Application of ALK antibody clone 1A4 in the diagnosis of non-small cell lung cancer with ALK fusion / 临床与实验病理学杂志

Purpose The aim of this study is to explore the application value of ALK(1A4)in ALK fused non-small cell lung cancer(NSCLC).Methods A total of 1 035 NSCLC specimens were collected.The expression of ALK(1A4)and ALK(D5F3)antibodies was detected by immunohistochemical(IHC)staining,and their consistency was analyzed.FISH and next-generation sequencing(NGS)were used to detect ALK positive,and the sensitivity and specificity of ALK in the two groups were evaluated.Results ALK fused NSCLC patients accounted for about 5.4％(56/1 035).The positive rate of ALK(1A4)was 7.2％(75/1 035),and that of ALK(D5F3)was 5.7％(59/1 035).The consistency between them was high,with a Kappa value of 0.874.The consistency of ALK(1A4)and ALK(D5 F3)antibodies with FISH was high,with Kappa values of 0.845 and 0.954,respectively.The consisten-cy of ALK(1A4)and ALK(D5F3)with NGS was also high,with Kappa values of 0.836 and 0.988,respectively.According to the FISH results,the sensitivities of ALK(1A4)and ALK(D5F3)antibodies were 100％and 98.2％,and the specifici-ties were 98.1％and 99.6％,respectively.Conclusion ALK(1A4)antibody has high sensitivity and slightly low specificity,and can be used for clinical screening of ALK fused NSCLC.

Predictive value of phase analysis of gated myocardial perfusion imaging for major adverse cardiac events in patients with coronary artery disease / 中华核医学与分子影像杂志

Objective:To evaluate the value of phase analysis of gated myocardial perfusion imaging (GMPI) in predicting major adverse cardiac events (MACE) in patients with coronary atherosclerotic heart disease.Methods:Patients who underwent two-day rest-stress GMPI in the Department of Nuclear Medicine of Beijing Hospital from September 2012 to January 2014 were selected as observed subjects and analyzed retrospectively. The general clinical information, GMPI images and related parameters including phase standard deviation (PSD), phase histogram bandwidth (PBW), entropy, left ventricular ejection fraction (LVEF), summed stress score (SSS), peak ejection rate (PER), peak filling rate (PFR) were noted. Patients were followed up until the onset of MACE (cardiac death, nonfatal myocardial infarction, and late revascularization within 60 d after GMPI). χ2 test, independent-sample t test or Wilcoxon rank sum test were used to compare data between different groups. The independent risk factors of MACE were obtained by Cox proportional risk regression model. Kaplan-Meier survival curve analysis was used to analyze the cumulative survival rate without MACE. Results:A total of 505 patients (235 males, 270 females, median age: 73 years) were followed up successfully, with a median follow-up period of 55.6(52.0, 60.5) months. There were 54 cases (10.7%) with MACE: 6 patients with cardiac death, 27 patients with non-fatal myocardial infarction, and 21 patients with late revascularization. The incidence of hypertension and hyperlipidemia in patients with MACE was significantly higher than that in patients without MACE ( χ2 values: 4.126, 6.021, both P<0.05); LVEF, PFR and absolute value of PER of patients with MACE were significantly lower ( t/ z values: 6.261, 5.683, -4.246, all P<0.05), while SSS, PSD, PBW and entropy were significantly higher ( t/ z values: 5.024, 5.874, 7.119, -6.405, all P<0.05). Cox proportional risk regression model showed that abnormal PBW(>80°), abnormal entropy(>58 J·mol -1·K -1) and SSS≥12 were independent risk factors for MACE (odds ratio( OR) values: 2.795(95% CI: 1.259-6.201), 3.213(95% CI: 1.468-7.029), 3.640 (95% CI: 1.999-6.628), all P<0.05). The 5-year cumulative MACE-free survival rates of abnormal PSD group(>26.7°), abnormal PBW group and abnormal entropy group were 51.2%, 63.2% and 46.7%, which were significantly lower than those of normal PSD group (92.3%; χ2=77.768, P<0.05), normal PBW group (94.2%; χ2=77.741, P<0.05) and normal entropy group (92.8%; χ2=117.437, P<0.05). The 5-year cumulative MACE-free survival rate (31.7%) of patients with abnormal PBW and SSS≥12 was significantly lower than that of patients with normal PBW or patients with abnormal PBW and SSS<12 (80.1%-94.4%; χ2=185.4, P<0.01). The combination analysis of entropy and SSS showed similar results. Conclusions:PBW and entropy obtained by GMPI phase analysis are independent risk factors for predicting MACE in coronary artery disease. GMPI phase analysis is useful for coronary artery disease risk stratification.

