Comparison of drug-eluting bead with conventional transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: A randomized clinical trial.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

On-site portable detection of gaseous methyl iodide using an electrochemical method.

We report an electrochemical device for portable on-site detection of gaseous CH3I based on PVIm-F for the first time. The device achieves detection of gaseous CH3I with a significant selectivity and a low detection limit (0.474 ppb) in 20 min at 50 °C and 50% relative humidity, which is of great significance for achieving real-time on-site monitoring of radioactive hazardous environments.

Bio-based ionic liquid filter with enhanced electrostatic attraction for outside filtration and inside collection of viral aerosols.

Hazardous biological pathogens in the air pose a significant public environmental health concern as infected individuals emit virus-laden aerosols (VLAs) during routine respiratory activities. Mask-wearing is a key preventive measure, but conventional filtration methods face challenges, particularly in high humidity conditions, where electrostatic charge decline increases the risk of infection. This study introduces a bio-based air filter comprising glycine ionic liquids (GILs) and malleable polymer composite (GILP) with high polarity and functional group density, which are wrapped around a melamine-formaldehyde (MF) resin skeleton, forming a conductive, porous GIL functionized ionic network air filter (GILP@MF). When subjected to low voltage, the GILP@MF composite efficiently captures VLAs including nanoscale virus particles through the enhanced electrostatic attraction, especially in facing high humidity bioaerosols exhaled by human body. The filtration/collection efficiency and quality factor can reach 98.3% and 0.264 Pa-1 at 0.1 m s-1, respectively. This innovative filter provides effective VLA protection and offers potential for non-invasive respiratory virus sampling, advancing medical diagnosis efforts.

Ionic Polyimine-Based Composite Membrane with Inductive and Complexation Synergistic Effects for Sensitive and On-Site Fluorescent Detection of Volatile Iodine.

Along with the development of nuclear power, concerns about radioactive emissions and the potential for nuclear leakage have been widely raised, particularly of harmful iodine isotopes. However, as a significant component of nuclear air waste, the enrichment and detection of air-dispersed gaseous iodine remain a challenge. In this work, it is focused on developing an attraction-immobilization-detection strategy-based fluorescence method for the on-site detection of volatile iodine, by employing a photoluminescent ionic polyimine network-polyvinylpyrrolidone (IPIN-PVP) composite membrane. This strategy synergizes ion-induced dipole interactions from IPIN and complexation effects from PVP, allowing effective iodine enrichment and immobilization. As a result, the optimized IPIN-PVP membrane exhibits rapid response times of 5 s and a low detection limit of 4.087 × 10-8 m for gaseous iodine. It also introduces a portable handheld detection device that utilizes the composite membrane, offering a practical solution for real-time on-site detection of volatile iodine. This innovation enhances nuclear safety measures and disaster management by providing rapid and reliable iodine detection capabilities.

Natural Products Treat Atopic Dermatitis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

Atopic dermatitis （AD） is a chronic， recurrent， inflammatory， and pruritus skin disease caused by multiple internal and external factors， ranking first in the global burden of skin diseases. Due to the adverse reactions and high costs of conventional treatments and biologics， the development of natural products has attracted much attention. The nuclear factor-κB （NF-κB） signaling pathway is a key pathway for inhibiting inflammation and modulating immunity. This paper summarizes the pharmacological effects and molecular mechanisms of natural products such as flavonoids， alkaloids， phenols， terpenoids， coumarins， glycosides， and anthraquinones via NF-κB signaling pathway， aiming to provide guidance for the development of natural products. Basic studies have shown that natural products have high safety and efficacy. Oral or topical administration of natural products can regulate the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， high mobility group box 1 protein （HMGB1）/receptor for advanced glycation endproducts （RAGE）， and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） signaling pathways to exert anti-inflammatory， anti-allergy， antioxidant activities， thus reversing the pathological changes of AD. However， it is worth noting that the clinical application of natural products is still insufficient， and more rigorous clinical trials are still needed to verify their effects. The basic experiments and clinical evidence prove that natural products may play a role in alleviating AD， which provide a basis for evaluating the functioning mechanism of natural active substances and enrich the candidates for the development of potential drugs.

Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production / 药学学报

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Hydrogen-bonding and π-π interaction promoted solution-processable covalent organic frameworks.

Covalent organic frameworks show great potential in gas adsorption/separation, biomedicine, device, sensing, and printing arenas. However, covalent organic frameworks are generally not dispersible in common solvents resulting in the poor processability, which severely obstruct their application in practice. In this study, we develop a convenient top-down process for fabricating solution-processable covalent organic frameworks by introducing intermolecular hydrogen bonding and π-π interactions from ionic liquids. The bulk powders of imine-linked, azine-linked, and ß-ketoenamine linked covalent organic frameworks can be dispersed homogeneously in optimal ionic liquid 1-methyl-3-octylimidazolium bromide after heat treatment. The resulting high-concentration colloids are utilized to create the covalent organic framework inks that can be directly printed onto the surface. Molecular dynamics simulations and the quantum mechanical calculations suggest that C‒H···π and π-π interaction between ionic liquid cations and covalent organic frameworks may promote the formation of colloidal solution. These findings offer a roadmap for preparing solution-processable covalent organic frameworks, enabling their practical applications.

Wnt/ß-catenin signaling activation promotes lipogenesis in the steatotic liver via physical mTOR interaction.

Background and aims: Wnt/ß-catenin signaling plays an important role in regulating hepatic metabolism. This study is to explore the molecular mechanisms underlying the potential crosstalk between Wnt/ß-catenin and mTOR signaling in hepatic steatosis. Methods: Transgenic mice (overexpress Wnt1 in hepatocytes, Wnt+) mice and wild-type littermates were given high fat diet (HFD) for 12 weeks to induce hepatic steatosis. Mouse hepatocytes cells (AML12) and those transfected to cause constitutive ß-catenin stabilization (S33Y) were treated with oleic acid for lipid accumulation. Results: Wnt+ mice developed more hepatic steatosis in response to HFD. Immunoblot shows a significant increase in the expression of fatty acid synthesis-related genes (SREBP-1 and its downstream targets ACC, AceCS1, and FASN) and a decrease in fatty acid oxidation gene (MCAD) in Wnt+ mice livers under HFD. Wnt+ mice also revealed increased Akt signaling and its downstream target gene mTOR in response to HFD. In vitro, increased lipid accumulation was detected in S33Y cells in response to oleic acid compared to AML12 cells reinforcing the in vivo findings. mTOR inhibition by rapamycin led to a down-regulation of fatty acid synthesis in S33Y cells. In addition, ß-catenin has a physical interaction with mTOR as verified by co-immunoprecipitation in hepatocytes. Conclusions: Taken together, our results demonstrate that ß-catenin stabilization through Wnt signaling serves a central role in lipid metabolism in the steatotic liver through up-regulation of fatty acid synthesis via Akt/mTOR signaling. These findings suggest hepatic Wnt signaling may represent a therapeutic strategy in hepatic steatosis.

Low-melting multicharge ionic liquids with [Ln(NO3)5]2- (Ln = Ho-Lu): structural, electrostatic, thermochemical, and fluorescence properties.

A series of green and safe heavy-rare-earth ionic liquids were obtained using a straightforward method. The stable structures of these ionic liquids, characterized by high-coordinating anions, were confirmed by nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and single crystal X-ray diffraction (XRD). These ionic liquids exhibited wide liquid phase intervals and excellent thermal stability. The bidentate nitrato ligands occupied a sufficient number of coordination sites on the lanthanide ions, resulting in the formation of water-free 10-coordination structures. To explain the anomalous melting points observed in these multi-charged ionic liquids, a combination of experimental data and theoretical studies was employed to investigate the relationship between the electrostatic properties and the melting point. The electrostatic potential density per unit ion surface and volume were proposed and utilized for melting point prediction, demonstrating good linearity. Furthermore, the coordinating spheres of the lanthanide ions in these ionic liquids were devoid of luminescence quenchers such as O-H and N-H groups. Notably, the ionic liquids containing Ho3+, Er3+, and Tm3+ exhibited long lifetime near-infrared (NIR) and blue emissions, respectively. The UV-vis-NIR spectra revealed numerous electronic transitions of the lanthanide ions, which were attributed to their unique optical properties.

