Risk of Bleeding Following Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. Design, Setting, and Participants: This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. Exposures: NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. Main Outcomes and Measures: The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Results: Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. Conclusions and Relevance: In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.

Cadmium stress interacts with nutrient availability and light condition to affect the growth of Hydrocotyle vulgaris.

Heavy metal pollution is becoming a serious problem in wetland and often co-occurs with nutrient availability and light conditions variation. We hypothesized that nutrient availability and light condition can affect the growth of wetland plants under heavy metal stress. To test this hypothesis, single ramets of a common, clonal wetland plant Hydrocotyle vulgaris were grown for four weeks at three levels of cadmium with three levels of nutrient availability under 30% or 100% light conditions. High level of nutrient availability and high light condition overall promoted growth of H. vulgaris under Cd stress. Under the two light conditions, responses of H. vulgaris to Cd treatments differed among three nutrient levels. Under 30% light condition, 2 mg L-1 Cd2+ treatment decreased total mass at the low nutrient level and decreased ramet number at the medium nutrient level; 0.5 and 2 mg L-1 Cd2+ treatments decreased leaf mass ratio at the low and the medium nutrient levels. Under 100% light condition, 2 mg L-1 Cd2+ treatments significantly decreased total mass at the high level of nutrients; 2 mg L-1 Cd2+ treatment decreased ramet number at the medium and the high nutrient levels and decreased leaf mass ratio at the medium nutrient levels. Our results suggested that Cd stress can interact with nutrient availability and light condition to affect the performance of wetland plants such as H. vulgaris.

H2O2/NIR-sensitive "two-step" nano theranostic system based hollow mesoporous copper sulfide/hyaluronic acid/JWH133 as an optimally designed delivery system for multidimensional treatment of RA.

Cannabinoid receptors are widely distributed in many cells in Rheumatoid arthritis RA and strengthening factor to boost the development of RA diseases. Here, the hollow mesoporous copper sulfide (CuS) was used as the carrier skeleton and the cannabinoid type 2 (CB2) receptor agonist JWH133 was efficiently loaded inside of CuS through adsorption, then the outer layer was modified with hyaluronic acid (HA) to prevent the leakage of internal drugs. After the CuS-JWH133@HA nano carrier reached the target area, HA responsive cracked under RA microenvironment to realize the first step of accurate drug delivery of JWH133, and the thermally responsive CuS under near-infrared (NIR) promoted the release of internal drugs. Then, JWH133 specifically combined CB2 receptors on the surface of macrophage, synovial cells and osteoblasts to realize the second step of drug delivery. The inflammatory factors secreted by cells are significantly inhibited, and the activity of osteoblasts was significantly enhanced. Therapeutic effect by CuS-JWH133@HA of RA was well verified by decreasing levels of inflammation in vivo and improvement of inflamed and swollen joints of mice. The CuS-JWH133@HA nanocomposite showed satisfactory multidimensional therapeutic effect of RA in vitro and in vivo, which provided a novel idea for RA treatment.

Adsorption properties and mechanism research of phosphorus with different molecular structures from aqueous solutions by La-modified biochar.

In order to explore the adsorption characteristics of phosphorus from molecules with different molecular structures and varying number of phosphate groups on metal-modified biochar, walnut shell biochar was modified with LaCl3 to prepare lanthanum-loaded biochar (BC-La). Adsorption of four polar components, namely phytic acid (IHP), adenosine-5'-disodium triphosphate (5-ATP), hydroxyethylidene diphosphonic acid (HEDP), and sodium pyrophosphate (PP), was studied. The adsorption properties and mechanism of phosphorus sorption by BC-La were analyzed by SEM-EDS and FTIR for the different structures. The results showed that the maximum adsorption capacity of BC-La for IHP, 5-ATP, HEDP, and PP was 85.85, 9.04, 15.80, and 14.45 mg/g, respectively. The adsorption capacity was positively correlated with the polarity of organic phosphorus. The adsorption behavior conformed to the quasi second-order kinetic fitting equation, and the increase of temperature was conducive to the removal of all four phosphorus pollutants. BC-La adsorbs IHP and HEDP mainly through electrostatic attraction. The adsorption of 5-ATP and PP is dominated by complexation. The La-modified biochar has broad prospects in water remediation, which can provide a theoretical basis for removal of different forms of phosphorus pollutants and prevention and control of water eutrophication.

