Sepsis is a systemic inflammatory response caused by infection. When this spreads to the lungs, it can lead acute lung injury (ALI) or more severe respiratory distress syndrome (ARDS). Pulmonary fibrosis potential complication of these conditions, and early occurrence pulmonary associated with higher mortality rate. The underlying mechanism ARDS-related remains unclear. To evaluate role mast cell in sepsis-induced elucidate its molecular mechanism. We investigated level...

Background/Objectives: The use of medicines in pediatrics and geriatrics is widespread. However, information on pharmacokinetics therapeutic drugs mainly comes from healthy adults, the pharmacokinetic parameters other age stages, including geriatrics, are limited. aim study was to develop a dynamic age-dependent physiologically based (PBPK) model predict humans at different ages. Method: PBPK models characterizing age-dependence were developed adults (20-59 years old) 1000 virtual...

Uptake transporter organic anion transporting polypeptides (OATPs), efflux transporters (P-gp, BCRP and MRP2) cytochrome P450 enzymes (CYP450s) are widely expressed in the liver, intestine or kidney. They coordinately work to control drug disposition, termed as “interplay of enzymes”. Cyclosporine A (CsA) is an inhibitor OATPs, P-gp, MRP2, CYP3As. Drug–drug interaction (DDI) CsA with victim drugs occurs via disordering interplay enzymes. We aimed establish a whole-body physiologically-based...

Abstract As a promising immune checkpoint of immunogenic cell death (ICD) and multifunctional calcium‐binding molecular chaperone, calreticulin (CALR) has been attracting increasing attention. CALR mainly locates in cellular endoplasmic reticulum significantly affects proliferation, invasion, induction apoptosis, angiogenesis breast invasive carcinoma (BRCA). overexpression might be correlated with worse outcome. Nonetheless, it remains obscure how correlates infiltration survival prognosis...

Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model simultaneously predict the pharmacokinetics of CES1 substrates and their metabolites in liver cirrhosis (LC) patients. Six (enalapril, benazepril, cilazapril, temocapril, perindopril oseltamivir) three (flumazenil, pethidine remimazolam) were selected. Parameters such as organ...

Background: Iodine deficiency (ID) is a global problem in individuals living an iodine-deficient environment, specifically mountainous regions. However, data regarding the iodine nutritional status of Tibetan people plateau are limited. Methods: A population-based survey was conducted from July 2016 to 2017 Lhasa, Tibet, including 12 communities Lhasa city and 10 surrounding rural areas. The evaluated using traditional nutrition indexes: urinary concentration (UIC), thyroid size, serum...

Transmembrane transport of metformin is highly controlled by transporters including organic cation (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs). Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, MATE1/2-K apical coordinately work to control disposition. Drug–drug interactions (DDIs) occur when co-administrated with perpetrators via inhibiting OCTs or MATEs. We aimed develop a whole-body physiologically based...

Keloid has brought great trouble to people and currently no uniformly successful treatment. It is urgent find new targets effectively prevent the progress of keloid. The current research mainly identifies differentially expressed genes (DEGs) in keloid through high-throughput sequencing technology bioinformatics analysis technology, screen therapeutic potential biomarkers. However, due different samples, control groups, small sample sizes, results obtained from studies are quite lack...

Background: Sepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial sepsis; however, their application septic patients limited because long-term hyperoxia may induce toxicity anesthetic has potential adverse consequences. This study was scheduled find the optimal combination protecting experimental sepsis its mechanisms. Methods: The effects combined therapy with on lung injury determined animal models induced by...

Objective Pain is a prevalent discomfort symptom associated with cancer, yet the correlations and potential mechanisms between pain efficacy of cancer immunotherapy remain uncertain. Methods Non-small cell lung (NSCLC) patients who received immune checkpoint inhibitors (ICIs) in inpatient department Guangdong Provincial Hospital Chinese Medicine from January 1, 2018, to December 31, 2021, were retrospectively enrolled. Through cox regression analysis, prognostic factors independent affecting...

Hepatic carboxylesterase 1(CES1) metabolizes many prodrugs into active ingredients or direct-acting drugs inactive metabolites. We aim to develop a semi-physiologically based pharmacokinetic model(Semi-PBPK model) simultaneously predict pharmacokinetics of CES1 substrates and their metabolites in liver cirrhosis(LC) patients. Six prodrugs(enalapril, benazepril, cilazapril, temocapril, perindopril oseltamivir) three (flumazenil, pethidine remimazolam) were selected. The parameters including...

