Population pharmacokinetic modeling and exposure-response analysis of anrikefon: insights and implications in clinical analgesia.

Background: Anrikefon (HSK21542), a potent and selective peripheral kappa opioid receptor (KOR) agonist developed by Haisco, effectively blocks pain and itch signals.

Aim: To develop a population pharmacokinetic (PK) model for anrikefon and conduct exposure-response (E-R) analysis for safety and efficacy in postoperative pain patients.

Method: The Population PK analysis uses NONMEM software with data from six trials.

Model informed dose regimen optimizing in development of leritrelvir for the treatment of mild or moderate COVID-19.

Introduction: Leritrelvir (RAY1216) acts as a main protease inhibitor that hinders the cleavage of viral precursor proteins, thereby inhibiting virus replication of SARS-CoV-2). This antiviral mechanism has shown significant efficacy against the novel coronavirus. Preclinical studies have demonstrated the potent antiviral activity and favorable safety profile of this compound.

Dose finding for ZSP1601 in patients with nonalcoholic steatohepatitis using population pharmacokinetics and exposure-response approach.

Introduction: ZSP1601 is a novel pan-phosphodiesterase inhibitor developed in China specifically for the treatment of nonalcoholic fatty liver disease (NAFLD).

Aim: The aim is to develop a population pharmacokinetic (pop PK) model for ZSP1601 by integrating data from two clinical studies. This undertaking aims to deepen our understanding of the clinical factors that influence ZSP1601 exposure while simultaneously investigating exposure-response (ER) relationships related to efficacy and safety.

Investigating biomechanical alterations and emptying patterns after various gastrojejunostomy strategy.

Gastrojejunostomy is a prominent approach in managing distal gastric cancer that is unresectable due to gastric outlet obstruction (GOO). Research has demonstrated that stomach-partitioning gastrojejunostomy (SPGJ) exhibits superior clinical efficacy compared to conventional gastrojejunostomy (CGJ), however, the underlying mechanism of this phenomenon remains elusive. This study constructed 3D models of the SPGJ and CGJ based on the computed tomography (CT) images obtained from a patient diagnosed with distal gastric cancer.

Identification of antigens in the Trichinella spiralis extracellular vesicles for serological detection of early stage infection in swine.

Background: Several studies have reported the roles of Trichinella spiralis extracellular vesicles in immune regulation and pathogen diagnosis. Currently, the T. spiralis muscle larvae excretory/secretory product (Ts-ML-ES) is the antigen recommended by the International Commission on Trichinellosis (ICT) for serological diagnosis of trichinellosis.

Serum ANGPTL4 and SIRT1 factor levels and the Carotid Atherosclerotic plaque stability relationship analysis.

This study was to investigate the relationship between the levels of Angiopoietin-Like Protein 4 (ANGPTL4) and Silent Mating-type Information Regulation 2 Homolog 1 (SIRT1) and the stability of carotid atherosclerotic plaque. For this purpose, 108 patients with coronary heart disease in our hospital from Jan 2021 to May 2022 were selected as the coronary heart disease (CHD) group and 80 patients with the healthy examination as the control group. Patients' serum levels of ANGPTL4 and SIRT1 were collected, and their stability of carotid atherosclerotic plaque was determined by carotid ultrasound.

Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis.

Background: The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans.

Objective: This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS).

Methods: We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS.

The gut microbiota contributes to changes in the host immune response induced by Trichinella spiralis.

The gut microbiota plays an important role in parasite-host interactions and the induction of immune defense responses. Trichinella spiralis is an important zoonotic parasite that can directly or indirectly interact with the host in the gut. Changes in the gut microbiota following infection with T.

Population Pharmacokinetic Analysis of Dorzagliatin in Healthy Subjects and Patients with Type 2 Diabetes Mellitus.

Background And Objectives: Dorzagliatin is a first-in-class small molecule glucokinase activator (GKA) that improves pancreatic insulin secretion behavior and regulates hepatic glucose conversion in a glucose concentration-dependent manner. The primary objective of this study was to develop a population pharmacokinetic model of dorzagliatin to evaluate the influence of covariates, such as demographic characteristics and liver and kidney function, on the pharmacokinetics of dorzagliatin and provide a basis for medication guidance.

Method: The pharmacokinetic data of dorzagliatin in this study came from six clinical trials.

Gastric emptying performance of stomach-partitioning gastrojejunostomy conventional gastrojejunostomy for treating gastric outlet obstruction: A retrospective clinical and numerical simulation study.

