Image quality and diagnostic value of ultra low-voltage, ultra low-contrast coronary CT angiography.

OBJECTIVE: To explore the image quality (IQ) and diagnostic value of 70 kVp turbo high-pitch coronary CT angiography (THP-CCTA) using automated tube voltage selection (ATVS) and 30 mL of low-concentration contrast agent. METHODS: Patients who underwent 70 kVp THP-CCTA using ATVS with 30 mL of contrast agent (group A) were prospectively enrolled, and those who underwent conventional CCTA (100/120 kVp, prospective sequential mode with 65-75 mL of contrast agent) (group B) were retrospectively selected for study. IQ was assessed subjectively on a 5-point scale, and diagnostic value was assessed based on invasive coronary angiography as the gold standard. Heart rate (HR), HR fluctuation (HRF), body mass index (BMI), effective radiation dose (ED), and iodine uptake (IU) were recorded. RESULTS: A total of 796 patients (398/398 in groups A/B) were included. Between-group differences in age, gender, BMI, HR, HRF, and IQ values were not significant. The ED/IU values were 0.3 ± 0.1 mSv/9.0 ± 0.0 g and 5.8 ± 1.8 mSv/22.9 ± 1.0 g in groups A and B, respectively (p < 0.01). The sensitivity, specificity, positive and negative predictive values, and accuracy of THP-CCTA for the diagnosis of ≥ 50% stenosis were 94.8%, 97.5%, 92.0%, 98.4%, and 96.9% respectively. The mean HR and coronary calcium score were independent predictors of diagnostic image quality, and the best cutoff values were 71.5 bpm and 444.1 respectively. CONCLUSION: This third-generation dual-source CT imaging modality, a 70-kVp THP-CCTA system using ATVS with 30 mL of low-concentration contrast agent, produces high-quality images with high diagnostic accuracy for significant stenosis, with ultra low ED and IU. This technique was most promising in individuals with an HR < 71.5 bpm and coronary calcium score < 444.1. KEY POINTS: • Turbo high-pitch CCTA using 70 kVp via automated tube voltage selection and 30 mL of low-concentration contrast agent is feasible. • This protocol provides high diagnostic accuracy for significant coronary stenosis and reduces radiation doses and iodine uptake significantly. • This protocol was most promising in individuals with an HR < 71.5 bpm and coronary calcium score < 444.1.

Bazedoxifene protects cerebral autoregulation after traumatic brain injury and attenuates impairments in blood-brain barrier damage: involvement of anti-inflammatory pathways by blocking MAPK signaling.

OBJECTIVE: Traumatic brain injury (TBI) is a significant cause of death and long-term deficits in motor and cognitive functions for which there are currently no effective chemotherapeutic drugs. Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator (SERM) and has been investigated as a treatment for postmenopausal osteoporosis. It is generally safe and well tolerated, with favorable endometrial and breast safety profiles. Recent findings have shown that SERMs may have therapeutic benefits; however, the role of BZA in the treatment of TBI and its molecular and cellular mechanisms remain poorly understood. The aim of the present study was to examine the neuroprotective effects of BZA on early TBI in rats and to explore the underlying mechanisms of these effects. MATERIALS AND METHODS: TBI was induced using a modified weight-drop method. Neurological deficits were evaluated according to the neurological severity score (NSS). Morris water maze and open-field behavioral tests were used to test cognitive functions. Brain edema was measured by brain water content, and impairments in the blood-brain barrier (BBB) were evaluated by expression analysis of tight junction-associated proteins, such as occludin and zonula occludens-1 (ZO-1). Neuronal injury was assessed by hematoxylin and eosin (H&E) staining. LC-MS/MS analysis was performed to determine the ability of BZA to cross the BBB. RESULTS: Our results indicated that BZA attenuated the impaired cognitive functions and the increased BBB permeability of rats subjected to TBI through activation of inflammatory cascades. In vivo experiments further revealed that BZA provided this neuroprotection by suppressing TBI-induced activation of the MAPK/NF-κB signaling pathway. Thus, mechanically, the anti-inflammatory effects of BZA in TBI may be partially mediated by blocking the MAPK signaling pathway. CONCLUSIONS: These findings suggest that BZA might attenuate neurological deficits and BBB damage to protect against TBI by blocking the MAPK/NF-κB signaling pathway.

The sodium pump α1 subunit regulates bufalin sensitivity of human glioblastoma cells through the p53 signaling pathway.

