Min Huang

• Chinese Academy of Sciences

Purpose High-dose methotrexate (HD-MTX) is the cornerstone of the therapy for acute lymphoblastic leukemia (ALL). However, severe adverse events are frequently reported despite standard supportive cares. Therefore, we aim to develop a new strategy to individualize HD-MTX and improve patient safety. Methods A retrospective study was conducted in wh...

Purpose The incidence of hemodynamic instability associated with dexmedetomidine (DEX) sedation has been reported to exceed 50%, with substantial inter-individual variability in response. Genetic factors have been suggested to contribute significantly to such variation. The aim of this study was to identify the clinical, pharmacokinetic, and geneti...

Clindamycin is a lincosamide antibiotic for the treatment of staphylococcal, streptococcal, and anaerobic bacterial infections. We conducted a single‐center, single‐dose, 2‐preparation, 2‐period, 2‐sequence, randomized, open‐label, 2 × 2 crossover study to evaluate the pharmacokinetics (PKs) and safety of the test and reference clindamycin hydrochl...

Our previous study shows that activation of pregnane X receptor (PXR) exerts hepatoprotection against lithocholic acid (LCA)-induced cholestatic liver injury. In this study we investigated whether PXR activation could inhibit hepatocyte pyroptosis, as well as the underlying mechanisms. Male mice were treated with mouse PXR agonist pregnenolone 16α-...

Aims There is limited real‐world data on cyclosporin A (CsA)‐induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI. Methods Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were...

Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD...

Highlights •A novel carryover elimination device based on the DBD plasma was developed. •The critical factors affecting the elimination efficiency were washing cycle, gas flow rate, and gas type. •Oxygen was proved indispensable for carryover elimination. •The generation of ROS and RNS were identified as the working mechanism of the device. •The qu...

Constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor α (PPARα) are members of the nuclear receptor superfamily, which regulates various physiological and pathological processes. Phase separation is a dynamic biophysical process that biomacromolecules form liquid-like condensates, which have been identified as a cont...

Background Previous studies have suggested that loss of the EGFR T790M gene mutation may contribute to the development of resistance to Osimertinib in non‐small cell lung cancer (NSCLC). Aims This study aims to assess the relationship between the clinical effectiveness of Osimertinib in NSCLC patients and the T790M mutation status following resist...

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines. Dose optimization guided by nudix hydrolase 15 (NUDT15) has significantly reduced the early leucopenia rate, but there are no definitive biomarkers for late risk leucopenia prediction. AIM To determine the predictive value of early monitoring of DNA...

The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer. Elucidation of the underlying mechanism by which oncogenic signaling mediates urea cycle reprogramming could help identify targetable metabolic vulnerabilities. In this study, we discovered that oncogenic activation of KRAS in non–small cell lung cancer (N...

Endotoxemia‐related acute liver injury has a poor prognosis and high mortality, and macrophage polarization plays a central role in the pathological process. Pregnane X receptor (PXR) serves as a nuclear receptor and xenosensor, safeguarding the liver from toxic stimuli. However, the effect and underlying mechanism of PXR activation on endotoxemic...

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that f...

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult s...

Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS) is a widely utilized technique for in vivo pharmaceutical analysis. Ionization interference within electrospray ion source, occurring between drugs and metabolites, can lead to signal variations, potentially compromising quantitative accuracy. Currently, method valid...

Background and Aim Gefitinib resistance is an urgent problem to be solved in the treatment of non‐small cell lung cancer (NSCLC). Tanshinone IIA (Tan IIA) is one of the main active components of Salvia miltiorrhiza , which exhibits significant antitumor effects. The aim of this study is to explore the reversal effect of Tan IIA on gefitinib resista...

Purpose Although somatic mutations were explored in depth, limited biomarkers were found to predict the resistance of EGFR tyrosine kinase inhibitors (EGFR-TKI). Previous studies reported N6-methyladenosine (m6A) levels regulated response of EGFR-TKIs; whether the germline variants located in m6A sites affected resistance of EGFR-TKIs is still unkn...