A Smart Nanoreactor Based on an O2-Economized Dual Energy Inhibition Strategy Armed with Dual Multi-stimuli-Responsive "Doorkeepers" for Enhanced CDT/PTT of Rheumatoid Arthritis.

Activated fibroblast-like synovial (FLS) cells are regarded as an important target for rheumatoid arthritis (RA) treatment via starvation therapy mediated by glucose oxidase (GOx). However, the hypoxic RA-FLS environment greatly reduces the oxidation process of glucose and leads to a poor therapeutic effect of the GOx-based starvation therapy. In this work, we designed a hollow mesoporous copper sulfide nanoparticles (CuS NPs)-based smart GOx/atovaquone (ATO) codelivery system (named as V-HAGC) targeting RA-FLS cells to realize a O2-economized dual energy inhibition strategy to solve the limitation of GOx-based starvation therapy. V-HAGC armed with dual multi-stimuli-responsive "doorkeepers" can guard drugs intelligently. Once under the stimulation of photothermal and acidic conditions at the targeted area, the dual intelligent responsive "doors" would orderly open to realize the controllable release of drugs. Besides, the efficacy of V-HAGC would be much improved by the additional chemodynamic therapy (CDT) and photothermal therapy (PTT) stimulated by CuS NPs. Meanwhile, the upregulated H2O2 and acid levels by starvation therapy would promote the Fenton-like reaction of CuS NPs under O2-economized dual energy inhibition, which could enhance the PTT and CDT efficacy as well. In vitro and in vivo evaluations revealed V-HAGC with much improved efficacy of this combination therapy for RA. In general, the smart V-HAGC based on the O2-economized dual energy inhibition strategy combined with enhanced CDT and PTT has the potential to be an alternative methodology in the treatment of RA.

Proximity hybridization induced rolling circle amplification for label-free SERS detection of the depression marker human apolipoprotein A4.

A new label-free method was developed for SERS detection of human apolipoprotein A4. Rolling circle amplification (RCA) was used, which could induce the production of AuNPs (poly adenine and adsorption gold nanoparticles). When there were two DNA labeled antibodies and target protein, MB1 (molecular beacon 1) was unfolded and the substrate was modified in the homogeneous solution, and the proximate complex was formed. The unfolded molecular beacon worked as a primer in the hybridization with the RCA template to start RCA, which could produce many long sequences of DNA containing amounts of adenines. The AuNPs were bound with the long-repeated adenine in the RCA product, causing accumulation of AuNPs on the surface of the electrode. It was indicated that the spectral characteristics of adenine at 736 cm-1 strongly dominated the SERS spectrum of DNA. Adenine worked as an internal marker for detecting human apolipoprotein A4 by using label-free SERS method. When the conditions were optimal, the detection of human apolipoprotein A4 was carried out from 10 pg mL-1 to 1000 ng mL-1, and the detection limit was low (4.1 pg mL-1). Meanwhile, the specificity was also excellent because the antibody could specifically bind with the corresponding antigen. In addition, since adenine was dominant in SERS spectra and the affinity between AuNPs and poly adenine was high, the detection procedure could be performed without any sophisticated modification. This method might provide a promising strategy for diagnosis in clinical practice.

Octahedral Pt-MOF with Au deposition for plasmonic effect and Schottky junction enhanced hydrogenothermal therapy of rheumatoid arthritis.

Hydrogen (H2) therapy is a novel and rapidly developing strategy utilized to treat inflammatory diseases. However, the therapeutic efficacy of H2 is largely limited with on-target off-synovium toxic effect, nonpolarity and low solubility. Herein, an intelligent H2 nanogenerator based upon the metal-organic framework (MOF) loaded with polydopamine and Perovskite quantum dots is constructed for the actualization of hydrogenothermal therapy. The biodegradable polydopamine with excellent photothermal conversion efficiencies is used for photothermal therapy (PTT) of rheumatoid arthritis (RA) and perovskite quantum dots (QDs) with unique photophysical properties are used as fluorescent signals for positioning Pt-MOF@Au@QDs/PDA nanoparticles. In addition, the Pt-MOF@Au@QDs/PDA catalyzer combines Au's surface plasmon resonance excitation with Pt-MOF Schottky junction, and exhibits extremely efficient photocatalytic H2 production under visible light irradiation. The Pt-MOF@Au@QDs/PDA achieves the aggregation of rheumatoid synovial cells by the extravasation through "ELVIS" effect (extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration) and extremely efficient photocatalytic H2 production. By combining PTT and H2 therapy, the Pt-MOF@Au@QDs/PDA relieves the oxidative stress of RA, and shows significant improvement in joint damage and inhibition of the overall arthritis severity of collagen-induced RA mouse models. Therefore, the Pt-MOF@Au@QDs/PDA shows great potential in the treatment of RA and further clinical transformation.

