Association between hyperuricemia and the risk of mortality in patients with osteoarthritis: A study based on the National Health and Nutrition Examination Survey database.

BACKGROUND: The purpose of this study was to evaluate the relationship between hyperuricemia and the risks of all-cause mortality and cardiovascular disease (CVD) mortality in patients with osteoarthritis (OA). METHODS: A retrospective cohort study was performed on 3,971 patients using data from the National Health and Nutrition Examination Survey database between 1999 and 2018. OA was diagnosed through specific questions and responses. The weighted COX regression models were used to explore the factors associated with all-cause mortality/CVD mortality in OA patients. Subgroup analyses were conducted based on age, gender, hypertension, dyslipidemia, CVD, and chronic kidney disease (CKD). Hazard ratio (HR) and 95% confidence interval (95% CI) were measured as the evaluation indexes. RESULTS: During the duration of follow-up time (116.38 ± 2.19 months), 33.69% (1,338 patients) experienced all-cause mortality, and 11.36% (451 patients) died from CVD. Hyperuricemia was associated with higher risks of all-cause mortality (HR: 1.22, 95% CI: 1.06-1.41, P = 0.008) and CVD mortality (HR: 1.32, 95% CI: 1.02-1.72, P = 0.036) in OA patients. Subgroup analyses showed that hyperuricemia was related to the risk of all-cause mortality in OA patients aged >65 years (HR: 1.17, 95% CI: 1.01-1.36, P = 0.042), in all male patients (HR: 1.41, 95% CI: 1.10-1.80, P = 0.006), those diagnosed with hypertension (HR: 1.17, 95% CI: 1.01-1.37, P = 0.049), dyslipidemia (HR: 1.18, 95% CI: 1.01-1.39, P = 0.041), CVD (HR: 1.30, 95% CI: 1.09-1.55, P = 0.004), and CKD (HR: 1.31, 95% CI: 1.01-1.70, P = 0.046). The association between hyperuricemia and a higher risk of CVD mortality was found in OA patients aged ≤ 65 years (HR: 1.90, 95% CI: 1.06-3.41, P = 0.032), who did not suffer from diabetes (HR: 1.36, 95% CI: 1.01-1.86, P = 0.048), who did not suffer from hypertension (HR: 2.56, 95% CI: 1.12-5.86, P = 0.026), and who did not suffer from dyslipidemia (HR: 2.39, 95% CI: 1.15-4.97, P = 0.020). CONCLUSION: These findings emphasize the importance of monitoring serum uric acid levels in OA patients for potentially reducing mortality associated with the disease.

Transcriptional regulation of Glis2 in hepatic fibrosis.

The role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)-a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFß1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.

Development and Application of a Standardized Testset for an Artificial Intelligence Medical Device Intended for the Computer-Aided Diagnosis of Diabetic Retinopathy.

Objective: To explore a centralized approach to build test sets and assess the performance of an artificial intelligence medical device (AIMD) which is intended for computer-aided diagnosis of diabetic retinopathy (DR). Method: A framework was proposed to conduct data collection, data curation, and annotation. Deidentified colour fundus photographs were collected from 11 partner hospitals with raw labels. Photographs with sensitive information or authenticity issues were excluded during vetting. A team of annotators was recruited through qualification examinations and trained. The annotation process included three steps: initial annotation, review, and arbitration. The annotated data then composed a standardized test set, which was further imported to algorithms under test (AUT) from different developers. The algorithm outputs were compared with the final annotation results (reference standard). Result: The test set consists of 6327 digital colour fundus photographs. The final labels include 5 stages of DR and non-DR, as well as other ocular diseases and photographs with unacceptable quality. The Fleiss Kappa was 0.75 among the annotators. The Cohen's kappa between raw labels and final labels is 0.5. Using this test set, five AUTs were tested and compared quantitatively. The metrics include accuracy, sensitivity, and specificity. The AUTs showed inhomogeneous capabilities to classify different types of fundus photographs. Conclusions: This article demonstrated a workflow to build standardized test sets and conduct algorithm testing of the AIMD for computer-aided diagnosis of diabetic retinopathy. It may provide a reference to develop technical standards that promote product verification and quality control, improving the comparability of products.

