Low-Intensity Pulsed Ultrasound: A Physical Stimulus with Immunomodulatory and Anti-inflammatory Potential.

Ultrasound has expanded into the therapeutic field as a medical imaging and diagnostic technique. Low-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound that plays a vital role in promoting fracture healing, wound repair, immunomodulation, and reducing inflammation. Its anti-inflammatory effects are manifested by decreased pro-inflammatory cytokines and chemokines, accelerated regression of immune cell invasion, and accelerated damage repair. Although the anti-inflammatory mechanism of LIPUS is not very clear, many in vitro and in vivo studies have shown that LIPUS may play its anti-inflammatory role by activating signaling pathways such as integrin/Focal adhesion kinase (FAK)/Phosphatidylinositol 3-kinase (PI3K)/Serine threonine kinase (Akt), Vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS), or inhibiting signaling pathways such as Toll-like receptors (TLRs)/Nuclear factor kappa-B (NF-κB) and p38-Mitogen-activated protein kinase (MAPK). As a non-invasive physical therapy, the anti-inflammatory and immunomodulatory effects of LIPUS deserve further exploration.

An overview of gram-negative bacteria with difficult-to-treat resistance: definition, prevalence, and treatment options.

INTRODUCTION: Difficult-to-treat resistance (DTR) is a newly proposed resistance phenotype characterized by resistance to all first-line drugs. The emergence of DTR as a new resistance phenotype has significant implications for clinical practice. This new concept has the potential to be widely used instead of traditional phenotypes. AREAS COVERED: This study carried out a detailed analysis about the definition, application, and evolution of various resistance phenotypes. We collected all the research articles on Gram-negative bacteria with difficult-to-treat resistance (GNB-DTR), analyzed the DTR in each region and each bacterial species. The advantages and doubts of DTR, the dilemma of GNB-DTR infections and the potential therapeutic strategies are summarized in the review. EXPERT OPINION: Available studies show that the prevalence of GNB-DTR is not optimistic. Unlike traditional resistance phenotypes, DTR is more closely aligned with the clinical treatment perspective and can help with the prompt selection of an appropriate treatment plan. Currently, potential treatment options for GNB-DTR include a number of second-line drugs and novel antibiotics. However, the definition of first-line drugs is inherently dynamic. Therefore, the DTR concept based on first-line drugs needs to be continuously updated and refined, considering the emergence of new antibiotics, resistance characteristics, and pathogen prevalence in different regions.

Effect of Food on the Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of SHR4640, a Selective Urate Transporter 1 Inhibitor, in Healthy Chinese Male Volunteers.

SHR4640, also named as ruzinurad, is a selective human urate transporter 1 (URAT1) inhibitor developed for the treatment of hyperuricemia and gout. This study evaluated the high-fat, high-calorie food effect on the pharmacokinetics and pharmacodynamics of SHR4640 in healthy Chinese male volunteers. In this open-label, randomized, 2-period crossover phase 1 trial, 14 healthy male subjects were randomized to receive a single 10-mg dose of SHR4640 under both fasted and fed conditions. The washout period was 7 days. Blood samples were collected for pharmacokinetic and pharmacodynamic analysis. Pharmacokinetic parameters were analyzed by a noncompartmental method. The safety of the drug was also evaluated in the trial. A total of 14 healthy male volunteers were enrolled in the study, and finally 13 healthy volunteers completed the study. A single 10-mg dose of SHR4640 was safe and well tolerated in healthy Chinese male volunteers. After single-dose administration of SHR4640, the 90%CIs of the geometric mean ratios of the area under the plasma concentration-time curve from time 0 to the last quantifiable concentration and the area under the plasma concentration-time curve from time 0 to infinity were within the equivalence criteria of 0.80-1.25. The 90%CIs of maximum plasma concentration was slightly outside the lower limit of bioequivalent criteria, with about 13.40% decrease in the fed versus fasted condition. The time to maximum concentration was slightly delayed under the fasted condition. A single 10-mg dose of SHR4640 was safe and well tolerated in this trial. The main pharmacokinetic parameters and serum uric acid lowering of SHR4640 were not affected by food effect; thus, SHR4640 can be recommended to be administered with or without food.