The relationship between coronary artery calcification and bone metabolic markers in maintenance hemodialysis patients.

BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS: Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.

LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.

A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 µg/mL in plasma and 0.05-300.00 µg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.

Morphological and clinical feasibility of C3 pedicle screw instrumentation in patients with congenital C2-3 fusion.

PURPOSE: Congenital C2-3 fusion (C2-3CF) is often involved in patients with atlantoaxial dislocation, and posterior occipitocervical fixation surgery is usually required. Hypoplasia of C2 pedicle is common in such patients, making C2 pedicle screws (PS) instrumentation inapplicable. Because of congenital fusion, C3PS instrumentation would be an ideal alternative for it will not sacrifice an additional motion segment; however, the morphological and clinical feasibility has not been previously reported. METHODS: We included 42 C2-3CF patients to this study and evaluated pedicle trajectories of C2 and C3 using a three-dimensional CT. Clinical applications of C3PS instrumentation were evaluated and followed. RESULTS: Among the 42 patients, 23 (54.8%) and 8 (19.0%) had C2 and C3 pedicle trajectory diameters <4.0 mm, respectively. The bisection line of the fused C2-3 lamina was used to represent the superior border of C3 articular mass; the entry point of C3 pedicle was located at 3 mm inferior to the assumed superior border and 3.2 mm medial to the lateral border. Bilateral C3PS instrumentations were successfully adopted in 22 patients. No spinal cord or vertebral artery injury occurred; postoperative CT showed a trajectory breach rate of 17.4% for C3PS. After mean of 3.6-year follow-up, no implant failure was documented. CONCLUSIONS: C3PS instrumentation is morphologically and clinically feasible for a large proportion of patients with C2-3CF and can serve as another reliable alternative for C2PS instrumentation. Preoperative evaluation of pedicle trajectory of C2-3CF with three-dimensional CT is highly valuable in the choice of proper fixation methods.

Experimental study on the effects of different exposure conditions and contrast agent concentrations on spectral computed tomography virtual non-contrast images.

Background: The early diagnosis of thrombosis and fat embolism is important for subsequent treatment regimens. Spectral computed tomography (CT) virtual non-contrast (VNC) scanning can not only accurately diagnose thrombosis and medium fat embolism but can also reduce the radiation dose and scanning time. However, there is a relative paucity of studies on what contrast concentration and exposure conditions are best for the quality of VNC images. To address this issue, this study aimed to investigate the effects of different exposure conditions and contrast concentrations on the quality of VNC images of low-density substances in spectral CT. Methods: Four solution groups [i.e., groups A (15 mgI/mL), B (10 mgI/mL), C (5 mgI/mL), and D (the control group)] were matched with normal saline and contrast agent groups. Four groups of solution, duck blood clots, and fat were injected into four sections of the pig large intestine, respectively. CT scans with different exposure amounts were performed under the condition of 120 KV. Comparing the true non-contrast (TNC) image based on solution D group with the VNC images of the other three solution groups. The differences in the CT values, standard deviation (SD) values, and contrast noise ratio (CNR) values of the duck blood and fat under different iodine concentrations and exposures were compared. The image quality was evaluated using a three-point method and the Kappa consistency test was performed. The consistency of the tissue CT values in the TNC and VNC images was analyzed by drawing Bland-Altman scatter plots. Results: The CT values of the duck blood in the VNC20mAs and VNCC groups were lower than those in the TNC groups (P<0.05). Under different exposures and contrast agent concentrations, the CT value of the fat in the VNC group was higher than that in the TNC group (P<0.05). The SD values of the duck blood and fat in three groups (i.e., groups A, B, and C) were lower than those in the TNC group (P<0.05). The CNR value of the duck blood in the VNC20mAs group was lower than that in the TNC group (Z=-2.10, P=0.04), and the CNR values of the duck blood and fat in the VNC group were higher than those in the TNC groups in the remaining different exposure and concentration groups (P<0.05). The CT values of the lesions in the two groups were consistent, and there were no statistically significant differences between the subjective scores of the TNC and VNC images (z=-1.34, P=0.18); the subjective evaluations of the two physicians had good consistency (K=0.80). Conclusions: Under the conditions of higher contrast agent concentrations and proper exposure conditions, the VNC images were better able to restore the CT values of the blood clots, reduce the SD values of the blood clots and fat. In addition, and improve the CNR values of the blood clots and fat. In addition, the quality of the two images was similar.