Downregulation of Histone H4 Lysine 16 Acetylation Ameliorates Autophagic Flux by Resuming Lysosomal Functions in Ischemic Neurons.

Autophagic/lysosomal dysfunction was a critical pathogenesis of neuronal death after an ischemic stroke, but what drove the impairment of autophagic flux remained elusive. Studies indicated that histone H4 lysine 16 acetylation (H4K16ac) drastically modulated the autophagic/lysosomal signaling pathway. Herein, we investigated whether the autophagic/lysosomal dysfunction in neurons could be restored by altering H4K16ac levels after cerebral ischemia. The rat model of ischemic stroke and the cell ischemia model in HT22 neurons were prepared by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively. The result showed that H4K16ac could be effectively reduced by intracerebroventricular administration with MG149 (a H4K16ac inhibitor) after an ischemic stroke. Moreover, attenuated H4K16ac greatly alleviated the autophagic/lysosomal dysfunction in penumbral neurons, as indicated by decreased autophagic substrates of LC3-II, insoluble SQSTM1, and ubiquitinated proteins, accompanied by increased lysosomal cathepsin D. Conversely, treatment with trichostatin A (TSA, a H4K16ac facilitator) aggravated the impairment of autophagic flux. This regulative machinery of H4K16ac on the autophagic/lysosomal signaling pathway was also manifested in the OGD model of HT22 neurons. Furthermore, H4K16ac attenuation-ameliorated autophagic flux significantly alleviated stroke brain injury, as reflected by decreased infarct size, neuron loss, and neurological deficits. Similarly, the H4K16ac inhibition-mitigated autophagic/lysosomal dysfunction markedly promoted neuron survival and cell viability in OGD HT22 neurons. However, H4K16ac downregulation-ameliorated autophagic flux in neurons and thereby induced neuroprotection could be greatly counteracted by the lysosomal inhibitor bafilomycin A1 (Baf-A1). Our data indicate that cerebral ischemia-elevated H4K16ac creates the autophagic/lysosomal dysfunction due to lysosomal inefficiency, suggesting that H4K16ac attenuation benefits poststroke neuroprotection by resuming lysosomal functions in neurons.

Boost of Gas Adsorption Kinetics of Covalent Organic Frameworks via Ionic Liquid Solution Process.

Adsorption, storage, and conversion of gases (e.g., carbon dioxide, hydrogen, and iodine) are the three critical topics in the field of clean energy and environmental mediation. Exploring new methods to prepare high-performance materials to improve gas adsorption is one of the most concerning topics in recent years. In this work, an ionic liquid solution process (ILSP), which can greatly improve the adsorption kinetic performance of covalent organic framework (COF) materials for gaseous iodine, is explored. Anionic COF TpPaSO3 H is modified by amino-triazolium cation through the ILSP method, which successfully makes the iodine adsorption kinetic performance (K80% rate) of ionic liquid (IL) modified COF AC4 tirmTpPaSO3 quintuple compared with the original COF. A series of experimental characterization and theoretical calculation results show that the improvement of adsorption kinetics is benefited from the increased weak interaction between the COF and iodine, due to the local charge separation of the COF skeleton caused by the substitution of protons by the bulky cations of ILs. This ILSP strategy has competitive help for COF materials in the field of gas adsorption, separation, or conversion, and is expected to expand and improve the application of COF materials in energy and environmental science.

Solvent-Responsive Reversible and Controllable Conversion between a Polyimine Membrane and an Organic Molecule Cage.

