Intramedullary Nail vs. Plate Fixation for Pathological Humeral Shaft Fracture: An Updated Narrative Review and Meta-Analysis of Surgery-Related Factors.

(1) Background: Pathological humeral shaft fracture (PHSF) is a frequently observed clinical manifestation in the later stages of tumor metastasis. Surgical interventions are typically recommended to alleviate pain and restore functionality. Intramedullary nail fixation (INF) or plate fixation (PF) is currently recommended for the treatment of PHSF. However, there is still no standard for optimal surgical treatment. Thus, we conducted a meta-analysis comparing the clinical outcomes of INF with PF for PHSF treatment. (2) Methods: We conducted searches in databases, such as Scopus, EMBASE, and PubMed, for studies published prior to May 2023. In total, nine studies with 485 patients were reviewed. (3) Results: There were no significant differences noted in the incidence of fixation failure, local recurrence, wound complication or overall complication. However, the INF group demonstrated a significantly lower incidence of postoperative radial nerve palsy than the PF group (OR, 5.246; 95% CI, 1.548-17.774; p = 0.008). A subgroup analysis indicated that there were no statistically significant differences in fixation failure or local recurrence among subgroups categorized by the design of intramedullary nail. (4) Conclusions: Considering the short life expectancy of end-stage patients, the choice of surgical method depends on the patient's individual condition, fracture and lesion patterns, the surgeon's experience, and comprehensive discussion between the surgeon and patient.

Nanosized Particles Assembled by a Recombinant Virus Protein Are Able to Encapsulate Negatively Charged Molecules and Structured RNA.

RNA-based molecules have recently become hot candidates to be developed into therapeutic agents. However, successful applications of RNA-based therapeutics might require suitable carriers to protect the RNA from enzymatic degradation by ubiquitous RNases in vivo. Because of their better biocompatibility and biodegradability, protein-based nanoparticles are considered to be alternatives to their synthetic polymer-based counterparts for drug delivery. Hepatitis C virus (HCV) core protein has been suggested to be able to self-assemble into nucleocapsid-like particles in vitro. In this study, the genomic RNA-binding domain of HCV core protein consisting of 116 amino acids (p116) was overexpressed with E. coli for investigation. The recombinant p116 was able to assemble into particles with an average diameter of approximately 27 nm, as visualized by electron microscopy and atomic force microscopy. Measurements with fluorescence spectroscopy, flow cytometry, and fluorescence quenching indicated that the p116-assembled nanoparticles were able to encapsulate small anionic molecules and structured RNA. This study demonstrates methods that exploit the self-assembly nature of a virus-derived protein for nanoparticle production. This study also suggests that the virus-derived protein-assembled particles could possibly be developed into potential carriers for anionic molecular drugs and structured RNA-based therapeutics.

Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) represents up to 20% of all breast cancers. This cancer lacks the expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The current therapeutic strategy for patients with this subtype is the use of cytotoxic chemotherapy and surgery. Luteolin is a natural herbal flavonoid and a potential therapeutic candidate for multiple diseases. The use of a treatment that combines Chinese herbal medicine and western medicine is rising in Asia. PURPOSE: The present study evaluates the effects and molecular mechanisms involved with luteolin treatment and evaluates whether this herb affects androgen receptor-positive breast cancer cell proliferation or metastasis. STUDY DESIGN: In vitro evaluation of the effect of luteolin on androgen receptor-positive TNBC cell proliferation and metastasis METHODS: Cell viability analysis was used for the cytotoxicity test. Colony formation and Bromodeoxyuridine (BrdU) staining-based proliferation experiments were used for cell proliferation. Wound healing and transwell assays were used for in vitro migration/invasion. The RT-qPCR analysis was used for gene expression. Furthermore, ChIP-qPCR analysis was used for epigenetic modification of gene promoters. RESULTS: Luteolin significantly inhibited the proliferation and metastasis of androgen receptor-positive TNBC. Furthermore, luteolin inactivated the AKT/mTOR signaling pathway and reversed the epithelial-mesenchymal transition (EMT). The combination of luteolin and inhibitors of AKT/mTOR synergistically repressed an androgen receptor-positive TNBC cell proliferation and metastasis. Luteolin also downregulated MMP9 expression by decreasing the levels of the AKT/mTOR promoting H3K27Ac and H3K56A on the MMP9 promoter region. CONCLUSION: Our findings indicate that luteolin inhibited the proliferation and metastasis of androgen receptor-positive TNBC by regulating MMP9 expression through a reduction in the levels of AKT/mTOR-inducing H3K27Ac and H3K56Ac.

Real time monitoring of accelerated chemical reactions by ultrasonication-assisted spray ionization mass spectrometry.

Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication-assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication-assisted spray ionization mass spectrometry (UASI-MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz-based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI-MS. The feasibility of using this approach for real-time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI-MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions.

Lysozyme-encapsulated gold nanocluster-based affinity mass spectrometry for pathogenic bacteria.

RATIONALE: Bacterial infections can be difficult to treat and can lead to irreversible damage to patients if proper treatment is not provided in time. Additionally, the emerging threat from antibiotic-resistant bacterial strains makes medical treatment even more difficult. Thus, rapid identification of infected bacterial strains is essential to assist diagnostics and medical treatment. METHODS: Lysozymes are glycoside hydrolases that can bind with peptidoglycans on bacterial cell walls. In this work, we demonstrated that lysozyme-encapsulated gold nanoclusters (lysozyme-AuNCs) with red photoluminescence can be used as affinity probes to concentrate pathogenic bacteria. After bacteria had been probed by the lysozyme-AuNCs in a sample solution, the lysozyme-AuNC-bacteria conjugates were readily spun down at a low centrifugation speed. The red emission from the AuNCs on the conjugates could be visualized with the naked eye under illumination of ultraviolet light. The bacteria in the conjugates can be identified by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) combined with principal component analysis (PCA). RESULTS: We demonstrated that pathogenic bacteria including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, pandrug-resistant Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and vancomycin-resistant Enterococcus faecalis (VRE) can be readily concentrated by the lysozyme-AuNCs and distinguished by the results combining MALDI-MS and PCA. Additionally, the possibility of using the current approach to differentiate E. faecalis from VRE was also demonstrated. The lowest detection concentration for E. coli using the current approach is ~10(6) cells/mL. CONCLUSIONS: The results indicated that the lysozyme-AuNCs are effective affinity probes for Gram-positive and Gram-negative bacteria. By combining the results from MALDI-MS and PCA, different bacteria can be easily distinguished. The current approach can be potentially used to assist the identification of bacteria from biological fluids.