Value of FDG PET/CT in the differential diagnosis of benign and malignant hilar mediastinal lymph nodes in patients with non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To investigate the diagnostic value of 18F-fluorodeoxyglucose (FDG) PET/CT in detecting N 1 or N 2 metastasis of lymph node (LN) with different densities in patients with non-small cell lung cancer (NSCLC). Methods:A total of 118 patients (68 males, 50 females, age range: 27-87 (65.4±10.8) years) with N 0-N 2 M 0 NSCLC in Beijing Hospital between October 2007 and December 2017 were included in this study. All patients underwent 18F-FDG PET/CT, followed by surgery within 1 month. The pathological findings of the resected hilar mediastinal LN were taken as the gold standard, and ratios of LN metastasis were calculated for different density groups (calcification, partial calcification, hyper density, hypodensity/isodensity). The cut-off values of LN size (short diameter) and the maximum standardized uptake value (SUV max) in the detection of N 1 and N 2 metastases was determined by the receiver operating characteristic (ROC) curve, and the diagnostic efficiencies were calculated. Independent-sample t test, Mann-Whitney U test and χ2 test (partition of χ2) were used for data analysis. Results:A total of 433 LN has the histopathologic results: 365 LN was in stage N 0, 68 LN was in stage N 1-N 2. There were no metastases in calcification group (0/8). The metastatic LN proportions in partial calcification group (28.6%, 8/28), hypodensity/isodensity group (20.3%, 44/217) were significantly higher than that in the hyper density group (8.9%, 16/180; χ2 values: 7.369, 9.945, both P<0.017 (threshold for partition of χ2)). There was no significant difference between the partial group and hypodensity/isodensity group ( χ2=1.021, P>0.017). The SUV max of N 1+ N 2 group was significantly higher than that in N 0 group (6.94 (4.51, 11.36) vs 2.45 (1.93, 3.42); z=-10.388, P<0.01). According to the ROC curve, the cut-off value of SUV max in detecting hilar and mediastinal LN was 3.66. The diagnostic sensitivity, specificity and accuracy for N 1+ N 2 metastasis was 85.3%, 78.9%, 80.0% respectively. The cut-off values of SUV max for hypodensity/isodensity group and hyper density group were 3.66 and 2.79 respectively, and the corresponding sensitivities, specificities, accuracies and positive predictive values (PPV) were 93.2%, 86.7%, 88.0%, 64.1% vs 93.8%, 57.9% ( χ2=10.724), 61.1% ( χ2=7.326, P<0.01), 17.9%( χ2=32.971, P<0.01). The specificity of LN size (1.0 cm)+ SUV max was significantly higher that of LN size or SUV max alone (94.2% vs 80.9%, 86.7%; χ2 values: 14.048, 5.661, both P<0.05) in hypodensity/isodensity group. The specificity and accuracy of LN size (1.0 cm)+ SUV max were significantly higher those of SUV max alone ( χ2 values: 58.043, 37.037, both P<0.01) in hyper density group. Conclusions:18F-FDG PET/CT is useful in diagnosing the N 1+ N 2 metastases in hypodensity/isodensity LN, but has limitation in diagnosing the partial calcification LN. Combination of lymph node short diameter and SUV max cut-off value can improve the diagnostic specificity or accuracy of 18F-FDG PET/CT for hypodensity/isodensity and high density LN.