Adaptive bionic self-correcting behavior offers an attractive property for chemical systems. Here, based on the dynamic feature of imine formation, we propose a solvent-responsive strategy for smart switching between an amorphous ionic polyimine membrane and a crystalline organic molecule cage without the addition of other building blocks. To adapt to solvent environmental constraints, the aldehyde and amine components undergo self-correction to form a polymer network or a molecular cage. Studies have shown that the amorphous film can be switched in acetonitrile to generate a discrete cage with bright birefringence under polarized light. Conversely, the membrane from the cage crystal conversion can be regained in ethanol. Such a membrane-cage interconversion can be cycled continuously at least 5 times by switching the two solvents. This work builds a bridge between the polymer network and crystalline molecules and offers prospects for smart dynamic materials.

Lead Sequestration in Perovskite Photovoltaic Device Encapsulated with Water-Proof and Adhesive Poly(ionic liquid).

The inevitable usage of toxic lead impedes the commercialization of lead halide perovskite solar cells, especially considering lead ions potentially unseals from the discarded and damaged devices and consequently contaminates the environment. In this work, we proposed a poly(ionic liquid) (PIL) cohered sandwich structure (PCSS) to realize lead sequestration in perovskite solar cells by a water-proof and adhesive poly([1-(3-propionic acid)-3-vinylimidazolium] bis(trifluoromethanesulphonyl)imide (PPVI-TFSI). A transparent ambidextrous protective shield manufactured from PPVI-TFSI was achieved and applied in lead sequestration for perovskite solar cells. PCSS provides robustness and water-resistance, which improves device stability toward water erosion and extreme situations (such as acid, base, salty water, and hot water). PPVI-TFSI exhibited excellent affinity toward lead with adsorption capacity of 516 mg·g-1, which assisted to prevent lead leakage in abandoned devices as proved in the test of wheat germination vividly. PCSS provides a promising solution for complex lead sequestration and management issues, which contribute to the commercialization of perovskite solar cells.

Gut microbial characteristical comparison reveals potential anti-aging function of Dubosiella newyorkensis in mice.

Introduction: Previous study has indicated Dubosiella newyorkensis may act as a potential probiotic in age-related diseases. However, its detailed role in aging has not yet been promulgated. This study aimed to explore the potential anti-aging role of Dubosiella newyorkensis by comparing the anti-aging effect of resveratrol in young and old mice. Method: Measurement of intestinal aging-related factors in colon and serum, and vascular endothelial function-related factors in serum were performed by enzyme-linked immunosorbent assay (ELISA). Gut microbial analysis of intestinal contents were identified by 16S rRNA gene sequencing. Results: The effect of Dubosiella newyorkensis on reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) in aged mice were greater than that of resveratrol. While the effect of Dubosiella newyorkensis on nitric oxide (NO) level was less than that of resveratrol, the reduction of vascular endothelial growth factor (VEGF) and pentosidine (PTD) was better than that of resveratrol in young mice. In young mice, Dubosiella newyorkensis promoted an increase in the beneficial genus Lactobacillus, Bifidobacterium and Ileibacterium less effectively as compared with resveratrol treatment. In aged mice, Dubosiella newyorkensis promoted the increase of Bifidobacterium, Ileibacterium less effectively than resveratrol, and promoted the increase of Akkermansia, Staphylococcus, Verrucomicrobiota expression better as compared with resveratrol treatment. Both young and old mice showed the same results for the remaining markers, including changes in gut microbial composition and predictions of function. Conclusion: Dubosiella newyorkensis has similar anti-aging functions with resveratrol. Dubosiella newyorkensis may even be more effective than resveratrol in reducing oxidative stress, improving vascular endothelial function, and redistributing gut microbiota. The research provides an innovative strategy of Dubosiella newyorkensis to improve aging.

Impacts of hydraulic conditions on microplastics biofilm development, shear stresses distribution, and microbial community structures in drinking water distribution pipes.

