3D Printing and Development of Optimized and Accurate, Personalized Surgical Plans for Complex Pelvic and Acetabular Fractures.

Context: Multiple high-energy injuries and complex, pelvic acetabular fractures are challenging injuries. With the help of a 1:1-sized solid model of the human body, 3D printing technology can achieve personalized customization of the surgical methods. Objective: The study intended to compare the clinical efficacy of three-dimensional (3D)-printing-assisted and traditional, open reduction and internal fixation in the treatment of complex pelvic acetabular fractures. Design: The research team conducted a randomized controlled trial and also provided a case study for one participant in the intervention group. Setting: The study took place at the First Affiliated Hospital of Yangtze University in Jingzhou, Hubei, China. Participants: Participants were 48 patients with complex pelvic acetabular fractures at the hospital between January and December 2018. Interventions: The research team randomly divided participants into two groups, with 24 participants in each group: (1) the 3D group, which received treatment in which surgeons used 3D-printing technology for preoperative planning, and (2) the routine group, which received routine treatment. Outcome Measures: The research team measured: (1) perioperative conditions, including operation time, intraoperative blood loss, and postoperative drainage volume; (2) fracture reduction quality; and (3) a case study of a postoperative imaging examination. Results: The 3D group's operation time (P = .001), intraoperative blood loss (P = .001), and postoperative drainage volume (P = .001) were significantly lower than those of routine group. According to the Matta imaging standards, the fracture reduction quality for the 3D group was excellent for 16 participants (66.66%), good for four participants (16.67%), and fair for four participants (16.67%), with the total quality rate at 83.33% for 20 participants. For the routine group, the quality was excellent for eight participants (33.33%), good for four participants (16.67%), and fair for 12 participants (50.00%), with the excellent and good rates at 50.00% for 12 participants. The 3D group's fracture reduction quality was significantly higher than that of the routine group (P < .05). Conclusions: 3D printing technology in the treatment of complex pelvic acetabular fractures can be helpful for surgeons to understand a fracture's characteristics; formulate an optimized and accurate, personalized surgical plan before an operation; improve the reduction's safety and accuracy; shorten the operation time; reduce the occurrence of postoperative complications; and improve clinical efficacy.

Comparative analysis of external locking plate and combined frame external fixator for open distal tibial fractures: a comprehensive assessment of clinical outcomes and financial implications.

BACKGROUND: Open distal tibial fractures pose significant challenges regarding treatment options and patient outcomes. This retrospective single-centre study aimed to compare the stability, clinical outcomes, complications, and financial implications of two surgical interventions, namely the external locking plate and the combined frame external fixator, to manage open distal tibial fractures. METHODS: Forty-four patients with distal open tibial (metaphyseal extraarticular) fractures treated between 2020 and 2022 were selected and formed into two main groups, Group A and Group B. Group A (19 patients) are patients that underwent treatment using the external locking plate technique, while Group B (25 patients) received the combined frame external fixator approach. Age, gender, inpatient stay, re-operation rates, complications, functional recovery (measured by the Johner-Wrush score), pain ratings (measured by the Visual Analogue Scale [VAS]), and cost analyses were evaluated for each group. Statistical analyses using SPSS were conducted to compare the outcomes between the two groups. RESULTS: The research found significant variations in clinical outcomes, complications, and cost consequences between Group A and Group B. Group A had fewer hospitalisation periods (23.687.74) than Group B (33.5619.47). Re-operation rates were also considerably lower in Group A (26.3%) than in Group B (48%), owing to a greater prevalence of pin-tract infections and subsequent pin loosening in the combination frame external fixator group. The estimated cost of both techniques was recorded and analysed with the locking average of 26,619.69 ± 9,602.352 and the combined frame average of 39,095.64 ± 20,070.077. CONCLUSION: This study suggests that although the two approaches effectively manage open distal tibia fractures, the locking compression plate approach (Group A) has an advantage in treating open distal tibia fractures. Shorter hospitalisation times, reduced re-operation rates, and fewer complications will benefit patients, healthcare systems, and budget allocation. Group A's functional recovery results demonstrate the locking plate technique's ability to improve recovery and patient quality of life. According to the cost analysis, the locking plate technique's economic viability and cost-effectiveness may optimise healthcare resources for open distal tibia fractures. These findings might improve patient outcomes and inform evidence-based orthopaedic surgery.

