Analysis of inflammatory factors and BDNF expression in the brain hippocampus of Alzheimer's disease-like mice caused by Aβ25-35 / 重庆医学

Objective To investigate the expression of inflammatory factors and brain-derived neurotro-phic factor(BDNF)in the brain hippocampus of Alzheimer's disease(AD)-like mice caused by amyloid β-protein 25-35(Aβ25-35).Methods A total of 40 six-week-old male Kunming mice were taken to construct an AD-like mouse model using bilateral ventricular injection of Aβ25-35,and were divided into the 0 d,7 d,14 d,and 28 d groups for observation,with 10 mice in each group.The Y-maze and new object recognition assay were used to test the learning and memory functions of the mice.The hematoxylin-eosin(HE)staining was used to observe the neuronal damage in the hippocampal region.Immunohistochemical staining was used to detect the expression levels of phosphorylated-tau(p-tau),CD11b and BDNF in hippocampus.ELISA was used to detect the expression levels of inflammatory factors in hippocampus,including interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF)-α,and real-time quantitative reverse transcription PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of BDNF.Results Aβ25-35 could impair memory and cognitive function in the mice.Compared with the 0 d group,the neuron number in the hippocampal tissue of mice in the 14 d and 28 d groups was significantly reduced(P<0.05),and the optical density values of p-Tau and CD11b,and expression levels of IL-1β and TNF-α in the hippocampal region of mice in the 14 d and 28 d groups were significantly increased(P<0.05).In addition,compared with the 0 d group,the relative expression levels of BDNF mRNA and protein in the hippocampal tissue of mice were sig-nificantly increased in the 7 d group(P<0.05),while the relative expression levels of BDNF mRNA and pro-tein were significantly decreased in the 14 d and 28 d groups(P<0.05).Conclusion Aβ25-35 may increase the expression of TNF-α,IL-1β and p-tau in hippocampal tissue by activating microglia,which in turn impaired the memory and cognitive functions of mice,and the expression level of BDNF in hippocampal tissue showed a first increase and then a decrease in the injury period.

A multicenter study on the prognostic value of SPECT myocardial blood flow quantitative technique in patients with intermediate stenoses of coronary arteries / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of myocardial flow reserve (MFR) measured by SPECT myocardial blood flow (MBF) quantitative technique in patients with intermediate stenoses of coronary arteries.Methods:From September 2019 to May 2021, patients with intermediate stenoses (50% to 80%) identified by invasive coronary angiography in Fuwai Hospital, Chinese Academy of Medical Sciences, Fuwai Center China Cardiovascular Hospital, and TEDA International Cardiovascular Hospital were prospectively included. All patients underwent a one-day rest/stress SPECT myocardial perfusion imaging (MPI) and SPECT MBF quantification. The radioactivity distribution of each segment of the MPI bullseye polar maps were obtained according to the standard 5-point method to obtain the summed stress score (SSS) and the summed difference score (SDS) to determine the existence of abnormality. ROC curve analysis was used to obtain the optimal prognostic cut-off value for MFR. The primary endpoint was defined as cardiovascular endpoint events. Survival and prognostic analyses were conducted by Kaplan-Meier method and Cox proportional hazard models. The difference of AUCs was analyzed by Delong test.Results:A total of 314 patients (194 males, 120 females; age (59.4±8.6) years) were enrolled. Over a median follow-up duration of 754 (range: 628-914) d, 54 patients had endpoint events. ROC curve showed that the prediction ability of MFR was significantly better than that of conventional MPI (AUCs: 0.713 and 0.512; z=3.76, P<0.001). The optimal prognostic cut-off value for MFR to predict endpoint events in patients with intermediate stenoses was 2.04. Cox multivariate analysis showed that MFR (hazard ratio ( HR)=0.434, 95% CI: 0.282-0.669, P<0.001) was an independent predictor of endpoint events in patients with intermediate stenoses. Kaplan-Meier survival analysis showed that the prevalence of endpoint events in patients with MFR≤2.04 was significantly higher than that in patients with MFR>2.04 (25.4%(43/169) vs 7.6%(11/145); χ2=21.27, P<0.001). Conclusion:The MFR measured by SPECT MBF quantitative technique has an independent predictive value for cardiovascular endpoint events in patients with intermediate stenoses.

α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State

BACKGROUND@#Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, antiinflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state. @*METHODS@#Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines. @*RESULTS@#HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6. @*CONCLUSION@#This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II).