Both microplastic and biofilm are contamination sources in drinking water, but their integrated impacts on water quality have been rarely studied, especially in drinking water distribution pipes with complex hydraulic conditions. This study explored the impacts of hydraulic conditions (0-2 m/s) on microplastic biofilm (MP-BM) development, shear stresses distribution, and microbial community structures. The research was conducted for two weeks using a pilot test device to simulate practical water pipes. The following were the primary conclusions: (1) According to morphology analysis, clusters (>5 µm) significantly increased in the plastisphere when the flow velocity ranged from 0.55 m/s to 0.95 m/s, and average size of clusters decreased when the flow velocity ranged from 1.14 m/s to 1.40 m/s (2) Characteristics of MP-BM impact shear stress on both plastisphere and pipe wall biofilm. Shear stresses were positively correlated with flow velocity, number of MP-BM, and size of MP-BM, while negatively correlated with diameters of pipes. (3) 31 genera changed strictly and monotonously with the fluid velocity, accounting for 15.42%. Opportunistic pathogens in MP-BM such as Sediminibacterium, Curvibacter, and Flavobacterium were more sensitive to hydraulic conditions. Moreover, microplastics (<100 µm) deserve more attention to avoid human ingestion and to prevent mechanical damage and bio-chemical risks.

Exploration of the Mechanism of Tripterygium Wilfordii in the Treatment of Myocardial Fibrosis Based on Network Pharmacology and Molecular Docking.

BACKGROUND: A network pharmacology study on the biological action of Tripterygium wilfordii on myocardial fibrosis (MF). METHODS: The effective components and potential targets of tripterygium wilfordii were screened from the TCMSP database to develop a combination target network. A protein-protein interaction network was constructed by analyzing the interaction between tripterygium wilfordii and MF; then, the Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Furthermore, molecular docking was utilized to verify the network analysis results. RESULTS: It was predicted that MF has 29 components contributing to its effectiveness and 87 potential targets. It is predicted that Tripterygium wilfordii has 29 active components and 87 potential targets for the treatment of MF. The principal active components of tripterygium wilfordii include kaempferol, ß-sitosterol, triptolide, and Nobiletin. Signaling pathways: AGE-RAGE, PI3K-Akt, and MAPK may be involved in the mechanism of its action.7 Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii. CONCLUSION: This study shows the complex network relationship between multiple components, targets, and pathways of Tripterygium wilfordii in treating MF.

Butyrate induces development-dependent necrotizing enterocolitis-like intestinal epithelial injury via necroptosis.

BACKGROUND: The accumulation of short-chain fatty acids (SCFAs) from bacterial fermentation may adversely affect the under-developed gut as observed in premature newborns at risk for necrotizing enterocolitis (NEC). This study explores the mechanism by which specific SCFA fermentation products may injure the premature newborn intestine mucosa leading to NEC-like intestinal cell injury. METHODS: Intraluminal injections of sodium butyrate were administered to 14- and 28-day-old mice, whose small intestine and stool were harvested for analysis. Human intestinal epithelial stem cells (hIESCs) and differentiated enterocytes from preterm and term infants were treated with sodium butyrate at varying concentrations. Necrosulfonamide (NSA) and necrostatin-1 (Nec-1) were used to determine the protective effects of necroptosis inhibitors on butyrate-induced cell injury. RESULTS: The more severe intestinal epithelial injury was observed in younger mice upon exposure to butyrate (p = 0.02). Enterocytes from preterm newborns demonstrated a significant increase in sensitivity to butyrate-induced cell injury compared to term newborn enterocytes (p = 0.068, hIESCs; p = 0.038, differentiated cells). NSA and Nec-1 significantly inhibited the cell death induced by butyrate. CONCLUSIONS: Butyrate induces developmental stage-dependent intestinal injury that resembles NEC. A primary mechanism of cell injury in NEC is necroptosis. Necroptosis inhibition may represent a potential preventive or therapeutic strategy for NEC. IMPACT: Butyrate induces developmental stage-dependent intestinal injury that resembles NEC. A primary mechanism of cell injury caused by butyrate in NEC is necroptosis. Necroptosis inhibitors proved effective at significantly ameliorating the enteral toxicity of butyrate and thereby suggest a novel mechanism and approach to the prevention and treatment of NEC in premature newborns.