Radiosynthesis and in-vivo evaluation of [125I]IBT: a single-photon emission computed tomography radiotracer for α7-nicotinic acetylcholine receptor imaging.

AIM: The aim of this study was to develop several novel α7-nicotinic acetylcholine receptor (nAChR) radioligands for the early diagnosis and treatment of Alzheimer's disease. PATIENTS AND METHODS: The study reported six compounds and studied the in-vitro receptor binding affinity, and selected the I-labeled IBT with good characteristics as a novel radioligand suitable for studying α7-nAChRs. After verifying the stability of the radiotracer [I]IBT, the biodistribution in vivo and regional brain biodistribution studies were carried out in mice. Blocking studies with methyllycaconitine citrate and nicotine were carried out under control and blocking conditions, and the metabolic stability was assessed in vivo in the plasma, brain, and liver. RESULTS AND CONCLUSION: The results of our study suggested that [I]IBT had affinity for α7-nAChRs. The in-vivo evaluation in mice of [I]IBT showed a high brain/blood ratio and excellent metabolic stability. The regional brain distribution studies and the blocking studies showed that it had favorable selectivity and specificity and was a potential α7-nAChRs radioligand.

Predictive value for adverse cardiac events of left ventricular diastolic function measured by gated myocardial perfusion imaging / 中华核医学与分子影像杂志

Objective To study the predictive value for adverse cardiac events (ACE) of left ventricular diastolic function measured by G-MPI. Methods Patients assessed by 2 days rest-stressed G-MPI during March 2012 to May 2013 in Beijing Hospital were collected and observed for the cumulative survival rate without ACE after G-MPI. ACE included cardiac death, non-fatal MI and late revascularization (60 d after the examination). Using quantitative gated SPECT (QGS) to get the LVEF and left ventricular peak filling rate (PFR). Using 17 segments, 5-point scoring system to get the summed stress score (SSS). Cox regression analysis was used to identify the independent predictors for ACE, and Kaplan-Meier method was used to investigate the cumulative survival rate without ACE.χ2 test was also used. Results A total of 11 patients who underwent early revascularization (within 60 d after G-MPI) were excluded and 139 patients (76 males, 63 females; average age 68.73 years) were assigned to different groups for outcome analysis, and 9 (6.5%, 9/139) patients had ACE in the whole group. Cox regression analysis showed that SSS, LVEF, PFR were the independent predictors for ACE (all P<0.05). Patients with PFR<2.1 EDV/s had a higher incidence of ACE than those with PFR≥2.1 EDV/s (14.3%(7/49) vs 2.2%(2/90), χ2=7.63, P<0.05). Kaplan-Meier survival analysis showed that the cumulative survival rate without ACE was lower in patients with PFR<2.1 EDV/s than that in patients with PFR≥2.1 EDV/s (67.7% vs 95.0%), and lower in patients with LVEF<50% than that in patients with LVEF≥50%(32.0% vs 90.8%), and also lower in patients with SSS≥8 than those with SSS<8(62.0% vs 94.7%; χ2 values: 11.92,11.27, 10.40, all P<0.01).Combining PFR with SSS and LVEF respectively, Kaplan-Meier survival analysis showed that the cumulative survival rate without ACE in patients with LVEF≥50% was higher than that in patients with LVEF<50% when PFR<2.1 EDV/s (76.7% vs 30.8%), and also higher in patients with SSS<8 than that in patients with SSS≥8 when PFR≥2.1 EDV/s (100% vs 72.2%; χ2 values: 7.14, 13.09, both P<0.01). Conclusion PFR of left ventricular diastolic function measured by G-MPI is one of the independent predictors for ACE, and it could effectively improve the predictive value for ACE if combined with LVEF and SSS.