Screening, identification and control of unknown estrogen-like compounds in Maillard reaction products of glucose-arginine/lysine model systems.

It was speculated that estrogen-like compounds may be produced by chemical reactions during food processing, such as Maillard reaction, which would disrupt the endocrine system of organisms. Herein, the Maillard reaction in the process of high temperature for long time was simulated by using model system, and unknown estrogen-like compounds produced during Maillard reaction were screened by colorimetric assay based on dual estrogen receptor (ER)-gold nanoparticles (AuNPs) and enzyme-linked immunosorbent assay (ELISA). Possible structures of estrogen-like compounds were inferred by ultra-performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS) in combination with a mass database, and finally the structure of estrogen-like compound, 2, 4-dihydroxy-1, 4-benzoxazin-3-one-2-o-ß-D-glucopyranoside (DIBOA-glc), was identified by high resolution orbitrap mass spectrometry (Orbitrap HRMS). This is the first study of the screening and identification of unknown estrogen-like compounds produced in Maillard reaction. Additionally, strategy of controlling the formation of DIBOA-glc by adding vitamin B6 in Maillard reaction was proposed, providing effective proposals for the safety control in actual food processing.

Metabolomic profiling reveals the mechanisms underlying the nephrotoxicity of methotrexate in children with acute lymphoblastic leukemia.

BACKGROUND: Methotrexate is widely recommended as a first-line treatment for the intensive systemic and consolidation phases of childhood acute lymphoblastic leukemia. However, methotrexate-induced nephrotoxicity is a severe adverse reaction, of which the mechanisms remain unclear. METHODS: An untargeted metabolomics analysis of serum from childhood acute lymphoblastic leukemia patients with delayed methotrexate excretion, with or without acute kidney injury, was performed to identify altered metabolites and metabolic pathways. An independent external validation cohort and in vitro HK-2 cell assays further verified the candidate metabolites, and explored the mechanisms underlying the nephrotoxicity of methotrexate. RESULTS: Four metabolites showed significant differences between normal excretion and delayed excretion, seven metabolites reflected the differences between groups with or without acute kidney injury, and six pathways were finally enriched. In particular, oxidized glutathione was confirmed as a candidate metabolite involved in the toxicity of methotrexate. We further explored the role of glutathione deprivation-induced ferroptosis on methotrexate cytotoxicity, and it was found that methotrexate overload significantly reduced cell viability, triggered reactive oxygen species and intracellular Fe2+ accumulation, and altered the expression of ferroptosis-related proteins in HK-2 cells. These methotrexate-induced changes were alleviated or reversed by the administration of a ferroptosis inhibitor, further suggesting that ferroptosis promoted methotrexate-induced cytotoxicity in HK-2 cells. CONCLUSIONS: Our findings revealed complex metabolomic profiles and provided novel insights into the mechanism by which ferroptosis contributes to the nephrotoxic effects of methotrexate.

The Role of Emotional Responses in the VR Exhibition Continued Usage Intention: A Moderated Mediation Model.

During COVID-19, many renowned galleries and art fairs used Virtual Reality (VR) exhibitions for art information dissemination and online displays. To avoid the risks of offline viewing of exhibitions, users can access a web-based VR exhibition platform for remote appreciation of artworks, gaining a rich art experience and thus contributing to physical and mental health. The reasons affecting users' continued usage intentions are not clear enough in the existing studies of VR exhibitions. Therefore, further studies are needed. This paper explores the relationship between users' escapist experience, aesthetic experience, presence, emotional responses, and continued usage intention through a survey of VR exhibition users. The survey data were collected from 543 users who had experienced the VR exhibition through an online survey website. The study results show that users' continued usage intentions are influenced by escapist experience and aesthetic experience. Presence plays a mediating role in the influence of escapist experiences and aesthetic experiences on continued usage intention. Emotional responses play a moderating role in the impact of user experience on continued usage intention. This paper provides a theoretical reference for the study of the impact mechanism of continued usage intention of VR exhibitions from the perspective of mental health. In addition, this study enables VR exhibition platforms to better understand the emotional state of users during art experiences to create and share healthy aesthetic information that can contribute to the management and enhancement of mental health. At the same time, it provides valuable and innovative guidance solutions for the future development of VR exhibitions.

Nanoplastic-induced vascular endothelial injury and coagulation dysfunction in mice.

Nanoplastics are the persistent pollutants in a variety of environments, representing a potential threat to human health. Notably, plastic particles have been detected in sample of human bloodstream. It is thus significant to investigate the effects of nanoplastics on the cardiovascular system owing to its ease transfer through the bloodstream to other organs. However, few studies have been performed to evaluate the cardiovascular toxicity of nanoplastics. Herein, we pursued to investigate the adverse cardiovascular impacts of polystyrene (PS), PS-NH2 and PS-COOH nanoplastics on mice. Experimental results demonstrated that the exposure to these nanoplastics could result in structural damage of vascular endothelial cells and inflammatory response. Moreover, it was found out that the dysfunctions of coagulation and prethrombotic state were caused by nanoplastics, which could be ascribed to the activation of JAK1/STAT3/TF signaling pathway. In summary, results clearly indicated that nanoplastic exposure lead to vascular toxicity to mice, which serves as a basis for future studies about the potential physiological threat of nanoplastics to humans.

Photothermal-based nanomaterials and photothermal-sensing: An overview.

Based on the excellent properties, photothermal nanomaterials have been widely used in many fields, such as trace substance detection, optical imaging, medical diagnosis and treatment. Different from colorimetric, fluorescent and electrochemical methods which often suffer from the problems of high background interference, operation procedure dependence and high cost, photothermal sensing can effectively break the limitations of the above methods and become an alternative strategy due to its high resolution and spatial controllability. Especially in recent years, the continuous development of new materials and the introduction of portable, low-cost and precision photothermal measuring equipment can significantly improve the application potential of photothermal detection. Here, we conducted comprehensive analyses on those studies. This review summarized the progress of photothermal detection over recent years, including the main types of photothermal nanomaterials and the generation principle of the photothermal effect, the relevant matching thermometry tools, and the applications in the designing of sensing strategies. It aims to provide a reference for researchers to synthesize nanomaterials with stable and high photothermal conversion efficiency and develop more effective and sensitive detection methods.

Population pharmacokinetics and dosing regimen optimization of levetiracetam in epilepsy during pregnancy.

AIMS: The pharmacokinetics of levetiracetam (LEV) significantly changed during pregnancy. It is a great challenge to predict the adjusted doses of LEV to reach the preconception target concentrations. This study aimed to establish a population pharmacokinetic model of LEV in women with epilepsy (WWE) during pregnancy to analyse the factors of pharmacokinetic variability and to develop a model-based individualized dosing regimen. METHODS: A total of 166 concentration-time points from 37 WWE during pregnancy treated with LEV were collected to analyse LEV pharmacokinetics with nonlinear mixed-effects modelling. The dosing regimen was optimized by Monte Carlo simulations based on the final model. RESULTS: The LEV pharmacokinetics in pregnant WWE were best described by a 1-compartment model of first-order absorption and elimination. The population typical value of apparent clearance (CL/F) in the final model was estimated to be 3.82 L/h (95% confidence interval 3.283-4.357 L/h) with a relative standard error of 7.2%. Both total body weight (TBW) and trimester of pregnancy were significantly associated with LEV-CL/F during pregnancy; LEV-CL/F increased by 42.72% when TBW increased from 55 to 65 kg from the first trimester to the second trimester. Monte Carlo simulations showed that dosing regimens for LEV should be individualized based on the patient's TBW and trimester of pregnancy to maximize the likelihood of achieving the therapeutic range. CONCLUSION: This first population pharmacokinetic study of LEV in WWE during pregnancy supports the use of a weight-based and pregnancy-based dosing regimen and can lay a foundation for further optimizing the individualized dosing regimens.

Development of a competitive ELISA based on estrogen receptor and weak competitive molecule for the screening of potential estrogens in foods.

Enzyme labeled competitive molecules are generally homologous with competitors in competitive broad-spectrum enzyme-linked immunosorbent assays (ELISA). It is speculated that the detectability will be improved when the competitiveness of competitive molecule is weak. Herein, common small molecule food hazard-estrogen disrupting chemicals (EDCs) were used as target model for verification. The dual-estrogen receptor (ER) and three estrogen-enzyme conjugates with various responses were used as recognizers and competitive molecules in ELISA. ELISA based on bisphenol (BPA)-horseradish peroxidase (HRP) has the highest detectability and can screen all six EDCs, in which BPA-HRP showed the weakest ER excitatory activity (Ka = 1.39 × 10-2 nmol·L-1) among three conjugates. The proposal showed good practicability with spiked recovery of 80.0-110 % for estrogens (17ß-estradiol, 17α-estradiol, BPA) in foodstuffs, and revealed biomarkers with weak competitiveness may be applied to other competitive procedures to improve detectability, and it provides sensitive pre-screening strategy for follow-up screening tool.

Development of a photothermal-sensing microfluidic paper-based analytical chip (PT-Chip) for sensitive quantification of diethylstilbestrol.

The continuous intake of diethylstilbestrol (DES) residue seriously threatens the health of consumers, so the rapid and sensitive detection of DES is helpful for timely food safety warning. In this study, a photothermal-sensing microfluidic paper-based analytical chip (PT-Chip) was developed for effectively screening of DES residue in foods. Competitive inhibition immunochromatography was introduced and the composite of black phosphorus nanosheets and gold nanoparticles (BP-Au) was used as signal indicators. Then, the test area was irradiated by an 808 nm laser and the photothermal transduction signal was recorded by a thermal imager to achieve sensitive photothermal detection. The amount of DES was obtained by analyzing the temperature change curve of test area. The PT-Chip can achieve accurate quantification of DES with a detection limit of 0.1 µg/L. And the successful determination of DES in different food samples indicating that the PT-Chip can be used as a promising detection device.

The serum acylcarnitines profile in epileptic children treated with valproic acid and the protective roles of peroxisome proliferator-activated receptor a activation in valproic acid-induced liver injury.

Valproic acid (VPA) is widely used as a major drug in the treatment of epilepsy. Despite the undisputed pharmacological importance and effectiveness of VPA, its potential hepatotoxicity is still a major concern. Being a simple fatty acid, the hepatotoxicity induced by VPA has long been considered to be due primarily to its interference with fatty acid ß-oxidation (ß-FAO). The aim of this study was to investigate the biomarkers for VPA-induced abnormal liver function in epileptic children and to determine potential mechanisms of its liver injury. Targeted metabolomics analysis of acylcarnitines (ACs) was performed in children's serum. Metabolomic analysis revealed that VPA -induced abnormal liver function resulted in the accumulation of serum long-chain acylcarnitines (LCACs), and the reduced expression of ß-FAO relevant genes (Carnitine palmitoyltrans-ferase (CPT)1, CPT2 and Long-chain acyl-CoA dehydrogenase (LCAD)), indicating the disruption of ß-FAO. As direct peroxisome proliferator-activated receptor a (PPARα)- regulated genes, CPT1A, CPT2 and LCAD were up-regulated after treatment with PPARα agonist, fenofibrate (Feno), indicating the improvement of ß-FAO. Feno significantly ameliorated the accumulation of various lipids in the plasma of VPA-induced hepatotoxic mice by activating PPARα, significantly reduced the plasma ACs concentration, and attenuated VPA-induced hepatic steatosis. Enhanced oxidative stress and induced by VPA exposure were significantly recovered using Feno treatment. In conclusion, this study indicates VPA-induced ß-FAO disruption might lead to liver injury, and a significant Feno protective effect against VPA -induced hepatotoxicity through reversing fatty acid metabolism.

