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【Objective】 To clarify the role and molecular mechanism of Tanshinone ⅡA (TanⅡA) in the pathological integration of granule cells in the dentate gyrus (DG) by using the mouse model of temporal lobe epilepsy (TLE). 【Methods】 Status epilepticus (SE) was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg. After two months, Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures. The DG was removed for staining of Timm, Prox-1, DCX and SynⅠ. PTEN, p-AKT, and p-S6 expressions were observed by Western blotting. 【Results】 TanⅡA decreased Timm score, SynⅠ, PSD-95 and pS6 levels, and increased the level of PTEN in the DG, and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells. Video surveillance showed that TanⅡA reduced the frequency of Racine’ grade 5 seizures. 【Conclusion】 TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.
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Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Subject(s)
Humans , Female , Prognosis , Breast Neoplasms/surgery , Ki-67 Antigen/analysis , Neoadjuvant Therapy/methods , gamma Catenin , Neoplasm, Residual , Disease-Free Survival , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Subject(s)
Humans , Female , Prognosis , Breast Neoplasms/surgery , Ki-67 Antigen/analysis , Neoadjuvant Therapy/methods , gamma Catenin , Neoplasm, Residual , Disease-Free Survival , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
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Humans , Neoplasms/pathology , Biomarkers , Prognosis , Oceans and Seas , China/epidemiologyABSTRACT
Objective Asymmetrical dimethylarginine (ADMA) levels have been associated with transient ischemic attack, however it is still difficult to define the effect of ADMA on the clinical result of TIA patients. This article aimed to investigate the effect of ADMA levels on ischemic stroke in TIA patients. Methods This study included 288 TIA patients treated in Department of Neurology in the Second Affiliated Hospital of Xi'an Medical College from January 2015 to December 2017. Blood ADMA was measured within 24 hours after patients’ admission. Patients were divided into low ADMA group (ADMA<0.62µmol/L, n=143) and high ADMA group (ADMA≥0.62µmol/L, n=145) according to the median blood ADMA level. The log-rank test was used to compare the survival rates of two groups. Multivariate Cox proportional hazards regression was used to analyze independent risk factors of ischemic stroke. Results In low ADMA group, 21 patients had ischemic stroke, and the stroke-free survival time was 18 (6-36) months. In high ADMA group, 32 patients had ischemic stroke, and the stroke-free survival time was 9 (3-33) months. There was a significant difference in the absence of stroke survival curves between the 2 groups (χ2=4.093, P=0.043). Multivariate Cox regression analysis showed that frequent TIA, high ABCD2 score, and high ADMA were independent risk factors for ischemic stroke. Conclusion Blood ADMA level is an important marker for predicting ischemic stroke in patients with TIA, which have certain significance for judging prognosis and guiding treatment.
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Objective:To investigate the awareness, use, price acceptance, satisfaction, feedback on quality problems, compliance and access methods of assistive devices for the old adults in Dongcheng, Beijing. Methods:From April to December, 2017, 166 homecare old adults from six communities of Dongcheng, Beijing accepted assistive devices after adaption, and were taught how to use. They were followed up once half a month for six months to investigate activities of daily living, satisfaction, awareness and expectation for their assistive devices. Results:There were 22% of them never used their assistive devices. For those assistive devices had been used, 62% were mobile products, 48% were homecare products, 44% were visual products, 20% were hearing products, and 4% were other products. The score of Quebec User Evaluation of Satisfaction with Assistive Technology was (4.04±0.46) in total, with 2% abandoning. Practicalness, good quality, multi-function and high performance-cost were the most important factors in mind to buy the assistive products. Common quality problems were infirmness of assembly (43%), rough appearance (27%), damaged parts (15%), hidden danger (13%), unsuitable size (3%), poor reliability (3%) and lack of structural strength (3%). The ways to obtain assistive devices included self-purchase (80%), government adaptation (13%), family and friends giving (6%), and lease (0%). Conclusion:Assistive devices can improve quality of life for the old adults. They prefer to choosing assistive devices of multi-function, cost-effective, for daily living, communication and homecare. Professional fitting, regular visit and maintenance can increase the satisfaction, and reduce abandonment of assistive devices. Assistive devices leasing service may help to promote the access of assistive devices.