Comparative analysis of FDG PET SUVmax cutoff values in detection of mediastinal lymph node metastasis and hilar/intralobar lymph node metastasis in patients with non-small cell lung cancer / 中华核医学与分子影像杂志

Objective To study the FDG SUVmax cutoff values in detection of metastases in mediastinal lymph nodes (MLN) and hilar/intralobar lymph nodes (HILN) in pre-operative patients with N0-2 stage NSCLC.Methods A total of 69 patients with stage N0-2 NSCLC (40 males,29 females,age 36-87 years) were included in this retrospective study.18F-FDG PET/CT was performed and followed by lung cancer resection with lymph node dissection in 1 month.The excised lymph nodes were compared one by one between their SUVmax and histopathology.The SUVmax cutoff value in detection of lymph node metastases was determined by the ROC curve.Mann-Whitney u test,x2 test,and Fisher exact test were used for data analysis.Results Metastatic MLN and (or) HILN were found in 21 of 69 NSCLC patients.The histopathologic results demonstrated metastases in 61 of 339 lymph nodes.The SUVmax of metastatic lymph nodes (4.95(3.46,7.19)) was significantly higher than that of benign lymph nodes (2.10(1.59,3.22);z=-7.576,P＜0.05).The SUVmax of metastatic HILN (6.32 (4.28,8.27)) was significantly higher than that of metastatic MLN (3.90(2.12,6.41);z=-2.921,P＜0.05).With cutoff of SUVmax ≥2.5,the sensitivity,specificity and accuracy in detection of all metastatic lymph nodes were 83.6％ (51/61),61.9％ (172/278)and 65.8％ (223/339) respectively,and the parameters were 74.2％ (23/31),79.6％ (160/201) and 78.9％ (183/232) for metastatic MLN,and 93.3％ (28/30),15.6％ (12/77) and 37.4％ (40/107) for metastatic HILN.The diagnostic sensitivities for metastatic MLN and for metastatic HILN were not significantly different (Fisher exact test,P＞0.05),while the specificities and accuracies between the two groups were significantly different (x2 values:96.7 and 56.1,both P＜0.05).According to ROC curves,cutoff values of SUVmax in detecting metastatic MLN and metastatic HILN were 2.78 and 4.93.With the specific cutoff value,the sensitivity,specificity and accuracy in detection of metastatic MLN were 71.0％ (22/31),87.1％ (175/201)and 84.9％(197/232),respectively.The corresponding data in detection of metastatic HILN were 73.3％ (22/30),77.9％(60/77) and 76.6％(82/107).Conclusion Different cutoff values of SUVmax in detecting metastatic MLN and metastatic HILN should be considered for more accurate lymph nodes staging in patients with NSCLC.

Resveratrol regulates iNOS to inhibit atherosclerosis in C57BL/6J mice / 中国病理生理杂志

AIM:To investigate the effect of resveratrol on the lipids ( CHOL, TG, LDL-C and HDL-C) , ni-tric oxide ( NO) , peroxynitrite anion ( ONOO-) and the expression of inducible nitric oxide synthase ( iNOS) in the artery of the mice with ovariotomy ( OVX) .METHODS:The lipid levels and NO level in the serum were measured .The chan-ges of atherosclerosis were evaluated with Oil Red O staining .The expression of iNOS was measured by DAB staining and Western blot .The ONOO-production was measured by DAB staining .RESULTS:Compared with sham group , the levels of the lipids and NO production in OVX +high fat (HF) group were increased (P<0.05).Compared with OVX+HF group, the levels of the lipids and NO production in resveratrol group were decreased (P<0.05).Fourteen weeks later, the atherosclerosis model was successfully established .Compared with OVX +HF group, the iNOS expression and the ONOO-production in resveratrol group were decreased ( P<0.05 ) , while those in sham group were increased ( P <0.05).CONCLUSION:Resveratrol prevents and treats atherosclerosis by inhibiting the iNOS expression in C 57BL/6J mice.