Comparison of the Safety and Efficacy of Remimazolam Besylate versus Dexmedetomidine for Patients Undergoing Fiberoptic Bronchoscopy: A Prospective, Randomized Controlled Trial.

Objective: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that is rapidly hydrolyzed to zolpidem propionic acid by tissue lipases. We designed this study to compare the safety and efficacy of remimazolam besylate alfentanil versus dexmedetomidine-alfentanil for fiberoptic bronchoscopy (FB). Methods: One hundred and twenty patients undergoing FB into this prospective randomized controlled trial were divided into two groups. The anesthesia induction consisted of 6 mg/kg/h of remimazolam besylate in the RA group and 0.5 µg/kg of dexmedetomidine in the DA group. 1-2 mg/kg/h of remimazolam besylate or 0.2-0.7 µg/kg/h of dexmedetomidine were administered to maintain during FB. The lowest oxygen saturation, success rate of FB, hemodynamics, time metrics, bronchoscopy feasibility, drug dose requirements, patient and bronchoscopist satisfaction scores, occurrence of intraoperative awareness, number of patients willing to repeat FB with the same sedation regimen, and occurrence and severity of adverse events. Results: The lowest oxygen saturation during the FB was significantly higher in the RA group (P = 0.001). Compared with the variables in the DA group, peripheral oxygen saturation, systolic blood pressure, and diastolic blood pressure were significantly lower at T2 and T3 in the RA group (P < 0.05). Heart rates were significantly higher from T2 to T4 in the DA group (P < 0.05). More patients experienced bradycardia in the DA group (P = 0.041). Compared with time metrics in the DA group, the induction time, fully-alert time, and recovery room-leaving time were all significantly shorter in the RA group (P < 0.05). The bronchoscopy feasibility scores in the RA group were significantly lower at T2, whereas they were lower at T3 in the DA group (P < 0.05). Conclusion: Remimazolam besylate is superior to dexmedetomidine when combined with alfentanil during FB, promoting faster patients' recovery, better operative conditions and respiratory stability with similar rates of occurrence and severity of adverse events.

Wavelength-switchable watt-level continuous wave near-infrared Pr3+:LiYF4 lasers pumped by an InGaN laser diode.

We report a high-performance wavelength-switchable near-infrared Pr3+:LiYF4 (Pr:YLF) laser by InGaN laser diode (LD) pumping. The 895, 922, and 924 nm lasers with low emission cross sections in the Pr:YLF crystal have been successfully realized using a birefringent filter Lyot as well as designing and optimizing optical thin films and the laser resonant cavity. The maximum output powers of the 895, 922, and 924 nm lasers are 2.01, 1.92, and 1.95 W, respectively. As far as we know, these are the highest power for Pr:YLF lasers at 895, 922, and 924 nm so far. The beam quality M x2 and M y2 factors are measured to be 1.85 and 1.71 at 895 nm, 1.94 and 1.67 at 922 nm, and 1.76 and 1.60 at 924 nm, respectively. The laser output power fluctuates within ±3%. In addition, the transmittance of the Lyot is theoretically calculated to achieve laser wavelength switching. The successful realization of the wavelength-switchable watt-level continuous wave near-infrared Pr:YLF laser can provide many practical applications in biomedicine and other fields.

Continuous selenite biotransformation and biofuel production by marine diatom in the presence of fulvic acid.

In this study, the biochemical response of Phaeodactylum tricornutum to varying concentrations of inorganic selenium (Se) was investigated. It was observed that, when combined with fulvic acid, P. tricornutum exhibited enhanced uptake and biotransformation of inorganic Se, as well as increased microalgal lipid biosynthesis. Notably, when subjected to moderate (5 and 10 mg/L) and high (20 and 40 mg/L) concentrations of selenite under fulvic acid treatment, there was a discernible redirection of carbon flux towards lipogenesis and protein biosynthesis from carbohydrates. In addition, the key parameters of microalgae-based biofuels aligned with the necessary criteria outlined in biofuel regulations. Furthermore, the Se removal capabilities of P. tricornutum, assisted by fulvic acid, were coupled with the accumulation of substantial amounts of organic Se, specifically SeCys. These findings present a viable and successful approach to establish a microalgae-based system for Se uptake and biotransformation.

Evaluating the hypolipidemic effect of garlic essential oil encapsulated in a novel double-layer delivery system.

