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1.
Infect Drug Resist ; 15: 69-81, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35046672

RESUMO

Purpose: This study retrospectively analyzed the genome characteristics of blaKPC-2 in multidrug-resistant Klebsiella pneumoniae collected from the ICU of a teaching hospital in Shanghai, China. Methods: From February 2018 to December 2019, 36 strains of multidrug-resistant Klebsiella pneumoniae were collected from the bronchoalveolar lavage fluid of critically ill patients. The genome of all isolates was obtained through the Illumina sequence, and single nucleotide polymorphisms of the blaKPC-2 gene were analyzed to explore blaKPC-2's evolutionary characteristics. Different strains' genetic relationships and homology were studied by constructing an evolutionary tree on a single copy orthologue. Pacbio combined Illumina sequence was conducted to evaluate the structure and potential mobility of drug-resistant plasmids of the strain KP-s26. Results: The distribution of resistance and virulence genes had little difference, but most strains had significant differences in the plasmid-encoded region. Most strains (31/36) carried the carbapenemase gene blaKPC-2, with no single nucleotide polymorphism in different strains. Extended-spectrum ß-lactamase resistance genes, such as blaCTX-M and blaSHV, were found in the isolates, but no metallo-ß-lactamases were detected. All strains with blaKPC-2 coexisted with chromosomal-associated fosfomycin resistance genes fosA6, and the coexistence of blaKPC-2 and blaCTX variants (blaCTX-M-15, blaCTX-M-65, and blaCTX-M-27) was also detected in 29/31 strains. The isolate KP-s26 carried five circular plasmids. pA and pB were conjugate plasmids, as they carried drug resistance genes and contained a complete IV secretion system. Conclusion: The blaKPC-2 carbapenemase gene is relatively conservative in the process of evolution; drug-resistant plasmids containing conjugated transfer elements contribute to the spreading of drug resistance. The coexistence of blaKPC-2 with fosA6 or blaCTX-M variants was associated with increased fosfomycin resistance and broad-spectrum ß-lactam resistance, respectively. Clinical Trials Registration: Clinical Trials.gov Identifier: NCT03950544.

2.
Prog Neurobiol ; 210: 102215, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995694

RESUMO

Major theories of consciousness predict that complex electroencephalographic (EEG) activity is required for consciousness, yet it is not clear how such activity arises in the corticothalamic system. The thalamus is well-known to control cortical excitability via interlaminar projections, but whether thalamic input is needed for complexity is not known. We hypothesized that the thalamus facilitates complex activity by adjusting synaptic connectivity, thereby increasing the availability of different configurations of cortical neurons (cortical "states"), as well as the probability of state transitions. To test this hypothesis, we characterized EEG activity from prefrontal cortex (PFC) in traumatic brain injury (TBI) patients with and without injuries to thalamocortical projections, measured with diffusion tensor imaging (DTI). We found that injury to thalamic projections (especially from the mediodorsal thalamus) was strongly associated with unconsciousness and delta-band EEG activity. Using advanced signal processing techniques, we found that lack of thalamic input led to 1.) attractor dynamics for cortical networks with a tendency to visit the same states, 2.) a reduced repertoire of possible states, and 3.) high predictability of transitions between states. These results imply that complex PFC activity associated with consciousness depends on thalamic input. Our model implies that restoration of cortical connectivity is a critical function of the thalamus after brain injury. We draw a critical connection between thalamic input and complex cortical activity associated with consciousness.

