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How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
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Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Neoplasm, Residual/pathology , Biomarkers, Tumor/genetics , Computational BiologyABSTRACT
Objective:To investigate the clinical efficacy and safety of intravenous thrombolysis with different doses of alteplase in the treatment of acute cerebral infarction in older adult patients.Methods:A total of 65 older adult patients with acute cerebral infarction (onset within 4.5 hours, age ≥ 75 years) who underwent intravenous thrombolysis in Wenzhou Central Hospital from February 2021 to February 2022 were included in this study. They were randomly assigned to undergo intravenous thrombolysis with either low dose alteplase (0.6 mg/kg, low dose group, n = 32) or standard dose alteplase (0.9 mg/kg, standard dose group, n = 33). The National Institutes of Health Neurological Stroke Scale score before and 24 and 48 hours after treatment, modified Rankin scale score before and 7, 14 and 90 days after treatment, serum C-reactive protein (CRP), neuron-specific enolase (NSE) and tumor necrosis factor-α (TNF-α) levels before and 24 hours after treatment, 24-hour incidence of intracranial hemorrhage, 24-hour incidence of symptomatic intracranial hemorrhage, and 90-day mortality were compared between the two groups. Results:Compared with before treatment, the National Institutes of Health Neurological Stroke Scale scores in each group were significantly decreased at 24 and 48 hours after treatment (low dose group, t24 h = 6.78, t48 h = 7.86; standard dose group: t24 h = 8.09, t48 h = 10.13, all P < 0.001). Compared with before treatment, the modified Rankin scale score in each group was significantly decreased at 7, 14 and 90 days after treatment (low-dose group: t7 d = 5.19, t14 d = 8.47, t90 d = 9.85; standard dose group: t7 d = 6.83, t14 d = 7.74, t90 d = 13.66, all P < 0.001). At 24 hours after treatment, serum levels of CRP, NSE, TNF-α in each group were significantly decreased (low-dose group: tCRP = 5.13 , tNSE = 4.22, tTNF-α = 34.29; standard dose group: tCRP = 4.87, tNSE = 5.53, tTNF-α = 31.98, all P < 0.001). At each time point after treatment, there were no significant differences in these indices between the two groups (all P > 0.05). The 24-hour incidence of intracranial hemorrhage in the low dose group was significantly lower than that in the standard dose group ( χ2 = 4.58, P = 0.032). There were no significant differences in incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (all P > 0.05). Conclusion:Intravenous thrombolysis with low dose alteplase (0.6 mg/kg) for the treatment of acute cerebral infarction in older adult patients exhibits equivalent clinical efficacy to that with standard dose alteplase (0.9 mg/kg), and the former is much safer than the latter.
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Objective To investigate w hether the iterative reconstruction (iDose 4 ) technique improves imaging quality of the low-radiation-dose w hole brain CT perfusion (CTP). Methods Thirty-five consecutive patients w ith clinical y suspected ischemic stroke w ere col ected. Bril iance 256 iCT w as used to perform low-radiation-dose w hole brain CTP, and the filtered back projection (FBP) and iDose 4 algorithm w ere used to conduct image reconstruction. The noise and signal to noise ratio of the 2 kinds of reconstruction algorithms, as w el as the imaging quality of each parameter map w ere compared. Results The effective dose of the w hole brain CTP w as 2.2 mSv. Compared w ith FBP, the noise of each region of interest in the iDose4 Tmax map was decreased significantly ( P<0.05) and the signal to noise ratio was increased significantly (P<0.05). The imaging quality scores (median, interquartile range) reconstructed by FPB group w ere significantly low er than by iDose 4 for cerebral blood flow (CBF) map ( 5.00 [3.00-6.00]vs. 6.00 [5.00-6.00]; Z= -2.784, P=0.005), cerebral blood volume (CBV) map ( 6.00 [5.00-6.00] vs. 6.00 [6.00-7.00]; Z= -3.674, P<0.001), and mean transit time (MTT) map (4.00 [3.00-5.00] vs. 5.00 [4.00-6.00]; Z=3.394, P=0.001). The proportions of the poor quality in CBF map ( 34.3%vs. 11.4%;χ2 =7.036, P=0.030), CBV map (11.4%vs.2.9%; χ2 =7.485, P=0.024 ) and MTT map (28.6%vs.11.4%;χ2 =5.318, P=0.070) reconstructed by FBP w ere significantly higher than by iDose 4 . Conclusions The iDose4 technique may improve imaging quality of low er-radiation-dose CTP.