The diagnostic performance of dual-layer spectral detector CT for distinguishing breast cancer biomarker expression and molecular subtypes.

To evaluate the diagnostic performance of dual-layer spectral detector CT for differentiation of breast cancer molecular subtypes. This study was done in a retrospective approach including 104 female patients histopathologically proven to have breast cancer. These patients underwent chest arterial and venous phase dual-layer SDCT. CT values, iodine concentrations (IC)s, and Z-effective (Zeff) values of the lesions and arteries in the same layer were determined for both arterial and venous phases. Parameter values were normalized, and slopes of the spectral curves (λHu) were calculated. Breast cancer biomarkers were also analyzed. Afterward, correlations between the obtained parameters and biomarkers were analyzed. Eventually, the diagnostic performance was assessed using ROC curves. ER or PR-negative patients generally showed significantly higher mean iodine concentrations, CT, and Z-effective values. HER2-positive patients showed significantly higher CTVE, ZeffVE, N-ZeffVE, ICART, ICVE, NICART, NICVE, and λVE. Only ICVE and ZeffVE differed significantly between Ki67-positive and negative patients. All parameters showed significant diagnostic value for subtypes except N-ZeffART. Luminal and non-luminal types differed significantly and ROC curves indicated that multi-factors had the best diagnostic efficacy. The dual-layer SDCT distinguishes breast cancer biomarker expression and molecular subtypes. Thus, it can be used for preoperative assessment of breast cancer.

Effect of gene transfecting at different times on mandibular distraction osteogenesis.

BACKGROUND: Recently, numerous research of gene therapy for mandibular distraction has been published. Based on previous study, the authors used New Zealand rabbits bilateral mandibular distraction model and used electroporation mediate gene therapy at different time, to explore the optimal time for gene therapy and obtain a better effect. METHODS: Forty-eight New-Zealand rabbits were used; after accomplished osteotomy and implant distraction devices on mandible bilaterly, the rabbits were randomly divided into 4 groups: groups A, B, and C were transfected recombinant plasmids pIRES-hBMP2-hVEGF165 via electroporation-mediated approach at latency period, distraction period, and consolidation period, respectively. Group D is a control group, only distracted without gene transfection. After 3 days of latency period, the device was activated at the rate of 1 mm per day for 10 days. Three rabbits of each group were sacrificed at 1, 2, 4, and 8 weeks of consolidation, respectively. The mandibles were harvested; the left was subject to radiograph examination for bone healing, and quantitative computed tomography detect for the bone mineral density (BMD) of newly formed bone in the distraction gap. The biomechanical properties of the new generation bone at the fourth and eighth weeks of consolidation of each group were detected using 3-point bending test. RESULTS: The BMD and the stiffness of newly formed bone increased with the pass of the consolidation time in each group. After 1 week of consolidation, there is no significant difference of BMD among groups A, B, and C. However, the BMD of groups A, B, and C is higher than that of group D. After 2, 4, and 8 weeks of consolidation, the BMD of group B is significantly higher than those of groups A, C, and D. The biomechanical parameters are also higher in group B than those of groups A, C, and D after 4 and 8 weeks of consolidation. CONCLUSIONS: It is better to transfect gene at distraction period than at other stages of DO; in this way, we can obtain more remarkable effect on new bone formation. It suggests that the distraction stage is the optimal time for gene therapy.

Assessment of early anthracycline-induced cardiotoxicity using segmental strain of cardiac magnetic resonance compared with global strain and functional parameters: an animal study.

