1.Effects of isorhamnetin on the development of gastric cancer by up-regulating SLC25A25-AS1
Yang ZHANG ; Jing WANG ; Lisha NA ; Aoran ZENG ; Bowen PANG ; Yulin LIU
China Pharmacy 2025;36(8):932-938
OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1(SLC25A25-AS1). METHODS Using BALB/c nude mice as the subjects, the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin (20 and 40 mg/kg) on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group, isorhamnetin group (70 μmol/L, similarly hereinafter), isorhamnetin+knocking down negative control group, isorhamnetin+knocking down SLC25A25-AS1 group, isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability, apoptosis, migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p (miR-212-3p) and SLC25A25-AS1, as well as phosphatase and tensin homologue deleted on chromosome 10 (PTEN), the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p, PTEN mRNA, and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group, tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly, and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group (P<0.05). miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group, the cell viability (intervened for 24, 48 h), migration number, invasion number and miR-212-3p expression of cells in the isorhamnetin group, isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated, while the apoptosis rate, mRNA and protein expressions of PTEN were significantly increased or up-regulated (P<0.05). Compared with isorhamnetin group and isorhamnetin+knocking down negative control group, the cell viability, migration number, invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated, while the apoptosis rate, mRNA and protein expressions of PTEN were significantly reduced or down-regulated (P< 0.05). Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group, the cell viability, migration number, invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated, while the apoptosis rate, PTEN mRNA and protein expressions were significantly increased or up-regulated (P<0.05). CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1, down-regulating miR-212-3p, and up-regulating the expression of PTEN, which is a downstream target of miR-212-3p.
2.Effects and mechanism of limonin on renal lesion,glucose metabolism,inflammation and oxidative stress in gestational diabetic rats
Na QU ; Kai ZHANG ; Lisha NA ; Ying CUI
China Pharmacy 2025;36(9):1082-1086
OBJECTIVE To explore the effects of limonin on renal lesions, glucose metabolism, inflammation, and oxidative stress in gestational diabetic rats and its possible mechanisms. METHODS The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group (intragastrical administration and tail vein injection of equal volume of normal saline), limonin low-, medium-, and high-dose groups (intragastrical administration of limonin, at doses of 12.5, 25.0 and 50.0 mg/kg, and equal volume of normal saline into the tail vein), and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun N-terminal kinase (JNK) activator Anisomycin 2 mg/kg ], with 12 rats in each group. In addition, 12 pregnant rats were selected as the control group (intragastrical administration and tail vein injection of equal volume of normal saline). They were given relevant medicine, once a day, for 14 consecutive days. After the last administration, fasting blood glucose (FBG), the levels of fasting insulin (FINS), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in the serum were detected; the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood urea nitrogen (BUN), and creatinine (Cr) in the renal tissue were detected; the pathological changes of renal tissue were observed; the expressions of proteins related to the JNK/nuclear factor-κB (NF-κB) signaling pathway in the renal tissue were detected. RESULTS Compared with control group, in model group, the rats showed pathological injuries in the kidney tissue, such as glomerular atrophy, edema of renal tubular epithelial cells; the levels of FBG, FINS, IL-1β, IL-6, TNF-α, MDA, BUN and Cr, HOMA-IR, as well as the phosphorylation levels of JNK and NF-κB 0453-6602005。E-mail:mcvi45@163.com p65 proteins were increased significantly (P<0.05), while the levels of SOD and GSH-Px were decreased significantly (P<0.05). Compared with model group, in each dose group of limonin, the degree of renal tissue lesions in rats was alleviated, and the above-mentioned indicators were significantly improved (P<0.05), showing an obvious dose-effect relationship (P<0.05). Compared with high-dose limonin group, in the combination group, the degree of renal tissue lesions in rats was relatively aggravated, and the changes in the above-mentioned indicators were significantly reversed (P<0.05). CONCLUSIONS Limonin has a certain improvement effect on renal lesions, glucose metabolism, inflammation, and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.