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and ß-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO ß-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.

Chiral Osmium(II)/Salox Species Enabled Enantioselective γ-C(sp3)-H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development.

Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp3)-H functionalization, among which the Os(II)/Salox species is found to be the most efficient for precise stereocontrol in realizing the asymmetric C(sp3)-H amidation. As exemplified by the enantioenriched pyrrolidinone synthesis, such tailored Os(II)/Salox catalyst efficiently enables an intramolecular site-/enantioselective C(sp3)-H amidation in the γ-position of dioxazolone substrates, in which benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording the corresponding chiral γ-lactam products with good er values (up to 99 : 1) and diverse functionality (>35 examples). The unique performance advantage of the developed chiral Os(II)/Salox system in terms of the catalytic energy profile and the chiral induction has been further clarified by integrated experimental and computational studies.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2023 ASH annual meeting.

Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based therapies specifically tailored for those with R/R AML remains scarce. Here, we provide a comprehensive overview of the latest data presented at the 65th American Society of Hematology Annual Meeting, shedding light on the progress and efficacy of VEN-based therapies for R/R AML.

Early enteral nutrition support for patients with acute pancreatitis in the inpatient setting: a best practice implementation project.

INTRODUCTION: Acute pancreatitis is a major disease that endangers the health and lives of people. Historically, clinical therapy has recommended. that patients with acute pancreatitis remain nil by mouth. As one of the therapies recommended in recent guidelines, early enteral nutrition support reduces the incidence of infectious complications and reduces the risk of severe conditions. However, early enteral nutrition support has not been optimally implemented within clinical practice for acute pancreatitis inpatients. OBJECTIVES: This evidence implementation project aimed to increase compliance with best practice recommendations for early enteral nutrition support, while standardizing the enteral nutrition support process and reducing the incidence of delayed enteral nutrition. METHODS: The project was guided by the JBI Evidence Implementation Framework, which is grounded in the audit and feedback process, as well as a seven-stage structured approach to identifying and managing barriers to compliance with recommended practices. RESULTS: In the baseline audit, compliance rates were low for all evidence-based audit criteria. Four of the eight criteria showed 0% compliance. However, after implementation, all eight criteria achieved a minimum compliance rate of 60%, with Site 2 achieving 90% to 100% compliance. In addition, nurses improved their knowledge and skills in early enteral nutrition support. The incidence of delayed enteral nutrition also fell from 86.2% to 20.7% at both study sites. The implementation strategy included a training program, psychological interventions, and financial and human resource support. CONCLUSION: This project not only significantly improved early enteral nutrition support for acute pancreatitis patients, but also increased nurses' knowledge and practice skills, standardized the process of enteral nutrition support, and reduced the incidence of delayed enteral nutrition. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A177.

Efficacy of cognitive functional therapy in patients with low back pain: A systematic review and meta-analysis.

BACKGROUND: Low back pain is a major public health problem worldwide, and there exists evidence that cognitive functional therapy may help improve patients' health condition. However, the utilization of cognitive functional therapy for low back pain is limited, and its clinical efficacy remains unclear. OBJECTIVES: To determine the efficacy of cognitive functional therapy in the management of disability, pain intensity, and fear-avoidance beliefs in low back pain patients. DESIGN: Systematic review and meta-analysis. METHOD: A comprehensive study search of Pubmed, Web of Science, Medline, CINAHL, Embase, PsycINFO, and the Cochrane Library databases was conducted from their inception to August 14th, 2023. Two researchers independently conducted the literature search and data extraction. All statistical analysis was performed using Stata Version 17.0. RESULTS: A total of eight randomized controlled trials were included. In the short-term, cognitive functional therapy significantly improved disability (7 studies, SMD = -1.05, 95 % CI = -1.74 to -0.35, I2 = 95.37 %, GRADE = very low), pain intensity (7 studies, SMD = -1.02, 95 % CI = -1.89 to -0.15, I2 = 97.21 %, GRADE = very low), and fear-avoidance beliefs (4 studies, SMD = -0.89, 95 % CI = -1.30 to -0.47, I2 = 82.49 %, GRADE = very low). In the medium-term, cognitive functional therapy also significantly improved disability (3 studies, SMD = -0.48, 95 % CI = -0.82 to -0.14, I2 = 77.97 %, GRADE = very low), pain intensity (3 studies, SMD = -0.34, 95 % CI = -0.58 to -0.10, I2 = 55.55 %, GRADE = very low), and fear-avoidance beliefs (2 studies, SMD = -0.62, 95 % CI = -1.19 to -0.04, I2 = 88.24 %, GRADE = very low). In the long-term, cognitive functional therapy significantly improved disability (4 studies, SMD = -0.54, 95 % CI = -0.95 to -0.13, I2 = 85.87 %, GRADE = very low) and fear-avoidance beliefs (3 studies, SMD = -0.76, 95 % CI = -1.17 to -0.34, I2 = 80.34 %, GRADE = very low). CONCLUSION: Cognitive functional therapy might be effective in reducing disability and fear-avoidance beliefs at any of short-, medium- and long-term follow-ups, and reducing pain at short- and medium-term follow-ups. No definitive conclusions can be drawn about the impact of cognitive functional therapy on low back pain patients due to the very low certainty evidence base. Additional rigorous randomized controlled trials are needed to further confirm these findings. REGISTRATION NUMBER: CRD42022287123 (PROSPERO).