α-Gal Nanoparticles in CNS Trauma: II. Immunomodulation Following Spinal Cord Injury (SCI) Improves Functional Outcomes

BACKGROUND@#Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-a-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord. @*METHODS@#α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints. @*RESULTS@#Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group. @*CONCLUSIONS@#Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.GRAPHICAL ABSTRACT Putative mechanism of therapeutic action by α-gal nanoparticles. A. Nanoparticles injected into the injured cord bind to anti-Gal antibodies leaked from ruptured capillaries. The binding of anti-Gal to α-gal epitopes on the α-gal nanoparticles activates the complement system to release complement cleavage chemotactic peptides such as C5a, C3a that recruit macrophages and microglia. These recruited cells bind to the anti-Gal coated α-gal nanoparticles and are further polarized into the M2 state. B. Recruited M2 macrophages and microglia secrete neuroprotective and prohealing factors to promote tissue repair, neovascularization and axonal regeneration (C.).

Relationship between myocardial viability and early application of intra-aortic balloon pump after coronary artery bypass grafting / 中国胸心血管外科临床杂志

@#Objective    To explore the relationship between myocardial viability in patients with coronary artery disease who underwent elective coronary artery bypass grafting (CABG) and early application of intra-aortic balloon pump (IABP) after coronary revascularization, and to provide relevant clinical reference for the pre-implantation of 16G single-lumen catheter in the femoral artery of high-risk patients to facilitate the addition of IABP after operation. Methods    This retrospective study included 521 patients (414 males and 107 females, aged 62.50±8.82 years) who underwent positron emission tomography (PET)-computed tomography (CT) perfusion-metabolism imaging prior to CABG surgery in our institution from December 2015 to August 2020. The myocardial viability information and left ventricular functional parameters were measured, including the proportion of non-viable myocardium (perfusion-metabolic imaging match), hibernating myocardium (perfusion-metabolic imaging mismatch) and dysfunctional myocardium (non-viable+viable myocardium), left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume (LVESV). The patients were divided into an IABP group and a non-IABP group  according to whether they received IABP treatment after revascularization. The clinical data were reviewed and compared to explore significant impact factors between the two groups. And the multivariate logistic regression analysis was performed to investigate the correlation between preoperative myocardial viability and early use of IABP after CABG. Results    In multivariate logistic regression analysis, the amount of non-viable, dysfunctional myocardium and LVESV value were identified as the independent predictors for the probability of IABP use in the initial postoperative period. Receiver operating characteristic analysis showed that 9.5% non-viable myocardium, 19.5% dysfunctional myocardium, and LVESV of 114.5 mL were the optimal cutoff for predicting early IABP implantation during CABG. Conclusion    The myocardial survival status displayed by preoperative PET-CT myocardial perfusion-metabolism imaging can predict the possibility of applying IABP in CABG perioperative period. In addition to routine pre-anesthesia assessment, anesthesiologists can conduct risk stratification assessment for patients with CABG according to the results of preoperative myocardial viability imaging, which is of great significance to ensure the perioperative safety of high-risk patients with CABG.

Research Advances of Artificial Intelligence in Radionuclide Myocardial Perfusion Imaging / 中国医学影像学杂志

With the continuous advancement of technology,the application of artificial intelligence in medical imaging has become increasingly widespread,notably revolutionizing the field of nuclear cardiology through the intelligent and precise development of radionuclide myocardial perfusion imaging.Artificial intelligence,particularly machine learning and deep learning,has shown immense potential in handling the voluminous and complex data associated with myocardial perfusion imaging.It plays a pivotal role in reducing image acquisition time and radiation dosage,enhancing image quality,optimizing diagnostic accuracy and automating processing and prognostic assessments.This paper summarizes the applications of artificial intelligence in various aspects of myocardial perfusion imaging,including data collection and processing,attenuation correction,image post-processing,diagnostic reporting and patient prognostic evaluation.The aim is to provide new insights and methodologies for research work,thereby promoting the intelligent and precise advancement of nuclear cardiology.

Primary study of motion correction effect on myocardial blood flow quantitative imaging with CZT SPECT / 中华核医学与分子影像杂志

Objective:To investigate the effect of motion correction (MC) on the calculated values of myocardial blood flow (MBF) and myocardial flow reserve (MFR) based on cadmium-zinc-telluride SPECT (CZT SPECT) images.Methods:Twenty-eight consecutive patients (10 males, 18 females, age: (60.75±11.62) years) with suspected or known coronary artery disease who underwent myocardial perfusion imaging (MPI) with dynamic CZT SPECT between June 2019 and August 2019 in TEDA International Cardiovascular Hospital were retrospectively analyzed. The MBF and MFR during rest imaging and stress imaging were quantitatively analyzed. Corridor 4DM software was used to calculate the stress MBF (sMBF) and MFR of the coronary artery branches and left ventricular (LV) before and after MC. The paired t test and Pearson correlation were used for data analysis. Results:The sMBF and MFR of LV before MC were (0.82±0.49) ml·min -1·g -1 and 1.69±0.68 respectively. After MC the two parameters increased to (1.05±0.64) ml·min -1·g -1 and 2.12±0.77 respectively ( t values: -4.87, -6.01, both P<0.001). The sMBF and MFR in left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA) and LV before MC were correlated with those after MC ( r values: 0.69-0.96, all P<0.001). If MFR <2.0 was used as the reference of impaired MFR, data before MC showed 19 patients (67.9%, 19/28) had impaired MFR, while 13 patients (46.4%, 13/28) had impaired MFR based on MFR values after MC. Conclusion:For MPI quantitative imaging with CZT SPECT, the calculated values of sMBF and MFR after MC is higher than those before MC, suggesting that MC is helpful to reduce the false positive results which may be caused by the " creep" effect of the heart.

