Radial Icicle Tree (RIT): Node Separation and Area Constancy.

Icicles and sunbursts are two commonly-used visual representations of trees. While icicle trees can map data values faithfully to rectangles of different sizes, often some rectangles are too narrow to be noticed easily. When an icicle tree is transformed into a sunburst tree, the width of each rectangle becomes the length of an annular sector that is usually longer than the original width. While sunburst trees alleviate the problem of narrow rectangles in icicle trees, it no longer maintains the consistency of size encoding. At different tree depths, nodes of the same data values are displayed in annular sections of different sizes in a sunburst tree, though they are represented by rectangles of the same size in an icicle tree. Furthermore, two nodes from different subtrees could sometimes appear as a single node in both icicle trees and sunburst trees. In this paper, we propose a new visual representation, referred to as radial icicle tree (RIT), which transforms the rectangular bounding box of an icicle tree into a circle, circular sector, or annular sector while introducing gaps between nodes and maintaining area constancy for nodes of the same size. We applied the new visual design to several datasets. Both the analytical design process and user-centered evaluation have confirmed that this new design has improved the design of icicles and sunburst trees without introducing any relative demerit.

The obesity paradox in ST-segment elevation myocardial infarction patients: A meta-analysis.

OBJECTIVE: The aim of this study was to investigate whether there was a difference in survival after initial percutaneous coronary intervention (PCI) among ST-segment elevation myocardial infarction (STEMI) patients with different body mass index (BMI). METHODS: Literature retrieval was conducted on PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain the published studies on the survival of STEMI patients with different BMI after initial PCI from the establishment of the database to 2022. All statistical analyses were performed using STATA16.0. RESULTS: Two hundred thirty-nine studies were retrieved, and 12 studies were eventually included. Meta-analysis showed that overweight patients [OR = 0.66, 95% CI (0.58, 0.76), p < .001] and obese patients [OR = 0.60, 95% CI (0.51, 0.72), p < .001] had lower in-hospital mortality than healthy-weight patients. Overweight patients [OR = 0.66, 95% CI (0.58, 0.74), p < .001] and obese patients [OR = 0.62, 95% CI (0.53, 0.72), p < .001] had lower short-term mortality than healthy-weight patients. In addition, overweight patients [OR = 0.63, 95% CI (0.58, 0.69), p < .001] and obese patients [OR = 0.59, 95% CI (0.52, 0.66), p < .001] also had lower long-term mortality than healthy-weight patients. There was no significant difference in in-hospital mortality [OR = 1.06, 95% CI (0.89, 1.27), p > .05], short-term mortality [OR = 1.04, 95% CI (0.89, 1.22), p > .05], and long-term mortality [OR = 1.07, 95% CI (0.95, 1.20), p > .05] between overweight and obese patients. CONCLUSION: This meta-analysis confirmed an obesity paradox in STEMI patients following PCI. The obesity paradox exists in in-hospital, short-term, and long-term conditions.

An Important Concern for the Analysis of Culprit Artery.

This case report describes a man in his 50s with hypertension and diabetes who presented to the emergency department with sudden-onset chest pain radiating to his left arm and profuse sweating.

Animal Models for Postoperative Implant-Related Spinal Infection.

Postoperative infections following implant-related spinal surgery are severe and disastrous complications for both orthopaedic surgeons and patients worldwide. They can cause neurological damage, disability, and death. To better understand the mechanism of these destructive complications and intervene in the process, further research is needed. Therefore, there is an urgent need for efficient, accurate, and easily available animal models to study the pathogenesis of spinal infections and develop new and effective anti-bacterial methods. In this paper, we provide a general review of the commonly used animal models of postoperative implant-related spinal infections, describe their advantages and disadvantages, and highlight the significance of correctly choosing the model according to the infection aspect under investigation. These models are valuable tools contributing to the better understanding of postoperative spinal infections and will continue to facilitate the invention of novel preventative and treatment strategies for patients with postoperative spinal infections. However, although they are valid and reproducible in some respects, the current animal models present certain limitations. Future ideal spinal infection animal models may assess the bacterial load of the same animal in real-time in vivo, and better mimic the human anatomy as well as surgical techniques. Strains other than Staphylococcus aureus account for a large proportion of postoperative spinal infections, and thus, the establishment of models to evaluate other types of microbial infections is expected in the future. Furthermore, novel transgenic models established on advancements in genome editing are also likely to be developed in the future.

Three-dimensional printed polylactic acid scaffold integrated with BMP-2 laden hydrogel for precise bone regeneration.

