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Objective:To investigate the effect of mid-ventricular obstruction (MVO) on left ventricular systolic function in patients with hypertrophic cardiomyopathy(HCM) by four-dimensional automatic left ventricular quantitation technology(4D Auto LVQ).Methods:Fifty-seven hypertrophic obstructive cardiomyopathy patients were selected from December 2020 to October 2022 in the First Affiliated Hospital of Zhengzhou University. According to the presence of MVO, HCM patients were divided into two groups: HCM 1 group, HCM without MVO ( n=34); HCM 2 group, HCM with MVO ( n=23). In addition, 25 healthy subjects in the same period were selected as the control group. Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including left ventricular longitudinal strain (GLS), circumferential strain (GCS), area strain (GAS), radial strain (GRS), segmental longitudinal strain (SLS) and area strain (SAS). The differences of these parameters among the three groups were compared. Results:①Compared with the control group, the thickness of the maximum basal segment of interventricular septum, the thickness of the middle segment of the maximum interventricular septum, the thickness of the apical segment of the interventricular septum, the thickness of the left ventricular posterior wall and left atrium diameter were significantly increased. Six-minute walk distance and the left ventricular end-diastolic diameter was decreased in the two groups of HCM(all P<0.05). Left ventricular outflow tract gradients in HCM 1 group was higher than HCM 2 group( P<0.05), but there was no significant difference in left ventricular ejection fraction among the three groups( P>0.05). There was significant difference in the incidence of left ventricular apical aneurysm among the three groups( P<0.05). ②Compared with the control group, the GLS in both HCM groups was lower, and it was lower in the HCM 2 group than in the HCM 1 group(all P<0.05) the GRS and GAS in both HCM groups were lower than in the control group ( P<0.05), and there was no significant difference between the two groups of HCM, and there was no significant difference in GCS among the three groups(all P>0.05). ③Compared with the control group, the SLS of basal segment, middle segment, apical cap, posterior septum, inferior wall and lateral wall in HCM group were significantly lower than those in control group. The SLS of apical segment of posterior septum, anterior septum, anterior wall, posterior wall, inferior wall and apical segment of posterior septum, lateral wall and inferior wall in HCM 2 group were significantly lower than HCM 1 group(all P<0.05), but there was no significant difference in SLS of posterior septum, anterior septum, anterior wall, lateral wall and inferior wall between the two groups(all P>0.05). ④Compared with the control group, the SAS of posterior septal basal segment, middle segment, anterior septal middle segment, anterior wall basal segment, middle segment, apical segment, lateral wall basal segment, middle segment, apical segment, posterior wall basal segment, middle segment, inferior wall basal segment, middle segment and apical cap in HCM groups were significantly lower than the control group(all P<0.05), but there was no significant difference in SAS between the two groups of HCM( P>0.05). Conclusions:4D Auto LVQ can quantitatively evaluate the damage of MVO on the left ventricular systolic function in patients with HCM, especially for the evaluation of local myocardial function damage in the medial segment and apical segment.
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Objective:To explore the application value of four-dimensional automatic left ventricular quantitation(4D Auto LVQ) technology, in evaluating the myocardial mechanics in patients with different risk stratifications of hypertrophic cardiomyopathy(HCM).Methods:A total of 88 HCM patients and 20 healthy volunteers were selected from February 2020 to February 2022 in the First Affiliated Hospital of Zhengzhou University. According to the HCM Risk-SCD score, HCM patients were divided into 3 groups: low-risk group( n=49), intermediate-risk group( n=21), and high-risk group( n=18). Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including global longitudinal strain(GLS) , global circumferential strain(GCS), global area strain(GAS), global radial strain(GRS), twist and torsion. The differences in these parameters among the four groups were compared. The predictive values of conventional ultrasound parameters and myocardial mechanical parameters in patients with intermediate- and high-risk HCM patients were analyzed by ROC curve. Results:①Left ventricular end-diastolic diameter, left ventricular end-diastolic volume, left ventricular end-systolic volume, and peak systolic velocity of mitral annulus in the low-, intermediate-, and high-risk groups were lower than those in the control group while left ventricular maximal wall thickness(LVMWT) and early diastolic peak velocity of mitral value orifice/early diastolic peak velocity of mitral annulus(E/e′) were higher, left atrial diameter(LAD) and left ventricular outflow tract gradients(LVOTG) in the intermediate- and high-risk groups were higher than the low-risk group(all P<0.05). ②Compared with the control group, the GLS of HCM patients was lower, and the GLS of the intermediate- and high-risk groups was lower than the low-risk group. GCS and GRS in the intermediate- and high-risk groups were lower than those in the low-risk group. GAS in the high-risk group was lower than the low-risk and the control group, but higher than the intermediate-risk group(all P<0.05). Compared with the control group, the twist and torsion in the intermediate- and high-risk groups were higher, but lower than the low-risk group, and the differences were statistically significant(all P<0.05). ③The ROC results showed that the area under the curve(AUC) of the model containing conventional ultrasound parameters(LVWMT, LAD, and LVOTG) for predicting intermediate- and high-risk HCM patients was 0.811, with a sensitivity of 0.769 and a specificity of 0.755. The AUC of the conventional ultrasound parameters combined with myocardial mechanical parameters was 0.904, as the sensitivity was 0.667 and the specificity was 0.980. Conclusions:4D Auto LVQ can evaluate the mechanical characteristics of LV myocardium in HCM patients with different risk stratifications. Myocardial mechanical parameters combined with conventional ultrasound parameters can improve the diagnostic performance of patients with intermediate- and high-risk HCM.
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Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.
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【Objective】 To screen the sterilizing-grade filters applicable for production of human coagulation factor Ⅷ/von Willebrand factor complex(FⅧ/VWF)and study the sterilization filtration process. 【Methods】 Four sterilizing-grade filters for FⅧ/VWF were evaluated through indicators such as filtration capacity, filtration flux, recovery rate of FⅧ activity, recovery rate of VWF activity, recovery rate of VWF antigen, recovery rate of protein and VWF molecular distribution. The sterilizing-grade filter with the best filtration performance was selected for further study. The study was designed by general full-factor design to determine the appropriate filitered protein concentration and filitered speed range through evaluating the total filtered protein amount, recovery rate of protein and filtration efficiency, and then the process operation parameters was determined. 【Results】 The filtration flux of Sartobran P, Sartopore 2 XLG, Sartopore Platinum and Sartopore 2 XLI were 1.71±0.01, 1.80±0.01, 1.34±0.01, and 1.81±0.04 L·(m2)-1·min-1, respectively; the recovery rates (%) of FⅧ activity were 97.09±2.82, 99.22±0.99, 96.87±1.85 and 93.76±1.21, respectively; the recovery rates (%) of VWF activity were 98.12±1.42, 99.95±1.85, 94.80±1.62 and 92.09±1.67, respectively. Between Sartopore 2 XLG and Sartobran P, the difference of filtration flux (P<0.001) was statistically significant; between Sartopore 2 XLG and Sartopore Platinum, the differences of the filtration flux (P<0.001) and VWF potency recovery rate (P<0.05) were statistically significant; between Sartopore 2 XLG and Sartopore 2 XLI, the differences of FⅧ potency recovery rate (P<0.01) and VWF potency recovery rate (P<0.01) were statistically significant. The optimal process operating space of Sartopore 2 XLG was protein concentration of 0.45-0.58 mg/mL, and filtration rate of 1.48-2.95 L·(m2)-1·min-1. 【Conclusion】 Sartopore 2 XLG is the most suitable filter for the production of FⅧ/VWF and the DoE test proves that it has good process operation space.