Diagnostic value of myocardial blood flow quantitative imaging with CZT SPECT in patients with high-risk coronary artery disease / 中华核医学与分子影像杂志

Objective:To investigate the diagnostic value of myocardial blood flow quantitative imaging with cadmium zinc telluride (CZT) SPECT in patients with high-risk coronary artery disease (CAD).Methods:A total of 148 patients (82 males, 66 females, age: (63.8±8.2) years) who successfully completed CZT SPECT dynamic acquisition and routine SPECT myocardial perfusion imaging (MPI) in TEDA International Cardiovascular Hospital from November 2018 to October 2020 were analyzed retrospectively. According to the results of coronary angiography (CAG), patients were divided into two groups: high-risk CAD group and low-to-medium-risk CAD group. At the case level, quantitative parameters (stress myocardial blood flow (sMBF), rest myocardial blood flow (rMBF) and myocardial flow reserve (MFR)), semi-quantitative parameters (summed stress score (SSS), summed rest score (SRS), summed difference score (SDS) and transient ischemic dilation (TID)) and left ventricular function parameters of two groups were compared. Diagnostic accuracy was evaluated by ROC curve analysis. At the vascular level, the correlation between the degree of coronary artery stenosis and some parameters was analyzed. Mann-Whitney U test, logistic regression, Spearman rank correlation analysis and DeLong test were used for statistical analysis. Results:Case level analysis showed that MFR and sMBF in high-risk CAD group were significantly lower than those in low-to-medium-risk CAD group (1.36(0.87, 1.64) vs 2.74(2.30, 3.33), 1.06(0.69, 1.48) vs 2.50(1.73, 2.95) ml·g -1·min -1; U values: 628.0 and 853.5, both P<0.001). MFR and SDS were independent predictors of high-risk CAD patients (odds ratio ( OR)=0.251(95% CI: 0.136-0.464), P<0.001; OR=1.188(95% CI: 1.026-1.375), P=0.021), and MFR was more capable of predicting high-risk CAD. MFR and sMBF had the highest accuracy in diagnosing high-risk CAD (AUCs: 0.885 and 0.844). Differences of AUCs between MFR and other parameters were statistically significant ( z values: 1.99-6.77, all P<0.05), and the best diagnostic cut-off value was ≤1.83 (sensitivity: 85.90%; specificity: 85.71%). Vascular level analysis showed that MFR and sMBF( R2 values: 0.39 and 0.35, both P<0.001) were negatively correlated with the degree of coronary stenosis, while SSS, SRS and SDS ( R2 values: 0.22, 0.12 and 0.14, all P<0.001) were positively correlated with the degree of coronary stenosis. Conclusion:Compared with conventional SPECT MPI, CZT SPECT myocardial blood flow quantitative imaging has better diagnostic efficacy and clinical value in patients with high-risk CAD.

Banded chromosome images recognition based on dense convolutional network with segmental recalibration / 生物医学工程学杂志

Human chromosomes karyotyping is an important means to diagnose genetic diseases. Chromosome image type recognition is a key step in the karyotyping process. Accurate and efficient identification is of great significance for automatic chromosome karyotyping. In this paper, we propose a model named segmentally recalibrated dense convolutional network (SR-DenseNet). In each stage of the model, the dense connected network layers is used to extract the features of different abstract levels of chromosomes automatically, and then the concatenation of all the layers which extract different local features is recalibrated with squeeze-and-excitation (SE) block. SE blocks explicitly construct learnable structures for importance of the features. Then a model fusion method is proposed and an expert group of chromosome recognition models is constructed. On the public available Copenhagen chromosome recognition dataset (G-bands) the proposed model achieves error rate of only 1.60%, and with model fusion the error further drops to 0.99%. On the Padova chromosome dataset (Q-bands) the model gets the corresponding error rate of 6.67%, and with model fusion the error further drops to 5.98%. The experimental results show that the method proposed in this paper is effective and has the potential to realize the automation of chromosome type recognition.