3.
Materials (Basel) ; 15(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35057235

RESUMO

Desulfurization ash and fly ash are solid wastes discharged from boilers of power plants. Their utilization rate is low, especially desulfurization ash, most of which is stored. In order to realize their resource utilization, they are used to modify loess in this paper. Nine group compaction tests and 32 group direct shear tests are done in order to explore the influence law of desulfurization ash and fly ash on the strength of the loess. Meanwhile, FLAC3D software is used to numerically simulate the direct shear test, and the simulation results and the test results are compared and analyzed. The results show that, with the increase of desulfurization ash's amount, the shear strength of the modified loess increases first and then decreases. The loess modified by the fly ash has the same law with that of the desulfurization ash. The best mass ratio of modified loess is 80:20. When the mass ratio is 80:20, the shear strength of loess modified by the desulfurization ash is 12.74% higher than that of the pure loess on average and the shear strength of loess modified by fly ash is 3.59% higher than that of the pure loess on average. The effect of the desulfurization ash on modifying the loess is better than that of the fly ash. When the mass ratio is 80:20, the shear strength of loess modified by the desulfurization ash is 9.15% higher than that of the fly ash on average. Comparing the results of the simulation calculation with the actual test results, the increase rate of the shear stress of the FLAC3D simulation is larger than that of the actual test, and the simulated shear strength is about 8.21% higher than the test shear strength.

4.
J Am Chem Soc ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851640

RESUMO

Natural transport channels (or carriers), such as aquaporins, are a distinct type of biomacromolecule capable of highly effective transmembrane transport of water or ions. Such behavior is routine for biology but has proved difficult to achieve in synthetic systems. Perhaps most significantly, the enantioselective transmembrane transport of biomolecules is an especially challenging problem both for chemists and for natural systems. Herein, a group of homochiral zirconium metal-organic cages with four triangular opening windows have been proposed as artificial biomolecular channels for enantioselective transmembrane transport of natural amino acids. These structurally well-defined coordination cages are assembled from six synthetically accessible BINOL-derived chiral ligands as spacers and four n-Bu3-Cp3Zr3 clusters as vertices, forming tetrahedral-shaped architectures that feature an intrinsically chiral cavity decorated with an array of specifically positioned binding sites mediated from phenol to phenyl ether to crown ether groups. Fascinatingly, the transformation of single-molecule chirality to global supramolecular chirality within the space-restricted chiral microenvironments accompanies unprecedented chiral amplification, leading to the enantiospecific recognition of amino acids. By virtue of the highly structural stability and excellent biocompatibility, the orientation-independent cages can be molecularly embedded into lipid membranes, biomimetically serving as single-molecular chiral channels for polar-residue amino acids, with the properties that cage-1 featuring hydroxyl groups preferentially transports the l-asparagine, whereas cage-2 attaching crown ether groups spontaneously favor transporting d-arginine. We therefore develop a new type of self-assembled system that can potentially mimic the functions of transmembrane proteins in nature, which is a realistic candidate for further biomedical applications.

6.
Molecules ; 26(23)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34885794

RESUMO

A novel synthetic pathway to approach 3-(imino)isoindolin-1-ones by the Co-catalyzed cyclization reaction of 2-bromobenzamides with carbodiimides has been developed. This catalytic reaction can tolerate a variety of substituents and provide corresponding products in moderate yields for most cases. According to the literature, the reaction mechanism is proposed through the formation of a five-membered aza-cobalacycle complex, which carries out the following reaction subsequence, including nucleophilic addition and substitution, to furnish the desired structures.

7.
Plant Cell ; 2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-34954802

RESUMO

Chromatin remodelers act in an ATP-dependent manner to modulate chromatin structure and thus genome function. Here, we report that the Arabidopsis (Arabidopsis thaliana) remodeler CHROMATIN REMODELING19 (CHR19) is enriched in gene body regions, and its depletion causes massive changes in nucleosome position and occupancy in the genome. Consistent with these changes, an in vitro assay verified that CHR19 can utilize ATP to slide nucleosomes. A variety of inducible genes, including several important genes in the salicylic acid (SA) and jasmonic acid (JA) pathways, were transcriptionally up-regulated in the chr19 mutant under normal growth conditions, indicative of a role of CHR19 in transcriptional repression. In addition, the chr19 mutation triggered higher susceptibility to the JA pathway-defended necrotrophic fungal pathogen Botrytis cinerea, but did not affect the growth of the SA pathway-defended hemibiotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Expression of CHR19 was tissue-specific and inhibited specifically by SA treatment. Such inhibition significantly decreased the local chromatin enrichment of CHR19 at the associated SA pathway genes, which resulted in their full activation upon SA treatment. Overall, our findings clarify CHR19 to be a novel regulator acting at the chromatin level to impact the transcription of genes underlying plant resistance to different pathogens.