3.Application of Two-Dimensional Speckle Tracking Technique to Assess Right Heart Function and Right Ventricle-Pulmonary Artery Coupling in Rheumatoid Arthritis
Lu PAN ; Xuan HUANG ; Tingting WANG ; Yanping XU ; Jingjing YE ; Wei CAO ; Lisha NA
Chinese Journal of Medical Imaging 2024;32(2):130-135
Purpose To assess the right atrial and right ventricular strain and right ventricular-pulmonary artery(RV-PA)coupling in rheumatoid arthritis(RA)via two-dimensional speckle tracking.Materials and Methods Sixty patients with RA in the General Hospital of Ningxia Medical University from June 2020 to June 2022 were prospectively selected,and all RA patients were divided into three groups according to pulmonary artery systolic pressure(PASP),including group A(n=20 cases)with PASP<33 mmHg,group B(n=20 cases)with PASP 33-39 mmHg as mild ePH,and group C(n=20 cases)PASP≥40 mmHg,twenty healthy individuals were selected as the control group.All subjects underwent transthoracic echocardiography,and right atrial and right ventricular systolic function was assessed by two-dimensional speckle tracking technique,and RV-PA coupling was assessed noninvasively by right ventricular free wall strain/pulmonary artery systolic pressure(RV FWS/PASP),pulmonary function was analyzed by pulmonary function instruments.Spearman's analysis was used to analyze the correlation between right heart function and RV-PA coupling to pulmonary diffusion function.Results There were statistical differences in right ventricular base diameter,right atrium diameter,tricuspid annular plane systolic excursion,inferior vena cava diameter,PASP,right ventricular global strain,RV FWS,right atrium strain-reservoi,right atrium strain-conduit(S-CD),RV FWS/PASP among the four groups(F/H=2.369-74.880,all P<0.05).Right atrium strain-reservoi[(36.0±7.9)%vs.(30.9±7.8)%],right atrium S-CD[(19.9±6.9)%vs.(15.3±4.7)%]and RV FWS/PASP(0.96±0.19 vs.0.56±0.13)in group B were significantly lower than those of group A(t=2.040,2.262,7.704,all P<0.05).There was a good correlation between diffusing capacity of the lung for carbon monoxide single-breathmethod and right ventricular global strain,RV FWS,right atrium S-CD and RV FWS/PASP in RA patients(r=0.392,0.472,0.431,0.572,all P<0.05).Conclusion The more increases of pulmonary artery pressures,the more decreases of right heart function in RA patients,and the more uncoupling in RV-PA.Right heart dysfunction and right ventricle-pulmonary artery uncoupling have developed in RA patients with PASP 33-39 mmHg,with association of pulmonary diffusion dysfunction.
4.Left atrial strain combined with electrocardiogram P-wave parameters for predicting recurrence of paroxysmal atrial fibrillation after pulmonary vein isolation
Xuan HUANG ; Lu PAN ; Lisha NA ; Li ZHOU ; Jingjing YE ; Tingting WANG
Chinese Journal of Interventional Imaging and Therapy 2024;21(7):385-389
Objective To observe the value of left atrial strain combined with electrocardiogram(ECG)P-wave parameters for predicting recurrence of paroxysmal atrial fibrillation(PAF)after pulmonary vein isolation(PVI)using radiofrequency catheter.Methods Totally 88 PAF patients who planned to receive the first PVI were prospectively enrolled and divided into recurrence group(n=30)and non-recurrence group(n=58)according to results of ECG within 6 months after PVI.The patients'basic data,the transthoracic echocardiography(TTE)parameters,including left atrial reservoir strain(LASr),left atrial conduct strain(LAScd)and left atrial contraction strain(LASct),as well as ECG parameters including P-wave duration,PR interval and P/PR(the ratio of P-wave duration to PR interval)were compared between groups.Multivariate logistic regression analysis was performed of parameters being statistically different between groups to screen independent predictors for recurrence of PAF after PVI.The receiver operating characteristic curve and the area under the curve(AUC)were used to evaluate the predicting efficacy of individual independent predictors alone and their combination,and DeLong test was used for comparison.Results No significant difference of patients'basic data was found between groups(all P>0.05).Compared with those in non-recurrence group,LASr and LAScd decreased while P/PR increased in recurrent group(all P<0.05).LASr(OR=0.805),LAScd(OR=0.850)and P/PR(OR=1.119)were all independent predictors for recurrence of PAF after PVI(all P<0.05),with AUC of 0.755,0.643 and 0.771,respectively,all lower than their combination(AUC=0.869)(all P<0.05).Conclusion TTE and ECG parameters could be used to predict recurrence of PAF after PVI.The predicting efficacy of the combination of LASr,LAScd and P/PR was better than that of each alone.
