Feasibility and safety of percutaneous intramyocardial septal cryoablation: A canine model with 6-month follow-up.

Echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The safety and feasibility of using this procedure for cryoablation are unknown. We aimed to investigate the feasibility and safety of echocardiography-guided percutaneous intramyocardial septal cryoablation (PIMSCA) for septal thickness reduction in a canine model. Eight canines underwent PIMSCA, and had electrocardiography, echocardiography(ECG), myocardial contrast echocardiography (MCE), serological and pathological examinations during the preoperative, immediate postoperative, and 6-month follow-up. All eight canines underwent successful cryoablation and continued to be in sinus rhythm during ablation and without malignant arrhythmias. MCE showed that the ablation area had decreased myocardial perfusion after the procedure. Troponin I levels were significantly elevated [0.010 (0.005, 0.297) ng/mL vs. 3.122 (1.152, 7.990) ng/mL, p < 0.05)]. At 6-month follow-up after the procedure, all animals were alive, with thinning of the interventricular septum (7.26 ± 0.52 mm vs. 3.86 ± 0.29 mm, p < 0.05). Echocardiography showed no significant decrease in the left ventricular ejection fractions (LVEF) (54.32 ± 2.93 % vs. 54.70 ± 2.47 %, p > 0.05) or changes by pulse-wave Doppler E/A (1.17 ± 0.43 vs. 1.07 ± 0.43, p > 0.05), E/e' (8.09 ± 1.49 vs. 10.05 ± 2.68, p > 0.05). Pathological findings proved the effectiveness of cryoablation in myocardial tissues. We observed pericardial effusions and premature ventricular complexes (PVCs) associated with the procedure. Our findings provided preliminary evidence of the safety and feasibility of PIMSCA in reducing interventricular septum, which provides a potentially new treatment option for HOCM.

The first Asian species of Polycaon Castelnau, and a new montane species of Melalgus Dejean from China (Coleoptera: Bostrichidae: Polycaoninae).

We describe Polycaon sinensis sp. n., the first Asian species of this otherwise American genus, and Melalgus plesiobatillus sp. n., from the same montane locality in China (Zhejiang). The following new synonym is proposed: Melalgus batillus (Lesne) (=Melalgus japonicum Chûjô syn. n.). We comment on the species, Melalgus borneensis (Lesne) sensu Borowski & Wegrzynowicz (2012), and provide a key to the Chinese species of Polycaoninae.

A Validated UHPLC-MS/MS Method to Quantify Eight Antibiotics in Quantitative Dried Blood Spots in Support of Pharmacokinetic Studies in Neonates.

OBJECTIVES: Conduction of pharmacokinetic (PK) study in pediatric patients is challenging due to blood sampling limits. The dried blood spots (DBS) method represents a potential matrix for microsampling in support of PK studies in children. Herein, we used the Capitainer® qDBS device to develop a DBS method that can collect an exact 10 µL volume of blood on a paper card. This DBS method was developed to simultaneously quantify the concentrations of eight antibiotics, including sulbactam, tazobactam, ampicillin, meropenem, cefotaxime, cefoperazone, piperacillin, and metronidazole using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). METHODS: The prepared DBS samples were extracted in methanol containing acetaminophen as the internal standard at 20 °C on a block bath shaker at 500 rpm for 30 min. The extracted antibiotics were eluted on an Acquity UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) using gradient elution with a total chromatographic run time of 6.5 min. The precursor and product ions of the analytes were detected by use of the multiple reaction monitoring (MRM) mode. RESULTS: No interfering peaks at the respective retention times of the analytes were observed in DBS samples. The lower limits of quantification (LLOQ) for the antibiotics were between 0.25 and 2.0 µg/mL, and satisfactory accuracies (intra/inter-assay bias -16.7 to +13.6%) and precisions (intra/inter-assay coefficient of variations 1.5-15.6%) were obtained for the analytes. As a proof of concept, the method was applied to DBS samples obtained from neonatal patients treated with ampicillin and piperacillin/sulbactam. CONCLUSIONS: The DBS method is simple and robust, and it can be used in children with limited blood sampling.

Development of polyanion-metal ion solution systems to overcome phospholipids-related matrix effects in LC-MS/MS-based bioanalysis.