Practice toward standardized performance testing of computer-aided detection algorithms for pulmonary nodule.

This study aimed at implementing practice to build a standardized protocol to test the performance of computer-aided detection (CAD) algorithms for pulmonary nodules. A test dataset was established according to a standardized procedure, including data collection, curation and annotation. Six types of pulmonary nodules were manually annotated as reference standard. Three specific rules to match algorithm output with reference standard were applied and compared. These rules included: (1) "center hit" [whether the center of algorithm highlighted region of interest (ROI) hit the ROI of reference standard]; (2) "center distance" (whether the distance between algorithm highlighted ROI center and reference standard center was below a certain threshold); (3) "area overlap" (whether the overlap between algorithm highlighted ROI and reference standard was above a certain threshold). Performance metrics were calculated and the results were compared among ten algorithms under test (AUTs). The test set currently consisted of CT sequences from 593 patients. Under "center hit" rule, the average recall rate, average precision, and average F1 score of ten algorithms under test were 54.68, 38.19, and 42.39%, respectively. Correspondingly, the results under "center distance" rule were 55.43, 38.69, and 42.96%, and the results under "area overlap" rule were 40.35, 27.75, and 31.13%. Among the six types of pulmonary nodules, the AUTs showed the highest miss rate for pure ground-glass nodules, with an average of 59.32%, followed by pleural nodules and solid nodules, with an average of 49.80 and 42.21%, respectively. The algorithm testing results changed along with specific matching methods adopted in the testing process. The AUTs showed uneven performance on different types of pulmonary nodules. This centralized testing protocol supports the comparison between algorithms with similar intended use, and helps evaluate algorithm performance.

Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma growth and metastasis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of tumour-related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2. METHODS: Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT-PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT-related markers. CCK-8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull-down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RESULTS: Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo. CONCLUSION: Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.

Core Decompression with Local Administration of Zoledronate and Enriched Bone Marrow Mononuclear Cells for Treatment of Non-Traumatic Osteonecrosis of Femoral Head.

OBJECTIVE: To investigate the efficacy and safety of core decompression (CD) with local administration of zoledronate and enriched bone marrow mononuclear cells (BMMCS) for the treatment of non-traumatic osteonecrosis of femoral head (ONFH). METHODS: A total of 17 patients (30 hips) diagnosed with stage II and III ONFH according to the 2019 revised Association for Research on Osseous Circulation (ARCO) staging criteria from 2012 to 2014 were retrospectively reviewed. The patients received the following therapy: the BMMCs and zoledronate were injected into the necrotic zone, respectively, along with CD. The mean age of the patients was 36.8 years; 14 were men and three were women. All patients included had non-traumatic ONFH and a minimum follow-up of 5 years, which ended when total hip arthroplasty (THA) was performed. Imaging modalities, including plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI) were taken pre- and postoperatively. Harris hip score (HHS) was used to evaluate the functional outcomes of femoral head necrosis. Kaplan-Meier analysis was adopted to determine the probability of survivorship with THA as the end point in this series of patients. The correlation between radiological progression or THA and related risk factors were further analyzed. All complications were recorded. RESULTS: With THA as the follow-up endpoint, All patients were followed up for an average of 69.1 ± 20.5 months (range, 18-95 months). Preoperative imaging found six hips (20%) at ARCO stage II, 14 hips (46.7%) at stage IIIA, 10 hips (33.3%) at stage IIIB. Fourteen hips (46.7%) shown progression radiologically, while six hips (20%) underwent TKA among these patients with hip preservation. The cumulative survival was 80% (95% CI, 0.608-905) at 5 years with THA as the end point. HHS improved from 63.3 ± 8.7 preoperatively to 74.6 ± 20.6 postoperatively (P = 0.000). Radiological progression was found to be associated with ARCO stage, Japanese Investigation Committee (JIC) type, and corticosteroid exposure (P = 0.047; P = 0.012; P = 0.031). However, no correlation was found between conversion to THA and the known risk factors. No major complication was reported, with only four patients complaining about general weakness and muscle soreness, and all disappeared within 2-3 days. CONCLUSIONS: The novel treatment modality could relieve pain, delay the progression of collapse, which might be an effective and safe method for hip preservation of early and mid-term ONFH. However, the effect of this method may be related to ARCO stage, JIC type, and corticosteroid exposure.