Background: The identification of anthracycline-induced cardiotoxicity holds significant importance in guiding subsequent treatment strategies, and recent research has demonstrated the efficacy of cardiac magnetic resonance (CMR) global strain analysis for its diagnosis. On the other hand, it is noteworthy that abnormal global myocardial strain may exhibit a temporal delay due to different cardiac movement in each segment of the left ventricle. To address this concern, this study aims to assess the diagnostic utility of CMR segmental strain analysis as an early detection method for cardiotoxicity. Methods: A serials of CMR scans were performed in 18 adult males New Zealand rabbits at baseline time (n=15), followed by scans at week 2 (n=15), week 4 (n=9), week 6 (n=6), and week 8 (n=5) after each week's anthracycline injection. Additionally, following each CMR scan, two to three rabbits were euthanized for pathological comparison. Cardiac functional parameters, global peak strain parameters, segmental peak strain parameters of the left ventricle, and the presence of myocardial cells damage were obtained. A mixed linear model was employed to obtain the earliest CMR diagnostic time. Receiver operating characteristic (ROC) analysis was performed to get the parameter threshold indicative of cardiotoxicity. Results: The left ventricular ejection fraction decreased at week 8 (P=0.002). There were no statistical differences in global strain throughout the experiment period (P>0.05). Regarding segmental strain analysis, the peak segmental radial strain of the apical lateral wall exhibited a decrease starting from week 2 and reached its lowest point at this week (P=0.011). Conversely, peak segmental circumferential strain of the apical anterior wall showed an increase at week 2 and reached its peak at week 6 (P=0.026). The cutoff strain value by ROC analysis for these two walls were 46.285 and -16.920, with the respective areas under the curve (AUC) 0.593 [specificity =0.267, sensitivity =1.000, 95% confidence interval (CI): 0.471-0.777] and 0.764 (specificity =0.733, sensitivity =0.784, 95% CI: 0.511-0.816). Peak segmental longitudinal strain of the apical anterior and apical lateral wall showed relatively delayed changes, occurring in the 4th week (P=0.030 and P=0.048), the cutoff values for these strains were -12.415 and -15.960, with corresponding AUCs of 0.645 (specificity =0.333, sensitivity =0.955, 95% CI: 0.495-0.795) and 0.717 (specificity =0.433, sensitivity =0.955, 95% CI: 0.566-0.902), respectively. Notably, the myocardial injury was also observed at the corresponding periods. Conclusions: Based on experimental evidence, the peak segmental strain of the apical lateral and anterior wall, as determined by CMR, demonstrated an earlier detection of anthracycline-induced cardiotoxicity compared to peak global strain and cardiac function.

[Multi-slice spiral computed tomography angiography of internal pudendal arteries: imaging and value].

OBJECTIVE: To investigate the feasibility and value of multi-slice spiral computed tomography angiography (CTA) in 3D imaging of internal pudendal arteries and their branches. METHODS: Using 64-slice spiral computed tomography, we performed hypogastric CTA for 156 twenty to seventy years old males without vascular diseases. We assigned them to groups A (n = 83, 20 to 55 yr old) and B (n = 73, 56 to 70 yr old), and included 7 male patients with arterial erectile dysfunction (AED) aged 43 to 70 years in group C. We conducted maximum intensity projection (MIP), volume rendering (VR) and vascular analysis on the internal pudendal arteries and their branches, divided the MIP and VR images into 3 levels according to the resolution and continuity of the internal pudendal arteries and their branches for blind evaluation, and measured their diameters at various positions. RESULTS: VR images of the internal pudendal arteries and their branches revealed significant differences between groups A and B (P<0.05), but not MIP images (P>0.05). There were no dramatic differences between MIP and VR in displaying internal pudendal arteries and their branches (P>0.05), nor any remarkable differences in the diameters of bilateral internal pudendal arteries and their branches at different levels in groups A and B (P>0.05). VR and MIP showed the 7 AED cases at grade III, and clearly revealed the degree and position of stenosis and occlusion in the internal pudendal arteries and their branches. CONCLUSION: CTA can display clear 3D images of internal pudendal arteries and their branches, and has a valuable role in the diagnosis and treatment of ED induced by internal pudendal artery diseases.

Management of fresh odontoid fractures using posterior C1-2 fixation without fusion: a long-term clinical follow-up study.

