Background Toluene and chlorobenzene have been designated as surrogate contaminants in the challenge test for evaluating the safety of recycling processes for food-contact recycled polyethylene terephthalate (rPET). Establishing a reliable analytical method is essential for ensuring the compliant use of rPET and safeguarding food safety. Objective To develop a rapid quantitative method for determining toluene and chlorobenzene in rPET using headspace gas chromatography-mass spectrometry (HS-GC-MS), as part of the challenge test for process safety evaluation. Methods The effects of different chromatographic columns and headspace conditions on detection of target analytes were investigated. Three columns HP-5 ms UI (30 m×0.25 mm×0.25 μm), DB-624 (30 m×0.32 mm×1.8 μm), and VF-WAXms (30 m×0.25 mm×0.25 μm) were compared for separation efficiency and peak shape. Headspace equilibration temperatures (50-100 ℃) and equilibration times (10-30 min) were evaluated to determine the optimal instrumental parameters. The effect of sample grinding on recovery was assessed to select the best pretreatment conditions. The established method was validated for selectivity, linearity, sensitivity, accuracy, and precision, and was subsequently applied to the analysis of 12 rPET samples. Results The target analytes achieved good separation and response within 15 min, under the optimized conditions using an HP-5 ms UI column, a headspace equilibration temperature of 60 ℃ and a 10 min equilibration time. Direct analysis without grinding yielded satisfactory recovery rates. Toluene and chlorobenzene showed excellent linearity (0.0030-5.0 mg·kg⁻¹, R²≥0.999). The limits of detection (LOD) and quantification (LOQ) were 0.00003 mg·kg⁻¹ and 0.00011 mg·kg⁻¹ for toluene respectively, and 0.00011 mg·kg⁻¹ and 0.00037 mg·kg⁻¹ for chlorobenzene respectively. The recoveries of the matrix spike at low and high spiking levels ranged from 88.6% to 110%, with relative standard deviations of 0.52%-4.9% (n=6). Among the 12 rPET samples from different recycling stages, three samples contained detectable levels of toluene (0.196-0.250 mg·kg⁻¹) and chlorobenzene (0.704-0.867 mg·kg⁻¹). Conclusion The proposed method is simple, rapid, highly sensitive, and accurate, making it suitable for determining toluene and chlorobenzene in food-contact rPET. It provides a robust technical approach for the safety evaluation of rPET recycling processes.

Implementation science (IS) aims to systematically analyze and address the real-world gaps from evidence to practice and the influencing factors of the context. It is necessary to carry out qualitative research to gather relevant implementation outcomes. Nevertheless, traditional qualitative analysis has issues such as consuming a great deal of time and energy, and it is unable to promptly provide the crucial data required for implementation science research. The Rapid Qualitative Analysis (RQA) method, through semi-structured interviews and the adoption of techniques such as immediate data condensation and matrix analysis, can effectively shorten the cycle of qualitative data collection and data processing. RQA can promptly identify social determinants of health such as structural barriers, facilitators, and the behavioral characteristics of target groups. It provides a real-time basis for public health decision-making, the interpretation of complex social phenomena, and the process and effectiveness evaluation of research projects. Although RQA is difficult to conduct in-depth theoretical analysis based on grounded theory, its efficiency and flexibility make it the preferred tool for large-scale and time-sensitive research. Thus, it has been widely applied in implementation science research. This paper sorts out the core concepts and commonly used technical methods of RQA, as well as the differences between RQA and traditional qualitative analysis. It also explores the applications of RQA in intervention optimization, process evaluation, and implementation outcome evaluation. By integrating specific cases, this paper clarifies its application value in the field of implementation science. In the future, it is advisable to explore the integration of RQA with technologies such as artificial intelligence and big data, in order to bridge the gap between the transformation of scientific research achievements into practice. Under circumstances of limited resources or tight time constraints, RQA can be used to efficiently conduct implementation science research, providing convenient and scientific methodological and technical support for accelerating evidence-based practice.

Organophosphate flame retardants (OPFRs) have been widely used as the main alternatives to bromine-based flame retardants, resulting in their widespread detection in environmental media and even in human blood. The potential health risks arising therefrom, particularly the direct impacts on the blood system, have become a focus in the field of environmental health. This article systematically reviewed the latest research progress on the hematotoxicity of OPFRs, covering three core aspects: the toxic effects aspect, which systematically elaborated on the bidirectional interference of OPFRs with coagulation function, their toxic effects on the hematopoietic system, and their disruptive effects on blood biochemical metabolism; the mechanistic analysis aspect, which dissected the multi-pathway, multi-target toxic mechanism network of OPFRs, including common pathways based on oxidative stress and inflammatory responses, the direct and indirect regulation of coagulation function mediated by nuclear receptors and endocrine disruption, and the disturbance of blood cell production at the source through disruption of the hematopoietic microenvironment; and the risk assessment aspect, which, in response to the limitations of traditional methods, focused on the application prospects and core advantages of novel approaches based on structure-activity relationships in filling data gaps and achieving precise risk prediction. This review aims to systematically summarize the research progress on the mechanisms of OPFR-induced hematotoxicity, providing systematic theoretical support for subsequent in-depth mechanistic studies, targeted epidemiological investigations, and the optimization of risk assessment models.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

