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Objective:To investigate the lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.
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Objective:To investigate the clinical, cerebrospinal fluid (CSF) and neuroimaging characteristics and their associations with prognosis in cerebral amyloid angiopathy(CAA)-related inflammation (CAA-ri).Methods:Seventeen patients with CAA-ri, 59 patients with CAA-related intracerebral hemorrhage (ICH) and 15 patients with CAA-related cognitive decline were recruited from Huashan Hospital, Fudan University from November 2015 to May 2020 and the First Affiliated Hospital of University of Science and Technology of China from January 2018 to May 2020. Vascular risk factors and imaging features of cerebral small vessel disease were compared among three groups. Clinical manifestations, CSF results, lesion features on magnetic resonance imaging, treatment options and follow-up data were collected in patients with CAA-ri. The good prognosis was defined by clinical and radiographic improvement with no disease recurrence. The associations between clinical characteristics and the immunosuppressive therapy or the good prognosis were analyzed by binary Logistic regression models.Results:Patients with CAA-ri showed earlier disease onset [(61.5±11.7) years vs (70.9±8.6) years, t=9.428, P=0.001] and more lobar cerebral microbleeds [69.0 (43.5, 134.3) vs 10.0 (5.0, 59.0), H=3.363, P=0.002] compared to patients with CAA-ICH, and higher prevalence of male (14/17 vs 6/15, χ2=6.099, P=0.014) and lower white matter hyperintensity Fazekas score [4.0 (2.0, 6.0) vs 6.0 (5.0, 6.0), H=2.461, P=0.042] compared to patients with CAA-related cognitive decline. In patients with CAA-ri, the immunosuppressive therapy was positively correlated with CSF protein>600 mg/L (odds ratio 16.50, 95% confidence interval 1.09-250.18, P=0.043), and during a follow-up of (3.0±1.9) years, the good prognosis was positively correlated with CSF protein<1 000 mg/L plus immunosuppressive therapy (odds ratio 20.00, 95% confidence interval 1.39-287.60, P=0.028). Conclusions:CAA-ri is a special subtype of CAA with earlier disease onset and higher prevalence of hemorrhagic imaging makers compared to CAA-ICH and CAA-related cognitive decline. CAA-ri patients with normal or slightly elevated CSF protein receiving immunosuppressive therapy are more likely to have good prognosis.
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Objective To assess the characteristics of brain glucose metabolism in patients with early Parkinson's disease (PD) accompanied by visuospatial working memory impairment using 18F-fluorodeoxyglucose (FDG) PET imaging.Methods Between January 2015 and March 2017,early PD patients with visuospatial working memory impairment (14 males,6 females,age:(55.7±6.7) years),early PD patients without visuospatial working memory impairment (13 males,7 females,age:(55.7±8.5) years) and healthy controls (14 males,6 females,age:(54.6±6.4) years) were included.Resting-state 18F-FDG PET was performed to obtain the brain glucose metabolism,Subsequently,statistical parametric mapping (SPM) was used to compare the brain glucose metabolic changes among different groups.Results Compared with the control group,hypermetabolism was observed in putamen,globus pallidus,thalamus,pons,cerebellum and primary motor cortex and hypometabolism was found in part of the occipital and temporal lobe in the groups ofearly PD (Zmax values:3.19-6.86,t values:2.11-9.96,all P<0.001).The PD group with visuospatial working memory impairment had hypometabolism regions in bilateral lateral prefrontal cortex and posterior parietal cortex compared with the group without visuospatial working memory impairment.Conclusion Abnormal metabolism of glucose in visual processing channels of brain in early PD patients may be one of the causes of visuospatial working memory impairment.
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Objective · To investigate the clinical effect of intravitreal injection of Conbercept in the treatment of diabetic macular edema (DME).Methods · Eleven patients (17 eyes) with DME (inflammatory type) received intravitreal injection of Conbercept monthly. After the first treatment, the patients were treated on demand. Follow-up after treatment for more than 6 months, the best corrected visual acuity (BCVA), central retinal thickness (CRT),diminished rate of DME and result of fundusfluorescein angiography(FFA) of DME eyes before and after treatment were compared. Results · During a follow-up of 7-29 months [(12±7) months], the injections were given 1-10 times [(4±3) times]. The results showed that the treatment effects on improving BCVA (logMAR) and diminishing of CRT were significant (t=7.306, P=0.001; t=5.272, P=0.000). The diminished rate of DME of our patients was 76.5%. Conclusion · Intravitreal injection of Conbercept in the treatment of DME is effective on reducing macular edema and improving visual acuity.
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Objective To investigate the alteration of nuclear factor kappa B( NF-κB) and tumor necrosis factor-a (TNF-α) mRNA and protein in hippocampus in chronic constrictive injury (CCI) model of rats. Methods Seventy-six male Wistar rats were randomly divided into 2 groups ( n = 38): the CCI group which received the chronic constriction injury and the sham group which received the sham operation as control. The mechanical and thermal nociceptive thresholds were assessed with paw withdrawal latency (PWL) to von Frey filaments and radiant heat at 1d before and ld,4d,7d,14d and 28d after CCI operation. Five animals were sacrificed at each time point for real-time polymerase chain reaction (real-time PCR) and another three animals sacrificed at 7d postoperation for immunofluorescence histochemical staining. Results The thresholds to mechanical and thermal stimuli decreased obviously after operation in CCI group. The expressions of TNF-α and NF-κB mRNA began to increase at ld( (2.079 ±0. 104)times and 4d( ( 1.640 ± 0.064) times) after operation and reached the peak at 7d ((2.748 ±0.147)times, (2.010 ±0.096)times) ,then the expressions of TNF-a mRNA began to decrease,while the expressions of NF-kB mRNA maintained at a high level throughout the experiment. The result of immunofluorescence histochemical staining revealed that NF-kB and TNF-α protein expressions at 7 day increased significantly on the hippocampus,which was consisted with NF-κB and TNF-a mRNA levels. Conclusion The activation NF-κB and TNF-α in hippocampus may be involved in the procession of neuropathic pain.