There are a large number of drug transporters widely distributed in various tissues and organs in the human body.They are involved in the membrane transport of numerous endogenous substances,toxins,and drugs.The transmembrane transport mediated by transporters not only plays an important role in maintaining the homeostasis of the internal environment,but also closely related to drug absorption,distribution,metabolism,and excretion processes.In clinical practice,drug-drug and drug-endogenous molecule interactions based on drug transporters may affect therapeutic efficacy or lead to toxic side effects.Therefore,it is particularly important to closely monitor and evaluate the risks of transporters mediated drug-drug interactions in the drug development and marketing process.This review summarized the classification,functions,tissue distribution and substrate specificity of typical drug transporters in new drug development.Subsequently,the research progress regarding drug-drug interactions involving 24 drug transporters for 55 newly approved drugs by the US Food and Drug Administration in 2023 is comprehensively reviewed.The aim is to provide reference for further drug-drug interaction research together with its scientific significance during new drug development stage.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

There are a large number of drug transporters widely distributed in various tissues and organs in the human body.They are involved in the membrane transport of numerous endogenous substances,toxins,and drugs.The transmembrane transport mediated by transporters not only plays an important role in maintaining the homeostasis of the internal environment,but also closely related to drug absorption,distribution,metabolism,and excretion processes.In clinical practice,drug-drug and drug-endogenous molecule interactions based on drug transporters may affect therapeutic efficacy or lead to toxic side effects.Therefore,it is particularly important to closely monitor and evaluate the risks of transporters mediated drug-drug interactions in the drug development and marketing process.This review summarized the classification,functions,tissue distribution and substrate specificity of typical drug transporters in new drug development.Subsequently,the research progress regarding drug-drug interactions involving 24 drug transporters for 55 newly approved drugs by the US Food and Drug Administration in 2023 is comprehensively reviewed.The aim is to provide reference for further drug-drug interaction research together with its scientific significance during new drug development stage.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

A 2-year-and-10-month-old boy presented with multiple masses in the neck and chest for over 3 months.The child had a history of unstable walking,with hard lumps visible at the injury sites after falls,which would resolve on their own.Following a recent injury,a mass was discovered in the posterior neck,protruding above the skin surface and accompanied by limited joint movement.Gradually,new masses were found on the left side of the neck,back near the scapular lower angle,in the scapular fossa,and along the left axillary midline.Magnetic resonance imaging examination showed diffuse low signal on T1-weighted images and high signal on T2-weighted images in the bilateral posterior neck and back muscles two months ago.A CT scan revealed muscle swelling,with areas of patchy low density and multiple nodular high-density ossifications within some muscles.Genetic testing results indicated a mutation in the ACVR1 gene,leading to the final diagnosis of progressive ossifying myositis in this patient.This article summarizes the etiology,diagnosis,and treatment of one case of progressive ossifying myositis,providing a reference for clinicians.

This study was aimed at investigating and analyzing a familial cluster of Brucella canis among dogs in Chaoyang District,Beijing.The goal was to describe the transmission modes and risks of this disease among urban pet dogs,to provide scientific evidence for its detection and prevention.Blood,urine,conjunctival swabs,oral and nasal swabs,reproductive tract swabs,and rectal swabs were collected from all dogs in an affected household.These samples underwent serological testing for brucellosis,qPCR detection,and bacterial culture.The isolated strains were identified with Bruce-Ladder PCR.Additionally,the dogs'medical and contact histories were reviewed and analyzed.Four dogs in the household were found to be infected with Brucella canis.One dog was found to be infected with Brucella canis,on the basis of positive qPCR or bacterial culture tests in urine,conjunctival swabs,and blood.The other three infected dogs had a history of roaming.No mating behavior was observed among the dogs in this study.This outbreak of Brucella canis probably spread through non-reproductive routes,with urine and ocular secretions from the infected dogs being potential significant sources of transmission.