Phospholipids-related matrix effects are a major source impacting the reproducibility of analyte quantification in LC-MS/MS-based bioanalysis. This study intended to evaluate different combinations of polyanion-metal ion based solution system for phospholipids removal and elimination of matrix effects in human plasma. Blank plasma samples or plasma samples spiked with model analytes were proceeded with different combinations of polyanions (dextran sulfate sodium (DSS) and alkalized colloidal silica (Ludox)) and metal ions (MnCl2, LaCl3, and ZrOCl2) followed with acetonitrile-based protein precipitation. The representative classes of phospholipids and model analytes (acid, neutral, and base) were detected using multiple reaction monitoring mode. The polyanion-metal ion systems were explored for providing balanced analyte recovery and phospholipids removal by optimizing reagent concentrations or adding formic acid and citric acid as the shielding modifiers. The optimized polyanion-metal ion systems were further evaluated for eliminating matrix effects of non-polar and polar compounds. Any combinations of polyanions (DSS and Ludox) and metal ions (LaCl3 and ZrOCl2) could completely remove phospholipids at best-case scenario, while the analyte recovery is low for compounds with special chelation groups. Addition of formic acid or citric acid can improve analyte recovery but significantly decrease the removal efficiency of phospholipids. Optimized ZrOCl2-Ludox/DSS systems provided efficient phospholipids removal (>85%) and adequate analyte recovery, and the systems also correctly eliminated ion suppression or enhancement of the non-polar and polar drugs. The developed ZrOCl2-Ludox/DSS systems are cost-effective and versatile for balanced phospholipids removal and analyte recovery and provide adequate elimination of matrix effects.

Defining Exposure Predictors of Meropenem That Are Associated with Improved Survival for Severe Bacterial Infection: A Preclinical PK/PD Study in Sepsis Rat Model.

Background: The pharmacokinetic/pharmacodynamic (PK/PD) index of carbapenems that best correlates with in vivo antimicrobial activity is percent time of dosing interval in which free drug concentration remains above MIC (%fT > MIC), while the magnitudes of the PK/PD index of carbapenems remains undefined in critically ill sepsis patients. Methods: A sepsis rat model was first developed by comparing the survival outcomes after intraperitoneal injection of different inoculum size (1−10 × 107 CFU) of Pseudomonas aeruginosa ATCC9027 (MIC = 0.125 mg/L) in neutropenic rats. The PK characteristics of the model drug meropenem in the developed sepsis rat model was then evaluated, and PK modeling and simulation was applied to design meropenem dosing regimens attaining various PD targets (40%fT > MIC, 100%fT > MIC, and 100%fT > 4 × MIC). The microbiological response and survival outcomes for different meropenem treatment regimens were investigated in the rat sepsis model (n = 12 for each group). Results: The optimal inoculum for the rat sepsis model was 1 × 107 CFU of Pseudomonas aeruginosa ATCC9027. A one-compartment model with first-order absorption best described the PK of meropenem in sepsis rats. Pronounced survival prolongation and lower hazard risk were observed in the treatment groups of 50 or 75 mg/kg/q2.4h (100%fT > MIC) and 75 mg/kg/q2h (100%fT > 4 × MIC) compared to the 75 mg/kg/q6h (40%fT > MIC) group, while meropenem groups with PD targets of 100%fT > MIC and 100%fT > 4 × MIC showed comparable survival curves. Microbiological response for different PD targets is inconclusive due to irregular bacterial counts in blood samples. Conclusions: The PD target of 40%fT > MIC is suboptimal for sepsis rats, and the aggressive 100%fT > 4 × MIC target does not provide a survival benefit against the target of 100%fT > MIC.

An UPLC-PDA assay for simultaneous determination of seven antibiotics in human plasma.