BACKGROUND: Critical bone defects remain challenges for clinicians, which cannot heal spontaneously and require medical intervention. Following the development of three-dimensional (3D) printing technology is widely used in bone tissue engineering for its outstanding customizability. The 3D printed scaffolds were usually accompanied with growth factors, such as bone morphometric protein 2 (BMP-2), whose effects have been widely investigated on bone regeneration. We previously fabricated and investigated the effect of a polylactic acid (PLA) cage/Biogel scaffold as a carrier of BMP-2. In this study, we furtherly investigated the effect of another shape of PLA cage/Biogel scaffold as a carrier of BMP-2 in a rat calvaria defect model and an ectopic ossification (EO) model. METHOD: The PLA scaffold was printed with a basic commercial 3D printer, and the PLA scaffold was combined with gelatin and alginate-based Biogel and BMP-2 to induce bone regeneration. The experimental groups were divided into PLA scaffold, PLA scaffold with Biogel, PLA scaffold filled with BMP-2, and PLA scaffold with Biogel and BMP-2 and were tested both in vitro and in vivo. One-way ANOVA with Bonferroni post-hoc analysis was used to determine whether statistically significant difference exists between groups. RESULT: The in vitro results showed the cage/Biogel scaffold released BMP-2 with an initial burst release and followed by a sustained slow-release pattern. The released BMP-2 maintained its osteoinductivity for at least 14 days. The in vivo results showed the cage/Biogel/BMP-2 group had the highest bone regeneration in the rat calvarial defect model and EO model. Especially, the bone regenerated more regularly in the EO model at the implanted sites, which indicated the cage/Biogel had an outstanding ability to control the shape of regenerated bone. CONCLUSION: In conclusion, the 3D printed PLA cage/Biogel scaffold system was proved to be a proper carrier for BMP-2 that induced significant bone regeneration and induced bone formation following the designed shape.

VCAM1 expression in the myocardium is associated with the risk of heart failure and immune cell infiltration in myocardium.

Ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) are the two most common etiologies of heart failure (HF). Both forms share common characteristics including ventricle dilation in the final stage. Immune mechanisms in HF are increasingly highlighted and have been implicated in the pathogeneses of IHD and DCM. A better understanding of adhesion molecule expression and correlated immune cell infiltration could enhance disease detection and improve therapeutic targets. This study was performed to explore the common mechanisms underlying IHD and DCM. After searching the Gene Expression Omnibus database, we selected the GSE42955, GSE76701, GSE5406, GSE133054 and GSE57338 datasets for different expressed gene (DEGs) selection and new cohort establishment. We use xcell to calculate immune infiltration degree, ssGSEA and GSEA to calculate the pathway and biological enrichment score, consensus cluster to identify the m6A modification pattern, and LASSO regression to make risk predicting model and use new combined cohort to validate the results. The screening stage revealed that vascular cell adhesion molecule 1 (VCAM1) play pivotal roles in regulating DEGs. Subsequent analyses revealed that VCAM1 was differentially expressed in the myocardium and involved in regulating immune cell infiltration. We also found that dysregulated VCAM1 expression was associated with a higher risk of HF by constructing a clinical risk-predicting model. Besides, we also find a connection among the m6A RNA modification ,expression of VCAM1 and immune regulation. Those connection can be linked by the Wnt pathway enrichment alternation. Collectively, our results suggest that VCAM-1 have the potential to be used as a biomarker or therapy target for HF and the m6A modification pattern is associated with the VCAM1 expression and immune regulation.

Effect of Whitlockite as a new bone substitute for bone formation in spinal fusion and ectopic ossification animal model.

BACKGROUND: Bone substrates like hydroxyapatite and tricalcium phosphate have been widely used for promoting spinal fusion and reducing the complications caused by autograft. Whitlockite has been reported to promote better bone formation in rat calvaria models compare with them, but no study investigated its effect on spinal fusion yet. Also, the higher osteoinductivity of whitlockite raised concern of ectopic ossification, which was a complication of spinal fusion surgery that should be avoided. METHODS: In this study, we compared the osteoinductivity of whitlockite, hydroxyapatite, and tricalcium phosphate porous particles with SD rat spine posterolateral fusion model and investigated whether whitlockite could induce ectopic ossification with SD rat abdominal pouch model. RESULTS: The micro-CT result from the posterolateral fusion model showed whitlockite had slightly but significantly higher percent bone volume than tricalcium phosphate, though none of the materials formed successful fusion with surrounding bone tissue. The histology results showed the bone formed on the cortical surface of the transverse process but did not form a bridge between the processes. The result from the abdominal pouch model showed whitlockite did not induce ectopic bone formation. CONCLUSION: Whitlockite had a potential of being a better bone substrate hydroxyapatite and tricalcium phosphate in spinal fusion with low risk of inducing ectopic ossification.

