EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis.

Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion. Dysregulation of Egfl7 has been frequently found in several types of cancers, such as malignant glioma, colorectal carcinoma, oral and oesophageal cancers, gastric cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, lung cancer, osteosarcoma, and acute myeloid leukemia. In addition, altered expression of miR-126, a microRNA associated with Egfl7, was found to play an important role in oncogenesis. More recently, our study has shown that EGFL7 is expressed in both the osteoclast and osteoblast lineages and promotes endothelial cell activities via extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and integrin signaling cascades, indicative of its angiogenic regulation in the bone microenvironment. Thus, understanding the role of EGFL7 may provide novel insights into the development of improved diagnostics and therapeutic treatment for cancers and skeletal pathological disorders, such as ischemic osteonecrosis and bone fracture healing.

Did angiodysplasia associated with heyde's syndrome disappear spontaneously?: a case report.

BACKGROUND: Heyde's syndrome can be easily overlooked or misjudged in clinical practice because it shares common clinical manifestations with multiple diseases as well as limited accuracy of several corresponding examinations for diagnosing Heyde's triad. Moreover, aortic valve replacement is often delayed in these patients due to the contradiction between anticoagulation and hemostasis. Herein, we present a rare case of atypical Heyde's syndrome. The patient's severe intermittent gastrointestinal bleeding was not completely cured even through a local enterectomy. In the absence of direct evidence of acquired von Willebrand syndrome (AVWS) or angiodysplasia, her long-standing gastrointestinal bleeding was finally stopped after receiving transcatheter aortic valve implantation (TAVI). CASE PRESENTATION: A 64-year-old female suffered from refractory gastrointestinal bleeding and exertional dyspnoea. A local enterectomy was performed owing to persistent hemorrhage and repeated transfusions; subsequently, histological examination revealed angiodysplasia. Heyde's syndrome was not suspected until 3 years later, at which time the patient started bleeding again and was also found to have severe aortic valve stenosis upon echocardiography. TAVI was consequently performed when the patient was in a relatively stable condition even though the predisposition to bleed, but there was no evidence of angiodysplasia and AVWS during angiography at that time. The patient's above symptoms were significantly relieved after TAVI and followed up for 2 years without any significant ischemic or bleeding events. CONCLUSIONS: The visible characteristics of angiodysplasia or a shortage of HMWM-vWFs should not be indispensable for the clinical diagnosis of Heyde's syndrome. Enterectomy could be a bridging therapy for aortic valve replacement in patients with severe hemorrhage, and TAVI may be beneficial for moderate to high surgical-risk patients even if they have a potential risk of bleeding.

Asperuloside alleviates lipid accumulation and inflammation in HFD-induced NAFLD via AMPK signaling pathway and NLRP3 inflammasome.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome of hepatic parenchymal cell steatosis caused by excessive lipid deposition, which is the chronic liver disease with the highest incidence in China. Asperuloside (ASP), a kind of iridoid compound, possesses natural pharmacological effects of anti-tumor, anti-inflammatory, antioxidant and anti-obesity. However, whether ASP can improve NAFLD remains unclear. PURPOSE: We aimed to investigate the effect of ASP on NAFLD mice induced by high-fat diet (HFD), and explore its mechanism in vivo and in vitro. METHODS: Pharmacodynamics of ASP was studied by HFD induction in NAFLD mice. HepG2 cells were induced by palmitic acid (PA) as cell model to investigate the effect of ASP on lipid deposition and inflammatory infiltration. Expression of Adenosine monophosphate - activated protein kinase (AMPK) signaling pathway and NOD-like receptor pyrin containing 3 (NLRP3) inflammasome were detected by Western blot and RT-PCR. Cytokines IL-1ß and TNF-α were detected by ELISA. RESULTS: ASP alleviated liver injury and inflammatory damage in mice with NAFLD. In addition, ASP improved lipid deposition as well as inflammatory response in HFD-induced NAFLD mice and PA-stimulated HepG2 cells. ASP ameliorated lipid deposition and inflammatory response by regulating the p-AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome. CONCLUSION: Our results suggest that ASP improve lipid deposition and inflammatory infiltration in NAFLD mice via regulating the AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome, which may be an effective candidate for the treatment of NAFLD.

Intervention of Compound Xueshuantong Capsule on the incidence of heart failure in patients with acute myocardial infarction after PCI based on the combination of disease and syndrome: A multi-center, randomized, double-blind, controlled trial.

