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Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.
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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 study the early renal function assessment value of urine kidney injury molecule-1(KIM-1)level in patients with unilateral obstruction renal diseases.Methods Seventy-eight patients with unilateral obstruction renal diseases were selected,and the glomerular filtration rate(GFR) was detected by 99Tcm-diethylene triaminepentaacetic acid (DTPA) renal dynamic imaging method. The patients were divided into 4 groups according to the GFR: normal renal function group with GFR>40 ml/(min·1.73 m2)25 cases(A group),low-injury renal function group with 20 ml/(min·1.73 m2)<GFR≤40 ml/(min·1.73 m2) 22 cases (B group), mid-injury renal function group with 10 ml/(min·1.73 m2) <GFR ≤ 20 ml/(min·1.73 m2) 16 cases (C group), serious-injury renal function group with GFR ≤ 10 ml/(min·1.73 m2) 15 cases (D group). Twenty-five healthy people were selected as control group (E group). The urine KIM-1 and serum creatinine and blood urea nitrogen levels were detected. The correlation among urine KIM-1, serum creatinine and blood urea nitrogen was analyzed. Results The urine KIM-1 in A group, B group, C group and D group was significantly higher than that in E group:(49.70 ± 9.23),(57.84 ± 10.06),(67.71 ± 7.36)and(65.84 ± 22.48)ng/L vs.(39.17 ± 3.28)ng/L,in A group and B group was significantly higher than that in C group and D group,in A group was significantly higher than that in B group, and there were statistical differences (P<0.05). There was no statistical difference in urine KIM-1 between C group and D group(P>0.05).There was no statistical difference in serum creatinine and blood urea nitrogen among 5 groups (P>0.05). The KIM-1 was negatively correlated with GFR(r=-0.441,P<0.01),and the serum creatinine and blood urea nitrogen were not correlated with GFR (r = -0.115 and 0.019, P>0.05). The receiver operating characteristic curve analysis result showed that the area under curve of urine KIM-1 in the diagnosis of kidney injury was significantly higher than that in serum creatinine and blood urea nitrogen(0.804 vs.0.441 and 0.567);the sensitivity and specificity were 82.6% and 66.7%,56.5% and 53.3%,66.9% and 66.7%.Conclusions The expression level of urine KIM-1 of unilateral obstructive nephropathy with different degree of kidney injury is a higher sensitivity marker compared with serum creatinine and blood urea nitrogen, which is helpful for diagnosing kidney injury early in clinic.
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Objective To investigate SIAH′s role in α-synuclein degradation, formation of Lewy bodies and neuronal death. Methods Proliferative activity of PC12 cells was measures by MTT assay after treatment with MPP and Rapamycin. Western Blot was applied determine the protein expression of LC3-Ⅱ, E1, SIAH-1, P53 and α-synucleinto. PCR was applied to measure protein related mRNA levels. Immunofluorescent techniques were used to detect the distribution of α-synuclein, SIAH-1 and LC3 in cells after SIAH antibody processing. Results MPP+ treatment increased α-synuclein, E1 expression and SIAH-1 activity, however, LC3-Ⅱ, P53 and α-synuclein protein levels decreased significantly. Anti-SIAH-1 antibody treatment reversed this trend, with E1 significantly increased. Rapamycin treatment reduced SIAH-1 and α-synuclein levels in the MPP+ group. SIAH-1 antibody significantly decreased the positive immuno-stain of α-synuclein, SIAH-1 and LC3, suggesting loss of co-localization. Conclusions Anti-SIAH-1 supports the clearance of non-aggregated α-synuclein by the UPS. SIAH plays a key role in the pathogenesis of Parkinson′s disease and is a potential therapeutic target of neurodegenerative diseases.
