Efficacy of Ultrasound-Guided Thoracic Paravertebral Block on Postoperative Quality of Recovery in Patients Undergoing Percutaneous Nephrolithotomy: A Randomized Double-Blind Placebo-Controlled Trial.

Purpose: This study aimed to examine the effectiveness of ultrasound-guided thoracic paravertebral block on postoperative quality of recovery in patients undergoing percutaneous nephrolithotomy. Patients and Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled patients scheduled for unilateral percutaneous nephrolithotomy. Patients were randomly allocated to receive thoracic paravertebral block either with 20 mL of 0.5% ropivacaine (PVB group) or an equal volume of saline (control group). The primary outcome was the quality of patient recovery at 24 h postoperatively, assessed using the 15-item Quality of Recovery scale. The secondary outcomes included the area under the curve of pain scores over time, time to first rescue analgesia, and postoperative 24 h morphine consumption. Results: We analyzed the data of 70 recruited participants. The median Quality of Recovery-15 score at 24 h postoperatively was 127 (interquartile range, 117-133) in the PVB group, which was significantly higher than 114 (interquartile range, 109-122) in the control group, with a median difference of 10 points (95% confidence interval, 5-14; P<0.001). The area under the curve of pain scores over time was lower in patients receiving thoracic PVB than in those receiving saline block (P<0.001). The median time to first rescue analgesia in the PVB group (10.8 h, interquartile range 7.1-22.8 h) was longer than that in the control group (1.9 h, interquartile range 0.5-4.3 h) (P<0.001). Similarly, the median postoperative 24-hour morphine consumption was nearly half as low in the PVB group as in the control group (P<0.001). The occurrence of postoperative nausea and vomiting, and pruritus were significantly higher in the control group (P=0.016 and P=0.023, respectively). Conclusion: Preoperative ultrasound-guided single injection of thoracic paravertebral block with ropivacaine improved the postoperative quality of recovery and analgesia in patients undergoing percutaneous nephrolithotomy.

Efficacy of systemic lidocaine in postoperative delirium in elderly patients undergoing laparoscopic colorectal surgery: study protocol for a multicentre, prospective, double-blind, randomised, parallel-group, superiority, placebo-controlled trial.

INTRODUCTION: Systemic lidocaine may reduce pain intensity and accelerate postoperative recovery. However, the efficacy of systemic lidocaine in cognitive function has not been established. This study protocol is designed to clarify the effectiveness of lidocaine in postoperative delirium (POD) in elderly patients scheduled for elective laparoscopic colorectal surgery. METHODS AND ANALYSIS: This is a prospective, multicentre, randomised, double-blind, parallel-group, placebo-controlled trial. One thousand and twenty elderly patients will be randomly allocated in a ratio of 1:1 to receive either systemic lidocaine (a bolus of 1.5 mg/kg, followed by an infusion of 1.5 mg/kg/hour until the end of the surgery) or identical volumes and rates of 0.9% saline. The primary outcome measure is the prevalence of POD during the first 5 postoperative days. Secondary outcomes include emergence agitation, the area under the curve of the Numeric Rating Scale pain scores over 48 hours, postoperative 48-hour cumulative opioid consumption, postoperative nausea and vomiting (PONV), recovery of bowel function, quality of recovery, and patient satisfaction with postoperative analgesia. ETHICS AND DISSEMINATION: The Ethical Committee of the Fujian Provincial Hospital approved the study protocol (ref: K2021-06-018). Other participating subcentres must also obtain ethics committee approval before the start of the study. We will obtain written informed consent from each patient before they are randomised. This study will be presented at scientific conferences and submitted to international journals. TRIAL REGISTRATION NUMBER: ChiCTR2100050314.

Bilateral Erector Spinae Plane Block for Quality of Recovery Following Posterior Lumbar Interbody Fusion: A Randomized Controlled Trial.

