Population Pharmacokinetics and Dosing Optimization of Norvancomycin for Chinese Patients with Community-Acquired Pneumonia.

Purpose: Determining the optimal dosage of norvancomycin (NVCM) for Chinese patients with community-acquired pneumonia (CAP) caused by gram-positive cocci remains uncertain. This research aimed to identify influential factors affecting NVCM pharmacokinetics and explore optimal dosage regimens via population pharmacokinetic (PPK) analysis.

Patients And Methods: A prospective analysis was conducted at the Second Hospital of Hebei Medical University (Shijiazhuang, China).

Clinical Efficacy and Safety of Vancomycin Based on Unbound Vancomycin Concentration Monitoring.

Objective: To monitor total trough concentration (Cmin_total) and unbound trough concentration (Cmin_free) of vancomycin in clinical samples and analyze the factors influencing them, and to assess their correlation with clinical efficacy and acute kidney injury (AKI).

Methods: Plasma samples were processed by protein precipitation, followed by hollow-fiber centrifugal ultrafiltration to separate unbound vancomycin from plasma. Thereafter, Cmin_total and Cmin_free were determined using high-performance liquid chromatography.

Zanubrutinib is effective in non-germinal-center B-cell-like diffuse large B-cell lymphoma with mutated , high expression, or over- expressed MYC/BCL-2.

To evaluate the effects of gene mutations on Bruton tyrosine kinase inhibitor, zanubrutinib's effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), we examined pooled data from four single-arm studies (BGB-3111-AU-003 [NCT02343120], BGB-3111-207 [NCT03145064], BGB-3111_GA101_Study_001 [NCT02569476], BGB-3111-213 [NCT03520920];  = 121). Objective response rate (ORR) was higher, though not statistically significant, in patients with activated B-cell-like (ABC)- and unclassified DLBCL (42.9% [21/49]) versus those with germinal-center B-cell-like DLBCL (14.

Simultaneous determination of colistin sulfate and tigecycline in human plasma by liquid chromatography-tandem mass spectrometry method.

Objective: To establish a high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS) to simultaneously determine colistin sulfate and tigecycline in human plasma.

Methods: Polymyxin B internal standard (20 µL) was added into 200 µL of plasma sample. The samples were treated with methanol-5% trichloroacetic acid (50:50, V/V) solution, and the protein precipitation method was adopted for post-injection analysis.

Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia?

Ciprofol is a novel compound that was independently developed in China. According to the Chinese product instructions approved by the China National Medical Products Administration and the information of official website, indications for ciprofol include sedation and anesthesia during the surgical/procedure of nontracheal intubation, induction and maintenance of general anesthesia, and sedation during intensive care. Ciprofol is a short-acting intravenous sedative based on the structural modification of propofol.

Therapeutic drug monitoring of free vancomycin concentration in practice: A new analytical technique based on the HFCF-UF sample separation method.

The aim of this study was to establish a method for free vancomycin concentration determination in human plasma and apply it to clinical therapeutic drug monitoring (TDM). The unbound vancomycin in plasma was separated by the hollow fiber centrifugal ultrafiltration (HFCF-UF) technique and analyzed by HPLC. Chromatographic conditions were optimized, the specificity, linearity, precision, recovery and stability of the method were examined, and plasma samples of patients were measured.

The Prognostic Significance of CD79B Mutation in Diffuse Large B-Cell Lymphoma: A Meta-analysis and Systematic Literature Review.

Introduction: Previous studies have shown that diffuse large B-cell lymphoma (DLBCL) subtype with both B-cell antigen receptor complex-associated protein beta chain (CD79B) and myeloid differentiation primary response 88 mutations (MYD88) had inferior outcome under standard immunochemotherapy. However, the prognostic significance of CD79B alone in DLBCL has not been fully elucidated. We conducted a meta-analysis to investigate the role of CD79B mutation on overall survival (OS) in patients with DLBCL.

Inhibition of imrecoxib on mRNA and protein expression of CYP2C11 enzyme in rats.

To evaluate the effect of imrecoxib on CYP2C11 enzyme activity, mRNA, and protein expression, a UPLC method was established. Tolbutamide was selected as the CYP2C11 enzyme-specific probe drug and incubated with imrecoxib in rat liver microsomes. The yield of 4-hydroxytolbutamide was measured using UPLC to investigate the effect of imrecoxib on CYP2C11 enzyme activity.

[Pharmacokinetic profiles of antifungal drugs during extracorporeal membrane oxygenation life support].

Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality.

A simple and accurate HFCF-UF method for the analysis of homocysteine, cysteine, cysteinyl-glycine, and glutathione in human blood.

The presence of reduced aminothiols, including homocysteine (Hcy), cysteine (Cys), cysteinyl-glycine (CG), and glutathione (GSH), is significantly increased in the pathological state. However, there have been no reports on the relationship between reduced aminothiols (Hcy, Cys, CG, and GSH) and different genders, ages, and drug combinations in human blood. The accurate quantification of these reduced thiols in biological fluids is important for monitoring some special pathological conditions of humans.