Analysis of the correlation between body mass index and coronary flow reserve in patients with chest pain and no obstructive coronary artery disease / 中华内分泌代谢杂志

Objective:To explore the correlation between body mass index(BMI)and coronary flow reserve(CFR)in patients with chest pain and no obstructive coronary artery disease(NOCA).Methods:This study was a single-center retrospective cross-sectional study. Sixty-six patients with chest pain and NOCA on coronary angiography who underwent PET/CT quantitative myocardial blood flow measurements at TEDA International Cardiovascular Hospital were retrospectively analyzed from August 2018 to October 2019. Pearson correlation analysis and linear regression analysis were used to explore the correlation between BMI and CFR. Patients were divided into 2 groups according to CFR: coronary microvascular dysfunction(CMD)group(CFR<2.5)and control group(CFR≥2.5). Logistic regression analysis was applied to analyze the association of BMI with CMD.Results:The proportions of female, obesity, and overweight plus obesity in CMD group were higher than those in control group( P<0.05). The levels of BMI and low density lipoprotein-cholesterol(LDL-C)were higher in CMD group compared with control group( P<0.05). Pearson correlation analysis showed that CFR was linearly correlated with BMI( r=-0.45, P<0.01), which still existed after adjusted by confounding factors using linear regression model( r=-0.371, P<0.01). Logistic regression analysis showed that BMI was dependently associated with CMD after adjusted by gender, age, hypertension, diabetic mellitus, and LDL-C. The OR value of CMD was 4.46(95% CI 1.47-13.55, P<0.01)with BMI increased by 5 kg/m 2. Conclusion:In patients with chest pain and NOCA, higher BMI is an independent risk factor of CMD.

Comparison of 18F-Flurpiridaz and 13N-NH3 · H2O PET/CT myocardial perfusion imaging in animal experiments / 中华核医学与分子影像杂志

Objective To explore the biodistribution and quantitative value of 18F-Flurpiridaz in mini-swine,and compare with 13N-NH3 · H2O.Methods Ten Bama mini-swine were divided into normal group and myocardial infarction group (n=5 in each group).Normal group was not treated and myocardial infarction group was modeled by thoracotomy and coronary artery ligation.Both groups were preceded by 13N-NH3 · H2O imaging,followed by 18F-Flurpiridaz imaging (time interval ＞40 min).Injection dosage of 2 tracers was the same (185-370 MBq).18F-Flurpiridaz whole-body PET/CT imaging was also performed in normal group.Biological distribution of 18F-Flurpiridaz was observed,and the ratio of radioactive uptake of 18F-Flurpiridaz between myocardium and adjacent tissues or organs was calculated.Image quality score and rest myocardial blood flow (rMBF) of 2 imaging tracers in normal group were measured and compared.MPI image quality score,cardiac function parameters such as summed rest score (SRS),myocardial infarction area percentage,total perfusion defect (TPD),and left ventricular ejection fraction (LVEF) of 2 imaging tracers were compared in myocardial infarction group.Data was analyzed by paired t test.Results In normal group,18F-Flurpiridaz in the myocardium was clearly observed,with high radioactive uptake maintaining within 2 h postinjection.The radioactivity count ratios of left ventricular myocardium to cardiac pool,the lungs and liver were high (5.19-12.87,4.17-50.51,2.08-6.92).The quality of 18F-Flurpiridaz MPI images in both groups was excellent (10/10).The rMBF (ml · g-1 · min-1) in different regions of left ventricle measured by 18F-Flurpiridaz and 13N-NH3 · H2O imaging were not significantly different (left anterior descending:0.98±0.06 vs 0.92±0.13;left circumflex:0.98±0.05 vs 0.88±0.12;right coronary artery:0.95±0.07 vs 0.88±0.15;left ventricle:0.96±0.07 vs 0.90±0.13;t values:from-1.70 to-0.90,all P＞0.05).There was no significant difference in SRS,myocardial infarction area percentage,TPD,rMBF or LVEF between 18F-Flurpiridaz and 13N-NH3 · H2O (SRS:10.6±4.1 vs 9.2±4.6;myocardial infarction area percentage:(15.2±9.0)％ vs (12.6±6.6)％;TPD:(11.6±6.3)％ vs (9.6±3.9)％;LVEF:(68.6±11.1)％ vs (71.4±11.3)％;t values:-2.33-2.75,all P＞0.05).Conclusions Comparing with 13N-NH3 · H2O,18F-Flurpiridaz has the advantages of good MPI image quality,accurate measurement of cardiac function parameters and quantitative potential of myocardial blood flow,which make it as a promising positron myocardial perfusion imaging agent.