Background: Valproic acid (VPA) is a first-line anti-epileptic drug with broad efficacy.Due to significant individual differences in drug metabolism, therapeutic drug monitoring (TDM) is commonly used. However, the conventional therapeutic range (50-100 μg/mL) is inadequate for predicting clinical outcomes.Additionally, the relationship between VP...

Intervention of the gut microbiome is a promising adjuvant strategy in cancer immunotherapy. Chemotherapeutic agents are recognized for their substantial impacts on the gut microbiome, yet their therapeutic potential as microbiome modulators remains uncertain, due to the complexity of microbiome‐host‐drug interactions. Here, it is showed that low‐d...

Introduction Natural products (NPs) play a crucial role in the development of therapeutic drugs. However, it is still highly challenging to identify the targets of NPs. Besides, NPs usually exert their pharmacological activities via acting on multiple targets or pathways, which also poses great difficulties for the target identification of NPs. Ob...

Purpose: To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. Method: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients...

Objective Improved understanding of cyclosporine A (CsA) pharmacokinetics in children undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) is crucial for effective prevention of acute graft-versus-host disease and medication safety. The aim of this study was to establish a population pharmacokinetic (Pop-PK) model that could b...

Background Myelosuppression is a common adverse effect in breast cancer patients receiving anthracyclines combined with cyclophosphamide chemotherapy. Screening potential biomarkers and building predictive models have implications for clinical management of myelosuppression. Methodology This study collected 103 breast cancer patients in Shenzhen,...

Budesonide (BUD), a locally acting glucocorticoid with low side effects, is recommended in several Crohn's disease (CD) drug treatment guidelines as the first choice for early treatment. Nevertheless, the extensive first-pass effect mediated by P-glycoprotein (P-gp) and Cytochrome P450 3A4 (CYP3A4) leads to low bioavailability and limits further ap...

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abund...

Objective The aim of this study was to systematically review the efficacy and safety of parecoxib and flurbiprofen axetil for perioperative analgesia in children through Bayesian network meta-analysis. Methods We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, VIP, and Wanfang Data databases on 18 July 2022...

Background: Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurre...

Introduction Thiopurines, azathiopurine (AZA) and mercaptopurine (6-MP) have been regularly used in the treatment of inflammatory bowel disease (IBD). Despite optimized dosage adjustment based on the NUDT15 genotypes, some patients still discontinue or change treatment regimens due to thiopurine-induced leukopenia. Methods We proposed a prospectiv...

Recently, we developed a novel microprobe electrospray ionization (μPESI) source and its coupled MS (μPESI-MS/MS) system. Here, we aimed to widely validate the μPESI-MS/MS method for quantitative analysis of drugs in plasma samples. Furthermore, the relationship between the quantitative performance of the μPESI-MS/MS method and the physicochemical...

8564 Background: The current study aimed to investigate the safety and efficacy of chemotherapy with PD-1 inhibitor, tislelizumab, for stage II-IV NSCLC. Meanwhile to explore the potential biomarkers for safety and efficacy of tislelizumab plus chemotherapy in NSCLC. Methods: This was an open-label, multicenter, phase 2 trial conducted at 3 hospita...

Ethnopharmacological relevance: Tripterygium wilfordii polyglycosides (TWP), extracted from the traditional Chinese herb Tripterygium wilfordii, has been widely used in the treatment of rheumatoid arthritis (RA). However, the toxicity of TWP to a variety of organs such as liver, kidney and testis greatly limits its clinical application. Salvia mil...

Background: Triptolide (TP) is an important active compound from Tripterygium wilfordii Hook F (TwHF), however, it is greatly limited in clinical practice due to its severe toxicity, especially testicular injury. Melatonin is an endogenous hormone and has beneficial effects on the reproductive system. However, whether triptolide-induced testicular...

Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined...

Cellular senescence is a state of proliferative arrest, and the development of carcinoma can be suppressed by conferring tumor cell senescence. Recently, we found that carnitine palmitoyltransferase 1C (CPT1C) controls tumor cell proliferation and senescence via regulating lipid metabolism and mitochondrial function. Here, 13C-metabolic flux analys...