OBJECTIVE: Posterior C1-2 fixation without fusion makes it possible to restore atlantoaxial motion after removing the implant, and it has been used as an alternative technique for odontoid fractures; however, the long-term efficacy of this technique remains uncertain. The purpose of the present study was to explore the long-term follow-up outcomes of patients with odontoid fractures who underwent posterior C1-2 fixation without fusion. METHODS: A retrospective study was performed on 62 patients with type II/III fresh odontoid fractures who underwent posterior C1-2 fixation without fusion and were followed up for more than 5 years. The patients were divided into group A (23 patients with implant removal) and group B (39 patients without implant removal) based on whether they underwent a second surgery to remove the implant. The clinical outcomes were recorded and compared between the two groups. In group A, the range of motion (ROM) of C1-2 was calculated, and correlation analysis was performed to explore the factors that influence the ROM of C1-2. RESULTS: A solid fracture fusion was found in all patients. At the final follow-up, no significant difference was found in visual analog scale score or American Spinal Injury Association Impairment Scale score between the two groups (p > 0.05), but patients in group A had a lower Neck Disability Index score and milder neck stiffness than did patients in group B (p < 0.05). In group A, 87.0% (20/23) of the patients had atlantoodontoid joint osteoarthritis at the final follow-up. In group A, the C1-2 ROM in rotation was 6.1° ± 4.5° at the final follow-up, whereas the C1-2 ROM in flexion-extension was 1.8° ± 1.2°. A negative correlation was found between the C1-2 ROM in rotation and the severity of tissue injury in the atlantoaxial region (r = -0.403, p = 0.024) and the degeneration of the atlantoodontoid joint (r = -0.586, p = 0.001). CONCLUSIONS: Posterior C1-2 fixation without fusion can be used effectively for the management of fresh odontoid fractures. The removal of the implant can further improve the clinical efficacy, but satisfactory atlantoaxial motion cannot be maintained for a long time after implant removal. A surgeon should reconsider the contribution of posterior C1-2 fixation without fusion and secondary implant removal in preserving atlantoaxial mobility for patients with fresh odontoid fractures.

Anatomic and morphometric analysis of manubrium sterni as a source of autograft for anterior cervical fusion surgery using quantitative 3-dimensional computed tomographic scans.

STUDY DESIGN: A morphologic study of manubrium sterni using 3-dimensional computed tomography (3D-CT). OBJECTIVE: To investigate the anatomic features of adult manubrium as a source of bone graft and to measure the sizes and available cancellous bone volume of manubrium. SUMMARY OF BACKGROUND DATA: Manubrium bone graft has been reported as a potential ideal material in anterior cervical fusion surgery, whereas the related applied anatomy is lacking in the literature. METHODS: One hundred twenty adult manubria from 68 male and 52 female patients were scanned and reformatted with 3D-CT. Configurations of manubrium was observed on 3D volume-rendered images. The breadths, height, medullar thickness, and thickness distribution of manubrium were evaluated. A safe area for procurement of graft was proposed and the available cancellous bone volume of manubrium was measured. RESULTS: Frontal manubrium bears a prominent pentagonal area, which was a bare area without muscle attachments. The breadths, height, and thickness of male manubrium were significantly larger than those of female manubrium. Maximal medullar thickness for male patient was 10.4 ± 1.1 (range, 8.8-12.8) mm, and for female patient it was 9.4 ± 1.4 (range, 6.6-11.9) mm. Minimal medullar thickness for male was 6.8 ± 1.1 (range, 4.9-9.4) mm, and for female it was 5.8 ± 0.9 (range, 4.2-7.4) mm. The thickest region of manubrium located at the level of lower clavicular notches, whereas the thinnest region located at the junction between upper two-thirds and lower third of manubrium. Available volume of cancellous bone was 10.1 ± 2.2 (range, 6.6-15.6) cm(3) in male and 7.7 ± 2.5 (range, 3.6-12) cm(3) in female. CONCLUSION: The size of male manubrium is significantly larger than that of female manubrium. Manubrium bone is far more sufficient for most adult anterior cervical fusion surgeries. Safe area for procurement of graft is defined as the upper two-thirds of manubrium, and the optimal site to access medullar cavity is suggested at bare area. However, because considerable variability of manubrium size exists, preoperative evaluation of manubrium is suggested to avoid pitfalls, especially when manubrium graft is intended in a female patient.

[Effect of gene transfection at different time on bone mineral density and strength of newly formed bone in mandibular distraction gap in rabbit].