Hybridization chain reaction triggered poly adenine to absorb silver nanoparticles for label-free electrochemical detection of Alzheimer's disease biomarkers amyloid ß-peptide oligomers.

Amyloid ß-peptide oligomer (AßO) has received extensive attention from researchers because of its clinical therapeutic intervention targets and the value of reliable biological macromolecules markers for early diagnosis of Alzheimer's disease. We have developed a novel label-free electrochemical detection sensor for AßO based on hybridization chain reaction (HCR)-triggered poly adenine to absorb silver nanoparticles (AgNPs). In this method, we first use the "capture probe" to immobilize the aptamer 1 on the surface of the gold electrode (GE) via poly adenine-Au. Next, aptamer 2 and AßO were deposited on the electrode surface. The HCR process was initiated by the aptamer 2 fragment as a primer, producing a large number of long DNA sequences, which contained many adenines. Thereafter, the HCR product with long-repeated adenines could absorb many AgNPs on the surface of the electrode, which were used for subsequent electrochemical stripping of the AgNPs. The concentration range of the electrochemical signal of AßO was 1 pM-10 nM, and the detection limit was 430 fM, which indicated that that the detection system has high selectivity for the target protein.

Proximity hybridization induced DNA assembly for label-free surface-enhanced Raman spectroscopic detection of carcinoembryonic antigen.

In our research, label-free and surface-enhanced Raman dyes-free Raman spectroscopy which was used to detect carcinoembryonic antigen (CEA) according to poly adenine (Poly A)-regulated self-assembly methods was developed and studied. CEA induced partial hybridization of Ab-H2 and Ab-H1, and Ab-H1-CEA-Ab-H2 (a sandwich proximity CEA-DNA complex) was formed, which unfolded molecular beacon 1 (MB1) and modified the substrate. Subsequently, MB2-AuNPs were hybridized with MB1, and Ab-H1-CEA-Ab-H2 was released via toehold regulated displacements of DNA strands. Therefore, hybridization processes of MB2 and MB1 were induced and promoted by CEA-DNA complexes which worked as catalysts. The misplaced target then induced a next round of strand exchange, and the signals for determination of CEA were amplified by AuNPs absorbed on the substrate. It was indicated that the spectral characteristics of adenine at 736 cm-1 were consistent with the SERS spectrum of DNA. Adenine acted as an internal marker for label-free SERS detection of CEA. Moreover, satisfactory stability and reproducibility were found. Meanwhile, the antibody could specifically recognize the corresponding antigen. Since adenine was dominant in SERS spectra, which was also proximal to Au surface, the sensitivity of the novel method was high without modifications. The analytical performance of this method in determining serum CEA was satisfactory.

K-line in patients with cervical ossification of the posterior longitudinal ligament: relationship with change in sagittal cervical curvature and laminoplasty outcomes.

INTRODUCTION: To analyze how K-line is related to change in sagittal cervical curvature and laminoplasty outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL). MATERIALS AND METHODS: The study retrospectively analyzed 81 patients with OPLL who had undergone posterior cervical single-door laminoplasty and arch plate fixation between June 2011 and June 2017. Fifty-five were K-line positive (K[+]) and 26 were K-line negative (K[-]). Clinical and radiological results were compared between the groups. Patients were followed up for at least 2 years. RESULTS: Before the operation, Japanese Orthopedic Association (JOA) score, visual analogue scale (VAS) score, neck disability index (NDI), and short-form-36 (SF-36) quality of life score did not differ significantly between the groups. Neurological function was improved in both groups after the procedure. At last follow-up, JOA score, VAS score, NDI, SF-36 score, and JOA score improvement rate differed significantly between the groups. Before the operation, at the 3-month and final follow-ups, C2-7 Cobb angle, T1 slope, and C2-7 SVA differed significantly between the groups. The changes were more marked in the K(-) group than in the K(+) group. The incidence of cervical kyphosis differed significantly between the groups (P < 0.05), as well as between patients with lordosis < 7° and those with lordosis ≥ 7°. CONCLUSIONS: K-line negativity and lordosis < 7° may predict kyphosis after laminoplasty in patients with OPLL. The cervical curvature in patients with OPLL tends towards kyphosis and anteversion after laminoplasty, which contributes to the reduced clinical effect of the procedure.