BACKGROUND: Erector spinae plane block, a novel ultrasound-guided fascial plane block, has become popular for perioperative pain management. This randomized controlled trial tested the hypothesis that preoperative bilateral erector spinae plane block improves the quality of recovery in patients undergoing posterior lumbar interbody fusion. METHODS: Eighty-four patients scheduled for elective posterior lumbar interbody fusion were enrolled. Patients were randomly administered either ultrasound-guided bilateral erector spinae plane blocks using 20 ml of 0.375% ropivacaine on each side (ESPB group, n = 42) or no block (control group, n = 42) after anesthesia induction. The primary outcome was the quality of recovery 24 h postoperatively, assessed using the 15-item quality of recovery questionnaire. RESULTS: The global postoperative 24-h quality of recovery-15 score was 117 [114-121] in the erector spinae plane block group and 108 [105-111] in the control group, with a median difference of 9 (95% confidence interval 7-12, P < 0.001). Compared with the control group, preoperative bilateral erector spinae plane blocks reduced the area under the curve of the numeric rating scale pain scores over 48 h, prolonged the time to first rescue analgesia, lessened postoperative 24 h morphine consumption, decreased the occurrence of postoperative nausea and vomiting, and improved patient satisfaction with postoperative analgesia. There were no block-related adverse events. CONCLUSION: We found that preoperative bilateral erector spinae plane blocks provided superior early quality of recovery, postoperative analgesia, and patient satisfaction scores in patients undergoing posterior lumbar interbody fusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027186, 4/11/2019.

Nonpeptidic Amphiphilic Xanthone Derivatives: Structure-Activity Relationship and Membrane-Targeting Properties.

We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 µ/mL) and lower hemolytic activity (80.2 µg/mL for 3a versus 19.7 µg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection.

N-Lipidated Peptide Dimers: Effective Antibacterial Agents against Gram-Negative Pathogens through Lipopolysaccharide Permeabilization.

Treating infections caused by multidrug-resistant Gram-negative pathogens is challenging, and there is concern regarding the toxicity of the most effective antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a fatty acid moiety onto a peptide dimer could maximize the interaction with lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier, thereby improving potency against Gram-negative pathogens. We systematically designed a series of N-lipidated peptide dimers that are active against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited synergy with select antibiotics in most of the combinations tested. 23 and 32 also displayed rapid bactericidal activity. Importantly, 23 and 32 were nonhemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These characteristics suggest that these compounds can overcome the limitations of current Gram-negative-targeted antimicrobials such as polymyxin B.

Amino acid modified xanthone derivatives: novel, highly promising membrane-active antimicrobials for multidrug-resistant Gram-positive bacterial infections.

Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compounds 5c and 6, which contain a hydrophobic xanthone core, lipophilic chains, and cationic amino acids, displayed very promising antimicrobial activity against multidrug-resistant Gram-positive bacteria, including MRSA and VRE, rapid time-kill, avoidance of antibiotic resistance, and low toxicity. The bacterial membrane selectivity of these molecules was comparable to that of several membrane-targeting antibiotics in clinical trials. 5c and 6 were effective in a mouse model of corneal infection by S. aureus and MRSA. Evidence is presented indicating that 5c and 6 target the negatively charged bacterial membrane via a combination of electrostatic and hydrophobic interactions. These results suggest that 5c and 6 have significant promise for combating life-threatening infections.

Design and synthesis of amphiphilic xanthone-based, membrane-targeting antimicrobials with improved membrane selectivity.

This work describes how to tune the amphiphilic conformation of α-mangostin, a natural compound that contains a hydrophobic xanthone scaffold, to improve its antimicrobial activity and selectivity for Gram-positive bacteria. A series of xanthone derivatives was obtained by cationic modification of the free C3 and C6 hydroxyl groups of α-mangostin with amine groups of different pKa values. Modified structures using moieties with high pKa values, such as AM-0016 (3b), exhibited potent antimicrobial properties against Gram-positive bacteria. Compound 3b also killed bacteria rapidly without inducing drug resistance and was nontoxic when applied topically. Biophysical studies and molecular dynamics simulations revealed that 3b targets the bacterial inner membrane, forming an amphiphilic conformation at the hydrophobic-water interface. In contrast, moieties with low pKa values reduced the antimicrobial activity of the parent compound when conjugated to the xanthone scaffold. This strategy provides a new way to improve "hits" for the development of membrane-active antibiotics that target drug-resistant pathogens.