Analysis of quantitative parameters measured with PET/CT and relative risk factors in female patients with coronary microvascular diseases / 中华核医学与分子影像杂志

Objective:To diagnose female coronary microvascular diseases (CMVD) without obstructive coronary artery disease through coronary flow reserve (CFR) measured with PET/CT imaging, and further analyze its related risk factors of quantitative parameters and clinical characteristics.Methods:From September 2017 to August 2019, a total of 75 female patients (age: 25-77 years) with clinically suspected CMVD from TEDA International Cardiovascular Hospital were retrospectively analyzed. All patients had negative results of coronary angiography (CAG) or coronary CT angiography (CCTA) and underwent 13N-NH 3·H 2O PET/CT dynamic quantitative imaging. Left ventricle (LV) coronary flow reserve (LV-CFR) value of 2.5 for critical value was divided into CMVD group and non-CMVD group. Clinical characteristics and quantitative parameters including rest LV-myocardial blood flow (MBF) and stress LV-MBF were respectively analyzed and compared between groups. Independent-sample t test, Mann-Whitney U test and Pearson correlation analysis were used to analyze the data. Results:Of 75 patients, 51 cases (68%) were diagnosed with CMVD and 24 cases (32%) with non-CMVD. Body mass index (BMI) of the CMVD group was higher than that of the non-CMVD group ((26.93±3.52) vs (23.83±3.42) kg/m 2, t=3.63, P=0.001), and LV-CFR was negatively correlated with BMI ( r=-0.341, P=0.003). The LV-CFR of the overweight group (BMI≥24 kg/m 2) was lower than that of non-overweight group (BMI<24 kg/m 2) (2.18±0.47 vs 2.54±0.55, t=-2.89, P=0.005). The rest LV-MBF in the CMVD group (0.74(0.65, 0.84) ml·min -1·g -1) was higher than that in the non-CMVD group (0.66(0.58, 0.75) ml·min -1·g -1; U=417.5, P=0.027), and the stress LV-MBF and LV-CFR was lower than that in the non-CMVD group ((1.53±0.35) vs (1.96±0.45) ml·min -1·g -1, 2.07(1.71, 2.34) vs 2.86(2.61, 2.95); t=-4.54, U=0, both P<0.001). In the hypertensive group, the CMVD sub-group had higher rest LV-MBF than the non-CMVD sub-group ((0.77±0.16) vs (0.65±0.13) ml·min -1·g -1; t=2.26, P<0.05), but lower stress LV-MBF ((1.49±0.34) vs (1.85±0.40) ml·min -1·g -1; t=-3.07, P<0.05) and LV-CFR(1.99(1.64, 2.23) vs 2.85(2.55, 2.95); U=0, P<0.05] than the non-CMVD sub-group. In the non-hypertensive group, stress LV-MBF and LV-CFR of the CMVD sub-group were lower than those of the non-CMVD sub-group (1.53(1.36, 1.97) vs 1.94(1.76, 2.16) ml·min -1·g -1, 2.35(1.94, 2.43) vs 2.87(2.65, 3.09); U values: 43.5 and 0, both P<0.05). LV-CFR of CMVD subgroup in hypertensive group was lower than that of CMVD subgroup in non-hypertensive group ( U=164.0, P=0.028). Conclusions:BMI is negatively correlated with LV-CFR in CMVD. The decrease of stress LV-MBF and the increase of rest LV-MBF in CMVD lead to the decrease of LV-CFR. Hypertension is one of the important influence factors for MBF and CFR.

Comparison of 18F-Flurpiridaz and 13N-NH3·H2O PET/CT myocardial perfusion imaging in animal experiments / 中华核医学与分子影像杂志

Objective@#To explore the biodistribution and quantitative value of 18F-Flurpiridaz in mini-swine, and compare with 13N-NH3·H2O.@*Methods@#Ten Bama mini-swine were divided into normal group and myocardial infarction group (n=5 in each group). Normal group was not treated and myocardial infarction group was modeled by thoracotomy and coronary artery ligation. Both groups were preceded by 13N-NH3·H2O imaging, followed by 18F-Flurpiridaz imaging (time interval >40 min). Injection dosage of 2 tracers was the same (185-370 MBq). 18F-Flurpiridaz whole-body PET/CT imaging was also performed in normal group. Biological distribution of 18F-Flurpiridaz was observed, and the ratio of radioactive uptake of 18F-Flurpiridaz between myocardium and adjacent tissues or organs was calculated. Image quality score and rest myocardial blood flow (rMBF) of 2 imaging tracers in normal group were measured and compared. MPI image quality score, cardiac function parameters such as summed rest score (SRS), myocardial infarction area percentage, total perfusion defect (TPD), and left ventricular ejection fraction (LVEF) of 2 imaging tracers were compared in myocardial infarction group. Data was analyzed by paired t test.@*Results@#In normal group, 18F-Flurpiridaz in the myocardium was clearly observed, with high radioactive uptake maintaining within 2 h postinjection. The radioactivity count ratios of left ventricular myocardium to cardiac pool, the lungs and liver were high (5.19-12.87, 4.17-50.51, 2.08-6.92). The quality of 18F-Flurpiridaz MPI images in both groups was excellent (10/10). The rMBF (ml·g-1·min-1) in different regions of left ventricle measured by 18F-Flurpiridaz and 13N-NH3·H2O imaging were not significantly different (left anterior descending: 0.98±0.06 vs 0.92±0.13; left circumflex: 0.98±0.05 vs 0.88±0.12; right coronary artery: 0.95±0.07 vs 0.88±0.15; left ventricle: 0.96±0.07 vs 0.90±0.13; t values: from -1.70 to -0.90, all P>0.05). There was no significant difference in SRS, myocardial infarction area percentage, TPD, rMBF or LVEF between 18F-Flurpiridaz and 13N-NH3·H2O (SRS: 10.6±4.1 vs 9.2±4.6; myocardial infarction area percentage: (15.2±9.0)% vs (12.6±6.6)%; TPD: (11.6±6.3)% vs (9.6±3.9)%; LVEF: (68.6±11.1)% vs (71.4±11.3)%; t values: -2.33-2.75, all P>0.05).@*Conclusions@#Comparing with 13N-NH3·H2O, 18F-Flurpiridaz has the advantages of good MPI image quality, accurate measurement of cardiac function parameters and quantitative potential of myocardial blood flow, which make it as a promising positron myocardial perfusion imaging agent.