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Regional healthcare platforms collect clinical data from hospitals in specific areas for the purpose of healthcare management. It is a common requirement to reuse the data for clinical research. However, we have to face challenges like the inconsistence of terminology in electronic health records (EHR) and the complexities in data quality and data formats in regional healthcare platform. In this paper, we propose methodology and process on constructing large scale cohorts which forms the basis of causality and comparative effectiveness relationship in epidemiology. We firstly constructed a Chinese terminology knowledge graph to deal with the diversity of vocabularies on regional platform. Secondly, we built special disease case repositories (i.e., heart failure repository) that utilize the graph to search the related patients and to normalize the data. Based on the requirements of the clinical research which aimed to explore the effectiveness of taking statin on 180-days readmission in patients with heart failure, we built a large-scale retrospective cohort with 29647 cases of heart failure patients from the heart failure repository. After the propensity score matching, the study group (=6346) and the control group (=6346) with parallel clinical characteristics were acquired. Logistic regression analysis showed that taking statins had a negative correlation with 180-days readmission in heart failure patients. This paper presents the workflow and application example of big data mining based on regional EHR data.
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Objective To explore the protective effect and mechanism of butylphthalide on cerebral ischemia reperfusion injury in mice.Methods The cerebral ischemia reperfusion injury model was established by middle cerebral ischemia occlusion (MCAO).Thirty mice were divided into sham group,ischemia reperfusion group(I/R group) and butylphthalide group (NBP group) with 10 in each group.Neurological defect score and brain infarction volume were detected by TTC to evaluate the treatment effects of butylphthalide.Western blot was used to detect expression of RIP,RIP3 and AIF.Immunocoprecipitation (IP) was used to detect the interaction of AIF and RIP3.Immunofluorescence(IF) was used to detect the nuclear translocation and co-localization of AIF and RIP3.Results Compared with the I/R group,NBP treatment reduced the neurological defect score (I/R:(2.60 ± 0.22),NBP:(1.90 ± 0.23),t =2.18,P< 0.05) and brain infarction volume(I/R:(38.32±2.22) %,NBP:(25.23±2.70) %,t=3.74,P<0.01).I/R elevated the expression of RIP1 and RIP3 whereas NBP significantly inhibited the expression of these two proteins (RIP1 (I/R:0.99±0.24,NBP:0.47±0.10,t=2.71,P<0.05);RIP3 (I/R:0.52±0.17,NBP:0.15±0.04,t=2.87,P<0.05)).I/R and NBP had no significant effects on the expression of AIF,but the IP results showed that I/R increased the interaction between AIF and RIP3 compared with the sham group.NBP alleviated the interaction between AIF and RIP3.IF results showed that the colocalization and nuclear expression of AIF and RIP3 increased after I/R whereas NBP treatment decreased the effect induced by I/R.Conclusion Butylphthalide alleviated cerebral ischemia reperfusion injury in mice through inhibiting the cell necroptosis.The mechanisms may correlate with decreasing the expression of RIP1 and RIP3 and alleviating the interaction and nuclear translocation of AIF and RIP3.
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Objective To explore a training system of high level professionals with international vision and meeting the develop-ment of assistive technology in China. Methods The training system was constructed in the theory framework of International Classification of Functioning, Disability and Health,and work process-oriented. Results and Conclusion A curriculum system with tree-type modes and a practice system with three-level and multi-form of assistive technology specialty were constructed,that was recognized by industry and society in the developing.
