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.

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.

·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.

Objective:To investigate the effects of carnosine on lipopolysaccharide(LPS)-induced inflammasome activation and pyroptosis in microglia,and to clarify its mechanism.Methods:Activation model of microglia was established by LPS(10 ng/ml).CCK-8 assay was used to detect cell activity of microglia treated with different concentrations of carnosine(0.2,1,5,20,50 mmol/L)for 6 h,and the cell activity of microglia pretreated with different concentrations of carnosine for 0.5 h and then stimulated with LPS for 6 h,to screen a suitable concentration.Then microglia were divided into control group,carnosine group(5 mmol/L),LPS group,and LPS+carnosine group:cell morphological changes in each group were observed under an inverted phase contrast microscope;levels of IL-1β,TNF-α and IL-6 in microglial culture medium were measured by ELISA;propidium iodide(PI)staining was used to detect py-roptotic cells;immunofluorescence was used to observe protein expression of Nod-like receptor protein 3(NLRP3).Results:Com-pared with control group,cell viability of microglia in LPS group was significantly decreased(P<0.01),the shape of microglia was mostly"amoeboid",levels of IL-1β,TNF-α and IL-6 in microglial culture medium were significantly increased(P<0.01),the posi-tive rate of PI and the number of NLRP3 positive cells were significantly increased(P<0.01).Compared with LPS group,cell viability of microglia in LPS+carnosine group was significantly increased(P<0.01),the number of"amoeboid"microglia was decreased,levels of IL-1β,TNF-α in microglial culture medium were significantly decreased(P<0.01),and the level of IL-6 was decreased(P<0.05),the positive rate of PI and the number of NLRP3 positive cells were both significantly decreased(P<0.01).Conclusion:Carnosine can inhibit LPS-induced microglia activation and inflammasome activation,thereby inhibiting cell pyroptosis and the release of inflammato-ry factors.

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.

Objective:To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups.Results:A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, β 2-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group ( P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years ( P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group ( P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, β 2-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis ( P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma ( P<0.05 for both). Conclusions:The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.

Objective:To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups.Results:A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, β 2-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group ( P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years ( P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group ( P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, β 2-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis ( P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma ( P<0.05 for both). Conclusions:The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.

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 (r values: 0.580, 0.522, 0.557, all P<0.05). The CFT uptake of ipsilateral caudate nucleus, anterior putamen, and posterior putamen were negatively correlated with UPDRS motor scores (r values: -0.496, -0.492, -0.457, all P<0.05), while those had no significant correlations with NMSS scores (r values: -0.420, -0.402, -0.355, all P>0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P<0.05). There were no significant correlations between CFT uptake in contralateral striatal, anterior putamen, posterior putamen and PDRP values, UPDRS motor scores, NMSS scores and ADL scores(r values: from -0.466 to -0.129, all P>0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01). Conclusion The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms.