Model-guided development of pharmacokinetic/pharmacodynamic cut-offs and evaluation of sitafloxacin dosing regimens against target pathogens.

Introduction: The establishment of clinical breakpoints for antimicrobial drug is crucial for guiding appropriate therapeutic interventions. This study aims to identify the pharmacokinetic/pharmacodynamic (PK/PD) cut-offs for using sitafloxacin against target pathogens to support clinical breakpoint establishment for antimicrobial drug sensitivity testing.

Methods: A population PK (PopPK) model was built (342 subjects) to calculate the dosing-regimen-dependent (50 mg q12 h, 100 mg q24 h and 100 mg q12 h) PK parameters of sitafloxacin-infected patients, which were combined with PD data and PK/PD target data.

Neuropsychological impact of Sanda training on athlete attention performance.

Background: Sanda, a martial art that primarily involves punching, kicking, and throwing techniques, requires athletes to maintain high levels of concentration during combat. Sanda principally involves striking the opponent to secure victory, with trauma frequently occurring to the head; however, it remains unclear whether prolonged training enhances or impairs the athletes' attentional capacities. This study aimed to investigate the impact of Sanda training on athletes' attention by employing attention network tests.

Association of Sleep Duration with Risk of All-Cause and Cause-Specific Mortality Among American Adults: A Population-Based Cohort Study.

Objective: To examine potential factors affecting sleep duration and explore its association with the risk of mortality among adults in the United States.

Methods: The study population consisted of adults aged 26 to 79 years who participated in the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2016. Sleep duration was classified into three categories: short (<7 hours), optimal (7-8 hours), and long (≥9 hours).

Quorum-Sensing Signal DSF Inhibits the Proliferation of Intestinal Pathogenic Bacteria and Alleviates Inflammatory Response to Suppress DSS-Induced Colitis in Zebrafish.

The imbalance of gut microbiota is an important factor leading to inflammatory bowel disease (IBD). Diffusible signal factor (DSF) is a novel quorum-sensing signal that regulates bacterial growth, metabolism, pathogenicity, and host immune response. This study aimed to explore the therapeutic effect and underlying mechanisms of DSF in a zebrafish colitis model induced by sodium dextran sulfate (DSS).

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019.

The Diagnostic Value of Ultrasound-guided Attenuation Parameter (UGAP) in metabolic fatty liver disease.

Objectives: To evaluate the diagnostic value of ultrasound-guided attenuation parameter (UGAP) in metabolic fatty liver disease (MAFLD) and to explore the correlation between the attenuation coefficient (AC) value of UGAP and commonly used clinical obesity indicators.

Methods: A total of 121 subjects who had physical examinations from November 2021 to March 2022 were prospectively selected; the height, weight, and waist circumference (WC) of all subjects were collected, and conventional ultrasound and UGAP examinations for all subjects.

Results: Under the standard of conventional ultrasound, among the 121 subjects, 53 had normal liver, 42 had mild fatty liver, 21 had moderate fatty liver, and 5 had severe fatty liver.

A randomised, double-blind, placebo-controlled, first-in-human phase I study to characterise the safety, pharmacokinetics and immunogenicity of 9MW1411 in healthy Chinese subjects.

Introduction: 9MW1411 is a humanised monoclonal antibody against Staphylococcus aureus alpha-toxin. The safety, pharmacokinetics (PK) and immunogenicity of 9MW1411 should be characterised in humans before further clinical development.

Methods: A single-centre, randomised, double-blind, placebo-controlled phase I clinical study was conducted in humans for the first time.

Contrast-enhanced Ultrasound of Xanthogranulomatous Endometritis: A Case Report and Literature Review.

Xanthogranulomatous endometritis (XGE) is a rare inflammatory disease, which can easily misdiagnose as cancer in imaging diagnosis. Diagnosis of XGE relies on histopathological examination and immunohistochemistry. In this study, a case of a 72-year-old female with XGE and elevated CA125 is presented, which was misdiagnosed as endometrial cancer in transvaginal ultrasonography and ovarian cystadenocarcinoma in CT.

Population pharmacokinetics and exposure-safety of lipophilic conjugates prodrug DP-VPA in healthy Chinese subjects for dose regime exploring.

