low dose VPA treated group (100 mg/kg, n=10), median dose VPA treated group (300 mg/kg, n=10) and high dose VPA treated group (600 mg/kg, n=10).The SD rat model of EAE was induced by immunizing with a guinea pigs′spinal cord homogenate (GPSCH).Normal saline and various doses of VPA were given to rats in according groups twice a day from day 0 to day 19 ( close to the peak stage of EAE ) .The severity of EAE was scored according to the signs and symptoms.Pathological changes were observed through Hematoxylin-Eosin staining, and then the degrees of inflammatory infiltration were evaluated .The numbers of activated neuroglia that expressed Iba-1 in cerebral and lumber cords were counted by immunohistochemistry .The expression of IFN-γ, IL-17 and IL-10 in cer-ebral and lumber cords were measured by ELISA .Results Compared with EAE group , rats in the low, me-dian and high dose VPA treated groups had lower incidence of EAE and prolonged latency , but only the me-dian dose treated group showed significant alleviation in clinical symptoms (P<0.05).Both the median and the high dose treated group showed decreased inflammatory cell infiltration in CNS (P<0.05).Immunohisto-chemistry results showed that the numbers of activated microglia were significantly inhibited in rats treated with median and high dose of VPA in comparison with those in EAE group (P<0.05).Results of ELISA demonstrated that the expression of IFN-γand IL-17 in both median and high dose VPA treated groups were significantly decreased compared with those in EAE group (P<0.05), but only the median dose treated group showed a remarkably increased expression of IL-10 (P<0.05).Conclusion VPA, especially medi-um dose of VPA ( 300 mg/kg ) , had neuroprotective effects on rats with EAE .The possible mechanism might be associated with the inhibited activation of microglia and the increased percentage of anti -inflammato-ry cytokines .
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Objective This study was designed to investigate the expression of T regulatory cells (Treg) in the peripheral blood and salivary gland of patients with primary Sj(o)gren's syndrome (pSS).Methods The expression of Treg was measured by flow-cytometry analysis in 23 pSS patients and 15 healthy controls.CD4 positive cells were sorted by immunomagnetic beads,Forkhead box protein P3 (Foxp3) mRNA was extracted,real time polymerase chain reaction (RT-PCR) was used to measure Foxp3 mRNA.For the study of salivary gland,five primary billary cirrhosis (PBC) patients without pSS were selected as the control group,the expression of CD4+T cells and Foxp3+ T cells in salivary gland was examined by immunohistochemistry.The result was analyzed by t test.Results The expression of Treg in the peripheral blood of pSS patients [(5±6)％] was lower than healthy controls [(10±5)％] (t=2.190,P=0.036).There was no significant difference in Foxp3-mRNA expression between pSS patients (0.08±0.05) and controls(0.09±0.03 ) (t=0.695,P＞0.05 ).The expression of CD4+ T cells [ ( 30± 10 )％ ] and Foxp3+ T cells [ ( 10.7±5.8 ) ％ ] in the salivary gland of pSS patients increased significantly when compared with PBC control group [CD4+T (11±6)％ and Foxp3+T(3.2+1.1)％ ] (t=4.072,2.840; P＜0.05).Conclusion For pSS patients,the expression of Treg decreases in the peripheral blood,but Treg increases in the salivary gland.The results of this study suggest that Foxp3plays an important role in the pathogenesis of pSS.
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Objective To investigate the role of different therapeutic regimens in primary biliary cirrhosis (PBC)complicating Sj(o)gren syndrome (SS).Methods A total of 79 patients diagnosed as PBC complicating SS were enrolled and randomly divided into three groups:Group U (29 patients) received ursodeoxycholic acid (UDCA) alone,Group UP (37 patients) received UDCA and prednisolone,Group UA (13 patients) received UDCA and azathioprine.The clinical and laboratory data were collected at 0,3,6 and 12 months after treatment.Results Fatigue and pruritus were improved in each group with no difference among them(P ＞ 0.05).The levels of ALT,AST,alkaline phophatase (ALP),gamma-glutamyl transferase (GGT),TBil,DBil,IgG,and IgM in the three groups were all decreased after treatment(P ＜0.05),while there were no statistical differences among the three groups (P ＞ 0.05).Conclusions The combination therapy of UDCA with prednisolone or azathioprine was not better than UDCA alone.The therapeutic policy of PBC complicating SS involved in the liver should settle PBC mainly.