Bufalin is the primary component of the traditional Chinese medicine "Chan Su," which has been widely used for cancer treatment at oncology clinics in certain countries. Evidence suggests that this compound possesses potent antitumor activities, although the exact molecular mechanism(s) require further elucidation. Therefore, this study aimed to further clarify the in vitro and in vivo antiglioma effects of bufalin and the molecular mechanism underlying the regulation of drug sensitivity. The anticancer effects of bufalin were determined by colony formation assays, apoptosis assays, and cellular redox state tests of glioma cells. Confocal microscopy was performed to determine the expression changes of the DNA damage biomarker γ-H2AX and the nuclear translocation of p53 in glioma cells. Western blotting and RT-PCR were used to detect the protein and gene expression levels, respectively. Here, we report that bufalin induced glioblastoma cell apoptosis and oxidative stress and triggered DNA damage. The critical roles of the sodium pump α1 subunit (ATP1A1) in mediating the XPO1-targeted anticancer effect of bufalin in human glioma were further confirmed. Mechanistic studies confirmed the important roles of Src and p53 signaling in mediating bufalin-induced apoptosis. Importantly, bufalin also inhibited the growth of glioma xenografts. In conclusion, our study indicated that therapies targeting the ATP1A1 and p53 signaling-mediated mitochondrial apoptotic pathways regulated by bufalin might be potential treatments for human glioma, and these findings will provide molecular bases for developing bufalin into a drug candidate for the treatment of malignant glioma.

Comparison of the perinatal outcome of twins conceived after assisted reproductive technologies versus those conceived naturally.

OBJECTIVE: To analyze whether twin pregnancies resulting from assisted reproductive technologies (ARTs) had an increased risk of obstetric complications or adverse neonatal outcomes. STUDY DESIGN: The obstetric and neonatal outcomes of 252 cases of twin pregnancies, including 108 cases conceived by ART and 144 cases of natural conception, delivered at our hospital between January 1, 2009, and December 31, 2011, were compared retrospectively. RESULTS: Mean maternal age in the ART group was significantly older than that of the control group (31.04 ± 3.63 vs. 28.81 ± 4.75, t = 2.88, p < 0.05). Among the gravidas (< 35 years old) the incidence of premature rupture in the ART group and the control group was statistically significant (22.09% vs. 10.48%, χ2 = 5.30, p < 0.05). The incidence of mild asphyxia of the second twin in the ART group and the control group was also statistically significant (23.53% vs. 12.20%, χ2 = 4.61, p < 0.05). However, there was no statistical difference in other maternal or neonatal complications of twins between the ART group and the control group. CONCLUSION: In this study, except for a higher incidence of morbidity, premature rupture of membranes, and mild asphyxia of the second twin, the obstetric complications or adverse neonatal outcome in the ART group were similar, which indicated that ART-conceived twin pregnancies were not at higher risk for obstetric complications or adverse neonatal outcome than were naturally conceived twin pregnancies.

Expression of Attractin in male reproductive tract of human and mice and its correlation with male reproduction.

The expression of Attractin mRNA and protein in testis and semen of human and male mice was investigated. Human testis and semen samples were all collected from Reproductive Center of Renmin Hospital, Wuhan University in December, 2012. Testis samples were collected from 7 cases of obstructive azoospermias when they were subjected to diagnosed testis biopsy, and 30 normal human semen samples were obtained from those cases of semen analysis. Adult mice testis tissues were obtained from 10 2-month-old male BALB/c mice, and 60 male mice at different ages were classified into 10 groups (day 1, 5, 10, 15, 21, 28, 35, 42, 56, and 120 respectively, n=6 each). The expression of Attractin mRNA and protein in testis was detected by RT-PCR and Western blotting respectively. Human semen samples were centrifuged into sperm plasma (SP) and sperm extract (SE), and mice sperm samples were collected from the epididymis of 10 adult male BALB/c mice. Western blotting was used to determine the Attractin protein expression level. Attractin mRNA and protein were expressed in the testis of both patients with obstructive azoospermias and adult Bcl/B mice. Quantitative RT-PCR revealed that no Attractin mRNA was detectable in day 1 male BALB/c mice group. The Attractin mRNA and protein levels were low on the day 10, and increased with age until day 56. On the day 120, the expression levels of Attractin were decreased. As for human semen samples, Attractin protein was expressed in both SP and SE, but didn't exist in samples from the epididymis of male BALB/c mice. It was suggested that Attractin acted as a novel active substance and was involved in male reproduction in both human and BALB/c mice, but it exerted a different expression profile in different mammal species.

