1.Correlation study of brain β-amyloid deposition and blood β-amyloid level in Alzheimer′s disease
Fangyang JIAO ; Weiwei LI ; Yanjiang WANG ; Jinju SUN ; Xiao CHEN ; Jianliang WEN ; Rongbing JIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(1):6-11
Objective:To assess the β-amyloid (Aβ) deposition of voxel-based PET imaging in Alzheimer′s disease (AD) and its relationships with blood biomarkers (Aβ).Methods:From January 2015 to December 2018, a total of 23 AD patients (9 males, 14 females, age (68.5±9.0) years; duration: (40.9±23.3) months; 8 mild patients, 15 moderate or severe patients) who underwent Aβ PET and with positive imaging results in Daping Hospital, Army Medical University were retrospectively enrolled. The information of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) were collected. Blood level of Aβ42, Aβ40 were measured. Differences of those metrics including Aβ42/Aβ40 between mild and moderate or severe patients were compared. For all 11C-Pittsburgh compound B (PIB) PET images, voxel-based one-sample independent t test analyses were performed. Voxel-based two-sample independent t test analyses were also performed between mild and moderate or severe patients. The voxel-based Pearson correlation analyses were run to assess the associations between blood metrics and Aβ deposition of 11C-PIB PET. Results:Comparing with mild patients, moderate or severe patients had lower MMSE (9.67±4.37 vs 17.13±2.80; t=4.349, P<0.001) and longer duration ((48.8±23.8) vs (26.0±13.5) months; t=-2.489, P<0.05). On voxel-wise analysis, amyloid PET illustrated brain Aβ deposition in bilateral frontal, right temporal, right occipital and posterior cingulate regions ( t values: 0.44-0.67, all P<0.001). Within AD, Aβ42/Aβ40 ( r values: from -0.62 to -0.41, 0.41-0.66, all P<0.05) were associated with amyloid PET, but not associated with Aβ42 ( r values: from -0.33 to 0, all P>0.05) or Aβ40 ( r values: from -0.41 to 0, all P>0.05). Conclusions:Based on voxel-wise analysis, 11C-PIB PET has comparable value for brain Aβ deposition. Aβ42/Aβ40 has the potential to predict brain Aβ deposition.
2.Diagnostic value and influencing factors of 11C-PIB in mild cognitive impairment and Alzheimer′s disease
Jinju SUN ; Xiao CHEN ; Fangyang JIAO ; Yi LUO ; Jianliang WEN ; Qiming LI ; Rongbing JIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(1):12-17
Objective:To investigate the diagnostic value of 11C-Pittsburgh compound B (PIB) in patients with mild cognitive impairment (MCI) and Alzheimer′s disease (AD) and explore the factors that may affect the binding of 11C-PIB. Methods:From January 2017 to December 2019, the 11C-PIB uptake of 6 patients with normal cognitive (NC; 3 males, 3 females, age: (64.5±12.3) years), 11 patients with MCI (4 males, 7 females, age: (64.5±9.8) years) and 21 patients with AD (7 males, 14 females, age: (68.1±9.1) years) from Daping Hospital, Army Medical University were retrospectively analyzed. Regional 11C-PIB binding was assessed by using standardized uptake value ratio (SUVR) and visual reading of 11C-PIB scan. Clinical data, including age, gender, education level, cognitive impairment, neuropsychological scale score, vascular risk factors (VRF), apolipoprotein E (ApoE) gene, were collected and differences among groups were analyzed by using one-way analysis of variance, least significant difference t test or Fisher exact test. Factors that affected the 11C-PIB binding were analyzed by multiple linear regression. Results:SUVR of cerebral lobe among NC, MCI and AD groups were significantly different (range of mean SUVR: 1.16-1.26, 1.19-1.35 and 1.40-1.61; F values: 5.331-9.279, all P<0.05). For positive PIB patients, SUVR of posterior cingulate and precuneus were increased in MCI group compared with NC group (1.20±0.15 vs 1.50±0.12, 1.18±0.15 vs 1.59±0.13; F values: 6.389 and 10.668, t values: -2.33 and -3.10, both P<0.05), and there were no significant differences in all lobes between MCI and AD group ( t values: from -1.29 to -0.51, all P>0.05). Visual analysis showed that the positive rates of PIB in frontal lobe (85.7%(18/21)), posterior cingulate (85.7%(18/21)), precuneus (81.0%(17/21)), temporal lobe (81.0%(17/21)) and occipital lobe (47.6%(10/21)) in AD were higher than those in MCI (4/11, 4/11, 4/11, 3/11 and 1/11, respectively; all P<0.05). Multiple linear regression showed that the degree of cognitive impairment were independent risk factors for SUVR of all lobes ( b values: 0.377-0.536, all P<0.05). The ApoE ε4 gene was independent risk factor for SUVR of precuneus ( b=0.290, P<0.05). Conclusion:11C-PIB is helpful for clinical diagnosis of MCI and AD patients and the degree of cognitive impairment and ApoE ε4 gene may be independent risk factors for increasing 11C-PIB binding.
3.The preparation of endostatin protein and the measurement of its biologic activity
Ping, ZHANG ; Tao, YUE ; Zhen-Yu, ZHU ; JianLiang, ZHENG ; Jian-Xian, LIN ; Wen-Xin, ZHANG ; Guan-Guang, FENG
International Eye Science 2005;5(5):841-846
·AIM: To investigate the preparation of endostatin protein and its biologic activity on vascular endothelial cell.· METHODS: pBlast-hEndostatin and pBlast-Mcs were identified by digesting with Nhe Ⅰ and Sal Ⅰ, by PCR reaction, by sequencing, and by Alignments of PCR products with gene bank using NCBIBLAST software. The identified pBlast-hEndostatin as well as pBlast-Mcs were then purified with QIAGEN Endofree plasmid maxi kit.The purified plasmids transfected human fibroblasts. The expression of endostatin was detected by RT-PCR, Westem-Blot and immunohistochemistry. The endostatin prorein produced by transfected fibroblasts was purified by ultrafiltration and affinity chromatography. The inhibitory action of endostatin on human umbilical vein endothelium was measured by MTT assay.· RESULTS: pBlast-hEndostatin was found to contain human endostatin gene. Endostatin protein was produced by transfected fibroblasts. The inhibitory ratio of 2.5,5,10,20,40,80mg/L endostatin on human umbilical vein endothelium for 48h were 8.5%,13.1%,27.7%,38.1%,56.7%,63.8% respectively. IC50 value was 34.5mg/L.No inhibition action was found on fibroblasts.·CONCLUSIONS: Endostatin protein can be produced by the transfected fibroblasts. The produced endostatin has inhibitory action on human umbilical vein endothelium and has no inhibition action on fibroblasts.
4.Geritinib in the targeted therapy of acute myeloid leukemia with FLT3 mutation: report of 5 cases and review of literature
Weiling LIANG ; Jihao ZHOU ; Yun CAI ; Lixin WANG ; Guoqiang LI ; Bingbing WEN ; Weiqiang ZHAO ; Gong ZHONG ; Jun WANG ; Jianliang CHEN ; Xiaolin PEI ; Li ZHOU ; Zhimei ZHU ; Hua YANG
Journal of Leukemia & Lymphoma 2022;31(11):669-674
Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.
5. Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease
Fangyang JIAO ; Jun TAO ; Jinju SUN ; Haosu ZHANG ; Yi LUO ; Jianliang WEN ; Zhenfan ZHAO ; Zhiqiang XU ; Rongbing JIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(6):349-355
Objective:
To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms.
Methods:
Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis.
Results:
There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (