Quantification of left atrial strain in patients with idiopathic inflammatory myopathy using cardiovascular magnetic resonance feature tracking.

BACKGROUND: Left atrial (LA) dysfunction is involved in idiopathic inflammatory myopathy (IIM). Multiparametric cardiovascular magnetic resonance (CMR) strain imaging is a feasible and reproducible tool for examining global and regional LA functions, as well as left ventricular (LV) function in IIM patients. AIM: The aim of this study was to evaluate the feasibility and reproducibility of LA strain occurrence and strain rate for LA function assessment using CMR in IIM cases. MATERIALS AND METHODS: A total of 36 IIM and 42 healthy control cases were included. Baseline ventricular function was comparatively assessed in both groups. LA strain occurrence and strain rate were examined by cine cardiac magnetic resonance imaging [MRI] utilizing an in-house semiautomated technique. LA global function indexes were quantitated, including reservoir, conduit, and booster-pump functions. RESULTS: A total of 78 participants were enrolled in this study. There was no significant difference in left/right ventricular routine functions between IIM patients and control individuals (p>0.05); the same results (p>0.05) was also observed between patients with high hs-cTnI and normal. However, LV mass index had significant difference (p1=0.003, p2<0.01). Compared with IIM patients and control individuals, only total strain (εs) (p4=0.046) and passive strain (εe) (p4=0.002) showed significant difference, and in cases with high hs-cTnI and normal hs-cTnI, there are differences for εs (p3=0.012) and εe (p4=0.047). The strongest association was found between εe and LV ejection fraction (LVEF) (r=0.581, p<0.01). CONCLUSION: IIM cases have altered LA reservoir and conduit functions, and LA strain could reflect LA function.

[Three-dimensional analysis of maxillary dentition during molar distalization with clear aligners under different movement designs: an in vitro experiment].

Objective: To investigate the three-dimensional force in the maxillary dentition under different movement designs for molar distalization with clear aligners Methods: Three groups were designed: simultaneous movement group (simultaneous distalization of maxillary first and second molars), second molar movement group (distalization of maxillary second molars) and first molar movement group (distalization of maxillary first molars). Ten clear aligners were made in each group, and the displacement was designed to be 0.2 mm. A force sensing device was established to measure the three-dimensional force on the upper dentition with the clear aligner. The device contained a model of the maxillary dentition consisting of 14 teeth, each tooth connected to an individual sensor. After the clear aligner was fitted, the data of 14 sensors were collected and analyzed using computer analysis software. The moving teeth were taken as the target teeth, and the rest of the teeth were anchorage. The data of the three-dimensional force in the three groups in each tooth position were measured and compared. Results: The sagittal forces on the first and second molars in the simultaneous movement group were (5.61±0.94) and (5.81±1.08) N, respectively, which were significantly smaller than those of the target teeth in the same position in other groups (P<0.05). The second molars in the first molar movement group received a sagittal reaction force, which was (-6.73±1.99) N. The anterior teeth in the three groups were all subjected to sagittal reaction force, and the force value was in a range of (-3.33 to 0.46) N. In the coronal direction, the second premolars of the simultaneous movement group received the reaction force in the palatal direction, and the force value was (-2.17±1.06) N. The first molars in the second molar movement group were also subjected to palatal reaction force of (-1.99±0.70) N. The second molars and second premolars in the first molar movement group were also subjected to palatal reaction force, which were (-2.85±0.57) and (-1.85±0.74) N, respectively. Compared with the sagittal and coronal forces, the target teeth and anchorage teeth in the three groups were less stressed in the vertical direction. Conclusions: The first and second molars distalized simultaneously, the correction force in the sagittal direction was relatively small. When first molar was moved distally alone, a greater reaction force in the sagittal direction was exerted on the second molar. Buccal displacement of the adjacent anchorage teeth should be designed to counteract the palatal reaction force on the anchorage teeth as the molars moved distally.

Texture analysis applied in T1 maps and extracellular volume obtained using cardiac MRI in the diagnosis of hypertrophic cardiomyopathy and hypertensive heart disease compared with normal controls.