Study on Quality Standard Improvement for Compound Child Antifebrile Suppository / 中国药房

OBJECTIVE：To improve the quality standard of Compound child antifebrile suppository. METHODS ：Based on the previous quality standard ，TLC identification methods were established for artificial cow-bezoar and Baphicacanthis Cusiae Rhizoma et Radix. HPLC method was established for content determination of choleic acid （CA），hyodeoxycholic acid （HDCA） and paracetamol. RESULTS ：TLC chromatogram of artificial cow-bezoar and Baphicacanthis Cusiae Rhizoma et Radix all showed the same color spots in the same position as the corresponding substance control or reference medicinal material ，while the negative samples had no interference. HPLC was performed on Welch Xtimate C 18 column（CA，HDCA）or Agilent ZORBAX SB-C 18 column（paracetamol）with mobile phase consisted of acetonitrile-0.5％ formic acetic acid （by gradient elution ，CA and HDCA ）or methanol-water（20∶80，V/V，paracetamol）at the flow rate of 1.0 mL/min. ELSD was used with a nitrogen flow-rate of 2.0 L/min at a drift tube temperature of 105 ℃（CA，HDCA）. The detection wavelength was set at 244 nm（paracetamol）. The linear ranges of CA，HDCA，paracetamol were 0.150 0-4.500 0，0.212 5-6.375 0，0.081 9-1.638 5 μg（all r＞0.999 2）. RSDs of precision ， reproducibility and stability tests were all lower than 3％（n＝6 or n＝7）. The average recoveries were 100.35％，101.39％， 98.81％（all RSD ＜3％，n＝6）. CONCLUSIONS ：Based on previous quality standard of Compound child antifebrile suppository ， TLC method is used to identify artificial cow-bezoar and Baphicacanthis Cusiae Rhizoma et Radix ，and the contents of CA ，HDCA and paracetamol are determined by HPLC ，which can effectively improve the quality control standard of the preparation.

Clinical Application and Mechanical Analysis of the Treatment of Multiple Rib Fractures and Flail Chest Using Three-wings Rib Plate / 中国医疗器械杂志

This research evaluated the clinical efficacy of three-wings rib plate in the treatment of multiple rib fractures and flail chest with mechanical analysis and clinical verification. The model of rib and three-wings rib plate was reconstructed. The contact simulation with pretension stress was applied to the plate's fixation, and it was found that the bearable stress of the rib fractures after fixation increased from the result which indicated a good fixation efficacy of the plate. Clinical data of 53 cases of rib fractures and flail chest treated with three-wings rib plate in Shanghai Pudong Hospital of Fudan University were retrospectively analyzed. After the operation, the pain of the patients was relieved. Postoperative CT reconstruction of the chest showed good restoration of the rib fractures, which verified the clinical efficacy of three-wings rib plate. The three-wings rib plate showed a high value in clinical use for treatment of rib fractures.

Effect of targeted regulation of the Wnt2 gene by microRNA(microRNA-21) on the proliferation and migration of HepG2 hepatoma cells / 临床肝胆病杂志