This study was aimed at investigating and analyzing a familial cluster of Brucella canis among dogs in Chaoyang District,Beijing.The goal was to describe the transmission modes and risks of this disease among urban pet dogs,to provide scientific evidence for its detection and prevention.Blood,urine,conjunctival swabs,oral and nasal swabs,reproductive tract swabs,and rectal swabs were collected from all dogs in an affected household.These samples underwent serological testing for brucellosis,qPCR detection,and bacterial culture.The isolated strains were identified with Bruce-Ladder PCR.Additionally,the dogs'medical and contact histories were reviewed and analyzed.Four dogs in the household were found to be infected with Brucella canis.One dog was found to be infected with Brucella canis,on the basis of positive qPCR or bacterial culture tests in urine,conjunctival swabs,and blood.The other three infected dogs had a history of roaming.No mating behavior was observed among the dogs in this study.This outbreak of Brucella canis probably spread through non-reproductive routes,with urine and ocular secretions from the infected dogs being potential significant sources of transmission.

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg^-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

Objective The metabolites of tolvaptan in rats were identified by ultra-performance liquid chromatography-quadrupole-exactive orbitrap high-resolution mass spectrometry(UFLC-Q-Exactive Orbitrap MS),and the possible metabolic pathways of tolvaptan in rats were discussed.Methods Plasma,urine and fecal samples from rats were collected after a single oral administration of 60 mg·kg-1 tolvaptan solid dispersion solution.The protein in the samples was precipitated with acetonitrile.UFLC-Q-exactive orbitrap MS technology was adopted for the sample analysis and the data were processed by Xcalibur 2.0 software.Results According to the retention time,precise relative molecular mass,characteristic fragment ions and related literature reports of each compound,35 metabolites were identified in rat biological samples.Moreover,23,26 and 30 metabolites in the plasma,urine and feces were identified,respectively.The major metabolic pathways of tolvaptan were identified as hydroxylation,carboxylation,hydrolysis,dehydrogenation,glucuronidation and acetylation.Conclusion Our study confirmed the major metabolites of tolvaptan in rats,enriched the metabolite spectrum of tolvaptan in vivo,and provided an experimental basis for the in-depth study of the pharmacodynamic substance basis of tolvaptan.

Objective To understand the distribution and antimicrobial resistance changes of bacteria isolated from pleural and peritoneal effusion in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Provincial Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacteria antimicrobial resistance surveillance method was imple-mented according to technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),and WHO-NET 5.6 software was used to analyze the data of bacteria isolated from pleural and peritoneal effusion as well as antimicrobial susceptibility testing results.Results From 2012 to 2021,a total of 28 934 bacterial strains were iso-lated from specimens of pleural and peritoneal effusions from member units of Hunan Provincial Antimicrobial Re-sistance Surveillance System,with 5 752 strains from pleural effusion and 23 182 from peritoneal effusion.The top five bacteria isolated from pleural effusion were Escherichia coli(n=907,15.8％),Staphylococcus aureus(n=535,9.3％),Klebsiella pneumoniae(n=369,6.4％),Staphylococcus epidermidis(n=452,7.9％),and Staphy-lococcus haemolyticus(n=285,5.0％).The detection rate of methicillin-resistant Staphylococcus aureus(MR-SA)from pleural effusion was 24.3％-39.2％,and that of methicillin-resistant coagulase negative Staphylococcus(MRCNS)was 58.8％-77.1％.The top five bacteria isolated from peritoneal effusion were Escherichia coli(n=8 264,35.6％),Klebsiella pneumoniae(n=2 074,9.0％),Enterococcus faecium(n=1 458,6.3％),Staphylo-coccus epidermidis(n=1 383,6.0％),and Pseudomonas aeruginosa(n=1 152,5.0％).The detection rate of MRSA from peritoneal effusion was 22.1％-52.4％,which presented a decreasing trend(P=0.004).The detec-tion rate of MRCNS was 60.4％-79.4％.The resistance rates of Enterobacterales from peritoneal effusion to ce-fazolin,cefuroxime,ceftriaxone and cefepime all showed decreasing trends(all P＜0.05).Vancomycin-,linezo-lid-,and teicoplanin-resistant Staphylococcus strains were not found in pleural and peritoneal effusions.The resis-tance rates of Enterococcus faecium to most tested antimicrobial agents were higher than those of Enterococcus fae-calis.The resistance rates of Enterobacterales to imipenem and meropenem were ≤8.5％.The resistance rates of non-fermentative Gram-negative bacilli to imipenem and meropenem were ≤43.3％.Conclusion The data structure of Hunan Antimicrobial Resistance Surveillance System for pleural and peritoneal effusions from 2012 to 2021 is relatively complete.The constituent and antimicrobial susceptibility of isolated pathogenic bacteria vary in different years.