The widespread use of triazole fungicides in agricultural production poses a potential risk to human health. This study investigates the interaction of five triazole fungicides, i.e., tebuconazole, triticonazole, hexaconazole, penconazole, and uniconazole with human renal transporters, including OAT1, OAT3, OCT2, OCTN1, OCTN2, MATE1, MATE2-K, MRP2,...

The quantitative analysis of drug plasma samples plays an important role in the drug development and drug clinical use. Our research team developed a new electrospray ion source-Micro probe electrospray ionization (μPESI) in the early stage, which was combined with mass spectrometry (μPESI-MS/MS) showing good qualitative and quantitative analysis p...

Objectives: Cytomegalovirus (CMV) and BK polyomavirus (BKPyV) infections after kidney transplant have become increasingly prevalent. Based on previous studies, the mammalian target of rapamycin (mTOR) inhibitors seem like attractive alternatives with antiviral activity. The objective of this systematic review and meta-analysis was to investigate t...

Aim: The aim of the research is to establish a population pharmacokinetic (PPK) model of Clindamycin hydrochloride capsules in Chinese health subjects and investigate the factors affecting the pharmacokinetic parameters to provide guidance for the individualized treatment of Clindamycin. Methods: Clindamycin concentrations were measured in 48 selec...

Background Pharmacogenomics (PGx) examines the influence of genetic variation on drug responses. With more and more Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines published, PGx is gradually shifting from the reactive testing of single gene toward the preemptive testing of multiple genes. But the profile of PGx genes, especia...

Rare data reported tacrolimus-induced liver injury (tac-DILI) in real world. We performed a nested case-control analysis of 1,010 renal transplant recipients. Recipients with tac-DILI were randomly matched at a ratio of 1:4 by the year of admission to the remaining recipients without tac-DILI to explore risk factors. The incidence of tac-DILI was 8...

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers t...

Methotrexate (MTX), a widely used chemotherapeutic drug, is critical for achieving long-term complete remission in contemporary maintenance therapy of acute lymphoblastic leukemia (ALL). MTX is intracellularly converted into methotrexate polyglutamates (MTXPGn) by folylpolyglutamate synthase after transporting into the cells. The intracellular leve...

Mixed lineage kinase domain-like (MLKL) is widely accepted as an executioner of necroptosis, in which MLKL mediates necroptotic signaling and triggers cell death in a receptor-interacting protein kinase 3 (RIPK3)-dependent manner. Recently, it is increasingly noted that RIPK3 is intrinsically silenced in hepatocytes, raising a question about the ro...

Curcumin (CUR), derived from dietary spice turmeric, is a polyphenolic compound with various biological and pharmacological activities. Tetrahydrocurcumin (THC) is one of the major reductive metabolites of CUR. A pharmacokinetic study using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for simultaneous determin...

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been widely used in the quantitative analysis of drugs. The ubiquitous concomitant drug scenario in the clinic has spawned a large number of co-analyses based on this technique. However, signal suppression caused by concomitant drugs during electrospray ionization may affect the quantifi...

Liver fibrosis can be characterized by the over-deposition of extracellular matrix (ECM). It has been reported that β-catenin/TCF4 interaction was enhanced in bile duct ligation (BDL) model, which implicated the critical role of β-catenin/TCF4 interaction during the progression of fibrosis. However, whether inhibiting β-catenin/TCF4 signaling atten...

Being the rate-limiting enzyme within the serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH) is abnormally overexpressed in numerous malignant tumor cells and is a promising target for cancer treatment. Here, we report a series of novel PHGDH inhibitors using a focused compound screening and structural optimization approach. The le...

Nicotinamide phosphoribosyltransferase (NAMPT) is identified as a promising target for cancer therapy. However, known NAMPT inhibitors are characterized by weak clinical efficacy and dose-dependent toxicity. There is an urgent need to develop new NAMPT intervention strategies. Using the proteolysis-targeting chimera (PROTAC) technology, we designed...

Study objective: The pharmacokinetics and pharmacodynamics of tacrolimus (TAC) vary greatly among individuals, hindering its precise utilization. Moreover, effective models for the early prediction of TAC efficacy in patients with nephrotic syndrome (NS) are lacking. We aimed to identify key factors affecting TAC efficacy and develop efficacy pred...