5.Research Progress on Mechanobiology of Mitochondria
Jing NA ; Lisha ZHENG ; Yubo FAN
Journal of Medical Biomechanics 2024;39(3):545-551
Mitochondria are highly dynamic organelles,which not only provide energy and material basis for cells,but also regulate cell proliferation,migration,differentiation,and apoptosis.Cell fate is regulated by mechanical cues from the microenvironment.Recent studies have shown that energy metabolism is regulated by mechanical cues.Mitochondria can act as mechanical sensors and hubs that connect the mechanics and metabolism to regulate cell fate.A deep understanding of the relationship between the mechanical microenvironment and mitochondrial metabolism provides sufficient guidance for promoting tissue regeneration and treating diseases.In this review,the progression in mitochondrial mechanobiology is mainly introduced and its potential applications in tissue regeneration and disease treatment are explored.
6.Impacts of hirudin on neuronal apoptosis and inflammatory response in rats with cerebral infarction by regulating RhoA/ROCK signaling pathway
Lisha NA ; Na QU ; Xue YU ; Zhaosheng LI
Chinese Journal of Immunology 2024;40(8):1640-1645
Objective:To investigate the impacts of hirudin(HRD)on neuronal apoptosis and inflammatory response in rats with cerebral infarction by regulating Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil-forming protein kinase(ROCK)signaling pathway.Methods:SD rats were grouped into Ct group,Model group,low-dose HRD group(HRD-L group,13.33 mg/kg),high-dose HRD group(HRD-H group,26.66 mg/kg),positive control Nimodipine group(NMDP group,40 mg/kg),U-46619(RhoA agonist,0.03 mg/kg)group and HRD-H+U-46619 group(26.66 mg/kg+0.03 mg/kg),with 24 rats per group.Except for the Ct group,rats in other groups constructed the rat model of cerebral infarction by the modified suture method.The rats in the Ct group only exposed the blood vessels without incision and suture insertion.After 1 hour of successful modeling,drug treatment was car-ried out,once a day for 4 weeks.Zea-Longa method was applied to evaluate the neurological function of rats;dry and wet weight meth-od was applied to detect the water content of rat brain tissue;2,3,5-triphenyltetrazolium chloride(TTC)staining was applied to deter-mine the volume of cerebral infarction in rats;TUNEL staining was applied to detect the apoptosis of neurons in the CA1 region of the hippocampus of rats.The levels of TNF-α,IL-1β and IL-6 in rat hippocampus were detected by ELISA;the protein expressions of cleaved-Caspase-3 Cleaved-Caspase-3,Bcl-2-associated X protein(Bax),RhoA,ROCK1 and ROCK2 in rat hippocampus were de-tected by Western blot.Results:Compared with Ct group,the neurological function scores,brain tissue water content,cerebral in-farction volume percentage,neuron apoptosis rate,levels of TNF-α,IL-1β,IL-6,the protein expressions of Cleaved-Caspase-3,Bax,RhoA,ROCK1 and ROCK2 increased in the Model group(P<0.05).Compared with Model group,the neurological function scores,brain tissue water content,cerebral infarction volume percentage,neuron apoptosis rate,levels of TNF-α,IL-1β,IL-6,the protein expressions of Cleaved-Caspase-3,Bax,RhoA,ROCK1 and ROCK2 decreased in HRD-L group,HRD-H group,NMDP group,however,the corresponding index changes in the U-46619 group showed an opposite trend(P<0.05).Compared with HRD-H group,the neurological function scores,brain tissue water content,cerebral infarction volume percentage,neuron apoptosis rate,levels of TNF-α,IL-1β,IL-6,the protein expressions of Cleaved-Caspase-3,Bax,RhoA,ROCK1 and ROCK2 were increased in the HRD-H+U-46619 group(P<0.05).Conclusion:HRD may inhibit neuronal apoptosis and inflammatory response in rats with cerebral infarction by inhibiting RhoA/ROCK signaling pathway.