Comparison of demineralized bone matrix and hydroxyapatite as carriers of Escherichia coli recombinant human BMP-2.

BACKGROUND: Autograft has been widely used in various orthopedic and dental surgery for its superior osteogenicity, osteoinductivity and osteoconductivity. But the available volume of the autograft is limited and the efficacy of it is highly affected by the condition of the patients. Therefore, growth factors such as Escherichia coli bone morphogenetic protein-2 (ErhBMP-2) has been widely used in some countries and regions with various carriers that could affect the effects of the growth factors. Demineralized bone matrix (DBM) has been widely used as a bone graft substitute and growth factor carrier, but its effect as a carrier of ErhBMP-2 was less investigated. MATERIALS AND METHODS: Rat calvaria defect model was used in this study. We implanted ErhBMP-2 with DBM or hydroxyapatite (HA) as a carrier in 8 mm calvaria defect and compared their bone regeneration effect in 4th week and 8th week after implantation with micro-CT and histology. The data was analyzed with one-way ANOVA method with Bonferroni post-hoc analysis. RESULT: The group with DBM as the carrier showed significantly higher bone volume and bone thickness than the groups with HA as the carrier in both weeks. And the histology sections showed less adipose tissue formed in the groups with DBM as the carrier. CONCLUSION: DBM could be a better carrier for ErhBMP-2 than HA.

Postoperative discal pseudocyst and its similarities to discal cyst: A case report.

BACKGROUND: Postoperative discal pseudocyst (PDP) is a rare condition that presents after surgery for lumbar disc herniation. Due to the lack of information, the diagnosis and treatment of PDP remain controversial. Herein, we report a PDP case that occurred following percutaneous endoscopic lumbar discectomy and received conservative treatment. Additionally, we review all the published literature regarding PDP and propose our hypothesis regarding PDP pathology. CASE SUMMARY: A 23-year-old man presented with a relapse of low back pain and numbness in his left lower extremity after undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation. Repeat magnetic resonance imaging demonstrated a cystic lesion at the surgical site with communication with the inner disc. The patient was diagnosed as having PDP. The patient received conservative treatment, which resulted in rapid improvement and spontaneous regression of the lesion, and had a favorable outcome in follow-up. CONCLUSION: PDP and discal cyst (DC) exhibit similarities in both histological and epidemiological characteristics, which indicates the same pathological origin of PDP and DC. The iatrogenic annular injury during discectomy might accelerate the pathological progression of DC. For patients with mild to moderate symptoms, conservative treatment can lead to great improvement, even inducing spontaneous regression. However, surgical cystectomy is necessary in patients with neurological deficits and where conservative treatment is ineffective.

Low shear stress regulates vascular endothelial cell pyroptosis through miR-181b-5p/STAT-3 axis.

Low shear stress and pyroptosis both play an important role in the onset and development of atherosclerosis (AS). MicroRNAs (miRNAs) are a kind of short (18-22) nucleotide sequences that can bind to the 3'-untranslated region (3'-UTR) of messenger RNA, thereby regulating programmed cell death including pyroptosis. However, the function of miRNAs in cells subjected to shear stress conditions is unknown. Therefore, we conducted the current study to demonstrate the effect of low shear stress on pyroptosis and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) stimulated by undisturbed shear stress (5 dynes/cm2 ) were the experimental group while HUVECs without shear stress treatment were the control group in our experiments. We observed that shear stress can suppress mechanosensitive miR-181b-5p expression, accompanying the elevated expression of NLRP3 inflammasome-dependent pyroptosis. Introduction of miR-181b-5p could alleviate NLRP3 inflammasome-dependent pyroptosis. Luciferase assay showed specific binding of miR-181b-5p to the 3'-UTR of signal transduction and transcriptional activation factor 3 (STAT-3) gene. Inhibition of STAT-3 gene expression at the posttranscriptional level results in the alleviation of NLRP3 inflammasome-dependent pyroptosis. Besides, the silencing of STAT-3 reduced anti-miR-181b-5p-mediated HUVEC pyroptosis via regulating NLRP3 inflammasome activation. Given the role of mechanosensitive miR-181b-5p and STAT-3 in the shear stress-induced pyroptosis, regulation of their expression levels may be a promising strategy to control AS.

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

BACKGROUND: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. METHODS: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. RESULTS: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). CONCLUSIONS: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. TRIAL REGISTRATION: chictr.org.cn, No. ChiCTR-TRC-12003513.

A novel 3D indirect co-culture system based on a collagen hydrogel scaffold for enhancing the osteogenesis of stem cells.