Ethnopharmacological relevance: Tripterygium wilfordii polyglycoside tablet (TWP), a traditional Chinese medicine preparation, has multiple pharmacological properties, including anti-inflammatory, immune-modulatory and anti-proliferative activities. However, the reproductive toxicity of TWP greatly limits its clinical application and the mechanism...

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-...

Proteolysis-targeting chimera (PROTAC) is emerging as a promising technology in targeted protein degradation and drug discovery. However, there is still a lack of effective chemical tools to real-time detect and track the protein degradation. Herein, the first fluorescent and theranostic PROTACs were designed for imaging the degradation of nicotina...

Anticancer drug discovery has yielded unprecedented progress in recent decades, resulting in the approval of innovative treatment options for patients and the successful implementation of personalized medicine in clinical practice. This remarkable progress has also reshaped the research scope of pharmacological research. This article, as a tribute...

Background and Aim: Tacrolimus (TAC) is a first-line immunosuppressant for the treatment of refractory nephrotic syndrome (RNS), but the pharmacokinetics of TAC varies widely among individuals, and there is still no accurate model to predict the pharmacokinetics of TAC in RNS. Therefore, this study aimed to combine population pharmacokinetic (PPK)...

Peroxisome proliferator-activated receptor α (PPARα) is closely related to lipid metabolism and various liver diseases. Previous study has shown that chronic treatment with PPARα agonist WY-14643 can induce liver tumors in rodents, but the implications of this process on lipid metabolism in the liver remain unclear. Thus, this study aimed to explor...

Triptolide (TP) is one of the major components of Tripterygium wilfordii, which is a traditional Chinese medicine widely used in the treatment of various autoimmune and inflammatory diseases. However, the cardiotoxicity induced by TP greatly limits its widespread clinical application. In view of the role of ROS-mediated oxidative stress in TP-induc...

St. John's wort (SJW) is a medicinal herb remedy for mild depression. However, long-term use of SJW has raised safety concerns in clinical practice because of drug–drug interactions. Excessive use of acetaminophen (APAP) causes severe hepatotoxicity, but whether SJW modulates APAP-induced liver injury remains unclear. In this study, the effect of l...

As a complex pathogenesis driven by immune inflammatory factors and intestinal microbiota, the treatment of inflammatory bowel disease (IBD) may rely on the comprehensive regulation of these important pathogenic factors to reach a favorable therapeutic effect. In the current study, we discovered a series of imidazo[4,5-c]quinoline derivatives that...

Aim: Wuzhi tablets are a dose-sparing agent for tacrolimus (TAC) in China and increase the bioavailability of TAC. The current study aimed to evaluate the pharmacokinetic interaction magnitude of Wuzhi and TAC and explore the potential determinants of this interaction. Methods: This study performed a retrospective, self-controlled study of 138 r...

Abstract Thiopurine dose optimization by thiopurine‐S‐methyltransferase (TPMT) or nudix hydrolase‐15 (NUDT15) significantly reduced the early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although 6‐thioguanine nucleotides (6TGN) was a makeshift in European, its function is controversial. In the present study, we a...

Aim Propofol and opioids are commonly used in anaesthesia, but are highly susceptible to haemodynamic instability, thereby threatening the patient's surgical safety and prognosis. The purpose of this study was to investigate the predictors of haemodynamic instability and establish its predictive model. Methods A total of 150 Chinese patients under...

Background Low cardiac output syndrome (LCOS) is the most serious physiological abnormality with high mortality for patients after cardiac surgery. This study aimed to explore the multidimensional data of clinical features and outcomes to provide individualized care for patients with LCOS.Methods The electronic medical information of the intensive...

The cytochrome P450 (CYP) enzymes play a pivotal role in drug metabolism. LC-MS/MS-based targeting technology has been applied to the analysis of CYP enzymes, promoting drug development and drug-drug interaction studies. Rat is one of the most commonly used models for drug metabolism assessment, but LC-MS/MS assay quantifying the abundance of CYP e...