7.Study on the effect and mechanism of isorhyncophylline on cognitive impairment in rats with acute cerebral infarction
Lisha NA ; Yichao CHEN ; Kai ZHANG ; Zhaosheng LI
Chinese Journal of Cerebrovascular Diseases 2024;21(7):444-454
Objective To investigate the effect of isorhyncophylline on cognitive impairment in rats with acute cerebral infarction and its corresponding mechanism.Methods SD rats were separated into acute cerebral infarction group,sham operation group,low-dose isorhyncophylline group,high-dose isorhyncophylline group,nimodipine group,and high-dose isorhyncophylline+ADU-S100 group,with 24 rates for each group.Except the sham operation group,the rats in other groups were treated with filament model to construct the model of acute cerebral infarction.In the sham operation group,only the right external carotid artery,common carotid artery and internal carotid artery were exposed,and the filament was not inserted.After successful modeling,the medication was administered once a day for 2 weeks.After the modeling was successful,the rats in the low dose group and the high dose group were given 5 mg/kg and 20 mg/kg respectively,and the same amount of isotonic saline was injected intraperitoneally.Nimodipine group rats were given 30 mg/kg nimodipine by intragastric administration,and the same amount of isotonic saline was also injected intraperitoneally.The rats in high dose isorhyncophylline+ADU-S 100 group were given 20 mg/kg isorhyncophylline by intragastric administration and 20 mg/kg ADU-S 100 intraperitoneally.Rats in sham operation group and acute cerebral infarction group were injected with 10 ml/kg isotonic saline by intragastric administration and intraperitoneal injection.The medication was administered once a day for 2 weeks.The Zela-Longa neurological function score was evaluated in all the rats 24 h after the final medication,and then Morris water maze test was conducted and their escape latency and the number of stays in the original platform quadrant were recorded.The levels of interleukin 6(IL-6)and tumor necrosis factor(TNF)α in serum were detected by enzyme-linked immunosorbent assay(ELISA).The water content of brain tissue was detected in each group.The volume of cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Evans blue was applied to detect blood-brain barrier permeability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of ZO-1 and occludin messenger RNA(mRNA)in brain tissue of each group.The expression of STING,phosphorylated tank-bound kinase 1(p-TBK1)and phosphorylated interferon regulatory factor 3(p-IRF3)in rat brain tissues was detected by western blot and compared between groups.Results Compared with sham operation group,the neurological function score([2.96±0.32]vs.0),brain tissue water content([86.9±3.2]%vs.[71.8±3.1]%),serum TNF-a([86.7±3.5]ng/L vs.[35.6±1.7]ng/L)and IL-6([167.8±6.1]ng/L vs.[50.2±2.2]ng/L)levels,cerebral infarction volume([28.6±1.3]mm3 vs.0 mm3),evans blue content([1.57±0.13]g/Lvs.