ObjectiveTo investigate the effect of targeted regulation of the Wnt2 gene by microRNA(miR-21) on the proliferation and migration of HepG2 hepatoma cells. MethodsQuantitative real-time PCR was used to measure the mRNA expression of miR-21 in HepG2 hepatoma cells and normal liver cell line LO2. HepG2 cells were transfected with miR-21 inhibitor, and then the expression of miR-21 and cell proliferation, migration, and apoptosis were analyzed for the inhibitor group and the control group. The protein expression of Wnt2 was measured for the two groups, and dual-luciferase reporter assay was used to verify the association between miR-21 and the Wnt2 gene. The t-test was used for comparison of continuous data between groups. ResultsThe relative expression of miR-21 in HepG2 cells was significantly higher than that in LO2 cells (1.978±0.035 vs 1.586±0.022, t=16.424, P＜0.05). After the transfection of miR-21 inhibitor, the inhibitor group had significantly lower expression of miR-21 than the control group (0.857±0.017 vs 1.684±0.039, t=33669, P＜0.05). Compared with the control group after the transfection of miR-21 inhibitor, the inhibitor group had a significant reduction in the proliferation ability of HepG2 cells (P＜0.05), a significantly lower number of cells passing through the Transwell chamber (83.72±15.06 vs 147.85±20.64, t=4.347, P＜0.05), and a significantly higher cell apoptosis rate (25.67%±3.95% vs 10.27%±2.14%, t=5937, P＜0.05). The inhibitor group had significantly lower relative expression of Wnt2 in HepG2 cells than the control group (0.862±0.127 vs 1.306±0.218, t=3.048, P＜0.05). TargetScan software showed that miR-21 inhibitor significantly inhibited the luciferase activity of the cells transfected with wild-type Wnt2-3′UTR plasmid (0.972±0.102 vs 0.612±0.092, t=4.219, P＜005), while there was no effect on the luciferase activity of the cells transfected with mutant Wnt2-3′UTR plasmid (0.982±0.093 vs 0911±0.128, t=0.972, P＞0.05). ConclusionInhibition of miR-21 expression can effectively inhibit the proliferation and migration of HepG2 cells, promote the apoptosis of HepG2 cells, and inhibit the over-activation of the Wnt signaling pathway, and therefore, it may become one of the potential target genes for liver cancer treatment.

A clinical study of myocardial viability in predicting the improvement of cardiac function after coronary artery bypass grafting in patients with ischemic heart failure / 中国胸心血管外科临床杂志

@#Objective    To explore the predictive value of myocardial vitality in the improvement of cardiac function after coronary artery bypass grafting (CABG) in patients with ischemic heart failure. Methods    From December 8, 2015 to November 12, 2018, 46 patients with ischemic heart failure who underwent CABG operation alone were collected retrospectively. There were 41 males and 5 females with an average age of 60.4±8.0 years. The myocardial vitality and number of different types of myocardium were measured. The clinical data of patients in the left ventricular ejection fraction (LVEF) improvement group (≥5%) and non-improvement group (<5%) were compared and analyzed. The  correlation between each index and LVEF improvement was analyzed by logistic multivariate regression analysis, and the boundary value of hibernating myocardium between LVEF improvement and non-improvement was obtained by receiver operating characteristic (ROC) curve. Results    There were significant differences in the number of hibernating myocardium (15.0%±12.3% vs. 4.3%±4.5%, P=0.000), the number of normal myocardium (74.7%±13.7% vs. 82.4%±8.6%, P=0.027), and cardiac function classification (NYHA) development (−0.7±0.7 vs. −0.3±0.5, P=0.047) between the two groups, but there was no significant difference in other indexes between the two groups (P>0.05). Logistic regression analysis showed that the number of hibernating myocardium was an independent factor affecting the improvement of LVEF after CABG in patients with ischemic heart failure (OR=1.366, 95%CI 1.033-1.807, P=0.029). The ROC curve showed that the threshold value, sensitivity and specificity of hibernating myocardium were 15.0%, 43.8% and 100.0%, respectively. Conclusion    The percentage of hibernating myocardium to left ventricular wall area ≥15.0% can accurately predict the improvement of LVEF in patients with ischemic heart failure after CABG. Preoperative myocardial vitality assessment has important diagnostic value in predicting the improvement of cardiac function in patients with ischemic heart failure after simple CABG.

Study on optimizing rapid acquisition time of CZT-SPECT myocardial perfusion imaging using different injection doses / 中华核医学与分子影像杂志