Tacrolimus Population Pharmacokinetic Model in Adult Chinese Patients with Nephrotic Syndrome and Dosing Regimen Identification Using Monte Carlo Simulations.

BACKGROUND: The study aimed to establish a population pharmacokinetic (PPK) model of tacrolimus for Chinese patients with nephrotic syndrome using the patient's genotype and Wuzhi capsule dosage as the main test factors. METHODS: Ninety-six adult patients with nephrotic syndrome, who were receiving tacrolimus treatment, were enrolled. A nonlinear mixed-effects model was used to determine the influencing factors of interindividual tacrolimus metabolism variation and establish a PPK model. To optimize the tacrolimus dosage, 10,000 Monte Carlo simulations were performed. RESULTS: The 1-chamber model of first-order absorption and elimination was the most suitable model for the data in this study. The typical population tacrolimus clearance (CL/F) value was 16.9 L/h. The percent relative standard error (RSE%) of CL/F was 12%. Increased Wuzhi capsule and albumin doses both decreased the tacrolimus CL/F. In CYP3A5 homozygous mutation carriers, the CL/F was 39% lower than that of carriers of the wild-type and heterozygous mutation. The tacrolimus CL/F in patients who were coadministered glucocorticoids was 1.23-fold higher than that of the control. According to the patient genotype and combined use of glucocorticoids, 26 combinations of Wuzhi capsule and tacrolimus doses were matched. The Monte Carlo simulation identified the most suitable combination scheme. CONCLUSIONS: An improved tacrolimus PPK model for patients with nephrotic syndrome was established, and the most suitable combination of Wuzhi capsule and tacrolimus doses was identified, thus, facilitating the selection of a more economical and safe administration regimen.

Deep learning joint models for extracting entities and relations in biomedical: a survey and comparison.

The rapid development of biomedicine has produced a large number of biomedical written materials. These unstructured text data create serious challenges for biomedical researchers to find information. Biomedical named entity recognition (BioNER) and biomedical relation extraction (BioRE) are the two most fundamental tasks of biomedical text mining. Accurately and efficiently identifying entities and extracting relations have become very important. Methods that perform two tasks separately are called pipeline models, and they have shortcomings such as insufficient interaction, low extraction quality and easy redundancy. To overcome the above shortcomings, many deep learning-based joint name entity recognition and relation extraction models have been proposed, and they have achieved advanced performance. This paper comprehensively summarize deep learning models for joint name entity recognition and relation extraction for biomedicine. The joint BioNER and BioRE models are discussed in the light of the challenges existing in the BioNER and BioRE tasks. Five joint BioNER and BioRE models and one pipeline model are selected for comparative experiments on four biomedical public datasets, and the experimental results are analyzed. Finally, we discuss the opportunities for future development of deep learning-based joint BioNER and BioRE models.

Microfluidic Paper-Based Analytical Devices for the Determination of Food Contaminants: Developments and Applications.

Food safety is an issue that cannot be ignored at any time because of the great impact of food contaminants on people's daily life, social production, and the economy. Because of the extensive demand for high-quality food, it is necessary to develop rapid, reliable, and efficient devices for food contaminant detection. Microfluidic paper-based analytical devices (µPADs) have been applied in a variety of detection fields owing to the advantages of low-cost, ease of handling, and portability. This review systematically discusses the latest progress of µPADs, including the fundamentals of fabrication as well as applications in the detection of chemical and biological hazards in foods, hoping to provide suitable screening strategies for contaminants in foods and accelerating the technology transformation of µPADs from the lab into the field.

Screening of Estrogenic-Disrupting Compounds in Dairy Products Based on the Estrogen Receptor Cocktail.