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Objective To investigate the effect evaluation of spironolactone in the treatment of hypertensive heart disease by the real time 3-dimensional echocardiography .Methods Totally 104 patients with hypertensive heart disease were in the study from Jan 2011 to Jan 2012 of our department and divided into objective group and control group .Conventional treatments were put in all the patients and the spironolactone was used in objective group patients only .The results of ventricular morphology and function indexes were compared be -tween the two groups, and then investigate the relationship between cystatin C (CycC) and left ventricular remodeling index (LVRI) at the same time.Results There were significant differences in the comparison of ventricular morphology and function indexes .The left ventric-ular end-diastolic volume(LVEDV), left ventricular end systolic volume (LVESV) and left ventricular ejection fraction (LVEF) of ob-jective group were more advantageous than flowse of control group for prognosis .The same results were observed in the comparison of Cys C and LVRI.Moreover, Cyc C and LVRI had certain correlation in the study .Conclusion The spironolactone can play a positive role in the treatment for the patients with hypertensive heart disease .In the meantime, the RT-3DE is a good evaluation method for the develop-ment of ventricular morphology and function .
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Objective To investigate the influence of electroacupuncturing Neiguan points on mitochondrial Ca2+release and cardiomyocyte apoptosis of diabetic cardiomyopathy in rats. Methods 30 Wistar rats were randomly divided into a control group, a model group and a treatment group(10 in each group). In the treatment group, after eight weeks electroacupuncture Neiguan point treating diabetic cardiomyopathy in rats, the myocardium was quickly removed,mitochondrial was extracted,dual-beam UV spectrophotometer was adopted to detecting Ca2+transportation by testing Ca2+indicator A Ⅲ absorbance, and Cardiomyocyte apoptosis was evaluated by terminal-deoxynucleotidyl transferase mediated deoxy-UTP nick end labeling (TUNEL). Results Ca2+ indicator A Ⅲ absorbance detection(0.051±0.014) and cardiomyocyte apoptosis(0.49±0.36)were more depressed in the treatment group than in the model group[(0.077±0.025), (0.53±0.04)], there were significantly different(P<0.05) Conclusion Effect of Electroacupuncturing Neiguan points decreased myocardial apoptosis index in rats with diabetic cardiomyopathy, which may be related to the reduction of mitochondrial Ca2+influx.
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Forty cases of type Ⅱ diabetes mellitus were treated by puncturing point Neiguan (PC 6), and the effect on their cardiac vegetative nerve functions were observed at 20 min, 40 min and 60 min after acupuncture respectively. The findings showed that all heart rate variables improved remarkably at the three time periods after acupuncture treatment, with significant differences (P＜0.01); but there was no significant difference in the curative effects among the three time periods.
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Objectives To investigate the clinic value of 99 Tc-MDP in the diagnosis of rheumatoid arthritis(RA).Methods The whole body bone imaging of 99 Tc-MDP were performed in 31 patients with RA and 20 controls with other arthritis(AR group) and 19 normal controls.X-ray,rheumatoid factor(RF),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),joint tender index and joint swollen index were detected in RA patients.Results Abnormal bone images were observed in 29 out of 31 patients, with a 93.5 % of coincidence in RA group, 80% and 10.5% of in AR group and normal group. 201 out of 226 (88.9%) patients with joint symptoms showed abnormal bone images. 95% abnormal bone image rate and 20% abnormal X ray rate were found in 20 early RA patients. The joint radiopharmaceutical uptake score correlated positively with JTI, JSI, CRP and ESR. Conclusions 99m Tc MDP bone imaging is a sensitive, functional, noninvasive but unspecific method in detecting RA. And in combination with clinical symptoms, signs and serological changes, it is of value to the diagnosis of early RA.