iPSC-derived cortical neurons to study sporadic Alzheimer disease: A transcriptome comparison with post-mortem brain samples.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by the progressive impairment of cognition and memory loss. Sporadic AD (sAD) represents approximately 95 % of the AD cases and is induced by a complex interplay between genetic and environmental factors called "Alzheimerogens". Heavy metals (e.g. copper) and pesticides (e.g. fipronil) can affect many AD-related processes, including neuroinflammation (considered as AD-inducing factor). Research would benefit from in vitro models to investigate effects of Alzheimerogens. We compared transcriptomics changes in sAD induced pluripotent stem cell (iPSC) derived cortical neurons to differentially expressed genes (DEGs) identified in post-mortem AD brain tissue. These analyses showed that many AD-related processes could be identified in the sAD iPSC-derived neurons, and furthermore, could even identify more DEGs functioning in these processes than post-mortem AD-brain tissue. Thereafter, we exposed the iPSCs to AD-inducing factors (copper(II)chloride, fipronil sulfone and an inflammatory cytokine cocktail). Cytokine exposure induced expression of immune related genes while copper-exposure affected genes involved in lipid and cholesterol metabolism, which are known AD-related processes. Fipronil-exposure did not result in significant transcriptomic changes, although prolonged exposures or higher doses may be necessary. Overall, we show that iPSC-derived cortical neurons can be beneficial in vitro models to identify Alzheimerogens and AD-related molecular mechanisms.

[Comparative study of different grading criteria of sacroiliac joint computed tomogrphy in ankylosing spondylitis].

Objective: To assess the value of different grading criteria of sacroiliac joint (SIJ) computed tomogrphy (CT) in ankylosing spondylitis (AS). Methods: Patients who had received SIJ CT examinations from June 2012 to December 2015 were enrolled.The CT scans were read by one rheumatologist.The difference between patients with sacroiliitis or without sacroiliitis was compared.The 1984 revision of modified New York (mNY) criteria, the criteria established by Lee (Lee criteria) and the Innsbruck criteria were used to evaluate SIJs on CT in patients with sacroiliitis. Results: Totally 2 714 patients were enrolled in this study.Thereinto 509 patients including 324 male and 185 female were detected with SIJs abnormality.The proportions of SIJs graded 3 or 4 by these three criteria were 79.37%, 82.91% and 76.32%, respectively.The consistency of grading between mNY criteria and Lee criteria was good (k=0.767, P<0.01). The correlation between Innsbruck criteria and other two criteria were satisfactory (r=0.866 and 0.839, respectively). There were more SIJs graded 3 by Lee criteria (64.44%), comparing with mNY criteria (60.90%). Forty five SIJs graded 1-3 by mNY criteria were graded 0 by Lee criteria, indicating that the latter criteria may have a better specificity. When evaluating the severity of SIJs, Innsbruck criteria has a better discrimination capability and the proportions of SIJs graded Ⅱ (A) to Ⅳ (B) were 10.71%, 8.94%, 26.82%, 20.92%, 10.12%, respectively. Conclusions: Lee criteria has a better diagnostic specificity with a reduction of difficulty in assessing procedure, while Innsbruck criteria is a more detailed grading system with a possibility to reflect the development of sacroiliitis.

[The application of (18)F fluorodeoxyglucose-positron emission tomography/computed tomography in the diagnosis and treatment of dermatomyositis].