The residue of estrogenic-disrupting compounds (EDCs) that are secreted by cows, added as drugs, and present in the feed may exist in dairy products. A gold nanoparticles (AuNPs)-estrogen receptor (ER) cocktail colorimetric assay equipped with ER cocktail solid phase extraction (SPE) was established to screen EDCs. Nine EDCs with high, moderate, and low estrogenic activity were selected to be the representative targets. The recognition range of the colorimetric assay combined with the ER cocktail SPE was wider than that of a single ERα or ERß. The lowest detection limit of the established assay was about 10-9 mg·mL-1. The detection limits of estrone, bisphenol A, and bisphenol B were about one order of magnitude lower than the method based on a single ER. The recoveries of the spiked nine EDCs were between 80.0% and 110.0%, and daidzein was identified in the dairy product. The developed method has potential application prospects in food safety and environmental monitoring.

Photothermal card reader assay using the commercial colloidal gold test strip for the rapid quantitative detection of food hazards.

The simple and rapid commercial colloidal gold test strip can only be used for qualitative or semi-quantitative detection, accompanied by weak detectability and false negative experimental results. Herein, a photothermal test strip assay which combined test strip with a portable photothermal card reader was established to achieve quantitative detection with excellent detectability. According to the photothermal effect produced by gold nanoparticles (GNPs) captured on the test line, the signal could be recorded by the reader. Thirteen food hazards including veterinary drug residues and pesticide residues were tested; the photothermal detectability in actual samples were about 23 (methyl parathion), 7 (enrofloxacin), 6 (sarafloxacin), 8 (sulfadiazine), 12 (sulfamethazine), 7 (paraquat), 6 (malachite green), 11 (amantadine), 13 (nitrofurazone), 6 (diethylstilbestrol), 12 (estriol), 21 (estrone), and 26 (17ß-estradiol) times better than the visual detectability. Our results demonstrated that the photothermal test strip assay could be used for sensitive, rapid, and quantitative detection of residues of food hazards.

Review on the Selection of Aptamers and Application in Paper-Based Sensors.

An aptamer is a synthetic oligonucleotide, referring to a single-stranded deoxyribonucleic acid or ribonucleic acid ligand produced by synthesis from outside the body using systematic evolution of ligands by exponential enrichment (SELEX) technology. Owing to their special screening process and adjustable tertiary structures, aptamers can bind to multiple targets (small molecules, proteins, and even whole cells) with high specificity and affinity. Moreover, due to their simple preparation and stable modification, they have been widely used to construct biosensors for target detection. The paper-based sensor is a product with a low price, short detection time, simple operation, and other superior characteristics, and is widely used as a rapid detection method. This review mainly focuses on the screening methods of aptamers, paper-based devices, and applicable sensing strategies. Furthermore, the design of the aptamer-based lateral flow assay (LFA), which underlies the most promising devices for commercialization, is emphasized. In addition, the development prospects and potential applications of paper-based biosensors using aptamers as recognition molecules are also discussed.

Dual-mode immunoassay for diethylstilbestrol based on peroxidase activity and photothermal effect of black phosphorus-gold nanoparticle nanohybrids.

Nanozyme-mediated 3,3',5,5'-tetramethylbenzidine (TMB) - H2O2 systems have spawned the establishment of multiple colorimetric sensing platforms that are effective but sometimes subject to low sensitivity. Taking temperature as the output signal, photothermal effects lead to new strategies for sensitive detection. In this paper, a colorimetric and photothermal dual-mode immunoassay for diethylstilbestrol (DES) was constructed. It is based on the oxidation reaction of TMB catalyzed by black phosphorus-gold nanoparticle (BP/Au) nanohybrids, and the kinetics as well as catalytic mechanism of the nanohybrids were investigated in detail for the first time. Herein, the nanohybrids playcatalytic and photothermal dual roles. Moreover, the one-electron oxidation product of TMB (oxidized TMB) not only acts as chromogenic agent but also an excellent NIR laser-driven photothermal agent. The temperature (ΔT/°C) was gauged by a portable digital thermometer. Through an indirect competition strategy, a simple, sensitive, and economic immunosensor was proposed. Higher DES content in the sample correlated with less BP/Au nanohybrids conjugated to the surface of ELISA microplate, a weaker color change, and a lower temperature variation when exposed to laser irradiation. This method was applied for DES determination in real samples with gratifying recovery rates, showing great promise in food safety inspection applications.