Phospholipid-valproic acid (DP-VPA)is a prodrug for treating epilepsy. The present study explored the pharmacokinetics (PK) and exposure safety of DP-VPA to provide a basis for future studies exploring the safe dosage and therapeutic strategies for epilepsy. The study included a randomized placebo-controlled dose-escalation tolerance evaluation trial and a randomized triple crossover food-effect trial in healthy Chinese volunteers.

Dose adjustment not required for contezolid in patients with moderate hepatic impairment based on pharmacokinetic/pharmacodynamic analysis.

Contezolid is an oxazolidinone antimicrobial agent newly approved for treatment of Gram-positive bacterial infections. It is primarily metabolized by the liver. This study aimed to assess whether it is required to adjust the dose of contezolid in patients with moderate hepatic impairment for clinicians to use the drug more rationally.

A simple and rapid HPLC-MS/MS method for therapeutic drug monitoring of amikacin in dried matrix spots.

Individualized treatment of amikacin under the guidance of therapeutic drug monitoring (TDM) is important to reduce the occurrence of toxicity and improve clinical efficacy. In the present study, we developed and validated a simple and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine the concentration of amikacin in dried matrix spots (DMS) which the matrix is serum. DMS samples were obtained by spotting volumetric blood onto Whatman 903® cards.

Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Mirogabalin in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Study.

Introduction: Mirogabalin is a treatment option for patients with neuropathic pain; however, safety, tolerability, and pharmacokinetics (PK) data specifically for Chinese individuals are limited to a single-dose study. We aimed to assess these for both single- and multiple-dose mirogabalin in healthy Chinese participants.

Methods: In this randomized, double-blind, placebo-controlled, phase I study, 54 healthy Chinese men and women aged 18-45 years were randomly allocated to receive single- (5, 10, or 15 mg, daily) or multiple-dose (5 mg titrated to 15 mg, twice-daily, over 22 days) oral mirogabalin or placebo.

Population pharmacokinetics of levornidazole in healthy subjects and patients, and sequential dosing regimen proposal using pharmacokinetic/pharmacodynamic analysis.

Although sequential treatment with levornidazole has been used for anaerobic infection in clinical practice, there is no evidence-based dosing regimen. This study aimed to evaluate the pharmacokinetics (PK) of levornidazole in healthy subjects and patients, and to propose an evidence-based sequential dosing regimen by pharmacokinetic/pharmacodynamic (PK/PD) analysis. A population PK model was built using the data of 116 Chinese subjects, including 88 healthy young subjects, 12 healthy elderly subjects, and 16 patients with intra-abdominal anaerobic infection.

Pharmacokinetics/pharmacodynamics of polymyxin B in patients with bloodstream infection caused by carbapenem-resistant .

Polymyxin B is a last-line therapy for carbapenem-resistant microorganisms. However, a lack of clinical pharmacokinetic/pharmacodynamic (PK/PD) data has substantially hindered dose optimization and breakpoint setting. A prospective, multi-center clinical trial was undertaken with polymyxin B [2.

Safety and clinical efficacy of linezolid in children: a systematic review and meta-analysis.

Background: We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial infections.

Methods: A systematic literature search was conducted up to April 23, 2021, using linezolid and its synonyms as search terms. Two reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort studies.

Recombinant Virus-like Particles of Human Parvovirus B19 with the Internal Location of VP1 Unique Region Produced by .

Human parvovirus B19 (HPV B19) is pathogenic to human, which can cause fifth disease, transient aplastic crisis, arthritis, myocarditis, autoimmune disorders, hydrops fetalis, and so on. Currently, no approved vaccines or antiviral drugs are available against HPV B19, and thus the development of effective vaccines is needed. The capsid of HPV B19 is composed of two types of proteins, i.

Pharmacokinetics and Safety of Doripenem in Healthy Chinese Subjects and Monte Carlo Dosing Simulations.

The aim of this study was to investigate the pharmacokinetics (PK) of doripenem in healthy Chinese subjects and evaluate the optimal dosage regimens of doripenem. A randomized, single-dose, three-period, self-crossover controlled extended-infusion clinical trial was conducted with 12 healthy Chinese subjects. Plasma and urine samples were collected to determine doripenem concentrations.