OBJECTIVE: To investigate the effect of gene transfection at different time on bone mineral density and strength of newly formed bone in mandibular distraction gap in rabbit, so as to explore the optimal time for gene therapy and enhance the therapeutic effect. METHODS: 48 New-Zealand rabbits were employed to receive mandibular osteotomy and implantation of distraction devices bilaterly. Then the rabbits were randomly divided into 4 groups as group A, B and C and D. The animals in group A, B, and C were transfected with recombinant plasmids pIRES-hBMP2-hVEGF165 via electroporation-mediated approach at latency period, distraction period, consolidation period respectively. Group D was used as control group without gene transfection. After 3 days of latency period, the distraction devices were activated at the rate of 0.8 mm per day for 10 days. Three rabbits in each group were sacrificed at 1 wk, 2 wk, 4 wk and 8 wk of consolidation respectively. The mandibles were harvested and the left mandible received X-ray examination for bone healing, and quantitative computed tomography (QCT) dectection for the bone mineral density (BMD) of newly formed bone in the distraction gap. The biomechanical properties of the new generation bone at 4 th and 8 th week of consolidation in each group were detected by three point bending test. RESULTS: The bone mineral density and the biomechanical strength of newly formed bone increased along the length of consolidation in each group. After 1 week of consolidation, there was no significant difference in BMD among group A (83.43 +/- 9.96), group B (92.29 +/- 11.25), group C (89.93 +/- 14.15), P > 0.05. But the BMD of group A, B and C was higher than that of group D (70. 31 +/- 3.30), P < 0.05. After 2wk, 4 wk and 8 wk of consolidation, the BMD of group B (137.54 +/- 7.20,492.93 +/- 17.57, 790.48 +/- 12.19) was significantly higher than those of group A (121.44 +/- 9.27, 396.15 +/- 15.70, 603.39 +/- 16.46), C (125.06 +/- 7.24, 464.15 +/- 15.45, 764.15 +/- 17.28), and D (98.86 +/- 8.13, 336.45 +/- 11.95, 577.89 +/- 18.43), P < 0.05. The biomechanical parameters were also higher in group B than those of group A, C and D after four and eight weeks of consolidation (P < 0.05). CONCLUSION: It is better to transfect gene at the beginning of distraction (distraction period) than at other stages of DO. In this way, more remarkable effect could be obtained on new bone formation. It suggests that the distraction stage is the optimal time for gene therapy.

[The effect of electroporation mediated gene therapy on bone mineral density and strength of new-formed bone in mandibular distraction gap in rabbit].

OBJECTIVE: To explore the effect of electroporation mediated gene therapy on bone mineral density and strength of new-formed bone in mandibular distraction gap, so as to enhance the osteogenesis and shorten the distraction term. METHODS: New-Zealand rabbits were employed. The distraction began after 3 days of latency period at the rate of 0. 8 mm per day for 7 days. After distraction, the rabbits were randomly divided into 5 groups to receive injection in the distraction gap with recombinant plasmid 2 microg (0.1 microg/microl) pIRES-hVEGF165-hBMP2 in group A, with recombinant plasmid pIRES-hBMP2 in group B, with recombinant plasmid pIRES-hVEGF165 in group C, with pIRES in group D, and with normal saline (NS) in group E. After injection, electroporation was performed in all the groups. After 1 week, 2 weeks, 4 weeks and 8 weeks of consolidation, all the animals underwent X-ray and quantitative computed tomography (QCT). The new-formed bone in distraction gap was selected as regions of interest (ROI) to measure the bone mineral density(BMD). Then the rabbits were sacrificed and the new-formed bone samples were harvested to detect 3-point crushing strength. RESULTS: BMD of newly formed bone in group A, B and C was markedly higher than that in group D and E (P < 0.01). After 2 weeks of consolidation, BMD in group A was much higher than that in the other groups, but there was no difference between group B and C. After 4 weeks of consolidation, BMD in group A and B was markedly higher than that in group C, D and E (P < 0.01). After 8 weeks of consolidation, BMD in group A was markedly higher than that in the other groups. While the BMD was not significantly different between group B and C, but the BMD in group B and C was higher than that in group D and E (P < 0.01). After 4 weeks of consolidation, the 3-point crushing strength of newly formed bone in group A was markedly higher than that in group B,C, D and E (P < 0.01), which was still the same after 8 weeks of consolidation. And the crushing strength in group B was higher than that in group C, D and E (P < 0. 05). CONCLUSIONS: Electroporation-mediated transfection of recombinant plasmid pIRES-hVEGF165-hBMP2 could greatly enhance osteogenesis and calcification. A combination of VEGF and BMP may promote osteogenesis and angiogenesis simultaneously, so as to magnify the effect of each growth factor, resulting a synergetic effect.