Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching.

PURPOSE: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. METHODS: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. RESULTS: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). CONCLUSION: PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Quantifying carotid stiffness in chronic kidney disease using ultrafast ultrasound imaging.

Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. Methods: This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. Results: PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). Conclusions: ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.

Multisite Percutaneous Bone Augmentation for the Treatment of Acetabular Osteolytic Metastases Involving the Articular Surfaces: A Randomised Trial.

INTRODUCTION: For patients with acetabular osteolytic metastases involving the articular surfaces, current treatments cannot efficiently rebuild the acetabular bone frame structure and strengthen bone defect area mechanics for weight-bearing. The purpose of this study is to show the operational procedure and clinical outcomes of multisite percutaneous bone augmentation (PBA) for the treatment of incidental acetabular osteolytic metastases involving the articular surfaces. METHODS: According to the inclusion and exclusion criteria, 8 patients (4 males and 4 females) were included in this study. Multisite (3 or 4 sites) PBA was successfully performed in all patients. The pain and function evaluation and imaging observation were examined by VAS and Harris hip joint function scores at the different time points (pre-procedure, 7 days, one month, last follow-up in 5-20 months). RESULTS: There were significant differences (p<0.05) in VAS and Harris scores before and after the surgical procedure. Moreover, these two scores had no obvious changes during the follow-up process (7 days after the procedure, one month after the procedure, and the last follow-up) after the procedure. CONCLUSION: The proposed multisite PBA is an effective and safe procedure for the treatment of acetabular osteolytic metastases involving the articular surfaces.

KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation.

Kinesin Family Member 15 (KIF15) is a plus end-directed microtubule motor, which exerts complex regulations in cancer biology. This study aimed to explore the functional role of KIF15 in leiomyosarcoma (LMS). Bioinformatic analysis was carried out using data from The Cancer Genome Atlas (TCGA)-Sarcoma (SARC). LMS cell lines SK-UT-1 and SK-LMS-1 were used as in vitro cell models. Results showed that LMS patients with high KIF15 expression had significantly worse survival than the low KIF15 expression counterparts. KIF15 knockdown slowed, while KIF15 overexpression increased the proliferation of SK-UT-1 and SK-LMS-1 cells. Co-IP assay confirmed mutual interaction between endogenous KIF15 and DEK (encoded by DEK proto-oncogene). KIF15 knockdown facilitated DEK degradation, while KIF15 overexpression slowed DEK degradation. In ubiquitination assay, a significant increase in DEK polyubiquitylation was observed when KIF15 expression was suppressed. USP15 physically interacted with both DEK and KIF15 in the cells. USP15 knockdown decreased DEK protein stability and canceled KIF15-mediated DEK stabilization. USP15 overexpression enhanced DEK stability, the effect of which was impaired by KIF15 knockdown. USP15 overexpression reduced DEK polyubiquitination. USP15 knockdown increased DEK polyubiquitination and canceled the effect of KIF15 overexpression on reducing DEK polyubiquitination. DEK overexpression enhanced the proliferation of SK-UT-1 and SK-LMS-1 cells. DEK knockdown decreased cell proliferation and canceled the effect of KIF15 overexpression on cell proliferation. In conclusion, this study revealed a novel mechanism that KIF15 enhances LMS cell proliferation via preventing DEK protein from degradation by increasing USP15 mediated deubiquitylation.

MicroRNA­20a promotes the proliferation and cell cycle of human osteosarcoma cells by suppressing early growth response 2 expression.

MicroRNAs (miRNAs) are crucial in cancer development. However, the underlying mechanisms of miRNAs in osteosarcoma (OS) remain largely uncharacterized. The present study investigated the role of miR­20a in OS cell proliferation. It was determined that miR­20a expression is markedly upregulated in OS tissues and cells compared with the matched adjacent normal tissues and h­FOB human osteoblast cell lines. Ectopic expression of miR­20a promoted the proliferation and anchorage­independent growth of OS cells, whereas inhibition of miR­20a reduced this effect. Bioinformatics analysis further revealed early growth response 2 (EGR2), as a potential target of miR­20a. Data from luciferase reporter assays showed that miR­20a directly binds to the 3'­untranslated region (3'­UTR) of EGR2 mRNA and represses expression at the transcriptional and translational levels. In functional assays, miR­20a promoted OS cell proliferation and the cell cycle, which could be suppressed by an inhibitor of miR­20a. In conclusion, the data provide compelling evidence that miR­20a functions as an onco­miRNA, which is important in promoting cell proliferation in OS, and its oncogenic effect is mediated primarily through direct suppression of EGR2 expression.

A SNP in the 5'UTR of GDF5 is associated with susceptibility to symptomatic lumbar disc herniation in the Chinese Han population.

PURPOSE: The aim of the present study is to assess whether the single nucleotide polymorphism in the GDF5 (+104T/C; rs143383) is associated with the symptomatic lumbar disc herniation in the Chinese Han population and the identification of the mechanisms of its action. METHODS: This study consisted of 231 patients with symptomatic lumbar disc herniation as the case group and 370 patients who had a lifetime lack of symptoms as the control group. PCR products were genotyped. Thirty-eight disc specimens derived from the cases were analyzed by immunohistochemical staining. The stain intensity of immunohistochemistry was quantified using a computerized image analysis system. RESULTS: Significant differences in genotypic and allelic frequencies were found between case group and control group (TT genotype P < 0.001; CC genotype P = 0.002; T allele P < 0.001). The T allele was more frequent in the case group regardless of gender (Female P = 0.018; Male P < 0.001). Significant differences were found in the genotype frequencies when stratified by gender except the comparison between the CC genotype and other genotypes combined among the female samples (P > 0.05). A semi-quantification of collagen protein in the nucleus pulposus showed that the average collagen protein content in TC group was higher than in TT group (P < 0.05). CONCLUSION: Our results suggested that the GDF5 polymorphism is associated with a susceptibility to symptomatic lumbar disc herniation in the Chinese Han population and type II collagen in the nucleus pulposus may be a key factor in susceptibility to symptomatic lumbar disc herniation.

Analysis of association between IL-1ß, CASP-9, and GDF5 variants and low-back pain in Chinese male soldier: clinical article.

OBJECT: Recent studies have suggested that genetic risk factors play an important role in the occurrence of low-back pain (LBP) and lumbar disc disease. The authors' study aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) and susceptibility to LBP related to military training. METHODS: In this case-control study, data from 892 Chinese male soldiers were retrospectively reviewed. The case group was made up of 305 soldiers with LBP related to military training and a control group of 587 soldiers without constant LBP for more than 2 weeks. Genomic DNA was extracted from peripheral blood leukocytes of all subjects and polymerase chain reaction products were genotyped. RESULTS: No association was found between the SNP of interleukin-1ß (IL-1ß; +3954C/T) and LBP at both the genotypic (p = 0.104) and the allelic (p = 0.098) level. However, the G allele of caspase-9 (CASP-9) and the T allele of growth differentiation factor 5 (GDF5) were more common in patients with LBP than in patients without LBP (p < 0.001). CONCLUSIONS: The findings in a Chinese military cohort indicated that CASP-9 (-1263A/G) and GDF5 (+104T/C) polymorphisms are associated with a susceptibility to LBP related to military training.