Enhanced Electroplasticity through Room-Temperature Dynamic Recrystallization in a Mg-3Al-1Sn-1Zn Alloy.

It has been well known that electric pulse can be utilized to enhance the plasticity of metals, which is attributed to the change of dislocation dynamics, e.g., localized planar slip to homogeneous wavy slip. Here, we show another effect of pulse current, which facilitates texture weakening through room-temperature dynamic recrystallization and additionally improve the plasticity of a polycrystalline Mg-3Al-1Sn-1Zn alloy. By conducting a tensile test under electrical pulse, we found that the peak flow stress and fracture strain depend strongly on current density. As peak current densities increases, the flow stress drops and the fracture strain increases. Our Electron Backscatter Diffraction results suggest that dynamic recrystallization occurs at room temperature, which develops a weakened texture. Our work provides a new insight into electroplasticity mechanism in Mg alloys.

Effect of Pulsed Current on the Tensile Deformation Behavior and Microstructure Evolution of AZ80 Magnesium Alloy.

In this work, the tensile deformation behavior of an as-extruded AZ80 magnesium alloy under pulsed current (PC) was investigated based on microstructure observations. We found that compared with the tensile tests at room temperature (RT) and given temperature (GT), the flow stress is reduced due to both thermal and athermal effects of pulsed current. A quasi-in-situ electron backscatter diffraction (EBSD) analysis reveals that at the same strain, the geometrically necessary dislocation (GND) density of the RT sample is the highest, followed by the GT sample and the PC sample. This proves that the athermal effect can promote the annihilation of dislocations and slow down dislocation pileup, which reduces the flow stress. In addition, the twinning behavior under different deformation conditions was studied; the twins are {10-12} tension twins, which are activated with the assistance of local stress. We found that the twin fraction in the PC sample is lower than that in the RT and GT samples, due to the least accumulation of GNDs at grain boundaries, which decreases the nucleation of {10-12} tension twins.

Ascending aortic distensibility and target organ damage in primary hypertension without diabetes.

To investigate the relationship between ascending aortic distensibility (AAD) and hypertensive target organ damage (TOD) and its potential value in prediction. One hundred and sixty seven primary hypertension inpatients who underwent coronary CTA examination were enrolled into our study. Retrospective ECG-triggering scanning mode were applied and the images were reconstructed every 5% phase in the entire R-R interval. Maximum and minimum ascending aortic areas as well as the AAD value were calculated on the interested slice. AAD (P < 0.001) and brachial-ankle pulse wave velocity (baPWV, P < 0.05) were changed significantly as the deterioration of TOD. Multivariate logistic regression analysis between TOD and its possible influence factors indicated that AAD was the only independent risk factor for the presence and severity of TOD. One standard deviation decrease on AAD would increase the risk of TOD significantly: TOD1 (odds ratio 0.45, P < 0.05), TOD2 (odds ratio 0.23, P < 0.05), and TOD3 (odds ratio 0.01, P < 0.05). The odds ratio of TOD in the third tertile group was found 5.47 times higher than that in the second tertile group, and the second tertile group TOD odds ratio was 6.4 times higher than that in the first tertile group. Decline of AAD can be taken as the independent predict factor for TOD in primary hypertension patients, superior to baPWV method and other conventional predictors. Without additional contrast media consumption and radiation dose, AAD derived from coronary CTA may provide early detection for hypertensive TOD.

Acetyl-L-carnitine: An effective antioxidant against cryo-damage on human spermatozoa with asthenospermia.

A variety of natural and artificial cryoprotectant extenders have been explored to enhance sperm recovery following cryopreservation-thawing process. The current investigation is aimed at evaluating the effect of acetyl-L-carnitine on human spermatozoa and reactive species oxygen (ROS) level after freezing-thawing process. The spermatozoa were collected from 35 male patients diagnosed as having asthenospermia. The cryopreservation of human spermatozoa treated with acetyl-L-carnitine at different concentrations (group B: 2.5 mmol/L, group C: 7.5 mmol/L, group D: 15 mmol/L) was compared with control (group A: no acetyl-L-carnitine given). For the frozen-thawed spermatozoa, the viability, motility and DNA integrity were measured by comet assay, acrosome integrity by FITC-PNA staining and ROS level was determined in each group. The results showed that there were no significant differences in motility and viability between group A and group B, while the motility and viability of spermatozoa in group C and group D were significantly increased as compared with those in group A. As compared with group A, the values for DNA integrity parameters including comet rate (CR), tail DNA percentage (TD), tail length (TL) and Oliver tail moment (OTM) were significantly reduced in group C and group D. Group C and group D also displayed a higher proportion of intact acrosome than group A. No significant difference in ROS level was found between group A and group B, while with the increase in acetyl-L-carnitine concentration, the ROS level in groups C and D was significantly reduced as compared with that in group A. In conclusion, acetyl-L-carnitine at a concentration of 7.5 mmol/L is an effective antioxidant against cryo-damage on post-thawed human spermatozoa.