Appropriate antibiotic dosing in critically ill patients requires concentration monitoring due to the occurrence of pathophysiological changes and frequent extracorporeal therapy that could significantly alter the normal pharmacokinetics of drugs. Herein, we describe an ultra-performance liquid chromatography with photodiode array (UPLC-PDA) for the simultaneous concentration determination of seven frequently used antibiotics (meropenem, cefotaxime, cefoperazone, piperacillin, linezolid, moxifloxacin, and tigecycline) in plasma from critically ill patients. The analytes were extracted from 200 µL human plasma by the addition of methanol for protein precipitation. The chromatographic separation was achieved using an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) with a water (containing 0.1% trifluoroacetic acid)/acetonitrile linear gradient at a flow rate of 0.5 mL/min in a 4.5 min turn-around time. PDA detection wavelength was set individually for the analytes. The method was fully validated according to the European Medicines Agency (EMA) guideline. The lower limits of quantification for the analytes were between 0.05 and 0.8 µg/mL. The method is accurate (intra/inter-assay bias -8.4 to +12.4%) and precise (intra/inter-assay coefficient of variations 0.9-10.1%) over the clinically relevant plasma concentration ranges (upper limits of quantification 5-400 µg/mL). The applicability of the method has been successfully demonstrated by analyzing plasma samples collected from critically ill patients undergoing continuous renal replacement therapy.

An annotated synopsis of the powder post beetles (Coleoptera: Bostrichidae) of Mainland China.

An updated and annotated synopsis of the family Bostrichidae of mainland China is presented, including sixty-eight species belonged to seven subfamilies (including eight tribes), and twenty-nine genera. Thirteen species are new records for mainland China, and numerous new provincial records are given. Four species, Dolichobostrychus yunnanus Lesne, 1913, Heterobostrychus ambigenus Lesne, 1920, Sinoxylon eucerum Lesne, 1932 and S. rejectum (Hope, 1845) are endemic to mainland China. The faunal elements present and their composition are discussed, and the zoogeographical distribution of species within mainland China.

Revision of the genus Xylodrypta Lesne 1901 (Coleoptera: Bostrichidae: Bostrichinae: Xyloperthini) with a new species and a key to species.

We revise the monospecific bostrichid genus Xylodrypta Lesne 1901, and describe a new species, X. lanna Liu Beaver from Thailand and Laos. A key is given to distinguish the two species of Xylodrypta.

Long noncoding RNA SNHG20 promotes gastric cancer progression by inhibiting p21 expression and regulating the GSK-3ß/ ß-catenin signaling pathway.

Recent studies have indicated that long non-coding RNAs (lncRNAs) play important regulatory roles in tumor development and progression. However, the contribution of small nucleolar RNA host gene 20 (SNHG20) to gastric cancer development remains largely unknown. The aim of the study is to investigate the functional significance of SNHG20 involved in gastric cancer (GC) progression. In the study, our results demonstrated that the expression levels of SNHG20 were remarkably up-regulated in GC cells. Functionally, SNHG20 promoted the GC MKN45 and BGC-823 cells proliferation and invasion. Furthermore, knockdown of SNHG20 significantly inhibited the epithelial-mesenchymal transition (EMT) in MKN45 and BGC-823 cells, whereas, the overexpression of SNHG20 had the promoting effects. Moreover, we found that overexpression of SNHG20 in MKN45 and BGC-823 cells significantly inhibited the expression of E-cadherin and p21 via binding to EZH2 and regulated the GSK-3ß/ß-catenin signaling pathway. Thus, the results showed that SNHG20 acted as an oncogene in GC and targeting SNHG20 may serve as a therapeutic target for GC.

Long noncoding RNAs expression profile and functional networks in rheumatoid arthritis.

The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis (RA) recently have drawn much attention; however, the underlying mechanisms remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in RA and identify promising targets for RA diagnosis and treatment. Microarray screening and real-time PCR of lncRNAs were performed by use of serum samples from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were verified in serum samples from 43 RA patients and 40 healthy controls by real-time PCR. We found that there were 73 up-regulated and 61 down-regulated lncRNAs as well as 128 up-regulated and 37 down-regulated mRNAs in serum samples of RA patients. Validation in RA clinical samples indicated 5 of these lncRNAs were significantly up-regulated including RNA143598, RNA143596, HIX0032090, IGHCgamma1, and XLOC_002730. Significant association was observed between these lncRNAs and the disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) as well as anti-cyclic citrullinated peptide (anti-CCP) antibody. Additionally, 55 of the differentially expressed mRNAs were associated with 41 lncRNAs and were involved in signaling pathways of toll like receptors (TLRs), nuclear factor-kappa B (NF-κB), and cytokine, especially the IRF3/IRF7 mediated signaling transduction. Our study firstly shows the specific profile of lncRNAs in the serum of RA patients and potential signaling pathways involved in RA pathogenesis, which may provide novel targets for the diagnosis and treatment of patients with RA.