Previously, we demonstrated that Schisandrol B (SolB) protected against lithocholic acid (LCA)-induced cholestatic liver injury (CLI) through pregnane X receptor (PXR). Additionally, growing evidence has revealed that pyroptosis is involved in CLI. Whether the hepatoprotective effect of SolB driven by PXR activation is related to pyroptosis in CLI...

Nuclear receptor pregnane X receptor (PXR) can induce significant liver enlargement through hepatocyte hypertrophy and proliferation. A previous report showed that during the process of PXR-induced liver enlargement, hepatocyte hypertrophy occurs around the central vein (CV) area while hepatocyte proliferation occurs around the portal vein (PV) are...

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication during ovarian stimulation. Even though the incidence of OHSS was relatively low in clinical practice, the consequence can be potentially devastating and life-threatening. Abnormal lipid metabolism may relate to the pathological development of OHSS, but there is still a r...

Abstract Objective Admission hyperglycemia is associated with poor prognosis in patients with acute myocardial infarction (AMI), but the effects of baseline diabetes status on this association remain elusive. We aim to investigate the impact of admission hyperglycemia on short and long-term outcomes in diabetic and non-diabetic AMI patients. Method...

Purpose: Although gefitinib prolonged the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients, unpredictable resistance limited its clinical efficacy. Novel predictive biomarkers with explicit mechanisms are urgently needed. Experimental design: A total of 282 NSCLC patients with gefitinib treatment were randomly assig...

Electrospray ionization mass spectrometry (ESI-MS) is widely used in drug development, therapeutic drug monitoring, and other fields. However, unstable mass spectral signals, especially during the initial stages of instrument operation, plague analysts. Generally, in quantitative experiments, the stability of response can be achieved by running the...

Background and Aim Research has shown that green tea catechins may influence the activity of drug metabolizing enzymes and drug transporters. We examined whether epigallocatechin-3-gallate (EGCG) affected the pharmacokinetics and pharmacodynamics of bisoprolol in rats. Methods A sensitive, specific liquid chromatography-tandem mass spectrometry (L...

Background Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied four-fold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmede...

Background and objective: Fenofibrate, an agonist of peroxisome proliferator activated receptor α (PPARα), has been widely used as a lipid-regulating agent in clinical practice. Recent studies found that fenofibrate can significantly induce hepatomegaly in mice, but the involved mechanisms remain unclear. Methods: The effect of fenofibrate on he...

Escitalopram, one of the Selective Serotonin Reuptake Inhibitors (SSRIs), has been widely used in the patients with major depression. In this study, a simple, sensitive and rapid method was established and validated for simultaneous quantification of Escitalopram (S-CT), desmethyl escitalopram (S-DCT), didemethyl escitalopram (S-DDCT) and escitalop...

Background: To minimize drug-related toxicity and monitor dosing regimens, an ultra-sensitive, simple and high-throughput analytical method for therapeutic drug monitoring (TDM) is required. Methods: A novel LC-MS/MS bioassay of levetiracetam (LEV), lamotrigi1/ne (LTG) and 10-hydroxycarbazepine (MHD) in human plasma was established. The analytes...

Clinical and genetic influencing factors on free fraction of mycophenolic acid (MPA) have rarely been discussed. The present study investigated whether the clinical and genetic factors could explain the variability in the pharmacokinetics of free MPA (fMPA) and total MPA (tMPA) in Chinese pediatric and adult renal transplant recipients. Twenty‐eigh...

Aim: IQZ23, a novel β-indoloquinazoline derivative, is a potential therapeutic agent for obesity and related metabolic disorders. To assist pharmacokinetics evaluation, a quantitative method for IQZ23 in rat plasma is required. Methods & Results: An LC-MS/MS assay for the determination of IQZ23 in rat plasma was developed and validated for the firs...

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore,...

Ginkgolide B (GKB) is a well-established neuroprotectant for acute ischemia stroke. However, its cerebral exposure and real-time response remain elusive in acute ischemia/reperfusion stage, and it hinders its usage in therapeutic window of ischemia stroke. Therefore, we investigate the exposure-response relationship of GKB (10 mg/kg, intravenously...