Proliferation and differentiation of neural stem cells in adult rats after cerebral infarction.

OBJECTIVE: To investigate proliferation and differentiation of neural stem cells in adult rats after cerebral infarction. METHODS: Models of cerebral infarction in rats were made and the time-course expression of bromodeoxyuridine (BrdU), Musashi1, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU and Musashi1 were used to mark dividing neural stem cells. GFAP and NeuN were used to mark differentiating neural stem cells. RESULTS: Compared with controls, the number of BrdU-labeled and BrdU-labeled with Musashi 1-positive cells increased strikingly 1 day after cerebral infarction; approximately 6 fold with a peak 7 days later; markedly decreased 14 days later, but was still elevated compared with that of controls; decling to the control level 28 days later. The number of BrdU-labeled with GFAP-positive cells nearly remained unchanged in the hippocampus after cerebral infarction. The number of BrdU-labeled with NeuN-positive cells increased strikingly 14 days after cerebral infarction, reached maximum peak in the hippocampus 28 days after cerebral infarction in rats. CONCLUSION: Cerebral infarction stimulate proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.

A new potential risk factor in patients with erectile dysfunction and premature ejaculation: folate deficiency.

We investigated serum folic acid (FA) levels in patients with erectile dysfunction (ED) and/or premature ejaculation (PE). Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time (IELT) was measured during a 4 weeks baseline period. Levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, total testosterone), homocysteine (Hcys), and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation (CIPE). The abridged International Index of Erectile Function-5 (IIEF-5) questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED (7.61 ± 3.97 ng ml⁻¹), PE (9.37 ± 3.40 ng ml⁻¹), and ED/PE (8.84 ± 4.28 ng ml⁻¹) patients than in healthy men (12.23 ± 5.76 ng ml -1 , P < 0.05). No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls (P > 0.05). There were positive correlations between serum FA concentrations and CIPE scores (r = 0.530, P < 0.01), IIEF-5 scores (r = 0.589, P < 0.01), and IELT (r = 0.445, P < 0.01); negative correlations with Hcys concentrations (r = -0.487, P < 0.01) were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.

Immunogenicity study of plasmid DNA encoding mouse cysteine-rich secretory protein-1 (mCRISP1) as a contraceptive vaccine.

PROBLEM: To examine the immunocontraceptive properties of the plasmid pcDNA-mCRISP1 and compare them to the corresponding recombinant mCRISP1 (r-mCRISP1). METHOD OF STUDY: RT-PCR and indirect immunofluorescence were performed to observe the mCRISP1 protein expression in COS-7 cells. Three groups of mice received three injections of r-mCRISP1, pcDNA-mCRISP1 or pcDNA vector, respectively. ELISA and Western blot were used to examine the immune responses and immunoreactivity of antisera. Sperm-egg penetration assay was performed to examine the effect of anti-mCRISP1 antibodies in vitro fertilization of mouse oocytes. Fertility and mean litter size were analysed by natural mating. Histological analysis was carried out to look for potential immunopathologic effects of the antibodies. RESULTS: COS-7 cells transfected with pcDNA-mCRISP1 present the expression of mCRISP1. Both r-mCRISP1 and pcDNA-mCRISP1 raised an immune response against r-mCRISP1 protein and native CRISP1 in mouse sperm. The titres of anti-mCRISP1 antibodies from DNA immunized mice were significantly lower than that of r-mCRISP1 immunized mice, but it lasted relatively longer. Male and female pcDNA-mCRISP1 injected animals presented a statistically significant reduction in their fertility with no signs of immunopathologic effects. CONCLUSION: These studies demonstrated the feasibility of generating an immune response to mCRISP1 protein by DNA vaccine and pcDNA-mCRISP1 plasmid causing significant anti-fertility potential.