Modified biochar improves the storage capacity and adsorption affinity of organic phosphorus in soil.

The loss of soil organic phosphorus can easily cause water eutrophication. In order to effectively reduce the loss of soil organic phosphorus, this manuscript investigated the adsorption of soil organic phosphorus by lanthanum modified biochar (BC), traditional adsorbent gypsum (GY) and zeolite (ZE) by taking phytic acid as the representative. The adsorption isotherm model and kinetic models were used to fit the phosphorus absorption characteristics of the adsorbents. The effects of initial pH and temperature on the adsorption capacity were discussed, and the adsorption mechanism of each adsorbent was explained by means of FTIR and XRD. The results showed that the adsorption capacity of phytate phosphorus followed the trend of BCTS > GYTS > ZETS > TS (soil), and the maximum phosphorus adsorption capacity obtained from Langmuir isotherm for treatment with BCTS was 2.836 mg g-1, and the treatment had the strongest affinity for phytate phosphorus and also the ability to store phosphorus. The adsorption process fits well with Langmuir isotherm equation and pseudo-second-order kinetic equation, and the adsorption behavior of phytate phosphorus was mainly controlled by the chemisorption of monolayer. When the concentration of phytate phosphorus was 100 mg L-1, percentage of modified biochar added to the soil was 3% and the pH was 6, the adsorption capacity reached the maximum, and the maximum adsorption capacity was 2.000 mg g-1. The results of FTIR and XRD characterization showed that complexation was the main adsorption mechanism. In this study, the combination of modified biochar and soil phytate phosphorus can provide a good theoretical basis for reducing the loss of soil organic phosphorus.

Ubiquitin-specific protease 3 attenuates interleukin-1ß-mediated chondrocyte senescence by deacetylating forkhead box O-3 via sirtuin-3.

Osteoarthritis (OA) affects approximately 12% of the aging Western population. The sirtuin/forkhead box O (SIRT/FOXO) signaling pathway plays essential roles in various biological processes. Despite it has been demonstrated that ubiquitin-specific protease 3 (USP3) inhibits chondrocyte apoptosis induced by interleukin (IL)-1ß, the role of USP3/SIRT3/FOXO3 in the senescence of chondrocytes in OA is unclear. This study initially isolated articular chondrocytes and investigated the role of USP3 in IL-1ß-induced senescence of chondrocytes. After USP3 was overexpressed or silenced by lentivirus, expressions of genes and proteins were detected using quantitative polymerase chain reaction and immunoblotting, respectively. Cell cycle analysis was performed using flow cytometry. Reactive oxygen species (ROS) levels and senescence were analyzed. Then, SIRT3 was inhibited or overexpressed to explore the underlying mechanism. We found that overexpression of USP3 hindered IL-1ß-mediated cell cycle arrest, ROS generation, and chondrocyte senescence. The inhibition of SIRT3 blocked the protective effect of USP3 on cell senescence, whereas the overexpression of SIRT3 abolished USP3-silencing-induced cell senescence. Furthermore, SIRT3 attenuated cell senescence, probably by deacetylating FOXO3. USP3 upregulated SIRT3 to deacetylate FOXO3 and attenuated IL-1ß-induced chondrocyte senescence. This study demonstrated that USP3 probably attenuated IL-1ß-mediated chondrocyte senescence by deacetylating FOXO3 via SIRT3.