AIM: To assess the potential of texture analysis (TA) applied in T1 maps and extracellular volume (ECV) obtained using cardiac magnetic resonance (CMR) in the diagnosis of hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) compared with normal controls (NC). Strain parameters were analysed to compare with final TA models. MATERIALS AND METHODS: This retrospective study included 66 HCM patients, 39 HHD patients, and 41 NC. Step-wise dimension reduction and feature selection were performed by reproducibility, machine learning, collinearity, and multivariable regression analysis to select the texture features that enable diagnosis of and differentiation between HCM and HHD. Strain parameters were calculated by short-axis and three long-axis cine sequences. RESULTS: Independent features in T1 maps and ECV analysis allowed for the differentiation between patients (HCM and HHD) and NC. Of the best-calculated model, the areas under the receiver operating curve (AUCs) were as follows: 0.969 for T1 map and 0.964 for ECV. To distinguish HCM from HHD, two independent features were screened out for both T1 and ECV maps. The AUCs were as follows: 0.793 for T1 map and 0.894 for ECV. Radial, circumferential, and longitudinal strain parameters could differentiate patients from NC, but only longitudinal strain parameters was significantly different between HCM and HHD. CONCLUSIONS: Texture analysis of T1 maps and ECV shows high accuracy in differentiating hypertrophic myocardium from NC, and HCM from HHD. Strain parameters are able to demonstrate the difference between patients and NC, but were less impressive in differentiating HCM and HHD.

Biventricular tissue tracking demonstrating associations between left ventricular myocardial extracellular volume, pulmonary artery pressure, and reduced right ventricular ejection fraction in patients with systemic lupus erythematosus using cardiovascular MRI.

AIM: To investigate the feasibility and prognostic value of biventricular strain analysis for patients with systemic lupus erythematosus (SLE) and relationship to left ventricular (LV) myocardial fibrosis, pulmonary hypertension (PAH), and right ventricular (RV) ejection fraction (RVEF). MATERIALS AND METHODS: A total of 50 SLE patients (47 women; 34.4±12 years) and 15 controls (13 women; 32.9±8.6 years) were imaged via echocardiography and a 3 T magnetic resonance imaging (MRI). Pulmonary artery systolic pressure (sPAP) was assessed using echocardiography. Biventricular global circumferential strain (GCS), global longitudinal strain (GLS), global circumferential strain rate (GCSR), and global longitudinal strain rate (GLSR) as well as LV myocardial extracellular volume (ECV) were derived for each subject. RESULTS: Elevated LV ECV was significantly associated with LV GCS (beta -0.428, p=0.000), GLS (beta 0.404, p=0.000), GCSR (beta -0.350, p=0.006), GLSR (beta -0.445, p=0.000) and RV GCS (beta -0.373, p=0.000), and the presence of reduced RVEF was significantly associated with LV GCS (beta -0.338, p=0.002), GLS (beta -0.465, p=0.000) and RV GCS (beta -0.465, p=0.000). Raised sPAP was significantly associated with RV GLS (beta 0.445, p=0.000) and GCSR (beta -0.387, p=0.001). Moreover, there were significantly correlations between LV and RV strain and strain rate. CONCLUSIONS: Biventricular strain analysis may be a better prognostic tool for patients with SLE as it allows greater comprehensive analysis and more definitive treatment planning compared to separate assessment of LV or RV contractility.

[Expression and significance of c-fos in resistant cell line TU177/VCR of larynx squamous cell carcinoma].

Objective: To explore the effect of c-fos on multidrug resistance of laryngeal cancer TU177 cells. Method: Increasing drug concentration gradient is adopted to establish the stability of the laryngeal cancer drug resistance in cell line; RT-PCR and Western blot were used to detect difference of the c-fos between TU177 and TU177/VCR cells; plasmids with human c-fos knockdown or over expression were transfected into TU177/VCR and TU177 cells respectively, and the effects of different treatment on cell proliferation were investigated with MTT. Results: The drug resistance of TU177/VCR cells was 26.25-fold in vincristine (VCR), 7.33-fold in Paclitaxel (TAX), 2.41 in cisplatin (DDP), and 5.50 in 5-fluorouracil (5-FU), comparing with TU177( P<0.05). The TU177/VCR cells had significantly higher c-fos expression compared to TU177 cells( P<0.05). The results showed that the IC(50) values of 5-FU for the NC group and c-fos shRNA group were (306.2±6.3)µmol/L and (81.3±3.9)µmol/L, respectively, which was decreased by 73% in the c-fos shRNA group compared to that in the NC group (P<0.05). Similarly, the results showed that the IC(50) values for 5-FU were (55.3±9.4) µmol/L in NC group and (288.1±7.3)µmol/L in c-fos WT group, which was increased 5.21-fold in c-fos WT cells. Conclusion: C-fos plays important role in multidrug resistance of larynx cancer cell TU177/VCR, and might become a new molecular target for laryngeal cancer treatment.