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Objectives: This study aims to analyze the relationship between late gadolinium enhancement cardiac magnetic resonance imaging (LGE-cMRI) detected scar formation of circumferential pulmonary vein and recurrence rate after catheter ablation in patients with atrial fibrillation, and to compare the efficacy of the single-step cryoballoon ablation with the point-by-point radiofrequency current ablation. Methods: A total of 56 patients with nonvalvular atrial fibrillation who underwent catheter ablation from July 2014 to December 2016 in Fujian Provincial Hospital were enrolled in this study. Among them, 27 patients underwent radiofrequency ablation (RFA), and 29 cases underwent cryoballoon ablation (CBA). Scar formation of circumferential pulmonary vein was detected by LGE-cMRI in all patients at 3 months after ablation. All patients were monitored by telephone or outpatient follow-up (patients complaint, ECG or 24-hour Holter, etc.) at 6 months post ablation. Recurrent atrial tachyarrhythmias were defined as ≥ 30 seconds AF, atrial flutter, or atrial tachycardia. Results: AF recurrence was defined in 13 (23.21%) patients. The ratio of scar formation in circumferential pulmonary vein was significantly lower in recurrence patients than that in the non-recurrent patients ([63.23±5.86]% vs [79.95±7.47]%, P<0.001). The ratio of scar formation in each pulmonary vein of 56 patients was as follows: (76.80±11.60)% in the left superior pulmonary vein, (78.90±10.64)% in the left inferior pulmonary vein, (83.35±9.44)% in the right superior pulmonary vein (P<0.05 vs the left superior pulmonary vein), which was significantly lower in the right inferior pulmonary vein (66.13±13.44)% than above veins (all P<0.05). The ratio of scar formation of all four pulmonary vein was significantly lower in recurrence patients than in the non-recurrent patients, especially in left superior pulmonary vein ([61.19±4.89]% vs [81.52±8.43]%) and the right lower pulmonary vein ([52.47±7.62] % vs [70.26±12.03]%), both P<0.001.Univariate analysis showed that the recurrence rate , the total ratio of scar formation in circumferential pulmonary vein and the ratio of scar formation in recurrence patients were similar between the CBA group and the RFA group. Conclusions: Lower circumferential pulmonary vein scar is associated with higher recurrence rate post catheter ablation in atrial fibrillation patients. The scar formation ratio is low in the right inferior pulmonary vein and the left superior pulmonary vein. The circumferential pulmonary veins scar after cryoablation and radiofrequency catheter ablation is equivalent, indicating the pulmonary vein isolation efficacy of the two procedual methods is comparable.
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Objective To explore the reparation role of recombinant human bone morphogenetic protein-4 mature peptide (rhBMP-4m) on hematopoietic system injury induced by irradiation in mice.Methods Ninety BALB/c mice were randomly divided into normal control group,model group and rhBMP-4m treatment group,with 30 mice in each group.The mice in model group and rhBMP-4m treatment group were irradiated by 60Co γ-ray(7.5 Gy) for 200 s;while the mice in normal control group did not receive irradiation.After irradiation,the mice in model group were given physiological saline 1.0 mL by peritoneal injection per day for 6 days;the mice in rhBMP-4m treatment group were given rhBMP-4m 0.5 mg by peritoneal injection per day for 6 days.The peripheral white blood cell count and marrow mononuclear cells,the percent of CD34 + cells in marrow mononuclear cells of mice were detected on the first,third,fifth,seventh,ninth day after irradiation;the number of spleen nodus and the pleen weight/body weight ratio were detected at the ninth day after irradiation.Results There was no statistic difference in the number of peripheral white blood cells of mice among the three groups on the first day after irradiation(P > 0.05).The peripheral white blood cell count of mice in model group was significantly lower than that in the normal control group on the third,fifth,seventh,ninth day after irradiation (P < 0.01).There was no statistic difference in the number of peripheral white blood cells of mice between rhBMP-4m treatment group and model group on the third,fifth day after irradiation (P > 0.05);the peripheral white blood cell count of mice in rhBMP-4m treatment group was significantly higher than that in model group on the seventh,ninth day after irradiation (P < 0.05).The number of marrow mononuclear cells of mice in model group was significantly lower than that in the normal control group at each time piont after irradiation(P < 0.05).There was no statistic difference in the number of marrow mononuclear cells of mice between the rhBMP-4m treatment group and model group on the first,third day after irradiation (P > 0.05);the number of marrow mononuclear cells of mice in rhBMP-4m treatment group was significantly higher than that in the model group on the fifth,seventh,ninth day after irradiation(P < 0.05).The proportion of CD34 + cells in mononuclear cells of mice in model group was significantly lower than that in the normal control group at each time piont after irradiation(P <0.01).There was no statistic difference in the proportion of CD34 + cells in mononuclear cells of mice between the rhBMP-4m treatment group and model group on the first,third day after irradiation (P > 0.05);the proportion of CD34 + cells in mononuclear cells of mice in rhBMP-4m treatment group was significantly higher than that in the model group on the fifth,seventh,ninth day after irradiation(P < 0.05).Compared with the normal control group,the number of spleen nodus was increased and the spleen weight/body weight ratio of mice was decreased in model group on the ninth day after irradiation(P < 0.05);the number of spleen nodus and the spleen weight/body weight ratio of mice in rhBMP-4m treatment group were significantly higher than those in the model group on the ninth day after irradiation (P < 0.01).Conclusion rhBMP-4m can accelerate the reconstruction of bone marrow hematopoietic system of mice with hematopoietic system injury induced by irradiation.