A multifunctional nano-therapeutic platform based on octahedral yolk-shell Au NR@CuS: Photothermal/photodynamic and targeted drug delivery tri-combined therapy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease that results from synovial hyperplasia. The hyperplasia of synovium directly degrades cartilage by secreting matrix-degrading enzymes and inducing cartilage degradation and even loss of joint function. In this study, a metal/semiconductor composite, octahedral copper sulfide shell, and gold nanorod core (Au NR@CuS) is designed for, photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT) combination therapy for RA to remove hyperplasia of the synovium. Upon laser irradiation, the coupling of the local surface electromagnetic field improves the electromagnetic field of the Au NR core and the absorption of light of the CuS shell, whereby the photothermal effect is enhanced. Due to the Fenton-like reactions and the integration of Au NR and CuS semiconductor photocatalyst inhibits hole recombination and provides a reaction site for photocatalysis, which introduces additional •OH to photodynamics therapy. In addition, the large octahedral void space in Au NR@CuS NPs can be used for loading a high quantity of drugs for chemotherapy, and modified with vasoactive intestinal peptide and hyaluronic acid (HA) formation VIP-HA-Au NR@CuS NPs to target synovial cells in RA. Under combination therapy, VIP-HA-Au NR@CuS NPs were shown to effectively inhibit the synovial cells and the edema degree of the CIA mouse was alleviated apparently. Both in vitro and in vivo studies indicate that the VIP-HA-Au NR@CuS NPs can provide a potential possibility for the treatment of RA.

Effect of ambrisentan on echocardiographic and Doppler measures from patients in China with pulmonary arterial hypertension.

BACKGROUND: We retrospectively evaluated the echocardiographic data of ambrisentan-treated patients with pulmonary arterial hypertension (PAH) (NCT01808313). METHODS: Change from baseline in right ventricle (RV) systolic function, right heart structure, and pulmonary artery systolic pressure (PASP) prognosis to Weeks 12 and 24 was evaluated by echocardiography. RESULTS: In the overall population, the mean tissue Doppler-derived tricuspid lateral annular systolic velocity (S') increased by 0.6 cm/s at both Weeks 12 (p < 0.001) and 24 (p = 0.004) and tricuspid annular plane systolic excursion increased by 0.13 cm at Week 12 and 0.15 cm at Week 24 (both p < 0.001). A marked decrease in transverse and longitudinal RV and RA diameter at Weeks 12 and 24 was observed. A significant decrease in diastolic eccentricity index at both Weeks 12 (-0.1; p = 0.02) and 24 (-0.1; p = 0.001). The decrease in PASP from baseline was significant at both Weeks 12 (-9.5 mmHg; p<0.001) and 24 (-7.6 mmHg; p<0.001), while a decrease in the estimated right atrium pressure was found to be significant at Week 24 (-0.8mmHg; p = 0.01). CONCLUSION: Significant improvements in a number of RV echocardiographic parameters were observed at Weeks 12 and 24 after ambrisentan treatment in patients with PAH.

PRP-chitosan thermoresponsive hydrogel combined with black phosphorus nanosheets as injectable biomaterial for biotherapy and phototherapy treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing destruction of bone and cartilago articularis. Traditional treatment methods have many side effects, or too concerne about the anti-inflammatory mechanisms but ignore osteanagenesis. In this work, a novel therapeutic platform combined black phosphorus nanosheets (BPNs) into platelet-rich plasma (PRP)-chitosan thermoresponsive hydrogel has been prepared for management of RA. The BPNs generate local heat upon near-infrared irradiation, and delivering reactive oxygen species (ROS) to the inflamed joints simultaneously for removing hyperplastic synovial tissue. The injectable chitosan thermoresponsive hydrogel can take control of the releasing of BPNs degradation products, which provide ample raw materials for osteanagenesis. In addition, the PRP can effectively improve the adhesion and increase capacity of mesenchymal stem cells on chitosan thermosensitive hydrogels. And this thermoresponsive hydrogel can protect articular cartilage by reducing the friction on the surrounding tissue. Drug delayed release property was indicated by the release and uptake of methotrexate. The edema degree of the arthritic mouse was reduced obviously by the BPNs/Chitosan/PRP thermoresponsive hydrogel. Both in vitro and in vivo studies suggest that the thermoresponsive hydrogel can provide a potential possibility for the management of RA.

Type-2 cannabinoid receptor regulates proliferation, apoptosis, differentiation, and OPG/RANKL ratio of MC3T3-E1 cells exposed to Titanium particles.