[FAT1 inhibits cell proliferation of esophageal squamous cell carcinoma through regulating the expression of CDK4/CDK6/CCND1 complex].

Objective: To explore the expression of FAT1 in esophageal squamous cell carcinoma (ESCC) tissues, and its effect on cell proliferation. Methods: The expression levels of FAT1 protein in human ESCC tissues and matched adjacent normal tissues were determined by immunohistochemistry (IHC). Lentivirus based knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assays was performed to examine the effect of FAT1 on the proliferation of these ESCC cells. Colony formation assay was used to detect the colony formation ability. Flow cytometry was performed to analyze the cell cycle and apoptosis. The expression levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR) and Western blot. Results: The relative expression of FAT1 in ESCC tissues was 66.97±21.53, significantly lower than 78.13±16.76 of adjacent normal tissues(P<0.05). Knockdown of FAT1 promoted cell proliferation and colony formation. In YSE2 cell, the division time in negative control (NC) group was (1 570±51) min, significantly longer than (1 356±31) min in shFAT1 group. In Colo680N cell, division time in NC group was (1 532±53) min, significantly longer than (1 290±30) min in shFAT1 group (P<0.05). Knockdown of FAT1 promoted G1-to S-phase transition and resulted in the upregulation of CDK4/CDK6/CCND1. Conclusion: FAT1 inhibits the proliferation and G1-to S-phase transition of ESCC cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.

Bifidobacteria Expressing Tumstatin Protein for Antitumor Therapy in Tumor-Bearing Mice.

Tumstatin (Tum) is a powerful angiostatin that inhibits proliferation and induces apoptosis of tumorous vascular endothelial cells. A nonpathogenic and anaerobic bacterium, Bifidobacterium longum (BL), selectively localizes to and proliferates in the hypoxia location within solid tumor. The aims of this study were to develop a novel delivery system for Tum using engineered Bifidobacterium and to investigate the inhibitory effect of Tum on tumor in mice. A vector that enabled the expression of Tum under the control of the pBBADs promoter of BL was constructed and transformed into BL NCC2705 by electroporation. The mouse colon carcinoma cells CT26 (1 × 10(7)/mL) were subcutaneously inserted in the left armpit of BALB/c mice. The tumor-bearing mice were treated with Tum-transformed BL, and green fluorescent protein (GFP)-transformed BL was used as a negative control. The microvessel density (MVD) in the transplanted tumor was determined, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling was used to detect apoptosis of vascular endothelial cells in transplanted tumor. The in vitro expression of Tum was examined in BL after l-arabinose induction. Bifidobacterium longum with pBBAD-Tum (BL-Tum) showed significant antitumor effect in tumor-bearing mice. The weight, volume, growth, and MVD, as well as the percentage of apoptotic vascular endothelial cells of transplanted tumors in the tumor-bearing mice treated with Tum-transformed BL were all significantly lower than those in the GFP negative control group. Intragastric administration, injection in tumor and vena caudalis injection of Tum-transformed BL exerted marked antitumor effects in tumor-bearing mice. This is the first demonstration of the utilization of Tum-transformed BL as a specific gene delivery system for treating tumor.

Serotonin inhibits the peptide FMRFamide response through a cyclic AMP-independent pathway in Aplysia.