Overview of Rapid Detection Methods for Salmonella in Foods: Progress and Challenges.

Salmonella contamination in food production and processing is a serious threat to consumer health. More and more rapid detection methods have been proposed to compensate for the inefficiency of traditional bacterial cultures to suppress the high prevalence of Salmonella more efficiently. The contamination of Salmonella in foods can be identified by recognition elements and screened using rapid detection methods with different measurable signals (optical, electrical, etc.). Therefore, the different signal transduction mechanisms and Salmonella recognition elements are the key of the sensitivity, accuracy and specificity for the rapid detection methods. In this review, the bioreceptors for Salmonella were firstly summarized and described, then the current promising Salmonella rapid detection methods in foodstuffs with different signal transduction were objectively summarized and evaluated. Moreover, the challenges faced by these methods in practical monitoring and the development prospect were also emphasized to shed light on a new perspective for the Salmonella rapid detection methods applications.

Redefining the age-specific therapeutic ranges of lamotrigine for patients with epilepsy: A step towards optimizing treatment and increasing cost-effectiveness.

OBJECTIVE: The pharmacokinetics of lamotrigine exhibits age-related characteristics. Nevertheless, current evidence regarding the therapeutic range of lamotrigine has been derived almost exclusively from studies in adult patients, and the applicability of this therapeutic range to the pediatric population remains unclear. The purpose of this study was to establish the appropriate age-specific therapeutic ranges of lamotrigine corresponding to adequate clinical responses for patients with epilepsy. METHODS: This prospective cohort study of therapeutic drug monitoring included 582 Chinese epilepsy patients receiving lamotrigine monotherapy. Patients were divided into three age-related subgroups: (1) toddler and school-age group (2-12 years old, n = 168), (2) adolescent group (12-18 years old, n = 171), and (3) adult group (>18 years old, n = 243). Patients with a reduction in seizure frequency of 50 % or greater than baseline were defined as responders, and the remaining patients were non-responders. The relationship between lamotrigine serum concentrations and clinical response was assessed using multivariate logistic regression analysis. A receiver operating characteristic curve was generated to determine the representative cut-off values of lamotrigine trough levels, to distinguish responders from non-responders. The upper margin of the therapeutic range of lamotrigine was determined by developing concentration-effect curves for the three age-related subgroups. RESULTS: The median trough levels of lamotrigine were significantly higher in responders than in non-responders from all three age-related groups (P < 0.0001). Results of logistic regression analysis revealed that higher serum concentrations of lamotrigine predicted a higher probability that seizure frequency would be reduced by more than 50 % compared to baseline (adjusted odds ratio: 1.228, 95 % CI: 1.137-1.327; P < 0.0001), and younger children were less likely to be responders (adjusted odds ratio: 1.027, 95 % CI: 1.012-1.043; P = 0.001). Based on a trade-off between sensitivity and specificity, the optimal cut-off values for lamotrigine trough concentrations corresponding to clinical response were 3.29 mg/L, 2.06 mg/L, and 1.61 mg/L in the toddler and school-age group, adolescent group, and adult group, respectively. By reducing interpatient variability, the results of the concentration-effect curves suggested no additional clinical benefit from a continued increase of doses for lamotrigine concentrations exceeding 9.08 mg/L, 8.43 mg/L, and 10.38 mg/L in the toddler and school-age group, adolescent group, and adult group, respectively. In conclusion, the therapeutic ranges of lamotrigine trough concentrations corresponding to adequate clinical response were 3.29-9.08 mg/L in the toddler and school-age group, 2.06-8.43 mg/L in the adolescent group, and 1.61-10.38 mg/L in the adult group. CONCLUSIONS: The study determined age-specific therapeutic ranges corresponding to optimal clinical efficacy for lamotrigine. Our findings lay the foundation for catalyzing novel opportunities to optimize treatment and reduce therapeutic costs. Based on the age-specific therapeutic ranges identified in this study, individualized and cost-effective algorithms for lamotrigine treatment of epilepsy patients may be developed and validated in larger cohort studies of therapeutic drug monitoring.