The type-2 cannabinoid receptor (CB2) is expressed in osteoblasts and plays a role in bone metabolism through regulation on bone mass and bone turnover, but the functional importance of CB2 in osteoblasts under Titanium (Ti) stimulation is incompletely understood. This study aimed to investigate the CB2 expression in osteoblasts under Ti stimulation and the effects of CB2 activation on proliferation, apoptosis, differentiation, mineralization, OPG, and RANKL expression of MC3T3-E1 cells exposed to Ti particles. MC3T3-E1 cells were incubated in the presence of Ti particles with or without CB2-specific agonist HU-308 and antagonist SR144528. Ti particles treatment obviously induced the CB2 expression in MC3T3-E1 cells, and reduced the cell survival in a dose- and time-dependent manner (p < 0.05). Addition of HU-308 could dose-dependently alleviate the Ti-induced decrease of cell survival (p < 0.05). The flow cytometry assay showed that comparing with the control group, the apoptosis rate and caspase-3 activity in the Ti group were significantly elevated (p < 0.05), which could be alleviated by HU-308. Moreover, HU-308 effectively attenuated the decrease of cell mineralization capability, alkaline phosphates (ALP) and osteocalcin activity, and increase of OPG/RANKL ratio induced by Ti particles treatment (p < 0.05). These effects were partially counteracted by combined treatment of CB2 antagonist SR144528 (p < 0.05). In conclusion, CB2 activation has a favorable inhibitory effect on Ti-induced reactions in MC3T3-E1 cell through modulating proliferation, apoptosis, differentiation, and RANKL expression. These findings suggest that activation of CB2 might be an effective therapeutic strategy to promote bone formation and reduce bone dissolution.

[Effect of carbon nanotubes on the crystallization behaviors of MC nylon 6].

Multi-walled carbon nanotubes bearing hydroxyl group were modified with toluene diisocyanate (TDI) and stabilized with caprolactam. The functionalized carbon nanotubes were used to prepare monomer casting polyamide 6(MC nylon 6)/carbon nanotubes nanocomposites. The results of FTIR proved that isocynate groups have been incorporated into carbon nanotubes successfully. XRD results showed that the addition of the functionalized carbon nanotubes has no significant influence on the crystal structure of MC nylon 6, whereas the untreated carbon nanotubes could hinder the growth of alpha2-crystal of nylon 6; with the loading of 0.3 Wt% of the functionalized carbon nanotubes, the crystallinity degree of the nanocomposites is almost equal to that of pure MC nylon 6, whereas as the loading increased to 0.5 Wt%, the crystallinity degree of MC nylon 6 decreased. DSC revealed that carbon nanotubes in MC nylon 6 acted as effective nucleation agents. The peak temperature of crystallization for MC nylon 6 increased by 10 degrees C from 173.4 to 183.5 degrees C, and the temperature range of crystallization decreased, indicating that the carbon nanotubes act as heterogeneous nucleation agents for MC nylon 6.

Safety and efficacy of transcatheter closure of atrial septal defects guided by transthoracic echocardiography: a prospective study from two Chinese Medical Centers.

The purpose of this study was to evaluate the safety and efficacy of transcatheter atrial septal defect (ASD) closure guided by transthoracic echocardiography (TTE). A total of 191 patients with ASD were recruited from two Chinese medical centers and TTE was carefully performed in multiple views to observe ASD number, position, diameter and relation with adjacent cardiac structures. All patients were divided into three groups based on their largest ASD diameters: 66 subjects with ASD diameter 5-14 mm (group A); 60 subjects with ASD diameter 15-20 mm (group B); and 65 subjects with ASD diameter 21-38 mm (group C). Atrial septal occluders (ASOs) were successfully deployed in 188 patients (98.4%) and ASD was successfully closed at 6-mo follow-up in 185 patients (96.9%). The difference between diameters of ASO and ASD (ASO-ASD) in groups A, B and C were 3.9 +/- 2.4 (0-7) mm, 5.0 +/- 2.6 (3-8) mm and 6.2 +/- 3.8 (5-11) mm, respectively. In group A, no complications occurred. In group B, only four patients had mild complications such as sinus bradycardia, transient hematuria and migraine, all of which disappeared after treatment. In group C, one patient developed ASO migration into the right atrium and two patients had their ASO migrated into the right ventricular outflow tract. Immediately after the closure, 60 (90.9%), 53 (88.3%) and 53 (82.8%) patients had complete ASD closure; 2, 4 and 6 patients had trivial residual shunts; 4, 3 and 2 patients had small residual shunts; and 0, 0 and 2 patients had moderate residual shunts in groups A, B and C, respectively. Most of the residual shunts were persistent at 6-mo follow-up. No embolism or death at procedure and 6-mo follow-up occurred. In conclusion, TTE is a reliable technique for measurement of ASD diameter, guidance of transcatheter ASD closure and evaluation of residual shunts. Transcatheter ASD closure guided by TTE is safe and effective, especially in patients with ASD