[0.96±0.08]g/L),STING([1.83±0.16]vs.[0.86±0.08]),p-TBK1([0.89±0.07]vs.[0.41±0.03]),and p-IRF3([0.67±0.05]vs.[0.13±0.01])protein expression in brain tissue were increased,expression of ZO-1([0.45±0.04]vs.[1.00±0.00])and occludin mRNA([0.23±0.02]vs.[1.00±0.00])in brain tissue were decreased,the escape latency was prolonged([33.6±1.6]s vs.[12.3±0.5]s),and the number of stays in the original platform quadrant([5.9±0.2]times vs.[15.7±0.4]times)was decreased in the acute cerebral infarction group 24 h after last medication administration(all P<0.05).(2)Compared with acute cerebral infarction group,the neurological function score([2.37±0.21],[1.14±0.17],[1.18±0.13]vs.[2.96±0.32]),brain tissue water content([81.8±3.0]%,[74.9±3.0]%,[74.3±2.9]%vs.[86.9±3.2]%),serum TNF-α([71.1±1.4]ng/L,[43.4±2.0]ng/L,[41.5±1.9]ng/L vs.[86.7±3.5]ng/L)and IL-6([129.8±5.4]ng/L,[81.2±3.8]ng/L,[80.0±3.6]ng/L vs.[167.8±6.1]ng/L)levels,cerebral infarction volume([21.7±1.0]mm3,[10.5±0.5]mm3,[10.7±0.5]mm3 vs.[28.6±1.3]mm3),evans blue content([1.39±0.12]g/L,[1.16±0.10]g/L,[1.18±0.19]g/L vs.[1.57±0.13]g/L),STING([1.50±0.14],[1.02±0.11],[1.01±0.09]vs.[1.83±0.16]),p-TBK1([0.75±0.05],[0.54±0.04],[0.52±0.05]vs.[0.89±0.07]),and p-IRF3([0.51±0.05],[0.25±0.02],[0.27±0.02]vs.[0.67±0.05])protein expression in brain tissue were decreased,expression of ZO-1([0.58±0.05],[0.87±0.07],[0.89±0.09]vs.[0.45±0.04])and occludin mRNA([0.36±0.03],[0.71±0.06],[0.69±0.05]vs.[0.23±0.02])in brain tissue were increased,the escape latency were shortened([28.6±1.0]s,[16.5±0.7]s,[16.4±0.7]s vs.[33.6±1.6]s),and the number of stays in the original platform quadrant([8.2±0.3]times,[12.8±0.5]times,[12.9±0.5]times vs.[5.9±0.2]times)were increased in the low-dose isorhyncophylline group,high-dose isorhyncophylline group,and nimodipine group(all P<0.05).(3)Compared with high-dose isorhyncophylline group,the neurological function score([2.12±0.14]vs.[1.14±0.17]),brain tissue water content([78.7±3.2]%vs.[74.9±3.0]%),serum TNF-a([59.7±2.1]ng/L vs.[43.4±2.0]ng/L)and IL-6([118.9±4.6]ng/L vs.[81.2±3.8]ng/L)levels,cerebral infarction volume([16.6±0.4]mm3 vs.[10.5±0.5]mm3),evans blue content([1.36±0.10]g/L vs.[1.16±0.10]g/L),and STING([1.37±0.12]vs.[1.02±0.11]),p-TBK1([0.67±0.05]vs.[0.54±0.04]),and p-IRF3([0.39±0.03]vs.[0.25±0.02])protein expression in brain tissue were increased,expression of ZO-1([0.63±0.05]vs.[0.87±0.07])and occludin mRNA([0.46±0.05]vs.[0.71±0.06])in brain tissue were decreased,the escape latency was prolonged([23.4±1.0]svs.[16.5±0.7]s),and the number of stays in the original platform quadrant([9.6±0.3]times vs.[12.8±0.5]times)was decreased in the isorhyncophylline high-dose+ADU-S100 group(all P<0.05).Conclusion Isorhyncophylline can inhibit inflammation,reduce blood-brain barrier damage,reduce cerebral edema,and improve cognitive impairment in rats with acute cerebral infarction,and the mechanism of which may be related to the inhibition of STING/TBK1/IRF3 pathway.