Three-Dimensional Distribution of Bone-Resorption Lesions in Osteonecrosis of the Femoral Head Based on the Three-Pillar Classification.

OBJECTIVE: To investigate three-dimensional distribution of bone-resorptive lesions based on the three-pillar classification and its effect on the disease progression of osteonecrosis of the femoral head (ONFH). METHODS: A total of 194 femoral head CT images from 117 patients diagnosed with ARCO stage II and III ONFH were retrospectively reviewed from April 2014 to February 2019. Three-dimensional structures of the femoral head and the bone-resorptive lesions were reconstructed. Using the three-pillar classification and coronal plane of the femoral head, we divided each femoral head into six regions to observe the location characteristics of bone-resorption lesions, and explore the destruction of different areas of the femoral head by the bone-resorptive lesions. Then the hips were divided into two groups based on whether they contained bone-resorption lesions and compared the difference of stage II and stage III between the two groups. RESULTS: The regional distribution revealed 39 (27.27%), 55 (38.46%), six (4.20%), 23 (16.08%), 17 (11.89%) and three (2.10%) bone-resorptive lesions in regions I, II, III, IV, V and VI respectively. The lateral pillar, AL (I + IV), contained 44.76% of the lesions, central pillar, C (II + V), 48.95%, and medial pillar, M (III + VI), 6.29%. Moreover, there were 81.82% bone-resorption lesions in anterolateral pillar, AL (I + II + IV), and 18.18% in posteromedial pillar, PM (III + V + VI). In all ONFH hips, the lateral pillar of 81(88.04%) femoral heads were affected, the central pillar of 84 (91.30%) femoral heads were affected, and the medical pillar of 29 (31.52%) femoral heads were affected. The ratio of ARCO stage III in the group with bone-resorption lesions was significantly higher than that of the group without bone-resorption lesions (76.09% vs 30.39%, P < 0.001). CONCLUSIONS: This study demonstrated that the bone-resorption lesions are mainly distributed in the lateral and central pillar of the femoral head, and the two pillars of the femoral head are usually involved by bone-resorption lesions. Furthermore, the ratio of ARCO stage III in the group with bone-resorption lesions was significantly higher than that of the group without bone-resorption lesions, suggesting that the bone-resorption lesions might accelerate the progression of ONFH.

Recombinant human epidermal growth factor combined with vacuum sealing drainage for wound healing in Bama pigs.

BACKGROUND: Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF. METHODS: We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups. RESULTS: An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score. CONCLUSIONS: A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.

Bioinformatic analysis of cytokine expression in the proximal and distal nerve stumps after peripheral nerve injury.

In our previous study, we investigated the dynamic expression of cytokines in the distal nerve stumps after peripheral nerve injury using microarray analysis, which can characterize the dynamic expression of proteins. In the present study, we used a rat model of right sciatic nerve transection to examine changes in the expression of cytokines at 1, 7, 14 and 28 days after injury using protein microarray analysis. Interleukins were increased in the distal nerve stumps at 1-14 days post nerve transection. However, growth factors and growth factor-related proteins were mainly upregulated in the proximal nerve stumps. The P-values of the inflammatory response, apoptotic response and cell-cell adhesion in the distal stumps were higher than those in the proximal nerve stumps, but the opposite was observed for angiogenesis. The number of cytokines related to axons in the distal stumps was greater than that in the proximal stumps, while the percentage of cytokines related to axons in the distal stumps was lower than that in the proximal nerve stumps. Visualization of the results revealed the specific expression patterns and differences in cytokines in and between the proximal and distal nerve stumps. Our findings offer potential therapeutic targets and should help advance the development of clinical treatments for peripheral nerve injury. Approval for animal use in this study was obtained from the Animal Ethics Committee of the Chinese PLA General Hospital on September 7, 2016 (approval No. 2016-x9-07).