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BACKGROUND: The muskrat is a seasonal breeder. Males secrete musk to attract females during the breeding season. The testosterone binding to the androgen receptor (AR) in musk glands of muskrat may play an important role conducting the musk secretion process. METHODS: The musk gland, testis and blood samples of musk rats are collected in both breeding and non-breeding seasons. Some part of the samples are kept in liquid nitrogen for transcriptome analysis and Western blotting test. Some part of the samples are kept in 70% alcohol for histology experiment, blood samples are kept at -20 °C for the serum testosterone measurement experiment. RESULTS: This study demonstrates that the quantity of secreted musk, the volume of the musk glands, the diameter of the gland cells and AR expression are all higher during the breeding season than at other times (p < 0.01). StAR, P450scc and 3ß-HSD expression in the Leydig cells of the testis were also higher during this season, as was serum testosterone. AR was also observed in the gland cells of two other musk-secreting animals, the musk deer and small Indian civet, in their musk glands. These results suggest that the testes and musk glands co-develop seasonally. CONCLUSION: The musk glands' seasonal development and musk secretion are regulated by the testes, and testosterone plays an important role in the seasonal development of musk glands.
Subject(s)
Animals , Male , Scent Glands/growth & development , Scent Glands/metabolism , Testis/metabolism , Fatty Acids, Monounsaturated/metabolism , Organ Size , Reference Values , Reproduction/physiology , Scent Glands/anatomy & histology , Seasons , Testis/growth & development , Testosterone/blood , Breeding , Enzyme-Linked Immunosorbent Assay , Fatty Acids, Monounsaturated/analysis , Immunohistochemistry , Receptors, Androgen/analysis , Receptors, Androgen/metabolism , Blotting, Western , Arvicolinae , Sequence Analysis, RNA , Leydig Cells/metabolismABSTRACT
OBJECTIVE:To establish a method for the simultaneous determination of paeoniflorin,baicalin and imperatorin in Urticaria pill. METHODS:HPLC was performed on the column of Alltima C18 with mobile phase of methanol-water-Phosphoric ac-id(55∶45∶0.2,V/V/V)at a flow rate of 1.0 ml/min,the detection wavelength was 230 nm for paeoniflorin,280 nm for baicalin and 300 nm for imperatorin,column temperature was 30 ℃,and the volume injection was 10 μl. RESULTS:The linear range was 5.40-54.0 μg/ml for paeoniflorin(r=0.999 8),11.29-112.9 μg/ml for baicalin(r=0.999 7)and 24.95-249.5 μg/ml for imperatorin (r=0.999 9),respectively;the linit of quantitation were 5.4、11.2、30.0 ng,the lirnit of detection were 1.8、2.8、7.5 ng;RSDs of pre-cision, stability and reproducibility tests were lower than 2%;recoveries were 95.88%-98.33%(RSD=0.95%,n=6), 96.86%-99.96%(RSD=1.20%,n=6)and 98.07%-100.55%(RSD=0.92%,n=6),respectively. CONCLUSIONS:The method is simple and accurate with strong specificity and good reproducibility,and can be used for the simultaneous determination of paeoni-florin,baicalin and imperatorin in Urticaria pill.