8.Clinical application of non-invasive myocardial work imaging in ST-segment elevation myocardial infarction patients with left ventricular remodeling after percutaneous coronary intervention
Xue YANG ; Quanrui MA ; Yanping XU ; Ying WANG ; Wei CAO ; Guangzhi CONG ; Yu HAO ; Lisha NA
Chinese Journal of Ultrasonography 2023;32(6):493-500
Objective:To explore the application value of non-invasive myocardial work imaging in evaluating the cardiac function of ST-segment elevation myocardial infarction (STEMI) patients with left ventricular remodeling (LVR) after percutaneous coronary intervention (PCI).Methods:One hundred and twenty-six patients with STEMI undergoing PCI in General Hospital of Ningxia Medical University from December 2021 to September 2022 were prospectively collected and divided into left ventricular remodeling group (LVR group, 34 cases) and non left ventricular remodeling group (NLVR group, 92 cases) according to whether there was left ventricular remodeling 3 months after surgery. General data were collected. Routine echocardiography and noninvasive myocardial work imaging were performed before, 1 week, 1 month, and 3 months after surgery, the differences in the above parameters between the two groups were compared. Pearson correlation analysis was used to analyze the correlation between the indicators.Logistic regression analysis was used to determine the independent risk factors of left ventricular remodeling after STEMI, and a predictive model was obtained. The diagnostic value of the model was judged by ROC curve.Results:①General information comparison: There were statistically significant differences between the two groups in BMI, systolic blood pressure, diastolic blood pressure, average number of stents implanted, and history of hyperlipidemia (all P<0.05), but there was no significant difference in other data (all P>0.05). There was no statistically significant difference in two-dimensional transthoracic echocardiography (2D-TTE) parameters and non-invasive myocardial work (MW) parameters between the two groups before and 1 week after operation (both P>0.05). ②2D-TTE parameter comparison: LVESV and LVEDV at 3 months after PCI in the LVR group were significantly higher than those in the NLVR group, and LVEF and E/A were significantly lower than those in the NLVR group (all P<0.05); There were no significant differences in other indexes between the two groups by conventional echocardiography at 3 months after PCI(all P>0.05). ③Comparisons of noninvasive myocardial work parameters: GLS, GWE, GWI, GCW at 1 month and 3 months after PCI in the LVR group were significantly lower than those in the NLVR group, and GWW were significantly higher than those in the NLVR group ( P<0.001). ④Correlation analysis: GLS, GWE, GCW, GWI and LVEDV were negatively correlated at 1 month after operation ( r=-0.42, -0.38, -0.50, -0.53, all P<0.001), GWW was positively correlated with LVEDV ( r=0.45, P<0.001). ⑤Logistic regression analysis: GLS<17%, GCW<1 900 mmHg%, GWW>105 mmHg%, and GWE<90 mmHg% at 1 month after PCI were independent predictors for LVR in STEMI patients after PCI (all P<0.05). The predictive model was Logit (P)=0.692GLS+ 0.804GCW+ 0.972GWW+ 0.880GWE. The AUC of this model was 0.886, 95% CI=0.845-0.926, which was significantly higher than single index, the sensitivity was 0.86, and the specificity was 0.79. Conclusions:GLS, GWE, GWI, GCW are positively correlated with LVR, while GWW is negatively correlated with left ventricular remodeling. Noninvasive myocardial work parameters are independent risk factors for left ventricular remodeling in patients with STEMI after PCI surgery. This technique can be used to evaluate LVR and has great clinical application value.
9.Early identification of familial hypertrophic cardiomyopathy mutation gene carriers by constructing Nomogram prediction model based on parametric characteristics of two-dimensional transthoracic echocardiography and three-dimensional speckle tracking imaging
Yiquan DUAN ; Qingqing LIANG ; Yanping XU ; Jingjing YE ; Fang WANG ; Xuan HUANG ; Liming WANG ; Lisha NA
Chinese Journal of Ultrasonography 2023;32(9):773-781
Objective:To explore the characteristics of echocardiographic parameters among the many parameters of two-dimensional transthoracic echocardiography(2D-TTE) and three-dimensional speckle tracking imaging (3D-STI) that can be used for early identification of familial hypertrophic cardiomyopathy(FHCM) mutation gene carriers, and construct a Nomogram prediction model, in order to provide a diagnostic method for early identification of G+ P- patients for clinical practice.Methods:A total of 15 FHCM families admitted to the General Hospital of Ningxia Medical University from November 2017 to August 2022 were enrolled.Whole exome sequencing and Sanger sequencing technology were used for gene detection, among which 54 were G+ P- and 75 were G-P-. Stratified random sampling was used to divide the subjects into training set ( n=90) and test set ( n=39) according to the ratio of 7∶3. Philips iE33 ultrasonic diagnostic instrument and TomTec offline software were used to obtain relevant ultrasonic parameters. Lasso regression and Logistic regression were used to screen echocardiographic parameters and obtain independent risk factors for early prediction of G+ P-, based on which a Nomogram prediction model was established. Results:①Lasso-Logistic regression showed that global longitudinal strain(GLS) ( OR=1.739, 95% CI=1.305-2.316) and left ventricular outflow trac velocity time integral(LVOT-VTI) ( OR=1.358, 95% CI=1.072-1.722) could be used as independent risk factors for early prediction of G+ P-. ②The Nomogram prediction model was established based on the above indicators. After 1000 internal verifications of Bootstrap self-sampling, the C-indices of the training set and the test set were 0.885 (95% CI=0.816-0.954), 0.878 (95% CI=0.764-0.992), which had good internal consistency. ③The results of the calibration curve showed that the risk of G+ P- predicted by the Nomogram model was basically consistent with the actual risk (training set P=0.990, test set P=0.961); the clinical decision curve shows that under different threshold probabilities, using this prediction model to provide patients with clinical decision-making could bring benefits to patients. Conclusions:Echocardiographic parameters GLS and LVOT-VTI can be used as independent risk factors to predict FHCM mutation gene carriers. The Nomogram prediction model has good discrimination, goodness of fit and clinical benefit in identifying whether the family members of FHCM patients carry the mutation gene, and it can provide a new idea and evaluation method for the early identification of FHCM mutation gene carriers by echocardiography.