Relationship Between the Free and Total Methotrexate Plasma Concentration in Children and Application to Predict the Toxicity of HD-MTX.

High-dose methotrexate (HD-MTX) can be highly effective as well as extremely toxic. Many drug molecules can bind to plasma proteins to different extents , whereas only the free drug can reach the site of action to exert a pharmacological effect and cause toxicity. However, free MTX concentrations in plasma have not been reported.

CYP2C9*3/*3 Gene Expression Affects the Total and Free Concentrations of Valproic Acid in Pediatric Patients with Epilepsy.

Purpose: To perform therapeutic drug monitoring (TDM) of total and free plasma valproic acid (VPA) concentrations in pediatric patients with epilepsy and to analyze related factors.

Patients And Methods: Pediatric epileptic patients treated in 2015-2019 in our hospital were assessed. Total and free plasma VPA concentrations were obtained by UPLC and LC-MS/MS, respectively.

Dualmarker: a flexible toolset for exploratory analysis of combinatorial dual biomarkers for clinical efficacy.

Background: An increasing number of clinical trials require biomarker-driven patient stratification, especially for revolutionary immune checkpoint blockade therapy. Due to the complicated interaction between a tumor and its microenvironment, single biomarkers, such as PDL1 protein level, tumor mutational burden (TMB), single gene mutation and expression, are far from satisfactory for response prediction or patient stratification. Recently, combinatorial biomarkers were reported to be more precise and powerful for predicting therapy response and identifying potential target populations with superior survival.

Corrigendum: Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy.

[This corrects the article DOI: 10.3389/fphar.2018.

Chemical genetic-based phenotypic screen reveals novel regulators of gluconeogenesis in human primary hepatocytes.

Insulin resistance is a pathophysiological hallmark of type 2 diabetes and nonalcoholic fatty liver disease. Under the condition of fat accumulation in the liver, suppression of hepatic glucose production by insulin is diminished. In order to gain deeper understanding of dysregulation of glucose production in metabolic diseases, in the present study, we performed an unbiased phenotypic screening in primary human hepatocytes to discover novel mechanisms that regulate gluconeogenesis in the presence of insulin.

Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy.

Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods.

A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis.

Background: Noninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. Although these data were encouraging, the application of circulating microRNA as biomarkers for patient screening and stratification need to be further assessed under well-controlled conditions.

Comparison of pharmacokinetics and safety of pegfilgrastim administered by two delivery methods: on-body injector and manual injection with a prefilled syringe.

Purpose: For patients with clinically significant risk of febrile neutropenia, pegfilgrastim administration should occur the day after myelosuppressive chemotherapy; however, a variety of factors may preclude patients from returning to the clinic the next day for pegfilgrastim administration, necessitating other strategies. This study compared the pharmacokinetics and safety of pegfilgrastim administered via an on-body injector applied to the subject's skin versus manual injection using a prefilled syringe.

Methods: Healthy subjects aged 18-50 years were randomized 1:1 to receive a single 6-mg subcutaneous pegfilgrastim dose from an on-body injector or a prefilled syringe.

Genomic analysis of the causative agents of coccidiosis in domestic chickens.

Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases.

Regional and global changes in TCRalphabeta T cell repertoires in the gut are dependent upon the complexity of the enteric microflora.

The repertoire of gut associated T cells is shaped by exposure to microbes, including the natural enteric microflora. Previous studies compared the repertoire of gut associated T cell populations in germ free (GF) and conventional mammals often focussing on intra-epithelial lymphocyte compartments. Using GF, conventional and monocolonised (gnotobiotic) chickens and chicken TCRbeta-repertoire analysis techniques, we determined the influence of microbial status on global and regional enteric TCRbeta repertoires.

Sequencing and analysis of chromosome 1 of Eimeria tenella reveals a unique segmental organization.

Eimeria tenella is an intracellular protozoan parasite that infects the intestinal tracts of domestic fowl and causes coccidiosis, a serious and sometimes lethal enteritis. Eimeria falls in the same phylum (Apicomplexa) as several human and animal parasites such as Cryptosporidium, Toxoplasma, and the malaria parasite, Plasmodium. Here we report the sequencing and analysis of the first chromosome of E.

Searching for discrimination rules in protease proteolytic cleavage activity using genetic programming with a min-max scoring function.

This paper presents an algorithm which is able to extract discriminant rules from oligopeptides for protease proteolytic cleavage activity prediction. The algorithm is developed using genetic programming. Three important components in the algorithm are a min-max scoring function, the reverse Polish notation (RPN) and the use of minimum description length.

Mining viral protease data to extract cleavage knowledge.

Motivation: The motivation is to identify, through machine learning techniques, specific patterns in HIV and HCV viral polyprotein amino acid residues where viral protease cleaves the polyprotein as it leaves the ribosome. An understanding of viral protease specificity may help the development of future anti-viral drugs involving protease inhibitors by identifying specific features of protease activity for further experimental investigation. While viral sequence information is growing at a fast rate, there is still comparatively little understanding of how viral polyproteins are cut into their functional unit lengths.