8.
Biomaterials ; 279: 121202, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34749072

RESUMO

Red blood cells (RBCs) are biocompatible carriers that can be employed to deliver different bioactive substances. In the past few decades, many strategies have been developed to encapsulate or attach drugs to RBCs. Osmotic-based encapsulation methods have been industrialized recently, and some encapsulated RBC formulations have reached the clinical stage for treating tumors and neurological diseases. Inspired by the intrinsic properties of intact RBCs, some advanced delivery strategies have also been proposed. These delivery systems combine RBCs with other novel systems to further exploit and expand the application of RBCs. This review summarizes the clinical progress of drugs encapsulated into intact RBCs, focusing on the loading and clinical trials. It also introduces the latest advanced research based on developing prospects and limitations of intact RBCs drug delivery system (DDS), hoping to provide a reference for related research fields and further application potential of intact RBCs based drug delivery system.

9.
J Cell Physiol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34796915

RESUMO

Excessive activity of osteoclasts contributes to skeletal diseases such as osteoporosis and osteolysis. However, current drugs targeting osteoclast have various deficiencies, placing natural compounds as substitutions of great potential. Roburic acid (RA) is a triterpenoid exacted from Radix Gentianae Macrophyllae, which exhibits inhibitory effects on inflammation and oxidation. By employing an in vitro osteoclastogenesis model, this study investigates the effects and mechanisms of RA on intracellular signaling induced by receptor activator of nuclear factor-κB ligand (RANKL). As expected, RA at a concentration scope from 1 to 10 µM dampened the osteoclast differentiation of bone marrow macrophages (BMMs) but without cell toxicity. Interestingly, RA showed no effect on osteoblastogenesis in vitro. Furthermore, RA mitigated F-actin ring formation, hydroxyapatite resorption, and gene expression in osteoclasts. Mechanistically, RA suppressed TNF receptor-associated factor 6 (TRAF6), the crucial adaptor protein following RANKL-RANK binding. On the one hand, RA downregulated the nuclear factor-κB (NF-κB) activity, extracellular regulated protein kinases (ERK) phosphorylation, and calcium oscillations. On the other hand, RA upregulated the antioxidative response element (ARE) response and the protein expression of heme oxygenase (HO)-1. These upstream alterations eventually led to the suppression of the nuclear factor of activated T cells 1 (NFATc1) activity and the expression of proteins involved in osteoclastogenesis and bone resorption. Furthermore, by using an ovariectomized (OVX) mice model, RA was found to have therapeutic effects against bone loss. On account of these findings, RA could be used to restrain osteoclasts for treating osteoporosis and other osteolytic diseases.

10.
Chin Med J (Engl) ; 134(22): 2685-2691, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759229

RESUMO

BACKGROUND: Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD). METHODS: One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups. RESULTS: At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05). CONCLUSIONS: The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

11.
Curr Pharm Des ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34766889

RESUMO

Due to the advantages of adjustable pore size, easy surface modification, high biocompatibility, and so on, mesoporous silica nanoparticles (MSNs) have attracted lots of attention. And they are widely used in the fields of biology and medicine research, mostly focusing on drug and gene delivery and bioimaging. This review introduces several commonly used synthetic methods of MSNs and the latest progress of MSNs in tumor therapy and diagnosis, mainly including the study about modified MSNs as drug carriers and the application of MSNs in bioimaging. The deficiencies of MSNs' application and prospects for its future clinical transformation are also discussed.

12.
Int J Mol Sci ; 22(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34768749

RESUMO

Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (MZF1) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.

