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Background and purpose: Laryngeal cancer is a refractory malignant tumor in otolaryngology. Radiotherapy and chemotherapy combined with surgery are often used, however, this treatment method has little improvement on the 5-year survival rate and mortality of patients, and is often accompanied by loss of laryngeal function and drug resistance. This study aimed to explore the effect of sonodynamic therapy (SDT) mediated by nanoacoustic sensitizer T-G-C particles on inhibiting human laryngeal cancer cells, and to provide a new non-invasive treatment for laryngeal cancer. Methods: Based on the synthesized T-G-C nanomaterials, the uptake of nanomaterials by Tu686 cells was evaluated under confocal laser scanning microscope, and the cell survival and apoptosis were evaluated by cell counting kit-8 (CCK-8) and Annexin Ⅴ- fluorescein isothiocyanate (FITC) reagent in the presence of ultrasound. BALB/c nude mouse xenograft model was established. The weight and tumor changes of mice were recorded during the treatment by injecting different types of drugs and ultrasonic irradiation in the tumor area, and the treatment effects were analyzed and compared. The apoptosis and necrosis of tumor cells and the production of reactive oxygen species (ROS) were compared by H-E, TUNEL, Ki-67 and DHE stainings. Results: Nanomaterials and cells incubated for 24 hours had no obvious toxicity, only led to the decline of cell survival rate under ultrasonic stimulation, and the cells showed mainly early apoptosis and late apoptosis. In the animal experiment, only after intratumoral injection of drugs and ultrasound treatment on the 1st, 3rd, 5th and 7th days, the tumor growth of mice in T-G-C+ultrasound group was significantly inhibited, and the tumor inhibition rate is 100%. After 16 d of treatment, obvious red fluorescence could be seen in the tumor area after ultrasound irradiation, which demonstrated that the core of tumor inhibition was the production of ROS. Conclusion: Biocompatible T-G-C nanoparticles stimulate the synergy of SDT and piezoelectric therapy when stimulated by ultrasound, and promote the early and late apoptosis of laryngeal cancer cells through ROS, which provides a combined treatment method for laryngeal cancer and promotes the application of multidisciplinary therapy in department of otolaryngology.

Aims and Objectives: To describe a grading system that can be used to evaluate core competency of clinical nurse specialists (CNSs) at different levels. Background: Evaluate core competence of CNSs at different levels reflects the quality of nursing and the development of the nursing profession. Design: This research employed the Delphi method. Methods: The STROBE checklist for observational cross‐sectional studies was followed to report this research study. This study consisted of two main phases: a literature review and semistructured interviews. Individual semistructured interviews were conducted with 11 healthcare experts and two patients. Two rounds of questionnaire surveys were administered to 21 nursing experts using the Delphi method. The CNSs were classified as primary, intermediate or advanced based on their years of work, professional titles and educational qualifications. Results: The graded competency evaluation system consisted of five first‐level indicators (clinical practice, consulting guidance and teaching, scientific research innovation, management and discipline development, and ethical decision‐making), 15 second level indicators, and 40 third‐level indicators. The authority coefficients (Cr) of the experts were.865 and.901. The Kendall's concordance coefficients of the three‐level indicators were.417,.289 and.316 for primary CNSs;.384,.294 and.337 for intermediate CNSs; and.489,.289 and.239 for advanced CNSs. Conclusion: The graded use evaluation system in clinical practice initially involves a comprehensive evaluation of the core abilities of CNSs. This is a tool for cultivating and grading the abilities of specialised nurses that can promote a practical upwards spiral. Relevance to Clinical Practice: The evaluation system can promote the scientific management and continuous improvement of CNSs in clinical nursing and can serve as a practical and objective reference for the effective management and development of CNSs. Patient or Public Contribution: Patients participated in the data collection process, during which they shared their health‐seeking experience with our research team. [ABSTRACT FROM AUTHOR]

Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos. In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC–MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-α was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment. [ABSTRACT FROM AUTHOR]

Summary: The NOD‐like receptor family pyrin domain containing 6 (NLRP6), a member of the NOD‐like receptor (NLR) family, acts as a cytosolic innate immune sensor that recognizes microbe‐associated molecular patterns. In some circumstances upon activation, NLRP6 recruits the adaptor apoptosis‐associated speck‐like protein (ASC) and the inflammatory caspase‐1 or caspase‐11 to form an inflammasome, which mediates the maturation and secretion of the pro‐inflammatory cytokines IL‐18 and IL‐1β. In other contexts, NLRP6 can exert its function in an inflammasome‐independent manner. Tight regulation of the NLRP6 inflammasome is critical in maintaining tissue homeostasis, while improper inflammasome activation may contribute to the development of multiple diseases. In intestinal epithelial cells, the NLRP6 inflammasome is suggested to play a role in regulating gut microbiome composition, goblet cell function and related susceptibility to gastrointestinal inflammatory, infectious and neoplastic diseases. Additionally, NLRP6 may regulate extra‐intestinal diseases. In this review, we summarize current knowledge on the NLRP6 inflammasome and its activation and regulation patterns, as well as its effector functions contributing to disease modulation. We discuss current challenges in NLRP6 research and future prospects in harnessing its function into potential human interventions. [ABSTRACT FROM AUTHOR]