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ObjectiveTo analyze the clinicopathologic characteristics and survival of ethnic minority female patients with triple negative breast cancer (TNBC) from Xinjiang Uygur Autonomous Region.Methods The clinicopathological characteristics,including age at diagnosis,size of tumor mass,lymphnode involvement,adjuvant therapy,recurrence of disease and survival of patient,of 48 ethnic minority patient cases with TNBC negative for estrogen receptor (ER),progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) were analyzed,whom were treated in our hospital from January 2001 to December 2005,including age at diagnosis,size of tumor mass,lymph node involvement,adjuvant therapy,recurrence of disease and survival of patients.ResultsOf the 48 patients,median age was 47 years,and 83.3 ％ (39 cases) of patients had stage Ⅱ or Ⅲ disease.The majority(85.4 ％,41 cases)of pathological types were grade Ⅱ or Ⅲ invasive ductal carcinomas,and lymph node involvement was detected in 56.2 ％ (27 cases) of these patients at initial diagnosis.46 patients were followed and had adjuvant therapy.Tumor-free survival and overall survival at 5 years were 43.5 ％ (20/46) and 52.2 ％ (24/46),respectively.Patients with lymph node involved had only 38.5 ％ (10/46) of overall survival at 5 years.ConclusionThe incidence of triple negative breast cancer of female patients in Xinjiang multiple minority groups is similar to domestic study,and the rates of over all survival is lower than that in Han Chinese patients. The female patients with TNBC in Xinjiang Uygur Autonomous Region multiple minority groups showed higher lymph node involvement at initial diagnosis and more distal metastasis.Patients with lymph node involved had poor survival.
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Objective To address the clinical features of the overlap of polymyositis (PM) and primary biliary cirrhosis (PBC),as well as its similarities to and differences from PBC/nPM patients.Methods Medical charts of 10 cases of PBC/PM inpatients admitted to Peking Union Medical College Hospital (PUMCH) from October 1989 to October 2009 were systemically reviewed.Two hundred and twenty-three cases were included as controls from the database of PBC patients in PUMCH at the same period by the statistic methods of t test,x2 test or Fisher exact test.Results ① Ten (2.67%) PBC patients had concurrent PM.② Male/Female ratio in PBC/PM group was 3/7 and the age at diagnosis was (54±8) years.No significant differences between the two groupsin these data (P＞0.05).③ Clinical features and laboratory findings of PBC/PM included: cardiomyopathy in 4 cases,respiratory muscle involvement in 2 cases,level A of Child-Pugh classification in 9 cases,level C in 1 case,positive antinuclear antibody in 10 cases,positive anti-mitochondrial antibody in 10 cases,positive M2 subtype in 7 cases,elevated erythrocyte sedimentation rate(ESR)in 9 cases.④ The significant difference between the two groups was ESR (P=0.047).Conclusion The concurrence of PBC and PM is not rare,and the inflammation of PBC/PM is likely more prominent than PBC/nPM.
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Objective To investigate the correlation between dyslipidemia and important organ damage in patients with active systemic lupus erythematosus (SLE) without treatment. Methods Serum sam-ples from 71 active SLE patients and 30 healthy controls were obtained to measure lipid profiles including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoproteinA1 (apoA1), apolipoproteinB100 (apoB) and lipoprotein a (LPa). Clinical parameters were recorded. Results The levels of serum TC, TG, LDL, apoB in active SLE patients were higher than those in healthy controls, in contrast,the levels of HDL,apoA1 were much lower (P<0.05 or P<0.01). Patients with important organ damages had longer disease course and elevated levels of serum TC, TG, LDL and apoB concentrations than those without organ damage (P<0.05 or P<0.01), especially in patients with cadiovascular diseases (CVD) (P<0.01). Moreover, these changes in lipid metabolism were positively correl-ated with disease course and negatively with C3 level (P<0.05 or P<0.01). The elevated serum TC and LDL concentrations were negatively correlated with C4 level (P<0.05). Conclusion Severe dyslipidemia is present in active SLE patients.It is correlated with disease course and disease activity. Increased serum TC, TG, LDL and apoB concentrations play key roles in patients with important organ damages.