Hot-Pressing Metal Covalent Organic Frameworks as Personal Protection Films.

Effective personal protection is crucial for controlling infectious disease spread. However, commonly used personal protective materials such as disposable masks lack antibacterial/antiviral function and may lead to cross infection. Herein, a polyethylene glycol-assisted solvent-free strategy is proposed to rapidly synthesize a series of the donor-acceptor metal-covalent organic frameworks (MCOFs) (i.e., GZHMU-2, JNM-1, and JNM-2) under air atmosphere and henceforth extend it via in situ hot-pressing process to prepare MCOFs based films with photocatalytic disinfect ability. Best of them, the newly designed GZHMU-2 has a wide absorption spectrum (200 to 1500 nm) and can efficiently produce reactive oxygen species under sunlight irradiation, achieving excellent photocatalytic disinfection performance. After in situ hot-pressing as a film material, the obtained GZHMU-2/NMF can effectively kill E. coli (99.99%), S. aureus (99%), and H1N1 (92.5%), meanwhile possessing good reusability. Noteworthy, the long-term use of a GZHMU-2/NWF-based mask has verified no damage to the living body by measuring the expression of mouse blood routine, lung tissue, and inflammatory factors at the in-vivo level.

Pore-Engineered Hydrogen-Bonded Supramolecular Fluorosensor for Ultrasensitive Determination of Copper Ions.

The selective quantification of copper ions (Cu2+ ) in biosamples holds great importance for disease diagnosis, treatment, and prognosis since the Cu2+ level is closely associated with the physiological state of the human body. While it remains a long-term challenge due to the extremely low level of free Cu2+ and the potential interference by the complex matrices. Here, a pore-engineered hydrogen-bonded organic framework (HOF) fluorosensor is constructed enabling the ultrasensitive and highly selective detection of free Cu2+ . Attributing to atomically precise functionalization of active amino "arm" within the HOF pores and the periodic π-conjugated skeleton, this porous HOF fluorosensor affords high affinity toward Cu2+ through double copper-nitrogen (Cu─N) coordination interactions, resulting in specific fluorescence quenching of the HOF as compared with a series of substances ranging from other metal ions, metabolites, amino acids to proteins. Such superior fluorescence quenching effect endows the Cu2+ quantification by this new HOF sensor with a wide linearity of 50-20 000 nm, a low detection limit of 10 nm, and good recoveries (89.5%-115%) in human serum matrices, outperforming most of the reported approaches. This work highlights the practicability of hydrogen-bonded supramolecular engineering for designing facile and ultrasensitive biosensors for clinical free Cu2+ determination.