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PURPOSE: Specific immunotherapy (SIT) is a suitable but uncommon treatment option for allergic rhinitis (AR) in China. The current understanding and attitude of Chinese ENT (ear, nose, and throat) specialists in regards to SIT is unclear. This study investigates current trends in the awareness and application status of SIT among Chinese ENT specialists. METHODS: We performed a nationwide, cross-sectional survey with a specially designed questionnaire given to 800 ENT specialists in China. A member of the trained research group conducted face-to-face interviews with each respondent. RESULTS: Most of the respondents considered AR (96.0%) and allergic asthma (96.0%) the most suitable indications for SIT. Of all respondents, 77.0% recommended the application of SIT as early as possible; in addition, SIT was considered 'relatively controllable and safe' by most respondents (80.6%). The highest allergen-positive rate in AR was associated with house dust mite (47.7%) and obvious differences existed among geographical regions. Conventional subcutaneous immunotherapy was the most highly recommended treatment option (96.2%). 'The high cost of SIT' (86.6%) and 'lack of patient knowledge of SIT' (85.2%) were probably the main reasons for the lower clinical use of SIT in China. CONCLUSIONS: Most cases showed that the opinions of Chinese ENT specialists appeared to be in agreement with recent SIT progress and international guidelines; however, many areas still need to enhance the standardization and use of SIT in China. Clinical guidelines for SIT require improvement; in addition, Chinese ENT specialists need continuing medical education on SIT.
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Humans , Asian People , Asthma , China , Cross-Sectional Studies , Surveys and Questionnaires , Education, Medical, Continuing , Immunotherapy , Nose , Pyroglyphidae , Rhinitis , Specialization , Surveys and QuestionnairesABSTRACT
AIM: To evaluate the effects of total flavonoid of chrysanthemum on the expressions of Fas and FasL in male rabbits with dry eye, and to investigate the therapeutic effects of the total flavonoid of chrysanthemum on dry eye. METHODS: Totally 150 male Japanses white rabbits were divided into blank group ( group A ) , sham -operated group ( group B ) , model group ( group C ) , androgen control treatment group (group D), and total flavonoid of chrysanthemum treatment group ( group E ) . The dry eye model was established with orchiectomy on group C, D and E. Rabbits in group E were treated with total flavonoid of chrysanthemum. Rabbits in group D were treated with androgen intramuscular injection. Rabbits in the group A, group B, group C was treated with normal saline. All rabbits were detected with Schirmer's Ⅰ test and tear break-up time (BUT). Fas, FasL were checked on immunohistochemistry. RESULTS:The Schirmer's I test values of group E was significantly higher than that of group C ( P CONCLUSION:The main component of chrysanthemum is flavonoid, which could significantly inhibit happening of dry eye in rabbit after androgen level lowered and lacrimal gland apoptosis and keep basic tears secretory volume and tear film stability.
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BACKGROUND: Restricted space and close contact with conspecifics in captivity may be stressful for musk deer, as they are highly territorial and solitary in the wild. So we tested the effects of crowding on stress of forest musk deer (Moschus berezovskii) in heterosexual groups, using fecal cortisol analysis as a non-invasive method. 32 healthy adults during non-breeding seasons were chose as our experimental objects. Group 1 was defined as higher crowding condition, with 10-15 m²/deer (6 enclosures, 10â and 6â); group 2 was defined as lower crowding condition, with 23-33 m²/deer (6 enclosures, 1010â and 6â). Every enclosure contained 1 male and 3 female. These patterns had been existed for years. RESULTS: The results showed that females in lower crowding condition (217.1 ± 9.5 ug/g) had significantly higher fecal cortisol levels than those in higher crowding condition (177.2 ± 12.1 ug/g). Interestingly, crowding seemed have no effect on male fecal cortisol levels (148.1 ± 9.1 ug/g and 140.5 ± 13.3 ug/g, respectively). At both groups, cortisol was significantly lower in males than in females. CONCLUSIONS: These results showed that chronic crowding may affect stress status of captive forest musk deer. The captive environment should consider the space need for musk deer.