Objective To explore the optimal and rapid imaging acquisition time and clinical ap-plicability when using high-and low-dose one day rest/stress myocardial perfusion imaging ( MPI) with cad-mium-zinc-telluride heart dedicated SPECT ( CZT-SPECT) . Methods The MPI data with high-dose rest/stress protocol in 51 patients (22 males, 29 females, age:(55.4±8.5) years) between November 2017 and December 2017 and those with low-dose protocol in 50 patients (27 males, 23 females, age:(59.1±12.8) years) between July 2018 and October 2018 were retrospectively analyzed. The MPI was performed with CZT-SPECT. Each patient received 296-370 MBq rest dose of 99Tcm-methoxyisobutylisonitrile (MIBI) for high-dose protocol, 111-222 MBq rest dose of 99 Tcm-MIBI for low-dose protocol. Stress dose was 3 times of the corresponding rest dose. Rest and stress scans were acquired 6 min and 4 min for high-dose protocol, while 8 min and 6 min for low-dose protocol in total. All rest or stress imaging data were reconstructed from list-mode raw data to obtain scan durations of 1 min, 2 min, etc, up to the maximum of acquisition time. Image quality at different acquisition times were evaluated, and myocardial perfusion and function parame-ters were compared. Paired t test, Wilcoxon signed rank test, Pearson correlation and Bland-Altman analyses were used for data analysis. Results The image quality was rated as excellent/good in all patients ( 100％, 51/51) when acquisition time≥3 min and ≥2 min respectively for rest and stress imaging with high-dose protocol, the similar results was obtained ( 100％, 50/50) when acquisition time≥4 min and≥3 min re-spectively for rest and stress imaging with low-dose protocol. The quantitative perfusion parameters(summed rest scores, summed stress scores, total perfusion deficit) and left ventricle ejection fraction ( LVEF) at shor-ter acquisition times (3 min/2 min, 4 min/3 min) were not significantly different from the results at the lon-ger acquisition times (6 min/4 min, 8 min/6 min;t values:from -1.196 to 1.597, z values:from -1.963 to 1. 945, all P>0. 05) . Those parameters at shorter and longer acquisition times showed strong correlations ( all r>0.700, all P<0.001) , and Bland-Altman analysis revealed good agreement between them. Conclusion The opti-mal acquisition time is 3 min/2 min for high-dose one-day rest/stress CZT-SPECT MPI, and 4 min/3 min for low-dose protocol, which can significantly shorten the MPI acquisition time, then reliable perfusion parameters and LVEF can be obtained under the premise of ensuring image quality, making it the better clinical applicability.

Study on optimizing rapid acquisition time of CZT-SPECT myocardial perfusion imaging using different injection doses / 中华核医学与分子影像杂志

Objective@#To explore the optimal and rapid imaging acquisition time and clinical applicability when using high- and low-dose one day rest/stress myocardial perfusion imaging (MPI) with cadmium-zinc-telluride heart dedicated SPECT (CZT-SPECT).@*Methods@#The MPI data with high-dose rest/stress protocol in 51 patients (22 males, 29 females, age: (55.4±8.5) years) between November 2017 and December 2017 and those with low-dose protocol in 50 patients (27 males, 23 females, age: (59.1±12.8) years) between July 2018 and October 2018 were retrospectively analyzed. The MPI was performed with CZT-SPECT. Each patient received 296-370 MBq rest dose of 99Tcm-methoxyisobutylisonitrile (MIBI) for high-dose protocol, 111-222 MBq rest dose of 99Tcm-MIBI for low-dose protocol. Stress dose was 3 times of the corresponding rest dose. Rest and stress scans were acquired 6 min and 4 min for high-dose protocol, while 8 min and 6 min for low-dose protocol in total. All rest or stress imaging data were reconstructed from list-mode raw data to obtain scan durations of 1 min, 2 min, etc, up to the maximum of acquisition time. Image quality at different acquisition times were evaluated, and myocardial perfusion and function parameters were compared. Paired t test, Wilcoxon signed rank test, Pearson correlation and Bland-Altman analyses were used for data analysis.@*Results@#The image quality was rated as excellent/good in all patients (100%, 51/51) when acquisition time ≥3 min and ≥2 min respectively for rest and stress imaging with high-dose protocol, the similar results was obtained (100%, 50/50) when acquisition time ≥4 min and ≥3 min respectively for rest and stress imaging with low-dose protocol. The quantitative perfusion parameters(summed rest scores, summed stress scores, total perfusion deficit) and left ventricle ejection fraction (LVEF) at shorter acquisition times (3 min/2 min, 4 min/3 min) were not significantly different from the results at the longer acquisition times (6 min/4 min, 8 min/6 min; t values: from -1.196 to 1.597, z values: from -1.963 to 1.945, all P>0.05). Those parameters at shorter and longer acquisition times showed strong correlations (all r>0.700, all P<0.001), and Bland-Altman analysis revealed good agreement between them.@*Conclusion@#The optimal acquisition time is 3 min/2 min for high-dose one-day rest/stress CZT-SPECT MPI, and 4 min/3 min for low-dose protocol, which can significantly shorten the MPI acquisition time, then reliable perfusion parameters and LVEF can be obtained under the premise of ensuring image quality, making it the better clinical applicability.

Research progress of 18F-Flurpiridaz PET myocardial perfusion imaging / 中华核医学与分子影像杂志

PET myocardial perfusion imaging (MPI) is increasingly used in non-invasive detection and evaluation of coronary artery disease (CAD). However, the wide application of common PET MPI agents (15O-H2O, 13N-NH3·H2O, 82Rb) in clinic is limited by their inherent shortcomings. The development of 18F-Flurpiridaz has opened up a new field of positron blood flow imaging agents. Preliminary results of pre-clinical and clinical trials showed that 18F-Flurpiridaz has important properties (high myocardial uptake, high resolution of perfusion defect, slow myocardial clearance, stable target/non-target ratio, and the ability of quantitative myocardial flow analysis) as an ideal PET MPI agent, so it has a good clinical application prospect. In this paper, the present application and progress of 18F-Flurpiridaz PET MPI are reviewed.