OBJECTIVE: To investigate the value of (18)F fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F FDG-PET-CT) in the diagnosis and the evaluation of disease activity and remission of dermatomyositis(DM). METHODS: DM patients who were admitted to the Department of Rheumatology, the People's Liberation Army General Hospital (PLAGH) and underwent (18)F FDG-PET-CT examination were retrospectively reviewed from January 2012 to May 2015.Gender and age matched healthy controls (HC) were also enrolled.The standardized uptake value (SUV) of proximal limb girdle muscles in both groups were recorded and compared, so as between patients with DM or subclinical DM.The correlation between myodynamia of proximal limb girdle muscle, creatine kinase(CK), CK-MB, serum ferritin and SUV of each muscle group were analyzed. RESULTS: There were 58 patients with DM and 29 controls consecutively recruited in the study.The SUV of upper arms (1.814±0.830) g/ml, shoulders (2.134±0.797) g/ml and hips (1.883±0.683) g/ml in patients with classic DM were significantly higher than those with subclinical DM [(0.938±0.218) g/ml, (1.152±0.315) g/ml, (0.945±0.249) g/ml; P<0.05]. SUV of muscles in newly diagnosed patients was (1.051±0.031) g/ml, which was higher than that in subclinical patients.But the difference was not statistically significant (P>0.05). The average SUV of evaluated muscles in DM group (2.033±0.858) g/ml was significantly higher than that in controls (1.076±0.167) g/ml (P<0.001). Receiver operating characteristic(ROC) analysis revealed the area under the curve(AUC) of abnormal SUV detected by (18)F FDG-PET-CT for diagnosing DM was 0.953.The myodynamia of upper arms and SUV was negatively correlated (rs=-0.440, P=0.031). However, the level of serum creatine kinase and SUV was positively correlated (rs=0.500, P=0.013). The average SUV of patients whose time to remission was less than 3 months (1.746±0.466) g/ml was obviously less than that of patients with 3 to 6 months to obtain remission (2.815±0.848) g/ml (P=0.015). CONCLUSIONS: The SUV of proximal limb girdle muscles detected by (18)F FDG-PET-CT has a positive diagnostic value for DM.Moreover, the SUV in upper arms is correlated with the muscle strength and the level of creatine kinase, which reflect disease activity. (18)F FDG-PET-CT might be an alternative method to evaluate the response of treatment.

[A preliminary exploration of low-dose semicoronal CT of the sacroiliac joints in the diagnosis of ankylosing spondylitis].

OBJECTIVE: To evaluate the clinical value of low-dose semicoronal computerized tomography (CT) of sacroiliac joints (SIJ) in the early diagnosis of ankylosing spondylitis (AS). METHODS: Patients who were diagnosed with AS and had received axial CT examination of SIJs over the past 2 years were recruited. All of them simultaneously underwent a low-dose semicoronal CT of SIJs. The clinical data were recorded. Radiation dose was compared between low-dose CT and the previous conventional axial CT. Image quality of low-dose CT was assessed and correlation between image quality and weight or body mass index (BMI) was analyzed. CT images of the two groups were graded by modified New York criteria, the Lee criteria and the Innsbruck criteria. The kappa coefficient was used to assess the consistency of grading between the two groups. RESULTS: Thirty-three patients were enrolled in this study. The effective dose (ED) of semicoronal SIJ CT was 3.37 mSv which was 49% lower than conventional axial CT (6.56 mSv). Lower dose had the potential protection of gonads. The quality of images in male patients with BMI<25 kg/m(2) and all female patients were good or excellent. There was a significant negative correlation between image quality and BMI (r=-0.746, P=0.000; r=-0.784, P=0.000; respectively). All patients were diagnosed as sacroiliitis by modified New York criteria and the grading of two groups was consistent. The consistency of grading between two groups was satisfactory no matter which classification criteria was used. (k=0.897 with Lee criteria; k=0.814 with Innsbruck criteria; P>0.05). CONCLUSIONS: The radiation dose of semicoronal SIJ CT is significantly lower than that of the conventional axial CT with comparable efficacy of diagnosis.

[Clinical value of Short Form-36 and clinical measures in a prospective cohort study of ankylosing spondylitis patients].

OBJECTIVE: To evaluate the clinical value of Short Form-36 (SF-36) questionnaire and the most commonly used clinical measures in a prospective cohort study of ankylosing spondylitis (AS) patients. METHODS: A total of 517 AS patients were collected from the Department of Rheumatology, Chinese PLA General Hospital from August 2013 to September 2015. The Quality of Life (QoL) was assessed by SF-36 questionnaire and compared with the general population. The correlations between QoL and clinical measures of AS, including the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI) et al, were analyzed. RESULTS: BASDAI and BASFI were significantly correlated with SF-36 scores (r>0.3, P<0.01). Logistic multiple regression analysis showed that BASDAI, BASFI, BASMI and education had close correlation with the baseline global QoL, physical and mental health. Among these clinical measures, BASDAI variation showed the most important influence on the change of global QoL, physical health and mental health (OR=0.235, 0.209, 0.125; P<0.01). CONCLUSIONS: SF-36 can objectively reflect the QoL of patients with AS. Clinical measures such as BASDAI and BASFI show great application value in this prospective cohort study of AS patients.