Rational Design of Guanidinium-Based Bio-MCOF as a Multifunctional Nanocatalyst in Tumor Cells for Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) has emerged as a promising approach to cancer treatment, which can break the intracellular redox state balance and result in severe oxidative damage to biomolecules and organelles with the advantages of being less dependent on external stimulation, having deep tissue-healing abilities, and being resistant to drug resistance. There is considerable interest in developing CDT drugs with high efficiency and low toxicity. In this study, a new guanidinium-based biological metal covalent organic framework (Bio-MCOF), GZHMU-1@Mo, is rationally designed and synthesized as a multifunctional nanocatalyst in tumor cells for enhanced CDT. The DFT calculation and experimental results showed that due to the ability of MoO42- ion to promote electron transfer and increase the redox active site, Cu3 clusters and MoO42- ions in GZHMU-1@Mo can synergistically catalyze the production of reactive oxygen species (ROS) from oxygen and H2O2 in tumor cells, as well as degrade intracellular reducing substances, GSH and NADH, so as to disrupt the redox balance in tumor cells. Moreover, GZHMU-1@Mo exhibits a potent killing effect on tumor cells under both normal oxygen and anaerobic conditions. Further in vitro and in vivo antiproliferation studies revealed that the GZHMU-1@Mo nanoagent displays a remarkable antiproliferation effect and effectively inhibits tumor growth. Taken together, our study provides an insightful reference benchmark for the rational design of Bio-MCOF-based nanoagents with efficient CDT.

Dual-Recognition Triggered Proximity Ligation Combined with a Rolling Circle Amplification Strategy for Analysis of Exosomal Protein-Specific Glycosylation.

Exosomal surface glycan reveals the biological function and molecular information on the protein, especially in indicating the pathogenesis of certain diseases through monitoring of specific protein glycosylation accurately. However, in situ and nondestructive measurement techniques for certain Exosomal glycoproteins are still lacking. In this work, combined with on-chip purification, we designed a proximity ligation assay-induced rolling circle amplification (RCA) strategy for highly sensitive identification of Exosomal protein-specific glycosylation based on a couple of proximity probes to target Exosomal protein and the protein-specific glycosylation site. Benefiting from efficient separation, scalable dual-recognition, and proximity-triggered RCA amplification, the proposed strategy could convert different protein-specific glycan levels to prominent changes in absorbance signals, resulting in accurate quantification of specific glycosylated Exosomal protein. When detecting the glycosylated PD-L1 on MDA-MB-231 exosomes and glycosylated PTK7 on HepG2 exosomes, the detection limits were calculated to be as low as 1.04 × 104 and 2.759 × 103 particles/mL, respectively. In addition, we further expand the dual-recognition site to investigate the potential correlation of Exosomal glycosylation with polarization of THP-1 cells toward the tumor-suppressive M1 phenotype. Overall, this strategy provides a universal tool for multiple analyses of diverse protein-specific glycosylated exosomes, exhibiting enormous potential to explore exosome function and search for new early diagnosis markers.

Recent progress in quantitative technologies for the analysis of cancer-related exosome proteins.

Exosomes are a kind of extracellular vesicles, which play a significant role in intercellular communication and molecular exchange. Cancer-derived exosomes are potential and ideal biomarkers for the early diagnosis and treatment monitoring of cancers because of their abundant biological information and contribution to the interaction between cancer cells and the tumor microenvironment. However, there are a number of drawbacks, such as low sensitivity and tedious steps, in conventional detection techniques. Furthermore, exosome quantification is not enough to accurately distinguish cancer patients from healthy individuals. Therefore, developing efficient, accurate, and inexpensive exosome surface protein analysis techniques is necessary and critical. In recent years, a considerable number of researchers have presented novel detection strategies in this field. This review summarizes the recent progress in quantitative technologies for the analysis of cancer-related exosome proteins, mainly including the detection methods based on aptamers, nanomaterials, and antibodies, discusses a roadmap for future developments, and aims to offer an innovative perspective of exosome research.

Simultaneous qualitative and quantitative determination of 104 fat-soluble synthetic dyes in foods using disperse solid-phase extraction and UHPLC-Q-Orbitrap HRMS analysis.

Public exposure to synthetic dyes through foods has attracted ongoing and serious attention. Here we developed and validated a simultaneous screening and quantitation method for the analysis of fat-soluble synthetic dyes that most frequently found in foods, using C18 d-SPE clean-up and UHPLC-Q-Orbitrap HRMS on Full-MS/dd-MS2 mode. During a single run, 104 dyes including 6 pairs of isomers were distinguished based on chromatographic separation and unique product ions. The method showed satisfactory linearity (R > 0.99), recoveries (61.3 %-118.8 %), precision (<20 %) and limit of quantification (0.05-0.5 mg/kg). For 98 % of test dyes, screening detection limits ranged from 2.5 to 25 µg/kg. The validated method was successfully applied to real commercial foodstuffs revealing the presence of two selected illegal dyes in three samples.