11ß­hydroxysteroid dehydrogenase­1 is associated with the activation of hepatic stellate cells in the development of hepatic fibrosis.

Hepatic fibrosis (HF) is a common complication of numerous chronic liver diseases, but predominantly results from persistent liver inflammation or injury. If left untreated, HF can progress and develop into liver cirrhosis and even hepatocellular carcinoma. However, the underlying molecular mechanisms of HF remain unknown. The present study aimed to investigate the role of 11ß­hydroxysteroid dehydrogenase­1 (11ß­HSD1) during the development of hepatic fibrosis. An experimental rat model of liver fibrosis was induced using porcine serum. 11ß­HSD1 gene expression levels and enzyme activity during hepatic fibrogenesis were assessed. 11ß­HSD1 gene knockdown using small interfering RNA and overexpression were performed in LX2­human hepatic stellate cells (HSCs). HSCs were stimulated with transforming growth factor­ß1 (TGF­ß1). Cell cycle distribution, proliferation, collagen secretion and 11ß­HSD1 gene activity in HSCs were compared before and after stimulation. As hepatic fibrosis progressed, 11ß­HSD1 gene expression and activity increased, indicating a positive correlation with typical markers of liver fibrosis. 11ß­HSD1 inhibition markedly reduced the degree of fibrosis. The cell proliferation was increased, the number of cells in the G0/G1 phase decreased and the number of cells in the S and G2/M phases increased in the pSuper transfected group compared with the N group. In addition, the overexpression of 11ß­HSD1 enhanced the TGF­ß1­induced activation of LX2­HSCs and enzyme activity of connective tissue growth factor. 11ß­HSD1 knockdown suppressed cell proliferation by blocking the G0/G1 phase of the cell cycle, which was associated with HSC stimulation and inhibition of 11ß­HSD1 enzyme activity. In conclusion, increased 11ß­HSD1 expression in the liver may be partially responsible for hepatic fibrogenesis, which is potentially associated with HSC activation and proliferation.

Study on in vitro performance verification protocol for left ventricular assist device.

OBJECTIVE: In vitro performance verification of ventricular assist devices using a mock circulatory loop is a prominent step to guarantee the system responses and the device performance and safety before the in vivo tests and ultimately clinical trials. METHODS: In this article, we performed a comprehensive literature research to establish a verification matrix consisting of 12 test cases, defined by a set of physiological parameters which are commonly used to characterize a physiological condition. The clinical hemodynamic indicators for defining successful mechanical support were used as the acceptance criteria. A mock circulatory loop was customized to simulate the test cases, and a full verification protocol was described in details. An example left ventricular assist device was incorporated in the loop to accomplish a standard ventricular assist device performance verification. RESULT: The test cases based on clinical data with sufficient safety margin represent our understanding in defining the extremes of operation. The mock circulatory loop was capable of generating the test conditions in the verification matrix and reproducing the Frank-Starling law of the native heart. The effect of the left ventricular assist device assistance (characterized by the total systemic flow, mean aortic pressure, and left atrial pressure) was well verified by the proposed protocol and acceptance criteria. CONCLUSION: To date, all left ventricular assist devices made in China have been evaluated according this protocol and some of them have entered the clinical trial stage. We are closely observing the clinical data in order to further improve the performance of the platform and encourage more advances in mechanical circulatory assist devices.

Chronic epididymitis and leptin and their associations with semen characteristics in men with infertility.

