SNPs and blood inflammatory marker featured machine learning for predicting the efficacy of fluorouracil-based chemotherapy in colorectal cancer.

Fluorouracil-based chemotherapy responses in colorectal cancer (CRC) patients vary widely, highlighting the role of pharmacogenomics in developing better predictive models. We analyzed 379 CRC patients receiving fluorouracil-based chemotherapy, collecting data on fluorouracil metabolism-related SNPs (TYMS, MTHFR, DPYD, RRM1), blood inflammatory markers, and clinical status. Six machine learning models-K-nearest neighbors, support vector machine, gradient boosting decision trees (GBDT), eXtreme Gradient Boosting (XGBoost), LightGBM, and random forest-were compared against multivariate logistic regression and a deep learning model (i.

mechanistic study on mycophenolate mofetil drug interactions: effect of prednisone, cyclosporine, and others.

Objective: The metabolism- and transporter-based drug-drug interactions (DDIs) between mycophenolate mofetil (MMF) and co-administered medications may be key factors for the high individual variability in MMF exposure. This study systematically assessed the influence of co-medications on the mycophenolic acid (MPA) pharmacokinetic (PK) process , particularly to provide mechanistic evidence of the metabolic interaction among steroids, cyclosporine (CsA), and MMF.

Methods: Based on a previous study, we hypothesized that there are three main DDI pathways affecting MMF PK .

Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression.

The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University.

A joint population pharmacokinetic model to assess the high variability of whole-blood and intracellular tacrolimus in early adult renal transplant recipients.

Tacrolimus (TAC) has high pharmacokinetic (PK) variability during the early transplantation period. The relationships between whole-blood and intracellular TAC concentrations and clinical outcomes remain controversial. This study identifies the factors affecting the PK variability of TAC and characterizes the relationships between whole-blood and intracellular TAC concentrations.

Inhibition of autophagy-related protein 7 enhances anti-tumor immune response and improves efficacy of immune checkpoint blockade in microsatellite instability colorectal cancer.

Background: The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) CRC is still poorly understood.

Treatment access and satisfaction on disease-modifying therapies of neuromyelitis optica spectrum disorder patients in China: a cross-sectional survey.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare and debilitating disease that has become more widely recognized in China. Legislative measures have been implemented by the government to improve treatment access for rare diseases.

Objectives: To investigate the diagnostic journey, treatment status, treatment accessibility, and treatment satisfaction of the NMOSD patients on disease-modifying therapies (DMTs) in China.

CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer.

As the world's fourth most deadly cancer, colorectal cancer (CRC) still needed the novel therapeutic drugs and target urgently. Although cyclin-dependent kinase 12 (CDK12) has been shown to be implicated in the malignancy of several types of cancer, its functional role and mechanism in CRC remain largely unknown. Here, we found that suppression of CDK12 inhibited tumor growth in CRC by inducing apoptosis.

Carfilzomib suppressed LDHA-mediated metabolic reprogramming by targeting ATF3 in esophageal squamous cell carcinoma.

Carfilzomib, a second-generation proteasome inhibitor, has been approved as a treatment for relapsed and/or refractory multiple myeloma. Nevertheless, the molecular mechanism by which Carfilzomib inhibits esophageal squamous cell carcinoma (ESCC) progression largely remains to be determined. In the present study, we found that Carfilzomib demonstrated potent anti-tumor activity against esophageal squamous cell carcinoma both in vitro and in vivo.

ESRRG-PKM2 axis reprograms metabolism to suppress esophageal squamous carcinoma progression and enhance anti-PD-1 therapy efficacy.

Background: Glycolysis under normoxic conditions, known as the Warburg effect, confers a selective advantage for the survival and proliferation of many tumors. In this study, we investigated the role of estrogen-related receptor gamma (ESRRG) in metabolic reprogramming in esophageal squamous cell carcinoma (ESCC).

Methods: Bioinformatics analysis indicated that ESRRG expression was decreased in ESCC tissue and associated with poor clinical outcomes.

Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database.

Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS). Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website.

Exploration on the development of public hospital-sponsored telemedicine platform: A case study in China.

Background: As a result of recent advancements, Internet hospitals have been a typic kind of telemedicine platform in China. The platforms can now provide a wide range of medical services while breaking through the limitations of time and space with excellent accessibility.

Objective: This study aims to give a comprehensive description on the role extension of a public hospital-sponsored Internet hospital in China from the aspects of the characteristics, patient's benefit and satisfaction, the workload of pharmacists and pharmaceutical care.

STAT3 and STAT6 polymorphisms predict the severity of adverse reactions in Chinese NSCLC patients receiving EGFR-TKIs therapy.

A total of 162 non-small cell lung cancer (NSCLC) patients were divided into discovery ( = 68) and validation ( = 94) groups. Nine Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway-related single nucleotide polymorphisms were selected to explore the potential associations between genetic polymorphisms and adverse drug reactions (ADRs). The TT genotype of STAT6 rs324011 was significantly associated with severe ADRs in the recessive genetic model (TT CC + CT, OR = 13.

Long way to go: Progress of orphan drug accessibility in China from 2017 to 2022.