13.
J Oral Biosci ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808363

RESUMO

OBJECTIVES: Platelet-rich fibrin (PRF) is widely used in wound healing because it contains several growth factors, including vascular endothelial growth factor (VEGF). In this study, we investigated the effects of advanced PRF (A-PRF) in early-stage gingival regeneration after tooth extraction. METHODS: Blood sample was collected from females beagle dogs (age: 12 months) before tooth extraction for A-PRF preparation. All animals were sacrificed by perfusion-fixation on postoperative days 1, 3, and 7. The upper jaws were prepared for hematoxylin and eosin staining and immunostaining (for CD34 and VEGF). The lower jaw samples were prepared for scanning electron microscope observations. Blood flow in the gingiva before and after surgery was measured using laser Doppler flowmetry. RESULTS: In the A-PRF group, a large number of microvessels were observed in the gingival tissue on postoperative day 1. The microvessels in the control group were fewer and sparse. Regarding the vascular resin cast, a large number of new blood vessels were observed on postoperative day 1 in the A-PRF group. A stronger CD34-positive signal was obtained around the blood vessels in the A-PRF group than in the control group. Further, a strong VEGF-positive signal was observed in the perivascular tissue in the A-PRF group. Gingival blood flow was significantly higher in the A-PRF group after surgery. CONCLUSION: A-PRF had a positive impact on angiogenesis in the gingiva through the induction of VEGF expression. Thus, A-PRF may be beneficial for gingival tissue regeneration.

14.
Small ; 17(47): e2104359, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34716653

RESUMO

MicroRNAs (miRs) play an important role in regulating gene expression. Limited by their instabilities, miR therapeutics require delivery vehicles. Tetrahedral framework nucleic acids (tFNAs) are potentially applicable to drug delivery because they prominently penetrate tissue and are taken up by cells. However, tFNA-based miR delivery strategies have failed to separate the miRs after they enter cells, affecting miR efficiency. In this study, an RNase H-responsive sequence is applied to connect a sticky-end tFNA (stFNA) and miR-2861, which is a model miR, to target the expression of histone deacetylase 5 (HDAC5) in bone marrow mesenchymal stem cells. The resultant bioswitchable nanocomposite (stFNA-miR) enables efficient miR-2861 unloading and deployment after intracellular delivery, thereby inhibiting the expression of HDAC5 and promoting osteogenic differentiation. stFNA-miR also facilitated ideal bone repair via topical injection. In conclusion, a versatile miR delivery strategy is offered for various biomedical applications that necessitate modulation of gene expression.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34710948

RESUMO

Covalent organic frameworks (COFs) hold great potentials for addressing the challenge of highly efficient oil-water separation, but they are restricted by the poor wettability and processability as crystalline membranes. Here we report the design and synthesis of two-dimensional (2D) robust COFs with controllable hydrophobicity and processability, allowing the COF layers to be directly grown on the support surfaces. Three 2D COFs with AA or ABC stacking are prepared by condensation of triamines with fluorine and/or isopropyl groups and perfluorodialdehyde. They all show excellent tolerance to water, acid, and base, with water contact angles (CA) of 111.5-145.8°. The two COFs with isopropyl and fluorine mixtures can grow as a coating on a stainless-steel net (SSN) substrate, whereas the one with only fluorine substituents cannot. The superhydrophobic COF@SSN coating with water CA of up to 150.1° displays high water-resistance and self-cleaning properties, enabling high oil-water separation performances with an efficiency of over 99.5 % and a permeation flux of 2.84×105  L m-2 h-1 , which are among the highest values reported for state-of-the-art membranes.