[In vitro evaluation of cutaneous allergic reaction induced by chemicals using dendritic cells].

OBJECTIVE: To investigate the use of dendritic cells derived from mice bone marrow to evaluate the cutaneous allergic reaction induced by chemical sensitizers. METHODS: Dendritic cells derived from mice bone marrow were cultured and administrated with 2, 4-dinitrochlorobenzene (DNCB), nickel sulfate (NiSO4), sodium dodecyl sulfate (SDS) and hexyl cinnamic aldehyde (HCA), respectively. Cell membrane molecule CD86 and extracellular IL-1 beta, IL-6 and IL-12 were detected after 0, 1, 6, 12, 24, 36, 48 hour's administration, respectively. RESULTS: CD86 expression reached the highest level after exposure to DNCB for 48 h, and increased by about 279% compared with the control (P < 0.05), while it was lower than that of control after administrated with NiSO4 and HCA for 1 h and 6 h, and SDS for 36 h, respectively (P < 0.05). Extracellular IL-1 beta increased greatly after exposure to NiSO4 just for 1 h, with the maximum at 48 h (298 pg/ml, P < 0.05), and after exposure to HCA for 6 h, with maximum at 48 h (84 pg/ml, P < 0.05). However, it didn't fluctuate significantly after administrated with DNCB and SDS respectively, compared with the control. Extracellular IL-6 increased significantly after exposure to NiSO4 for 1 h, with the maximum at 24 h (2152 pg/ml, P < 0.05). After exposure to HCA, extracellular IL-6 reached the maximum at 1 h (1403 pg/ml), and then it was decreased quickly, but still higher than the control (P < 0.05), while it didn't change significantly after treatment with DNCB and SDS, compared with the control (P > 0.05). Extracellular IL-12 was not detected out among all the groups. CONCLUSION: Chemical sensitizer DNCB could induce the high expression of CD86 on DC membrane, and NiSO4 and HCA could induce DC to release IL-1 beta and IL-6. However, the irritant SDS had no such effect.

Effect of amino-modified silica nanoparticles on the corrosion protection properties of epoxy resin-silica hybrid materials.

In this paper, a series of organic-inorganic hybrid materials consisting of epoxy resin frameworks and dispersed nanoparticles of amino-modified silica (AMS) were successfully prepared. First of all, the AMS nanoparticles were synthesized by carrying out the conventional acid-catalyzed sol-gel reactions of tetraethyl orthosilicate (TEOS) in the presence of (3-aminopropyl)-trimethoxysilane (APTES) molecules. The as-prepared AMS nanoparticles were then characterized by FTIR, 13C-NMR and 29Si-NMR spectroscopy. Subsequently, a series of hybrid materials were prepared by performing in-situ thermal ring-opening polymerization reactions of epoxy resin in the presence of as-prepared AMS nanoparticles and raw silica (RS) particles. The as-prepared epoxy-silica hybrid materials with AMS nanoparticles were found to show better dispersion capability than that of RS particles existed in hybrid materials based on the morphological observation of transmission electron microscopy (TEM). The hybrid materials containing AMS nanoparticles in the form of coating on cold-rolled steel (CRS) were found to be much superior in corrosion protection over those of hybrid materials with RS particles when tested by a series of electrochemical measurements of potentiodynamic and impedance spectroscopy in 5 wt% aqueous NaCI electrolyte. The increase of corrosion protection effect of hybrid coatings may have probably resulted from the enhancement of the adhesion strength of the hybrid coatings on CRS coupons, which may be attributed to the formation of Fe-O-Si covalent bond at the interface of coating/CRS system based on the FTIR-RAS (reflection absorption spectroscopy) studies. The better dispersion capability of AMS nanoparticles in hybrid materials were found to lead more effectively enhanced molecular barrier property, mechanical strength, surface hydrophobicity and optical clarity as compared to that of RS particles, in the form of coating and membrane, based on the measurements of molecular permeability analysis, dynamic mechanical analysis, contact angle measurements and ultraviolet-visible transmission spectra, respectively.