1. The S-K+ conductance was isolated by voltage-clamping near the resting potential pleural mechanosensory neurons of Aplysia in culture. This background conductance is modulated in opposite directions by two distinct, transmitter-controlled second-messenger cascades: it is enhanced by the peptide FMRFamide through the 12-lipoxygenase pathway of arachidonic acid, and it is decreased by serotonin (5-HT) through adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphorylation. 2. The dose-dependent activating effect of FMRFamide (0.01-500 microM) on the S-K+ conductance was measured in the presence and the absence either of 1-100 microM 8-bromo-cAMP (8b-cAMP, a membrane-permeable and hydrolysis-resistant analogue of cAMP), or of 0.01-0.1 microM 5-HT. 3. When 8b-cAMP was applied, it produced a slow inward current response due to closure of the S-K+ conductance. This response was antagonized by FMRFamide in a dose-dependent mode. Application of 100 microM FMRFamide, in the presence of 1-10 microM 8b-cAMP, produced an outward current response larger than the control FMRFa response and equal to the sum of the responses to FMRFamide alone and to 8b-cAMP alone. Similarly, at 500 microM, FMRFamide completely antagonized the closing action of maximal 8b-cAMP levels (100 microM). This observation confirms previous work that indicated that FMRFamide can reopen S-K+ channels closed by FMRFamide. 4. In contrast, in the presence of moderate concentrations of 5-HT (0.01 microM), which produce a slow inward current due to the closing of the S-K+ conductance, FMRFamide elicited a response that only partially antagonized this 5-HT action. Under maximal 5-HT concentrations (0.1 microM), the 5-HT response was not antagonized by any FMRFamide concentration: instead, the FMRFamide response was smaller than the control response without 5-HT. This experiment suggests that 5-HT, with an action independent from cAMP, inhibits the effect of FMRFamide on the S-K+ channel. 5. The dose-dependent inhibitory effect of 5-HT (0.001-10 microM) on the S-K+ conductance was measured in the presence and the absence either of FMRFamide (1-50 microM), which stimulates the release and metabolism of arachidonic acid in Aplysia sensory neurons or of arachidonic acid (25 microM). 6. Under these conditions, supramaximal concentrations of 5-HT could not completely suppress the slow outward current evoked by FMRFamide or by arachidonic acid, indicating that a component of the arachidonic-mediated response to FMRFamide is resistant to actions that maximally increase the S-K+ channel phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)

[Influence of emotional stress and behavior during acute myocardial infarction on prognosis].

Seventeen cases of acute myocardial infarction (AMI) with emotional stress (group A) and 54 cases with basically stable emotion (group B) were compared with respect to three major complications (arrhythmia, cardiac insufficiency of grade 3 and 4 and cardiogenic shock) and therapeutic effect. The results showed that the incidences of the three complications in group A were significantly higher than those in group B (P less than 0.05), and the clinical condition was more serious in the former group. Response to narcotics showed that number of patients requiring more than 3 injections of either dolantine 50 mg or morphine 5 mg was significantly greater in group A than in group B (P less than 0.001). Sigma ST was not found to be significantly different between the two groups. However, the duration of elevation of ST segment was significantly longer in group A than in group B (P less than 0.01). It is suggested that relief of myocardial ischemia is slow in group A. There were five patients in group A with extended infarct size and died during the acute stage. None in the group B showed extension of infarction. The mortality rate in group A significantly higher than that in group B (53% VS 3.7%, P less than 0.001) and it bears no relation with sex, age and the site of infarction on admission. The greater the emotional upheaval the more unfavorable the prognosis. It is shown that excessive emotional stress is an important risk factor of AMI and aggressive measures are required to prevent worsening of the condition.

Calcium antagonists fail to protect mammalian spinal neurons after physical injury.

Most investigations of calcium antagonists as treatments for experimental spinal cord injury (SCI) have not demonstrated significant reduction of tissue damage or improvement in neurologic outcome. Many of these studies were prompted by reports that these agents increase blood flow to ischemic tissues. However, in vitro studies of renal and neuronal tissues subjected to an anoxic stress have shown that the calcium antagonists can confer direct protection on stressed parenchymal cells. We have used a tissue culture model of nerve cell injury to investigate whether calcium antagonists increase the probability of survival of spinal cord neurons after a defined physical trauma. Preliminary toxicity studies determined the maximum nontoxic dosages of verapamil (80 microM), nifedipine (10 microM), and chlorpromazine (10 microM) for neurons in our cultures. Preselected neurons (100-200 per study) were subjected to amputation of one primary dendrite at a distance of 100 microns from the perikaryon. Erythrosine B tests of viability conducted 24 h after lesioning failed to demonstrate that neurons injured in the presence of any one of these agents had an increased probability of survival compared to operated control neurons. Viability evaluations conducted 2 h after injury with phase contrast microscopy showed no evidence of slowed deterioration. Correction for other lesion physical parameters (lesion diameter and the extent of proximal segment retraction) also failed to reveal any increased protection by these agents. We conclude that calcium antagonists alone will not be useful for treatment of the primary injury of SCI.