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Objective To study the impact of Paeoniflorin (PF) on α-synuclein degradation pathway. Methods PC12 cells were treated with or without MPP+ (0.5mM) for 24 h, then treated with Paeoniflorin (50 uM) or Rapamycin (0.2 μg/ml) for 24 h. The proliferative activity of cells was detected with the MTT method , and then the protein expression levels of α-synuclein, microtubule-associated protein light chain 3 (LC3-II) and E1 were detected by Western Blot. The expressions of α-synuclein and LC3 were detected by confocal microscopy. Results (1) CAT and SOD activity were significantly decreased after PF and RAPA treatment compared with MPP+ (P < 0.001). (2)MPP+ activated both LC3-Ⅱand E1. MPP+ promoted the increase ofLC3-Ⅱ but inhibited E1. PF significantly upregulated both LC3-Ⅱ (autophagy) and E1 expression (ubiquitin-proteasome pathway) (P < 0.001), promoted degradation of α-synuclein, and reduced cell damage. (3) MPP+enhanced immunofluorescence signal of intracellular α-synuclein and LC3. Fluorescence intensity of α-synuclein decreasedafter PF treatment. Conclusion PF may significantly upregulate both autophagy and ubiquitin proteasome pathways, promote the degradation of α-synuclein and reduce cell damage. These findings suggest Paeoniflorin may be a potential therapy for neurodegenerative diseases.
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Objective To investigate the levels of activated Stat3 (p‐Stat3) and the expression levels of SOCS3 as well as their clinical significance and its impact on the pathogenesis ,progression ,and prognosis in patients with gastric cancer .Methods The levels of p‐Stat3 and SOCS3 were tested in 53 cases of gastric cancer tissues (test group) and 27 cases of adjacent non cancerous tis‐sues (control group) by immunohistochemistry (IHC) .The clinical pathological and follow up data were analyzed .Results The levels of activated p Stat3 were significantly higher in gastric cancer tissues than in non cancerous tissues .The levels of SOCS3 were lower in cancer tissues than in non cancerous control tissues (P<0 .05) .p‐Stat3 showed significantly different levels among TNM stages and tumor differentiation ,and the expression levels of SOCS3 were negatively associated with cancer invasion ,lymph node metastasis and TNM stages in cancer patients (P<0 .05) .Furthermore ,a negative correlation was observed between the levels of activated p‐Stat3 and SOCS3 in gastric cancer tissues (r= -0 .492 ,P<0 .05) .Kaplan Meier survival analyses indicated that the p‐tat3 levels were negatively correlated with total survival of gastric cancer patients ,the higher the levels of p‐Stat3 was ,the lower the total survival rate would be (χ2 = -5 .05 ,P<0 .05) .On the contrary ,the levels of SOCS3 showed a positive correlation with total survival (χ2 =10 .852 ,P<0 .05) .Conclusion Increased a p‐Stat3 and decreased expression of negative Stat3 regulator SOCS3 may play important roles in the development and progression of gastric cancer ,both of which would potentially serve as prognostic mark‐ers for gastric cancer .
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Renal cell carcinoma (RCC) is a common urologic malignancy, comprising 2% to 3% of all malignant diseases. Lym-phangiogenesis significantly affects the lymphatic metastasis of tumors. Vascular endothelial growth factors and their receptors have important functions in the spread of cancer cells. Vascular endothelial growth factor-C, which links the vascular endothelial growth factor receptor-3, can increase lymphangiogenesis and promote lymphatic metastasis. These findings direct research efforts toward lymphangiogenesis in malignant diseases and a possible targeted therapy. An increasing number of studies on the lymphatic vessel of renal cell carcinoma have drawn considerable interest in the treatment of renal cell carcinoma. This paper summarizes recent studies on lymphangiogenesis and the clinical significance of renal cell carcinoma.
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Subcortical ischemic vascular dementia is a subtype of vascular cognitive impairment. Its major pathological features are lacunar infarcts and deep white matter changes, and its major clinical manifestation is executive function impairment. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) provides an opportunity for the study of pure subcorticai ischemic vascular dementia in the absence of Alzheimer's disease. There is currently lack of the gold standard for diagnosing subcortical ischemic vascular dementia. Imaging examination plays an important role in its diagnosis, while the treatment must first consider the control of vascular risk factors, especially hypertension.