16.
Ecotoxicol Environ Saf ; 226: 112833, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34600291

RESUMO

Manganese (Mn) is an essential metal in humans and animals. However, excess Mn entered environment due to the wide application of Mn in industry and agriculture, and became an environmental pollutant. Exposure to high doses of Mn is toxic to humans and animals (including chickens). Liver is a target organ of Mn poisoning. Nevertheless, there were few studies on whether Mn poisoning damages chicken livers and poisoning mechanism of Mn in chicken livers. Herein, the aim of this study was to explore if oxidative stress, heat shock proteins (HSPs), and inflammatory response were involved in the mechanism of Mn poisoning-caused damage in chicken livers. A chicken Mn poisoning model was established. One hundred and eighty chickens were randomly divided into one control group (containing 127.88 mg Mn kg-1) and three Mn-treated groups (containing 600, 900, and 1800 mg Mn kg-1, respectively). Histomorphological structure was observed via microstructure and ultrastructure. Spectrophotometry was used to detect total antioxidant capacity (T-AOC) and inducible nitric oxide synthase (iNOS) activity, as well as nitric oxide (NO) content. And qRT-PCR was performed to measure mRNA expression of inflammatory genes (nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and iNOS) and heat shock protein (HSP) genes (HSP27, HSP40, HSP60, HSP70, and HSP90). Multivariate correlation analysis, principal component analysis, and cluster analysis were used to demonstrate the reliability of mechanism of Mn poisoning in our experiment. The results indicated that excess Mn led to inflammatory injury at three contents and three time points. Meanwhile, we found that NO content, iNOS activity, and NF-κB, TNF-α, COX-2, PGE2, and iNOS mRNA expression increased after Mn treatment, meaning that exposure to Mn induced inflammatory response via NF-κB pathway in chicken livers. Moreover, excess Mn decreased T-AOC activity, indicating that Mn exposure caused oxidative stress. Furthermore, mRNA expression of above five HSP genes was up-regulated during Mn exposure. Oxidative stress triggered the increase of HSPs and the increase of HSPs mediated inflammatory response induced by Mn. In addition, there were time- and dose-dependent effects on Mn-caused chicken liver inflammatory injury. Taken together, HSPs participated in oxidative stress-mediated inflammatory damage caused by excess Mn in chicken livers via NF-κB pathway. For the first time, we found that oxidative stress can trigger HSP70 and HSPs can trigger poisoning-caused inflammatory damage, which needs to be further explored. This study provided a new insight into environmental pollutants and a reference for further study on molecular mechanisms of poisoning.


Assuntos
Manganês , NF-kappa B , Animais , Galinhas/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Fígado/metabolismo , Manganês/toxicidade , NF-kappa B/genética , Estresse Oxidativo , Reprodutibilidade dos Testes
17.
Artigo em Inglês | MEDLINE | ID: mdl-34694243

RESUMO

ABSTRACT: ZIP12, a plasmalemmal zinc transporter, reportedly promotes pulmonary vascular remodeling (PVR) by enhancing proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms of ZIP12 facilitating PASMCs proliferation remain incompletely appreciated. It has been acknowledged that proliferation-predisposing phenotypic switching of PASMCs leads to PVR. Given that hypoxia triggers phenotypic switching of PASMCs and ZIP12 mediates PVR, this study aims to explore whether ZIP12-mediated phenotypic switching of PASMCs contributes to hypoxia-induced PVR. Rats were exposed to hypoxia (10% O2) for 3 weeks to induce PVR, and primary rat PASMCs were cultured under hypoxic condition (3% O2) for 48 hours to induce proliferation. Immunofluorescence, quantitative RT-PCR and Western blot analysis were performed to detect the expression of target mRNAs and proteins. EdU incorporation and MTS assay were conducted to measure the proliferation of PASMCs. As revealed, hypoxia up-regulated ZIP12 expression (both mRNA and protein) in pulmonary arteries and PASMCs; knockdown of ZIP12 inhibited phenotypic switching of PASMCs induced by hypoxia. We propose that HIF-1α/ZIP12/pERK pathway could represent a novel mechanism underlying hypoxia-induced phenotypic switching of PASMCs. Therapeutic targeting of ZIP12 could be exploited to treat PVR in hypoxic pulmonary hypertension.

18.
Small ; 17(38): e2101857, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34350696

RESUMO

Although organosulfur compounds can protect lithium anodes, participate in the redox reaction, and suppress the shuttle effect, the sluggish electrochemical dynamics of their bulk structure and the notorious shuttle effect of covalent long-chain sulfurs largely impede their actual applications. Herein, sulfurized carbon nanotube@aminophenol-formaldehyde (SC@A) with covalently linked short-chain sulfurs is firstly synthesized by in situ polymerization of aminophenol-formaldehyde (AF) on the surface of carbon nanotubes (CNTs) followed by acetone etching and inverse sulfurization processes, forming mesoporous yolk-shell organosulfur nanotubes with abundant internal joints between the yolk of CNTs and the shell of sulfurized AF for the first time. In situ Raman spectra, in situ XRD patterns, and ex situ XPS spectra verify that the covalent short-chain sulfurs bring about a reversible solid-solid conversion process of sulfur, thoroughly avoiding the shuttle effect. The mesoporous yolk-shell structure with abundant internal joints can effectively accommodate the volume change, fully expose active sites and efficiently improve the transport of electrons and lithium ions, thus highly promoting the solid-solid electrochemical reaction kinetics. Therefore, the SC@A cathode exhibits a superior specific capacity of 841 mAh g-1 and a capacity decay of 0.06% per cycle within 500 cycles at a large current density of 5.0 C.