BACKGROUND: Heart failure (HF), manifested as a severe or end stage of various cardiac diseases, is characterized by increased incidence, mortality, re-hospitalization, and economic burden. Myocardial infarction (MI) is one of the most common and important causes of HF. Since 2005, acute MI (AMI)-associated mortality in China has been on the rise, and MI accounts for 23.1% of the causes of HF. Traditional Chinese medicine (TCM) has the unique advantages of controlling angina pectoris and HF symptoms, and improving patients' quality of life. Compound Xueshuantong Capsule (CXSTC), also named as Fufang Xueshuantong Capsule, has the effect of increasing cardiac output and protecting myocardial function. In this trial, we aim to investigate the efficacy and safety of CXSTC in the prophylactic treatment of post-infarction HF and attempt to provide a clinical evidence-based basis for the prophylactic treatment of HF after AMI using TCM. METHODS: This will be a multi-center, randomized, double-blind, placebo-parallel controlled trial. A total of 300 patients diagnosed with AMI and undergoing percutaneous coronary intervention within 12 hours of diagnosis will be randomized 1:1 into 2 groups: the control group that will be administered conventional Western medicine plus placebo and the trial group that will be administered XST along with the conventional Western medicine. The duration of treatment will be 3 months and the follow-up will be up to 6 months for both groups. The main efficacy indicator is the incidence of HF. The secondary efficacy indicators are cardiac function classification, 6-minute walk test score, TCM syndrome score, survival quality score, brain natriuretic peptide level, ultrasensitive C-reactive protein level, and cardiac ultrasound result. Data will be collected to analyze the underlying mechanisms by using IBM SPSS 23.0 software. DISCUSSION: By investigating the efficacy and safety of CXSTC, this study will provide a clinical evidence base for the use of TCM in the prophylactic treatment of post-infarction HF.

Model for nerve visualization in preoperative image data based on intraoperatively gained EMG signals.

While removing bone tissue of the mastoid, the facial nerve is at risk of being injured. In this contribution a model for nerve visualization in preoperative image data based on intraoperatively gained EMG signals is proposed. A neuro monitor can assist the surgeon locating and preserving the nerve. With the proposed model gained EMG signals can be spatially related to the patient resp. the image data. During navigation the detected nerve course will be visualized and hence permanently available for assessing the situs.

Nerve block using a navigation system and ultrasound imaging for regional anesthesia.

During the last few years, regional anesthesia using ultrasound imaging has increased dramatically in both clinical and research areas. This method provides a direct noninvasive imaging of the targeted nerve and the tissue around it in real time. Furthermore, it allows anesthetists to observe the injected anesthetics for optimal distribution. However, there are still some major limitations to this method such as poor visibility of the standard needle tip and shaft, tricky location estimation of needle tip, and difficult needle alignment before and during insertion. This article presents the concept of a new application field of medical navigation for regional anesthesia using ultrasound imaging, to avoid the above-mentioned drawbacks. In addition, a laboratory experiment on a phantom to verify the effectiveness, safety, precision and handling of the navigation method in comparison with standard ultrasound-guided regional anesthesia is described. During the experiment ten test persons who have no experience in this field should touch a target in a phantom, avoiding contact with the simulated blood vessels and nerve. Each test person was asked to repeat the test five times with and without navigation assistance, respectively. Thereafter, a two-sample one-tailed paired t-test with a significance level of 1% was applied to statistically analyze the difference. The results show that navigation assistance significantly improves effectiveness, safety, precision and handling of ultrasound-guided regional anesthesia.

Surgical assistance for instruments' power control based on navigation and neuromonitoring.

In order to prevent nerve injuries during ear-nose-throat (ENT) and skull base surgery, the method Navigated Control Functional is presented. Thereby, the power of active instruments is controlled based on position information, provided by a surgical navigation system, and nerve activity information, provided by a neurophysiologic monitoring system. Electrical stimulation is usually required for the extraction of distance information from neurophysiologic signals (e.g., Electromyography (EMG)). However, this article presents an experiment to investigate a possible relationship between EMG signals and the nerve-instrument distance without additional electrical stimulation. The EMG signals and position information were recorded intra-operatively during ear surgery. An off-line statistical analysis with Spearman's rank correlation coefficient was accomplished. The results show that there is occasionally some correlation at a statistically significant level of 5%. They highly depend on time range, the selected threshold value and time window. Moreover, all the observed correlations are positive against an expected negative correlation.

Accuracy study of a new assistance system under the application of Navigated Control® for manual milling on a head phantom.

In this article, a technical study of a new assistance system to support surgeons in milling on the temporal bone is presented. In particular, the overall accuracy of a new assistance system was investigated experimentally under conditions close to surgical practice. For the experiment, the assistance system has been used with its associated navigation system for ear-nose-throat (ENT) surgery. A specially constructed head phantom allowed the implementation of reproducible experiments. Thereby, N = 10 specimens were milled by three test persons without medical knowledge and the distance between points on the milled surface and the security zone around the planned nerve for each specimen were calculated. The result was as follows: None of the 10 milled specimens overlapped more than 2mm with the security zone, the average distances to the planned surface of the security zone for each specimen were between 0.01mm and 2.23mm, and the corresponding standard deviations varied from 0.41mm to 1.17mm. But it also shows some variation in averages and standard deviations and it was often too little material removed. This deviation is probably caused by the patient registration and the tool calibration.