Over 400 million patients worldwide suffer from rare diseases. Access to orphan drugs is, therefore, crucial for this population. China has been actively working on improving orphan drug accessibility in the past decades, especially since 2018 when the First National List of Rare Diseases was announced.

Germline genetic variations in methotrexate pathway are associated with pharmacokinetics, outcome, and toxicity in patients with primary central nervous system lymphoma.

Background: High-dose methotrexate (HD-MTX)-based regimens are the standard treatment for patients with primary central nervous system lymphoma (PCNSL); however, MTX has extensive interpatient variability in pharmacokinetics and clinical outcomes, with genetic variation an important factor involved in the variability in drug response.

Methods: 123 PCNSL patients who received 524 courses of chemotherapy were genotyped for 42 single nucleotide polymorphisms in MTX pathway. The relationship between these polymorphisms and the pharmacokinetics, clinical outcomes, and toxicity of MTX was explored using both univariate and multivariate analyses.

Azithromycin ameliorated cigarette smoke-induced airway epithelial barrier dysfunction by activating Nrf2/GCL/GSH signaling pathway.

Background: Airway epithelium is the first barrier against environmental insults, and epithelial barrier dysfunction caused by cigarette smoke (CS) is particularly relevant to chronic obstructive pulmonary disease (COPD) progression. Our study was to determine whether Azithromycin (AZI) ameliorates CS-induced airway epithelial barrier dysfunction and the underlying mechanisms.

Methods: Primary bronchial epithelial cells (PBECs), human bronchial epithelial cells (HBECs), Sprague Dawley rats and nuclear factor erythroid 2-related factor 2 (Nrf2)-/- mice were pretreated with AZI and subsequently exposed to CS.

Sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment and risk of osteomyelitis: A pharmacovigilance study of the FAERS database.

Several clinical trials have indicated that the use of canagliflozin increases the risk of lower extremity amputation. Although the US Food and Drug Administration (FDA) has withdrawn its black box warning about amputation risk for canagliflozin, the risk still exists. We sought to estimate the association between hypoglycemic medications, especially sodium-glucose co-transporter-2 inhibitors (SGLT2is), and adverse events (AEs) before the irreversible outcome of amputation as a promising early warning, based on the FDA Adverse Event Reporting System (FAERS) data.

Rationale and design of a prospective study evaluating population pharmacokinetics and pharmacodynamics of rivaroxaban in Chinese patients with non-valvular atrial fibrillation.

Introduction: Rivaroxaban is one of the most commonly used non-vitamin K antagonists for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Different individual exposures exist for Asian and non-Asian populations, and dose selection is different for Japanese and non-Japanese subjects. Few studies have investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in Chinese patients and provided a solid reference for dose selection and individualised therapy.

Donor and recipient polymorphisms of MAPK signaling pathway genes influence post-transplant liver function in Chinese liver transplant patients taking tacrolimus.

Tacrolimus (TAC) is an immunosuppressive drug that is widely used for patients who underwent liver transplantation. In addition to inhibiting the action of calcineurin, TAC also exerts its immunosuppressive effects by interfering with mitogen activated protein kinase (MAPK) pathway. In this study, we investigated the impact of both recipient and donor genetic polymorphisms of MAPK kinase kinase (MAP3K) genes on clinical events in Han Chinese liver transplantation recipients taking TAC.

Serious adverse reaction associated with the COVID-19 vaccines of BNT162b2, Ad26.COV2.S, and mRNA-1273: Gaining insight through the VAERS.

Serious adverse events following immunization (AEFI) associated with the COVID-19 vaccines, including BNT162b2 (Pfizer-BioNTech), Ad26.COV2.S (Janssen), and mRNA-1273 (Moderna), have not yet been fully investigated.

A high-performance liquid chromatography-tandem mass spectrometry method for quantification of perampanel in human plasma: Effect of concomitant anti-seizure medications on perampanel concentration in patients with epilepsy.

Perampanel is a first-in-class α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist and a novel anti-seizure medication. It is currently used as adjunctive treatment for partial seizures in patients over 12 years of age. With the increasing clinical application of perampanel, monitoring its concentration under certain clinical conditions is important.

Applying machine learning to the pharmacokinetic modeling of cyclosporine in adult renal transplant recipients: a multi-method comparison.

The aim of this study was to identify the important factors affecting cyclosporine (CsA) blood concentration and estimate CsA concentration using seven different machine learning (ML) algorithms. We also assessed the predictability of established ML models and previously built population pharmacokinetic (popPK) model. Finally, the most suitable ML model and popPK model to guide precision dosing were determined.

Skin cancer signal associated with phosphodiesterase inhibitors: gaining insight through the FDA pharmacovigilance database.

Background: Panoramic views of post-marketing safety profiles, such as cancer signal, of phosphodiesterase 5A (PDE5A) inhibitors have yet to be fully evaluated.

Research Design And Methods: Data from the FDA Adverse Event Reporting System (FAERS) concerning the timeframe between January 1, 2004 to 30 June 2022 was analyzed through a disproportionality study to understand the association between sildenafil, tadalafil, and vardenafil and cancer. This association was identified using the Reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) approaches.