Subject(s)
Animals , Male , Female , Deer/physiology , Hydrocortisone/analysis , Crowding/psychology , Feces/chemistry , Seasons , Breeding , Deer/psychology , Fatty Acids, Monounsaturated , Forests , Sex Factors , Statistics, Nonparametric , Housing, AnimalABSTRACT
In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.
Subject(s)
Humans , Adaptor Proteins, Signal Transducing , Chemistry , Genetics , Metabolism , Cell Aggregation , Genetics , GPI-Linked Proteins , Metabolism , Gene Knockdown Techniques , HEK293 Cells , HSC70 Heat-Shock Proteins , Genetics , Metabolism , Heat-Shock Response , Genetics , Interferon Regulatory Factor-3 , Genetics , Metabolism , Interferon-beta , Genetics , NF-kappa B , Genetics , Prions , Metabolism , Receptors, Retinoic Acid , Metabolism , Viruses , Metabolism , VirulenceABSTRACT
<p><b>OBJECTIVE</b>To establish different degrees and duration of animal hypoxia model of sleep apnea hypopnea syndrome according to the mechanism of intermittent hypoxia, to observe the effect of c-fos protein and apoptosis, and to explore the mechanism of nervous system injury.</p><p><b>METHODS</b>By using the model of chronic intermittent hypoxia in rats, male Wistar rats (n = 72) were randomly divided into three groups: 5% of chronic intermittent hypoxia group (the fraction of oxygen volume reduced to 5% under hypoxia), 10% of chronic intermittent hypoxia group (the fraction of oxygen volume reduced to 5% under hypoxia) and control group. The levels of on c-fos protein and apoptosis of hippocampal cell in three groups were detected at the 2nd, 4th, 6th and 8th week respectively. The expression of c-fos protein in hippocampal cell was detected by immunohistochemical method and the apoptosis of hippocampal cell was detected by TUNEL.</p><p><b>RESULTS</b>The relative quantity of c-fos protein and apoptotic index in CIH groups were significantly higher than that of the control group on the 2nd, 4th, 6th and 8th weeks (F were 44.52, 57.56, 24.20 and 13.18, P < 0.05), and these were higher obviously in 5% CIH group than that in 10% CIH group (P < 0.05). The expression of c-fos protein and apoptotic index in two CIH groups was different depending upon the different degree and duration of chronic intermittent hypoxia. With increased exposure time, the expression of c-fos protein and apoptotic index was high generally at first, peaked at 6th week, then down at 8th week (P < 0.05). While it in UC group was invariability in different time (P > 0.05). The correlation between the relative quantity of c-fos protein and apoptotic index in two CIH groups was positive (r were 0.816 and 0.701, P < 0.01).</p><p><b>CONCLUSION</b>Moderate and severe intermittent hypoxia induced the excessive expression of c-fos protein in hippocampus, caused nerve cell apoptosis, and may play an important role in the mechanism of early brain injury of intermittent hypoxia.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Hippocampus , Cell Biology , Metabolism , Hypoxia , Neurons , Metabolism , Oxidative Stress , Proto-Oncogene Proteins c-fos , Metabolism , Rats, Wistar , Sleep Apnea, Obstructive , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the correlation of exposure and sensitization to house dust mites among rhinitis patients, and the consistency of skin prick test (SPT) and serum specific IgE (sIgE) in the detection of sensitization in a steppe environment of inner Mongolia.</p><p><b>METHODS</b>Three hundreds and fourteen patients with rhinitis symptoms were recruited in this study in a hospital setting at Xilinhot City, inner Mongolia. All patients underwent medical history investigation, anterior rhinoscopy, and allergen tests in vivo (SPT) and in vitro (sIgE). Dust samples were collected from mattresses in patient's bedroom. The concentrations of group I major allergen of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) were measured by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using a SPSS 17.0 software (t test, χ(2) test and so on).