In this study, the paracrine effect between adipose-derived mesenchymal stem cells (ADSCs) and osteoblasts was investigated in collagen-based three-dimensional (3D) scaffolds. 3D encapsulation of mesenchymal stem cells in hydrogel scaffolds was conducted for bone tissue regeneration. Osteoblasts were encapsulated in alginate microbeads with uniform size, which could be controlled by varying the supply voltage using electrostatic droplet extrusion. Osteoblast-encapsulated microbeads were embedded with ADSCs in collagen bulk hydrogel scaffolds with a high survival rate. The separated space between the two types of cells made it possible to confirm ADSC differentiation into osteogenic lineages in the 3D collagen hydrogel scaffold by the paracrine effect in vitro. Furthermore, co-cultured ADSC and osteoblasts showed enhanced bone formation compared with the ADSC monoculture group in the rat calvarial defect model. The system developed in this study provides a novel in vitro tissue model for bone regeneration without exogenous factors, and it has the potential to be used to study the paracrine effect in various co-culture systems in the near future.

BMP-2 and hMSC dual delivery onto 3D printed PLA-Biogel scaffold for critical-size bone defect regeneration in rabbit tibia.

3D printing technology has various advantages, and the incorporation of bioactive substances into the 3D printed scaffold provides the biological and architectural characteristics of the scaffolds, which is very important for obtaining a good osseointegration effect. In this relation, this study prepared a novel porous hollow cage poly(lactic acid) (PLA) 3D printed scaffold and combined recombinant human bone morphogenetic protein-2 (rhBMP-2) and/or mesenchymal stem cells (MSCs) with Biogel composed of gelatin and alginate. Then, the scaffolds were used to evaluate the resulting bone regeneration through both in vitro and in vivo tests. The experimental group was divided into four groups as follows: only PLA scaffold (PLA); PLA scaffold filled with BMP-2 loaded on Biogel (P-BG-B2); PLA scaffold filled with MSCs encapsulated Biogel (P-BG-M); PLA scaffold filled with both BMP-2 and MSCs loaded on Biogel (P-BG-B2-M). Then in vitro results showed that the PLA-Biogel-based scaffold increased cell proliferation, and the P-BG-B2-M group showed a higher alkaline phosphatase activity and bone-related gene expression than was seen with the P-BG-M group at all the time points. It was shown that four weeks post-operative micro-CT analysis showed that within the defect site the P-BG-B2 group had a significantly higher percent bone volume (BV/TV) than the PLA group and P-BG-M group. And, out of the defect site, the P-BG-B2-M group BV/TV was shown significantly higher than the PLA group (p < 0.05). Histologically, defects in the P-BG-B2-M group showed a homogeneous new bone distribution, however the P-BG-B2 group and P-BG-M group presented a notably higher bone formation in the internal region than in the proximal region of the bone defect site. In conclusion, the 3D PLA-Biogel-based scaffold adapted rhBMP-2 and MSCs with carrier PLA showed good biocompatibility and high possibility as an effective and satisfactory bone graft material.

Relationship between Long Noncoding RNA H19 Polymorphisms and Risk of Coronary Artery Disease in a Chinese Population: A Case-Control Study.

METHODS: We collected 732 samples from Liaoning Province, China, and three polymorphisms in long noncoding RNA H19 were genotyped using the KASP platform. RESULTS: Our data showed that H19 rs2735971 and rs3024270 variant genotypes were associated with a decreased risk of CAD (rs2735971, P = 0.003, odds ratio (OR) = 0.6195, 95% confidence interval = 0.44 - 0.84; rs3024270, P = 0.030, OR = 0.65, 95% confidence interval = 0.44 - 0.96). No significant association with the risk of CAD was found for H19 rs2839698 polymorphism (P > 0.05). In haplotype analysis, H19 polymorphisms of rs2735971-rs2839698-rs3024270 A-C-C haplotype reduced the risk of CAD by 0.61-fold (P = 0.004, OR = 0.61, 95% confidence interval = 0.43-0.86). In addition, we found that rs2839698 interacted with smoking (P interaction = 0.027), and according to multifactor dimensionality reduction analysis, the three-factor model including H19 rs2839698-smoking-drinking was the best model for the risk of CAD (testing balanced accuracy = 0.6979). CONCLUSION: Our study demonstrated that some genotypes of H19 rs2735971 and rs3024270 polymorphisms, as well as rs2735971-rs2839698-rs3024270 A-C-C haplotype, were associated with the risk of CAD in a Chinese population, and these genotypes have the potential to be biomarkers for predicting CAD risk. We also found that rs2735971-rs2839698-rs3024270 A-C-C may have a significantly lower risk of CAD. The recessive genetic model of rs3024270 could predict the severity of CAD.