Effect of edaravone on ERK-CREB signaling pathway in hippocampus of aged rats with postoperative cognitive dysfunction / 中华麻醉学杂志

Objective:To evaluate the effect of edaravone on the extracellular signal-regulated kinase (ERK)-cAMP responsive element binding protein (CREB) signaling pathway in the hippocampus of aged rats with postoperative cognitive dysfunction (POCD).Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 650-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), POCD group (group P), edaravone group (group E) and ERK inhibitor group (group I). The rats received laparotomy under 3% sevoflurane anesthesia to prepare POCD model in P, E and I groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and I groups, ERK inhibitor PD98059 0.3 mg/kg was injected via the tail vein in group I. The open field test was performed at 3 days after operation to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats on 3-7 days after operation. The rats were sacrificed after the end of Morris water maze test, and hippocampal tissues were obtained for determination of the expression of phosphorylated ERK (p-ERK), phosphorylated CREB (p-CREB), synaptophysin and postsynaptic density protein 95 (PSD-95) (by Western blot) and dendrite length and density of dendrites in hippocampal CA1 area (using Golgi staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was down-regulated, and the dendritic length and density of hippocampal neurons were reduced in group P ( P<0.05). Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was up-regulated, and the dendritic length and density of hippocampal neurons were increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was down-regulated, the dendritic length of hippocampal neurons was shortened, and the density of hippocampal neurons was decreased in group I( P<0.05). Conclusions:The mechanism by which edaravone improves POCD may be related to activating ERK/CREB signaling pathway and changing synaptic plasticity in hippocampal CA1 region in aged rats.

Role of PI3K/Akt/mTOR signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats.Methods:Sixty healthy male Sprague-Dawley rats, aged 20 months, weighing 600-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), operation group (group O), edaravone group (group E) and PI3K inhibitor LY294002 group (group LY). The rats received laparotomy under 3% sevoflurane anesthesia in O, E and LY groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups, and LY294002 0.3 mg/kg was simultaneously injected via the tail vein in group LY. Open field test was performed at 3 days after surgery to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats. The rats were sacrificed after the end of behavioral experiment to isolate hippocampal tissues for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), synaptophysin (SYP) and postsynaptic density protein 95 (PSD 95) (by Western blot ) and dendrite length in hippocampal CA1 area (using Golgi staining). The density of dendrites was calculated. Results:There were no statistically significant differences in exercise speed, distance, and time of staying at the center between the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was up-regulated, the dendritic length of neurons in hippocampal CA1 region was prolonged, and the density of neurons in hippocampal CA1 region was increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, and the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group LY ( P<0.05). Conclusions:The mechanism by which edaravone reduces postoperative cognitive dysfunction is related to activating PI3K/Akt/mTOR signaling pathway and improving synaptic plasticity in aged rats.

Natural orifice transluminal endoscopic lithotripsy with intelligent control of renal pelvic pressure for staghorn calculi with infection: a case report with surgical video / 中华泌尿外科杂志

Percutaneous nephrolithotripsy is the first line treatment for complete staghorn calculi, but there are risks such as renal function damage, bleeding, and infection. A case of complete staghorn calculi 8.3 cm×4.5 cm and mean CT value of 1 321 HU was reported. Urine culture suggested proteus mirabilis infection. The patient was given sensitive antibiotics for 3 days, and was treated with one session of natural orifice transluminal endoscopic lithotripsy with intelligent control of renal pelvic pressure. KUB on the first postoperative day showed residual stones of 1.0 cm×0.5 cm. There were no complications.