PROBLEM: The aim of this study was to ascertain the associations between serum leptin levels and chronic epididymitis and semen parameters in patients with infertility. METHOD OF STUDY: A total of 846 patients who were diagnosed as primary infertility were enrolled and divided into four groups. The general information, blood lipids, reproductive hormones, and semen parameters were collected. Receiver operating characteristic (ROC) curves of leptin were plotted for diagnosis of the poor sperm quality. We used Student's t test and the chi-squared test to analyze their relationships and used logistic regression analysis to evaluate potential confounding factors. RESULTS: Receiver operating characteristic curve revealed that leptin had better sensitivity and specificity at the concentration of 6.02 (0.565 and 0.917). Isolated epididymitis or elevated leptin had no effect on sperm concentration and sperm membrane function, but the combination of these conditions would reduce the concentration and normal morphology rate both (P = 0.002, P = 0.005). Epididymitis or elevated leptin can affect the motility of sperms, the former presented more significance (P = 0.000), and the co-existence would further reduce the sperm motility (P = 0.001). CONCLUSION: Low sperm motility and sperm normal morphology were found to be associated with chronic epididymitis and high leptin. Simultaneously suffering from chronic epididymitis and high leptin could produce a more serious effect on sperm quality.

Aligned fibers enhance nerve guide conduits when bridging peripheral nerve defects focused on early repair stage.

Nerve conduits enhance nerve regeneration in the repair of long-distance peripheral nerve defects. To help optimize the effectiveness of nerve conduits for nerve repair, we developed a multi-step electrospinning process for constructing nerve guide conduits with aligned nanofibers. The alignment of the nerve guide conduits was characterized by scanning electron microscopy and fast Fourier transform. The mechanical performance of the nerve guide conduits was assessed by testing for tensile strength and compression resistance. The biological performance of the aligned fibers was examined using Schwann cells, PC12 cells and dorsal root ganglia in vitro. Immunohistochemistry was performed for the Schwann cell marker S100 and for the neurofilament protein NF200 in PC12 cells and dorsal root ganglia. In the in vivo experiment, a 1.5-cm defect model of the right sciatic nerve in adult female Sprague-Dawley rats was produced and bridged with an aligned nerve guide conduit. Hematoxylin-eosin staining and immunohistochemistry were used to observe the expression of ATF3 and cleaved caspase-3 in the regenerating matrix. The recovery of motor function was evaluated using the static sciatic nerve index. The number of myelinated fibers, axon diameter, fiber diameter, and myelin thickness in the distal nerve were observed by electron microscopy. Gastrocnemius muscle mass ratio was also determined. The analyses revealed that aligned nanofiber nerve guide conduits have good mechanical properties and can induce Schwann cells, PC12 cells and dorsal root ganglia to aggregate along the length of the nanofibers, and promote the growth of longer axons in the latter two (neuronal) cell types. The aligned fiber nerve conduits increased the expression of ATF3 and cleaved caspase-3 at the middle of the regenerative matrix and at the distal nerve segment, improved sciatic nerve function, increased muscle mass of the gastrocnemius muscle, and enhanced recovery of distal nerve ultrastructure. Collectively, the results show that highly aligned nanofibers improve the performance of the nerve conduit bridge, and enhance its effectiveness in repairing peripheral nerve defects.

Differentiation of adipose-derived stem cells into Schwann cell-like cells through intermittent induction: potential advantage of cellular transient memory function.

BACKGROUND: Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory. METHODS: Here, we propose an intermittent induction method with alternate use of complete and incomplete induction medium to induce differentiation of adipose-derived stem cells (ASCs) to SCLCs. The time dependence of traditional induction methods and the efficiency of the intermittent induction method and traditional induction methods were evaluated and compared using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and co-culture with the dorsal root ganglion (DRG) in vitro. Cell transplantation was used to compare the effects of the traditional induction method and the intermittent induction method in repairing sciatic nerve defects in vivo. RESULTS: The results of the present study indicated that the intermittent induction method is more efficient than traditional methods for inducing ASCs to differentiate into SCLCs. In addition, SCLCs induced by this method were closer to mature myelinating Schwann cells and were capable of secreting neurotrophins and promoting DRG axon regeneration in vitro. Furthermore, SCLCs induced by the intermittent induction method could repair sciatic nerve defects in rats by cell transplantation in vivo more effectively than those produced by traditional methods. CONCLUSION: Intermittent induction represents a novel strategy for obtaining seed cells for use in nerve tissue engineering.