Background and Study Aims: For bowel preparation, using a reduced volume of polyethylene glycol (PEG) solution without influencing its effectiveness would be preferable. While simethicone shows great potential as an adjunctive agent, data on its use are limited. We aimed to clarify whether simethicone added to low-volume PEG solution improved bowel cleansing. PATIENTS AND METHODS : Consecutive adult patients registered for colonoscopy were recruited from seven medical centers in South China between 15 April and 15 July 2015 and prospectively randomized into two groups: 2 L PEG (conventional group) and 2 L PEG plus simethicone (simethicone group). The primary endpoint was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included cecal intubation time, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS : We included 290 and 289 patients in the conventional and simethicone groups, respectively, for analysis. The proportion with acceptable bowel cleansing (BBPS ≥ 6) was significantly higher in the simethicone group than in the conventional group (88.2 % vs. 76.6 %; P < 0.001). The mean (SD) BBPS score was significantly lower in the conventional group (6.5 [1.8] vs. 7.3 [1.7]; P < 0.001), as was the bubble score (2.5 [0.7] vs. 2.8 [0.5]; P < 0.001). The average cecal intubation time was significantly shorter in the simethicone group (6.3 [3.1] vs. 7.5 [5.1] minutes; P < 0.001). The ADR in the right colon was higher in the simethicone group than in the conventional group (16.6 % vs. 10.3 %; P = 0.03). Safety and compliance, including the taste, smell, and dosage of PEG, were similar for both groups.Conclusions: Simethicone added to low-volume PEG solution improves bowel-cleansing efficacy, with similar safety and compliance, shorter cecal intubation time, and higher ADR. [ABSTRACT FROM AUTHOR]

The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4, respectively. The computational analysis showed that these four mutants were capable of interacting with EphA2. Their potential neuroprotective effects were examined in mouse focal ischemia/reperfusion (I/R) model. EM2 exhibited strong neuroprotective effects, including reduced brain infarct volume, neuronal apoptosis, cerebral edema, and improved neurological scores. The EM2-mediated protection was associated with a comparative decrease in BBB leakage, inflammatory infiltration, and higher expression levels of tight junction proteins, such as zonula occludens-1 and Occludin. I/R-induced high expression of Rho-associated protein kinase 2 (ROCK2) was down-regulated after EM2 treatment. Moreover, EM2 reduced agonist doxazosin-induced EphA2 phosphorylation and cells rounding in PC3 cells, indicating EphA2-antagonizing activity of EM2. These finding provided evidences of the neuroprotection of EphA2 antagonist and a novel approach for ischemic stroke treatment. These results also suggested that a receptor agonist can be switched to an antagonist by substituting one or more relevant residues.

Ethnopharmacological Relevance: Herbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue., Aim of This Study: To develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae., Materials and Methods: In this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments., Results: 32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = -20.26); YXB was significantly associated with AS (Z = -4.532), MI (Z = -29.11), RhFv (Z = -6.945), OA (Z = -39.97), and GA (Z = -13.03); and WBFK was significantly associated with MI (Z = -205.5), SLE (Z = -37.65), RhFv (Z = -42.45), and GA (Z = -17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments., Conclusions: The modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos . In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC-MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-α was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment.

Background and Study Aims: For bowel preparation, using a reduced volume of polyethylene glycol (PEG) solution without influencing its effectiveness would be preferable. While simethicone shows great potential as an adjunctive agent, data on its use are limited. We aimed to clarify whether simethicone added to low-volume PEG solution improved bowel cleansing. PATIENTS AND METHODS : Consecutive adult patients registered for colonoscopy were recruited from seven medical centers in South China between 15 April and 15 July 2015 and prospectively randomized into two groups: 2 L PEG (conventional group) and 2 L PEG plus simethicone (simethicone group). The primary endpoint was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included cecal intubation time, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS : We included 290 and 289 patients in the conventional and simethicone groups, respectively, for analysis. The proportion with acceptable bowel cleansing (BBPS ≥ 6) was significantly higher in the simethicone group than in the conventional group (88.2 % vs. 76.6 %; P  < 0.001). The mean (SD) BBPS score was significantly lower in the conventional group (6.5 [1.8] vs. 7.3 [1.7]; P  < 0.001), as was the bubble score (2.5 [0.7] vs. 2.8 [0.5]; P  < 0.001). The average cecal intubation time was significantly shorter in the simethicone group (6.3 [3.1] vs. 7.5 [5.1] minutes; P  < 0.001). The ADR in the right colon was higher in the simethicone group than in the conventional group (16.6 % vs. 10.3 %; P  = 0.03). Safety and compliance, including the taste, smell, and dosage of PEG, were similar for both groups., Conclusions: Simethicone added to low-volume PEG solution improves bowel-cleansing efficacy, with similar safety and compliance, shorter cecal intubation time, and higher ADR., Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

A new cool-tip radiofrequency (RF) ablation therapeutic instrument based on impedance control algorithm is introduced in this paper. The equipment is composed of hardware system and software system. The RF power output and real time data acquisition are completed by the hardware system, while the software is used mainly to finish the control of the ablation range, the core of which is impedance control algorithm, and it also used to complete the display of the real time data in the course of the experiment. The impedance algorithm has solved the problem of impedance increased rapidly during the RF ablation, which has also expanded the scope of ablation. The pig liver experiments showed that the impedance control algorithm had strong adaptability. It also obtained a result of ablation range up to 3.5-4.5 cm single needle. It has the high clinical practical value of one-time inactivation of 3-5 cm tumor.