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Objective To study the characteristics of T regulatory cells (Treg) in primary biliary cirrhosis (PBC), and to analyze the significance of Treg in PBC. Methods Peripheral blood Treg cells of 27 PBC patients and 14 healthy controls were detected by tricolour flowcytometry. Simultaneously the expression of forkhead box p3 (Foxp3) mRNA was determined by real-time RT-PCR assay. The expression of Foxp3 positive T cells in liver was exmined by immunohistochemistry. Results The percentage of Treg in the peripheral blood was lower in PBC (P<0.01) than in healthy control group. The mRNA expression of Foxp3 had no significant difference (P>0.05) between the two groups. The infiltration of Foxp3 positive T cells in liver tissue was different in different pathological stages and different degree of inflammation of the portal area. Conclusion The possible reason for Treg decreasing in the peripheral blood of PBC and Treg increasing in local inflammatory portal area of liver is the result of local inflammation which then lead to migration of peripheral Treg in autoimmunity.
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Objective To analyze risk factors of elasticity of common femoral artery(CFA)and popliteal artery(PoA)in type 2 diabetic(T2DM)patients by echo-tracking(ET)technique.Methods Thirty healthy subjects(control group)and sixty-eight T2DM patients were enrolled in this study.The stiffness β of common femoral and popliteal artery were automatically measured by ET technique.The differences in ordinary and biochemical indices between control group and T2DM group were compared and analyzed by the method of linear regression and multiple linear regression.Results In both control and the T2DM group,β of CFA and PoA were significantly correlated with age,systolic blood pressure.TC, LDL,ApoB and LPa of CFA were also significantly correlation with β in T2DM group(P<0.05).Conclasions The stiffness of CFA and PoA in patients with T2DM increased followed by the increase of age, systolic blood pressure,TC,VLDL,ApoB and LPa.
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Objective To investigate the significance and characteristics of T lymphocyte subsets and co-stimulatory CD28 in peripheral blood of patients with primary biliary cirrhosis. Methods Tri-colour flow-cytometry was used to detect the levels of T lymphocyte subsets in peripheral blood in 98 patients with primary biliary cirrhosis and 30 age and gender matched healthy controls. Results Compared to control group the percentage of CD4+ T increased and CD8+ T lymphocyte decreased in the PBC group. The CD4+/CD8+ ratio in the PBC group was higher than that in the control group (P<0.05). And the percentage of CD4+CD28- T cells and CD8+CD28- T cells increased, too (P<0.05). Conclusion There are immunological abnormalities in PBC and the expression of co-stimulator CD28 is significantly decreased. CD8+CD28-T lymphocytes may have immune regulatory effect in PBC.
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Objective To attempt using the synthetic poly-peptides in the carboxyl terminal of gp210 antigen as the substrate for anti-gp210 antibody detection and search for a simple assay method of detecting anti-gp210 antibody. Methods The enzyme linked immunosorbent assay (ELISA) method for anti-gp210 antibody detection was set-up by chessboard test. Anti-gp210 antibody was tested in the serum of both patients with primary biliary cirrhosis (PBC) and the control group by ELISA and immuno-blotting. Results The working concentration of gp210's antigen was 5 μg/ml. The optical density higher than 0.61 (x+3s) was designated as the positive cutoff of anti-gp210 antibody. There was no statistical difference between the two assays (P=0.617). And there was very strongly positive correlation between them (P=0.000, r=0.868). Conclusion The sensitivity and specificity are basically consistent between the assays using synthetic poly-peptides of gp210 antigen and native antigen as the detecting substrates. The former substrate is preferred to be used for the testing of anti-gp210 antibody in clinical laboratories.