Bilateral endobronchial metastases from hepatocellular carcinoma (HCC): A case report with literature review.

Hepatocellular carcinoma presenting with endobronchial metastases is extremely rare, with less than 15 cases reported over the last 4 decades. We describe a case of a 62-year-old male who first presented with pulmonary symptoms secondary to bilateral endobronchial metastatic disease from newly diagnosed hepatocellular carcinoma.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting.

Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

A New Predictive Nomogram for the Risk of Delayed Incision Healing After Open Posterior Lumbar Surgery: A Retrospective Study.

STUDY DESIGN: This was a primary research study. OBJECTIVE: A risk nomogram was established and externally validated by exploring the related risk factors for delayed incision healing in patients undergoing open posterior lumbar surgery. SUMMARY OF BACKGROUND DATA: The use of a nomogram model to predict prognosis in patients with delayed incision healing is an evolving field given the complex presentation of patients with this condition. PATIENTS AND METHODS: This study reviewed 954 patients with data collected from January 2017 to December 2021 who were randomized into a training set and a validation set (7:3). We built a prediction model based on a training set of 616 patients. The "least absolute shrinkage and selection operator" regression model was applied to screen out the optimal prediction features, and binary logistic regression was used to develop a prediction model. The discrimination, calibration, and clinical applicability of the prediction model were assessed by using the area under the curve, C -index, calibration curve, and decision curve analysis. RESULTS: Postoperative delayed incision healing occurred in 214 (24.4%) patients. The least absolute shrinkage and selection operator regression model showed that smoking, white blood cell count, infection, diabetes, and obesity were involved in delayed incision healing ( P ≠ 0). A binary logistic regression model confirmed that smoking [odds ratio (OR) = 3.854, 95% CI: 1.578~9.674, P = 0.003], infection (OR = 119.524, 95% CI: 59.430~263.921, P < 0.001), diabetes (OR = 3.935, 95% CI: 1.628~9.703, P = 0.003), and obesity (OR = 9.906, 95% CI: 4.435~23.266, P < 0.001) were predictors of delayed incision healing, and a nomogram model was established. The area under the curve was 0.917 (95% CI: 0.876-0.959). The calibration curve showed good consistency. Decision curve analysis showed that when the risk threshold of delayed incision healing was >5%, the use of this nomogram was more clinically valuable. CONCLUSIONS: Smoking, infection, diabetes, and obesity are risk factors for delayed incision healing. The nomogram model could be used to predict the risk of delayed incision healing and could provide a reference for early clinical intervention.

Localized Simple Multiple Kernel K-Means Clustering with Matrix-Induced Regularization.

Multikernel clustering achieves clustering of linearly inseparable data by applying a kernel method to samples in multiple views. A localized SimpleMKKM (LI-SimpleMKKM) algorithm has recently been proposed to perform min-max optimization in multikernel clustering where each instance is only required to be aligned with a certain proportion of the relatively close samples. The method has improved the reliability of clustering by focusing on the more closely paired samples and dropping the more distant ones. Although LI-SimpleMKKM achieves remarkable success in a wide range of applications, the method keeps the sum of the kernel weights unchanged. Thus, it restricts kernel weights and does not consider the correlation between the kernel matrices, especially between paired instances. To overcome such limitations, we propose adding a matrix-induced regularization to localized SimpleMKKM (LI-SimpleMKKM-MR). Our approach addresses the kernel weight restrictions with the regularization term and enhances the complementarity between base kernels. Thus, it does not limit kernel weights and fully considers the correlation between paired instances. Extensive experiments on several publicly available multikernel datasets show that our method performs better than its counterparts.

An Update on Clinical Utility of Musculoskeletal Ultrasonography in Knee Osteoarthritis.

In knee osteoarthritis (KOA), timely and accurate assessment of the severity is essential to help orthopedic surgeons determine the most appropriate therapeutic strategies and evaluate disease outcomes and responses for corresponding treatments. In KOA, musculoskeletal ultrasonography (MSUS) could effectively help detect various abnormalities, including synovitis, osteophytes, and cartilage damage. Further, MSUS could be used to monitor the response to different therapies in KOA, to guide local diagnostic and therapeutic procedures. In the future, applications based on continuously evolving US tools could enhance the clinical utility of MSUS in KOA.