Traditional Chinese medicine （TCM） clinical trials face challenges such as low participant compliance， insufficient geographical coverage， and cost-effectiveness imbalances. Decentralized clinical trials （DCT）， enabled by digital technology for remote data collection and monitoring， offer a new direction for TCM clinical trial research. This article systematically reviews three novel clinical trial design models. Combining the holistic concept and indivi-dualized treatment characteristics of TCM， it analyzes the challenges currently faced in TCM DCT practice， including the digitization and standardization of TCM theory， data security， privacy protection and patient engagement difficu-lties， insufficient ethical review and regulatory system adaptation， inadequate personnel training， and a shortage of interdisciplinary talent. Addressing these challenges， the article proposes methodological recommendations for DCT implementation that align with the principles of TCM diagnosis and treatment. These recommendations include promoting the intelligentization and standardization of TCM practices， constructing a full-chain data security and privacy protection system， improving the ethical framework and clarifying regulatory responsibilities， and cultivating and building interdisciplinary talent and capabilities， which provide theoretical and technical references for establishing standardized DCT practices in TCM.

This paper summarizes professor LI Guolie's clinical experience in treating orthostatic hypotension （OH） based on the theory of "raising the clear and directing the turbid downward". It is considered that the core pathogenesis of OH lies in the body's transition from a supine to an upright position， during which dysfunction of the middle jiao （焦） transformation and transportation， along with impaired pivot function， hinders the ascending of clear yang and the descending of turbid yin. Treatment should follow the general principle of "ascending the clear and directing the turbid downward"， placing emphasis on distinguishing the primary and secondary aspects. For cases where the clear yang fails to ascend， the self-formulated Li's Shengqing Jiangzhuo Decoction （李氏升清降浊汤）is used to supplement qi， raise the clear， and strengthen the middle jiao. For cases where the turbid yin fails to descend， the self-formulated Wuxiang Qingzhuo Beverage（五香清浊饮）with modifications is applied to resolve phlegm， eliminate stasis， harmonize the middle， and descend the turbid.

Traditional Chinese medicine （TCM） clinical trials face challenges such as low participant compliance， insufficient geographical coverage， and cost-effectiveness imbalances. Decentralized clinical trials （DCT）， enabled by digital technology for remote data collection and monitoring， offer a new direction for TCM clinical trial research. This article systematically reviews three novel clinical trial design models. Combining the holistic concept and indivi-dualized treatment characteristics of TCM， it analyzes the challenges currently faced in TCM DCT practice， including the digitization and standardization of TCM theory， data security， privacy protection and patient engagement difficu-lties， insufficient ethical review and regulatory system adaptation， inadequate personnel training， and a shortage of interdisciplinary talent. Addressing these challenges， the article proposes methodological recommendations for DCT implementation that align with the principles of TCM diagnosis and treatment. These recommendations include promoting the intelligentization and standardization of TCM practices， constructing a full-chain data security and privacy protection system， improving the ethical framework and clarifying regulatory responsibilities， and cultivating and building interdisciplinary talent and capabilities， which provide theoretical and technical references for establishing standardized DCT practices in TCM.

This paper summarizes professor LI Guolie's clinical experience in treating orthostatic hypotension （OH） based on the theory of "raising the clear and directing the turbid downward". It is considered that the core pathogenesis of OH lies in the body's transition from a supine to an upright position， during which dysfunction of the middle jiao （焦） transformation and transportation， along with impaired pivot function， hinders the ascending of clear yang and the descending of turbid yin. Treatment should follow the general principle of "ascending the clear and directing the turbid downward"， placing emphasis on distinguishing the primary and secondary aspects. For cases where the clear yang fails to ascend， the self-formulated Li's Shengqing Jiangzhuo Decoction （李氏升清降浊汤）is used to supplement qi， raise the clear， and strengthen the middle jiao. For cases where the turbid yin fails to descend， the self-formulated Wuxiang Qingzhuo Beverage（五香清浊饮）with modifications is applied to resolve phlegm， eliminate stasis， harmonize the middle， and descend the turbid.

Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.