</p><p><b>RESULTS</b>Among a total of 314 patients, the prevalence of positive SPT for Der p and Der f was 5.7% and 22.0%, respectively; and the prevalence of positive sIgE for Der p and Der f was 9.2% and 7.6%, respectively. Sensitization rates for house dust mites (Der p and/or Der f) were lower than those of pollens. The pollen allergen with the highest positive rate was mugwort (SPT, 51.9%; sIgE, 47.1%). Diagnostic tests using SPT as the gold standard for sensitization showed that the positive likelihood ratio of sIgE was 4.27 for Der p and 10.64 for Der f, and the Kappa value was 0.20 for Der p and 0.35 for Der f, respectively. A total of 276 dust samples collected from patient's mattresses were measured. The concentrations of Der p 1 and Der f1 were detectable in 2 (0.7%) and 4 (1.4%) mattress samples, respectively. There was positive correlation between the exposure levels of Derp 1 and the SPT positive reaction to Der p (r(s) = 0.156, P = 0.01), but no significant correlation was found between the exposure levels of Der p 1 and the sIgE positive reaction to Der p (r(s) = 0.116, P = 0.055). There was no significant correlation between the exposure levels of Der f 1 and the SPT as well as sIgE positive reaction to Der f 1(r(s) = 0.05, P = 0.931; r(s) = 0.07, P = 0.245).</p><p><b>CONCLUSIONS</b>In the steppe environment of inner Mongolia, exposure to house dust mites are very low, and the Der p and Der f are not the major allergens in patients with allergic rhinitis. Also, it was not a simple dose-response relationship between exposure and sensitization to house dust mites. In such a specific environment, there is lower consistency between the results of SPT and sIgE in the detection of sensitization to house dust mites. Therefore, it is recommended that the allergen testing in vivo and in vitro should be combined for clinical diagnosis.</p>
Subject(s)
Adolescent , Adult , Aged , Animals , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Allergens , Allergy and Immunology , Antigens, Dermatophagoides , Allergy and Immunology , China , Environmental Exposure , Hypersensitivity , Diagnosis , Allergy and Immunology , Hypersensitivity, Immediate , Diagnosis , Allergy and Immunology , Immunoglobulin E , Blood , Pyroglyphidae , Allergy and Immunology , Rhinitis , Diagnosis , Allergy and Immunology , Skin TestsABSTRACT
<p><b>OBJECTIVE</b>To analyze and compare the differences of clinical characteristics and comorbidities between patients with non-allergic rhinitis (NAR) and allergic rhinitis (AR).</p><p><b>METHODS</b>A total of 556 out-patients were enrolled from January 2010 to June 2011. The chief complaints of the patients included at least two of the following nasal symptoms: nasal congestion, rhinorrhea, sneezing, and nasal itching. Based on the results of the disease history, physical examination and allergen skin prick test, the patients were classified into NAR group (n = 206) and AR group (n = 350). Detailed information including general data, nasal symptoms and signs, accompanied symptoms and comorbidities were obtained by questionnaires. A scoring was adopted to estimate the severity of disease. SPSS 13.0 software was applied for statistical analysis.</p><p><b>RESULTS</b>The mean age of NAR patients (31.8 ± 16.7) was older than that of AR patients (26.3 ± 14.8), and the difference was significant (t = 4.01, P = 0.0001). While there was no significant difference on gender distribution between two groups (χ² = 0.12, P = 0.73). The percentage of nasal congestion was not significantly different between NAR and AR patients (89.8% and 92.0%, respectively; χ² = 0.26, P = 0.611). However, the symptoms of rhinorrhea, sneezing, nasal itching, eyes itching, lachrymation, wheeze and cough were more popular in AR patients than those in NAR patients (all P < 0.05). Moreover, above symptoms (except cough) were more serious in AR patients, and the symptom scores were significantly higher than those in NAR patients (all P < 0.05). Most of patients with NAR (67.0%) and AR (62.9%) were moderate-severe persistent (χ² = 1.25, P = 0.264). Accompanied asthma were more common in patients with AR (12.6%) compared with NAR (2.4%), while hypertension were more common in patients with NAR (7.3%) compared with AR (1.7%), and the differences were significant (both P < 0.05).</p><p><b>CONCLUSION</b>NAR and AR are two different disease entities, which have different clinical characteristics, as well as different comorbidities. Further clinical study should be done on the rhinitis phenotypes.</p>