10.Study of the correlations between left ventricular twist and morphology and global systolic function by three-dimensional speckle tracking imaging in adult patients with hypertrophic cardiomyopathy
Mei JIA ; Qing LI ; Jingjing YE ; Liwen LIU ; Qian CHEN ; Lisha NA
Chinese Journal of Ultrasonography 2021;30(5):369-375
Objective:To evaluate the changes of left ventricular (LV) myocardial systolic strain and twist motion including global longitudinal strain(GLS), global circumferential strain(GCS), global radial strain(GRS), global area strain(GAS), LV basal segment rotation angle (Rotation-basal), LV apical segment rotation angle (Rotation-apical), LV twist angle (Twist), LV torsion(Torsion) by three-dimensional speckle tracking imaging(3D-STI) in adult patients with hypertrophic cardiomyopathy (HCM), and further to analyze the correlations between LV twist and its morphology and global systolic function.Methods:A total of 45 patients with HCM from the General Hospital of Ningxia Medical University from September 2017 to June 2019 were enrolled. In addition, 50 healthy subjects were recruited as a control group. Left atrial dimension(LAD), interventricular septal end-diastole dimension(IVSD), LV posterior wall end-diastole dimension (LVPWD), LV mass index(LVMI) and other parameters were respectively measured by conventional two-dimensional transthoracic echocardiography. LV end-diastole volume(EDV), LV end-systole volume(ESV), calculated stroke volume(SV) and LV ejection fraction (LVEF) were respectively measured by 3D transthoracic echocardiography. Full-volume 3D dynamic images were performed using matrix transducer X5-1. LV Rotation-basal, Rotation-apical, Twist and Torsion, GLS, GCS, GRS and GAS were respectively analyzed by off-line TomTec software. The differences of those parameters between the two groups were compared. The correlations between 3D-Torsion parameters and those parameters by two-dimensional echocardiography was further analyzed.Results:Compared with control group, LAD, IVSD, LVPWD and LVMI of HCM group were increased(all P<0.01), EDV, ESV, SV, LVEF and E/A were decreased(all P<0.01). Compared with control group, GLS, GCS and GRS of HCM group were decreased(all P<0.01). Rotation-basal, Rotation-apical, Twist and Torsion were increased(all P<0.01), and there was no significant difference of GAS between the two groups( P>0.05). In HCM group, IVSD was not correlated with Rotation-basal ( P>0.05), but negatively correlated with Rotation-apical, Twist and Torsion ( r=-0.327, -0.439, -0.374; all P<0.05); LVEF and LVMI were not correlated with Rotation-basal, Rotation-apical, Twist and Torsion (all P>0.05). Conclusions:①3D-STI can detect the earlier subtle changes of left ventricular three-dimensional systolic strain in HCM patients; ②LV three-dimensional Twist inereases considerably in HCM patients; ③LV Twist, Torsion and Rotation-apical are significantly decreased with the increase of IVSD in HCM patients; However, LVEF and LVMI are not significantly correlated with Rotation-basal, Rotation-apical, Twist and Torsion.

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