Pharmacokinetics and Pharmacodynamics of Colistin Methanesulfonate in Healthy Chinese Subjects after Multi-Dose Regimen.

Colistin methanesulfonate (CMS) is an important treatment option for infections caused by carbapenem-resistant Gram-negative organisms (CROs). This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) profiles and safety of CMS in Chinese subjects following a recommended dosage. A total of 12 healthy Chinese subjects received CMS injections at 2.

Clinical Pharmacology and Utility of Contezolid in Chinese Patients with Complicated Skin and Soft-Tissue Infections.

This study aimed to build a population pharmacokinetic (PopPK) model for contezolid tablet (MRX-I) in healthy subjects and adults with complicated skin and soft-tissue infections (cSSTIs) to further evaluate the efficacy and safety of contezolid and recommend the optimal dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. PopPK analysis was performed using a nonlinear mixed-effects model (NONMEM) to examine the effects of age, body weight, sex, liver and renal functions, albumin, food, dosage strength, and subject type on the PK parameters of contezolid. PK/PD analysis was combined with the MIC of contezolid, clinical/microbiological efficacy, and nonclinical study data.

Case Report: Therapeutic Drug Monitoring of Polymyxin B During Continuous Renal Replacement Therapy in Two Pediatric Patients: Do Not Underestimate Extracorporeal Clearance.

Polymyxin B has become the last choice for patient with carbapenem-resistant bacterial infection. However, the optimal dosing of polymyxin B in critically ill children receiving continuous renal replacement therapy (CRRT) remains unclear. Two cases of critically ill pediatric patients (7 years old) with acute kidney injury requiring continuous renal replacement (CRRT) received polymyxin B treatment due to carbapenem-resistant organism bloodstream infections.

Proteomic Response Revealed Signaling Pathways Involving in the Mechanism of Polymyxin B-Induced Melanogenesis.

Polymyxin B is a last-line antibiotic for extensively resistant Gram-negative bacterial infection. Skin hyperpigmentation is a serious side effect induced by polymyxin B that severely compromises the psychological health and compliance of patients. The literature lacks mechanistic studies that explain how hyperpigmentation occurs, and this substantially hinders the development of intervention strategies and improved compliance.

Polymyxin B Combined with Minocycline: A Potentially Effective Combination against bla-harboring CRAB in In Vitro PK/PD Model.

Polymyxin-based combination therapy is commonly used to treat carbapenem-resistant (CRAB) infections. In the present study, the bactericidal effect of polymyxin B and minocycline combination was tested in three CRAB strains containing bla by the checkerboard assay and in vitro dynamic pharmacokinetics/pharmacodynamics (PK/PD) model. The combination showed synergistic or partial synergistic effect (fractional inhibitory concentration index ≤0.

Novel Findings of Retinal and Choroidal Features Utilizing Optical Coherence Tomography Angiography Analysis in Patients With Autoimmune Posterior Uveitis.

To analyze the quantitative parameters acquired by optical coherence tomography angiography (OCTA) in patients with autoimmune posterior uveitis. OCTA images of 65 eyes affected with uveitis and 65 normal control (NC) eyes were obtained. The central macular thickness (CMT), retinal thicknesses, foveal avascular zone (FAZ) area, foveal density 300 μm (FD300), and vascular density (VD) were compared among acute uveitic eyes, chronic uveitic eyes, and NC eyes.

Development and validation of ultra-performance liquid chromatography-tandem mass spectrometric methods for simultaneous and rapid determination of contezolid and its major metabolite M2 in plasma and urine samples and its application to a study in subjects with moderate liver impairment.

Contezolid is a novel oxazolidinone antibiotic with good antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus. For the purpose to further characterize the pharmacokinetics of contezolid and its major metabolite M2, accurate and rapid ultra-performance liquid chromatography-tandem mass spectrometric assays (UPLC-MS/MS) were developed and validated for simultaneous quantification of contezolid and M2 in human plasma and urine. The plasma samples were pretreated by liquid-liquid extraction.