This study evaluated the gastric emptying performance of stomach-partitioning gastrojejunostomy (SPGJ) conventional gastrojejunostomy (CGJ) for treating gastric outlet obstruction (GOO). First, 73 patients who underwent SPGJ (n = 48) or CGJ (n = 25) were involved. Surgical outcomes, postoperative recovery of gastrointestinal function, delayed gastric emptying, and nutritional status of both groups were compared.

Systematic exploration of the underlying mechanism of gemcitabine resistance in pancreatic adenocarcinoma.

Resistance to gemcitabine is the main challenge of chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Hence, the development of a response signature to gemcitabine is essential for precision therapy of PDAC. However, existing quantitative signatures of gemcitabine are susceptible to batch effects and variations in sequencing platforms.

Extracellular vesicles from Trichinella spiralis: Proteomic analysis and protective immunity.

Trichinella spiralis (T. spiralis) derived extracellular vesicles (EVs) have been proposed to play a key role in regulating the host immune responses. In this study, we provided the first investigation of EVs proteomics released by T.

The Biological Function Delineated Across Pan-Cancer Levels Through lncRNA-Based Prognostic Risk Assessment Factors for Pancreatic Cancer.

Long non-coding RNAs (lncRNAs) play key roles in tumors and function not only as important molecular markers for cancer prognosis, but also as molecular characteristics at the pan-cancer level. Because of the poor prognosis of pancreatic cancer, accurate assessment of prognosis is a key issue in the development of treatment plans for pancreatic cancer. Here we analyzed pancreatic cancer data from The Cancer Genome Atlas and The Genotype Tissue Expression database using Cox regression and lasso regression in analyses using a combination of the two databases as well as only The Cancer Genome Atlas database (Cancer Genome Atlas Research Network et al.

The immune protection induced by a serine protease from the Trichinella spiralis adult against Trichinella spiralis infection in pigs.

Trichinellosis is a major foodborne parasitosis caused by Trichinella spiralis. In the present study, a serine protease gene from an adult T. spiralis (Ts-Adsp) cDNA library was cloned, expressed in Escherichia coli and purified by Ni-affinity chromatography.

Disruption of Epithelial Barrier of Caco-2 Cell Monolayers by Excretory Secretory Products of Might Be Related to Serine Protease.

The physical barrier is composed of epithelial cells which are joined together through intercellular connections. It serves to prevent pathogenic microorganisms from departing the intestinal lumen to invade the host. The excretory secretory (ES) products of are critical for invasion.

Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease.

Background And Objective: Thyroid eye disease (TED) is characterized by inflammation/expansion of orbital tissues, proptosis, and diplopia. Teprotumumab is the first US Food and Drug Administration-approved therapy for TED, administered as an initial intravenous infusion of 10 mg/kg followed by 20 mg/kg every 3 weeks for an additional seven infusions. The objective of this article is to discuss the pharmacokinetics and exposure-response profile for teprotumumab in patients with TED.

Young Blood Rescues the Cognition of Alzheimer's Model Mice by Restoring the Hippocampal Cholinergic Circuit.

An increasing number of studies have demonstrated the benefits of young individual-derived blood for aging-related diseases. However, the effects of young blood on the cognitive and cholinergic transmission defects in aging-associated Alzheimer's disease (AD) remain elusive. In the current study, we showed that young blood serum delivered intravenously attenuated deficits in hippocampal-dependent learning and memory, alleviated hippocampal Aβ plaque pathology, restored synapse formation and synaptic plasticity, repaired the hippocampal cholinergic circuit, and triggered several canonical neuroprotective mechanisms [including repressor element 1-silencing transcription factor (REST)/Forkhead box protein O1 (FOXO1) signaling] in aged AD model mice.

Population Pharmacokinetics Study of Nemonoxacin Among Chinese Patients With Moderate Hepatic Impairment.

Purpose: Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone that has been approved for the treatment of community-acquired pneumonia (CAP) in adults. The goals of this study were to evaluate the pharmacokinetic (PK) and population PK parameters of nemonoxacin and to provide the appropriate dose adjustment recommendations for patients with hepatic impairment.

Methods: An open-label, single-dose, parallel group (moderate hepatic impairment group and healthy control group) PK study of nemonoxacin was conducted.

Model-based comparing efficacy of fluoxetine between elderly and non-elderly participants with major depressive disorder.

Background: The high heterogeneity was existed among the studies of the elderly participants with major depressive disorder (MDD), which may lead to incorrect conclusions in the previous meta-analysis. This study used model based meta-analysis to compare the efficacy of fluoxetine between the elderly and non-elderly participants with MDD and to explain the heterogeneity among the studies.

Methods: A comprehensive literature search was conducted in the public databases, involving utilization of fluoxetine for treating MDD in the acute-phase.