Keloid (KD) is a complex fibroproliferative disease, but the exact mechanisms underlying keloid pathogenesis remain to be elucidated. The primary fibroblasts (KFs) culture in vitro has always been fundamental measure study of keloid. However, traditional methods have some limitations, such as long cycle, low specimen utilization rate and so on.Improve explants method sts.We proposed an improved new "explants multiple method"-reusing for harvesting KFs specific times. Meanwhile, purity,...

Viral infection, typically disregarded, has a significant role in burns. However, there is still lack of biomarkers and immunotherapy targets related to viral infections Virus-related genes (VRGs) that were extracted from Gene Oncology (GO) database included as hallmarks. Through unsupervised consensus clustering, we divided patients into two VRGs molecular patterns (VRGMPs). Weighted gene co-expression network analysis (WGCNA) was performed study the relationship between burns VRGs. Random...

Background: Immunosuppression is an important trigger for infection and a significant cause of death in patients with severe burns. Nevertheless, the prognostic value immune-related genes remains unclear. This study aimed to identify biomarkers related immunosuppression Methods: The gene expression profile clinical data 185 burn 75 healthy samples were obtained from GEO database. Immune infiltration analysis set variation utilized disorder circulating immune cells. A weighted co-expression...

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on osimertinib uncommon mutations. Here, we report case a 68-year-old man advanced concurrent as well TP53 and RB1 patient was treated first-line therapy achieved remarkable progression-free survival 15 months. His symptoms were significantly alleviated dose tolerated....

This planned multicenter observational study will evaluate the overall survival of those undergoing integrated Chinese and Western medicine for stage IIIb-IVb non-small cell lung cancer analyze factors related to prognosis.The prospective cohort enroll patients with NSCLC from March 1, 2019, December 31, 2025, follow them 5 years. We plan collect data on patients' demographics, treatment, survival, institutional review board ethics committee reviewed protocol. All provide informed consent...

Abstract Conclusion : The current study revealed the prognostic and immunogenetic values of DRGs, especially SLC7A11 SLC3A2 , which might be potential biomarkers targets for immunotherapy LUAD. Background Lung adenocarcinoma (LUAD) has highest incidence in lung cancers, ranks first mortality among various cancers. Programmed cell death is crucial to development Disulfidptosis a novel type associated with high expression glucose starvation, however, role disulfidptosis related genes (DRGs)...

Abstract Cancer is a serious disease that threatens human health. Radiation, chemotherapy, and surgical excision are the main strategies used to treat tumors. However, important targets vital genes have gradually come light. TIMPs, inhibitors of matrix metalloproteinase, were related tumor progression. It still uncertain, nevertheless, how they affect progression prognosis pan-cancer. Therefore, profiles TIMP gene family expression in various cancers evaluated via The Genome Atlas (TCGA)...

In this study, we evaluated a deep learning model on diagnosing pregnancy outcomes based ultrasound images of early gestation. A data set 1909 in 613 women with pregnancies gestational age between 4 and 9 weeks from Zhujiang Hospital (2019.12-2022.05, 1090 291 miscarriage, 819 322 normal pregnancy) were collected retrospectively. The containing total was called 1, the yolk sacs 2, without 3. And sacs, there which came patients whose sac did not contain sac, while showed other since sections...

The lethality of torsades de pointes (TdP) by drugs is one main reasons that some were withdrawn from the market. In order to assess drug-induced TdP risks, a model cardiac ionic current suppression in human ventricular myocytes (ToR-ORd model), combined with maximum effective free therapeutic plasma concentration or myocyte was often used, latter proved be more relevant and accurate. We aimed develop whole-body physiologically-based pharmacokinetic (PBPK) model, incorporated cardiomyocyte...

Abstract Background and objective: Acupoint application (AA) therapy , a traditional Chinese medicine external treatment method, is recommended as complementary for treating new coronavirus pneumonia (COVID-19) can help improve curative effects, promote patient recovery, immunity to prevent disease, but the mechanism not clear. We sought explore key targets mechanisms of Ephedra Asarum, main components used in AA, COVID-19 this study. Methods: The active compounds related Asarum AA were...