Anomalous resonant reflection in a Fabry-Perot cavity filled with weakly scattering medium.

In this work, we fabricated a metallic Fabry-Perot cavity, filled with a weakly scattering medium of unsintered solgel silica, on a glass substrate. We found anomalous asymmetric resonance reflection spectra of this structure, besides the effects of scattering loss in cavity. The asymmetric reflection is shown to be dependent on the media on both sides of the cavity. It is thought that, as the weakly scattering medium locates between highly reflecting boundaries and the cavity length is far less than the mean free path of light in the medium, light scattering in the medium is enhanced at the resonance conditions and the scattering centers act as elementary sources emitting the scattered incoherent light to the outside of the cavity from both its ends. The asymmetric reflection then results from lossy total internal reflection of the scattered light at one of the boundaries, eventually leaking to the outside of the cavity with the higher index and contributing to the measured backside reflectance.

Comparisons of three different doses of alirocumab application in patients with hypercholesterolemia: a meta-analysis.

INTRODUCTION: Low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels are associated with incidence of cardiovascular disease (CVD). Alirocumab has been considered as an efficacious, safe and promising therapeutic modality for hypercholesterolemia. The purpose of this study is to compare the differences of the three different doses of alirocumab in patients with hypercholesterolemia. EVIDENCE ACQUISITION: Randomized controlled trials were identified from PubMed, EMBASE, PMC and Cochrane-library databases. The inter-comparison of different doses were performed by subgroups analysis. Meta-analyses were performed by the Review Manager 5.3 and STATA 13.0 software. EVIDENCE SYNTHESIS: A total of nine studies involving 3870 patients were included in this meta-analysis. Alirocumab administered at 75-150 mg every 2 weeks (Q2W) resulted in a greater percent change from baseline in LDL-C concentrations (MD, -55.17; 95% CI: -64.35 to -45.99; P<0.05), and HDL-C levels (MD, 7.70; 95% CI 5.94 to 9.46; P<0.05) than other two doses (300 mg every 4 weeks [Q4W], 150 mg every 2 weeks [Q2W]). There was no difference in achieving the treatment goal of LDL-C (≤1.8 mmol/L), in other serum lipid parameters (total cholesterol [TC], triglyceride [TG]), and in the incidence of adverse events. CONCLUSIONS: The results demonstrate that alirocumab at a dose of 75-150 mg Q2W should be preferred in patients with hypercholesterolemia.

Gene expression profiling analysis reveals fur development in rex rabbits (Oryctolagus cuniculus).

Fur is an important economic trait in rabbits. The identification of genes that influence fur development and knowledge regarding the actions of these genes provides useful tools for improving fur quality. However, the mechanism of fur development is unclear. To obtain candidate genes related to fur development, the transcriptomes of tissues from backs and bellies of Chinchilla rex rabbits were compared. Of the genes analyzed, 336 showed altered expression in the two groups (285 upregulated and 51 downregulated, P ≤ 0.05, fold-change ≥2 or ≤0.5). Using GO and KEGG to obtain gene classes that were differentially enriched, we found several genes to be involved in many important biological processes. In addition, we identified several signaling pathways involved in fur development, including the Wnt and MAPK signaling pathways, revealing mechanisms of skin and hair follicle development, and epidermal cell and keratinocytes differentiation. The obtained rabbit transcriptome and differentially expressed gene profiling data provided comprehensive gene expression information for SFRP2, FRZB, CACNG1, SLC25A4, and SLC16A3. To validate the RNA-seq data, the expression levels of eight differentially expressed genes involved in fur development were confirmed by qRT-PCR. The results of rabbit transcriptomic profiling provide a basis for understanding the molecular mechanisms of fur development.

Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration.

The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

Use of electrospinning to construct biomaterials for peripheral nerve regeneration.

A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.