19.
Front Surg ; 8: 689782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262933

RESUMO

Objective: To identify the effect of music on outpatient-based cystoscopy. Methods: We systematically reviewed the effect of music on all reported outpatient for cystoscopy and extracted data from randomized trials from inception to February 3, 2021, with no language restrictions. The analysis was completed via STATA version 14.2. Results: A total of 27 studies were initially identified, and 6 articles containing 639 patients were included in the final analysis. In terms of post-procedural pain perception, a pooled analysis of 6 articles containing 639 patients showed that music seems to improve discomfort in patients who undergo cystoscopy (WMD: -1.72; 95%CI: -2.37 to -1.07). This improvement remained consistent in patients undergoing flexible cystoscopy (FC) (WMD: -1.18; 95% CI: -1.39 to -0.98) and rigid cystoscopy (RC) (WMD: -2.56; 95% CI: -3.64 to -1.48). The music group also had less post-procedural anxiety than those in no music group during cystoscopy (WMD: -13.33; 95% CI: -21.61 to -5.06), which was in accordance with the result of FC (WMD: -4.82; 95% CI: -6.38 to -3.26) than RC (WMD: -26.05; 95% CI: -56.13 to 4.04). Besides, we detected a significantly lower post-procedural heart rate (HR) in the music group than no music group during cystoscopy (WMD: -4.04; 95% CI: -5.38 to -2.71), which is similar to the results of subgroup analysis for FC (WMD: -3.77; 95% CI: -5.84 to -1.70) and RC (WMD: -4.24; 95% CI: -5.98 to -2.50). A pooled analysis of three trials indicated that patients in the music group had significantly higher post-operative satisfaction visual analog scale (VAS) scores than those in the no-music group during RC. However, there was no significant difference between the music group and no music group regarding post-procedural systolic pressures (SPs) during cystoscopy (WMD: -3.08; 95% CI: -8.64 to 2.49). For male patients undergoing cystoscopy, the music seemed to exert a similar effect on decreasing anxiety and pain, and it might serve as a useful adjunct to increase procedural satisfaction. Conclusions: These findings indicate that listening to music contributes to the improvement of pain perception, HR, and anxiety feeling during cystoscopy, especially for male patients undergoing RC. Music might serve as a simple, inexpensive, and effective adjunct to sedation during cystoscopy.

20.
Cell Rep ; 36(4): 109420, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320345

RESUMO

Dysregulated glycine metabolism is emerging as a common denominator in cardiometabolic diseases, but its contribution to atherosclerosis remains unclear. In this study, we demonstrate impaired glycine-oxalate metabolism through alanine-glyoxylate aminotransferase (AGXT) in atherosclerosis. As found in patients with atherosclerosis, the glycine/oxalate ratio is decreased in atherosclerotic mice concomitant with suppression of AGXT. Agxt deletion in apolipoprotein E-deficient (Apoe-/-) mice decreases the glycine/oxalate ratio and increases atherosclerosis with induction of hepatic pro-atherogenic pathways, predominantly cytokine/chemokine signaling and dysregulated redox homeostasis. Consistently, circulating and aortic C-C motif chemokine ligand 5 (CCL5) and superoxide in lesional macrophages are increased. Similar findings are observed following dietary oxalate overload in Apoe-/- mice. In macrophages, oxalate induces mitochondrial dysfunction and superoxide accumulation, leading to increased CCL5. Conversely, AGXT overexpression in Apoe-/- mice increases the glycine/oxalate ratio and decreases aortic superoxide, CCL5, and atherosclerosis. Our findings uncover dysregulated oxalate metabolism via suppressed AGXT as a driver and therapeutic target in atherosclerosis.

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