Reliability of transthoracic echocardiography in estimating the size of Amplatzer septal occluder and guiding percutaneous closure of atrial septal defects.

BACKGROUND: In China, transthoracic echocardiography (TTE) is popularly used for pre-intervention examination for atrial septal defect (ASD) and for guiding ASD closure. However, the ability to determine ASD size and the safety and efficacy of TTE for guiding ASD closure still has not been widely accepted. This study aimed to evaluate the efficacy and safety of TTE used before, during and after transcatheter ASD closure with Amplatzer septal occluders (ASO). METHODS: Sixty-eight subjects (15 men and 53 women; mean age (33.7 +/- 17.3) years) were enrolled. TTE was used to measure the diameters and guide transcatheter closure of ASD. The ASD was examined by long-axis view, basal short-axis view, apical four-chamber view and the subcostal view to observe position, diameter and relation with neighbouring structures. The largest diameter was selected as the reference diameter. Patients were divided into 3 groups according to the ASD reference diameter: 22 subjects with ASD diameter 4 - 14 mm (group A); 21 subjects with ASD diameter 15 - 20 mm (group B); and 25 subjects with ASD diameter 21 - 33 mm (group C). RESULTS: ASD was occluded successfully in groups A and B. In group C, occlusion failed in 2 cases; 1 case remained with a 3-mm residual shunt sustained until 6-month follow-up. However, at 6-month follow-up, no case of thromboembolism, ASO dislocation or death occurred in the three groups. The diameter of ASD measured by TTE could accurately predict the ASO size that could successfully occlude the ASD, especially in patients with ASD < 20 mm. The ASD diameter measured by TTE correlated well with ASO size (r = 0.925, P < 0.001; r = 0.976, P < 0.001; r = 0.929, P < 0.001 respectively). CONCLUSIONS: ASD diameter measured by TTE can accurately estimate the size of the ASO needed for successful closure of ASD. The larger the ASD, the much larger the ASO needed. TTE is a satisfactory guiding imaging tool for ASD closure.

Multivessel percutaneous coronary intervention in Chinese patients with acute myocardial infarction and simple nonculprit arteries.

BACKGROUND: Multivessel percutaneous coronary intervention (PCI) for patients during acute myocardial infarction (AMI) is currently controversial. In this study, we investigated the significance of multivessel PCI in Chinese patients with ST-segment elevation AMI and relatively simple lesions in nonculprit arteries. METHODS: We reviewed all consecutive primary PCI of ST-segment elevation AMI in our hospital between 2002 and 2005. The patients with multivessel disease and ACC/AHA type A/B1 lesions in nonculprit arteries who underwent multivessel PCI were identified (n = 105, multivessel PCI group), and 120 patients with single-vessel disease and treatment with primary PCI were enrolled as control subjects (single-vessel PCI group). The primary end points were the occurrences of 6-month major adverse cardiac events (cardiogenic death, nonfatal reinfarction, and target vessel revascularization). The secondary end points included procedure time, angiographic success rate, TIMI grade, reperfusion arrhythmia, ST-segment resolution, and left ventricular ejection fraction. RESULTS: All patients with multivessel PCI tolerated the operations well and had similar TIMI 3 and angiographic success rates but longer procedure times than those patients with single-vessel PCI. There were no significant differences in reperfusion arrhythmia, ST-segment resolution, left ventricular ejection fraction, or 6-month MACEs between both groups. CONCLUSIONS: This study suggests that multivessel PCI is effective and safe for Chinese patients with ST-segment elevation AMI and simple lesions in nonculprit arteries.