Biosynthesis of fluorescent allophycocyanin alpha-subunits by autocatalytic bilin attachment.

Allophycocyanin (APC) is one of the phycobiliproteins expressed in cyanobacteria. Phycobiliproteins contain a covalently bound chromophore, and thus, they are valuable as fluorescent probes. Biosynthesis of a functional phycobiliprotein is achieved by a bilin attachment process between the chromophore and apoprotein. Chromophore lyases are necessary to catalyze the chromophorylation of cyanobacterial phycobiliproteins, such as C-phycocyanin, and phycoerythrocyanin. To identify the lyase that catalyzes the chromophorylation of the APC alpha-subunit (ApcA), we searched the entire genomes of two cyanobacteria, Synechocystis sp. PCC6803 and Anabaena sp. PCC 7120; however, these genomes do not appear to encode an APC-specific chromophore lyase. In this study, chromophorylated ApcA (chromo-ApcA) was obtained via a spontaneous bilin attachment reaction. The absorption and fluorescence characteristics of chromo-ApcA were similar to those of the native APC alpha-subunit. The extent of chromophore attachment to apo-ApcA was comparable to that of the lyase-catalyzed reactions for other phycobiliproteins. These results indicate that ApcA has autocatalytic bilin:biliprotein lyase activity.

Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human dermal fibroblasts.

Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation and extracullar matrix synthesis in wound healing. The precise mechanism, however, in molecular and gene expression levels still remains partially understood. Using cDNA microarray technology, the alternation of genes expression profiles was determined in a human dermal fibroblast in vitro in the presence of asiaticoside (30 microg/ml). Fifty-four genes, with known functions for cell proliferation, cell-cycle progression and synthesis of the extracellular matrix, were significantly up-regulated in our "whole-genes nest" expression profile at various timepoints. Furthermore, mRNA levels and protein productions of certain genes responsible for extracellular matrix (ECM) synthesis (e.g. encoding type I and type III collagen proteins) were evaluated by Northern blot and radioimmunoassay, respectively. As a result, there is a close correlation among the gene profile, mRNA and protein production in the cells response to asiaticoside stimulation. This information could be used for exploring the target genes in response to asiaticoside in fibroblasts.

Expression of metallothionein gene during embryonic and early larval development in zebrafish.

Metallothionein (Mt) has been considered as a molecular marker of metal pollution in aquatic ecosystems. Less is known about the expression of mt gene during embryogenesis. Here, we report the cloning, sequencing, and the expression pattern of mt gene during developmental stages in zebrafish. The zebrafish embryogenesis when takes place in a medium containing a dosage of 1000 microM zinc resulted in high mortality, indicating the deleterious effect of zinc on development. The zebrafish mt gene consists of three exons encoding 60 amino acids with 20 conserved cysteine residues. RT-PCR result indicates the maternal contribution of Mt transcripts. Using digoxigenin (DIG)-labeled anti-sense RNA probe, whole-mount in situ hybridization was performed to observe the expression pattern of zebrafish mt gene during embryonic and early larval stages. Stronger as well as ubiquitous expression of mt gene during early embryonic stages narrowed to specific expression after hatching. The mt promoter region contains seven copies of putative metal-responsive elements (MREs), which are shown to be important for the high level activity by deletion analysis. The expression of mt gene during embryogenesis implies its significant role on development.

[Effect of Jingtian compound on the delay of skin aging].

In order to study whether Jingtian compound extracted from herbs could delay the process of skin aging, the skin on the back of Guinea pigs (6 and 15 months old) were shaved topically and applied with and without 0.5% Jingtian compound for 30 days by self-control design. The possible alterations caused by Jingtian compound were observed by histological and biochemical techniques. Results showed that the number and the activity of fibroblast in dermis was increased prominently compared with the control. The activities of superoxide dismutase, glutathion peroxidase and the hydroxyproline level of acid soluble collagen in dermis were enhanced, and the malondialdehyde content was inhibited concomitantly. It is suggested that Jingtian compound might play a protective role on skin aging.