A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

Inteins are unique protein insertion sequences capable of self-excision, enabling the covalent ligation of flanking extein peptides via amide bond formation. This process proceeds spontaneously without requiring external enzymes, cofactors, or chemical reagents, granting inteins exceptional biocompatibility and traceless performance in protein engineering applications. Split inteins represent a specialized and versatile subclass whose splicing domains are encoded by two separate gene fragments rather than a single continuous open reading frame. These fragments, known as the N-terminal (IntN) and C-terminal (IntC) split inteins, associate through non-covalent interactions including hydrophobic forces, hydrogen bonds, and van der Waals forces to assemble into an active three-dimensional structure, which then drives efficient extein ligation and enables protein trans-splicing. Protein trans-splicing mediated by split inteins has become a cornerstone for traceless protein ligation owing to its high specificity and irreversibility, fundamentally reshaping strategies for protein modification, assembly, and functional regulation. Compared with traditional chemical ligation methods, split intein systems require no complex chemical derivatization of peptide fragments and can operate efficiently at micromolar concentrations under physiological conditions, thus avoiding structural and functional damage caused by organic reagents. In contrast to enzymatic ligation tools such as sortase, split inteins eliminate the need for additional enzymes or cofactors, simplifying reaction systems, reducing costs, and minimizing non-specific side products. These distinctive advantages render split inteins highly promising for applications in chemical biology, synthetic biology, and biopharmaceutical development. In recent years, deepened mechanistic understanding has established structure-guided rational design as the primary approach to overcoming key limitations of split inteins, including intrinsic aggregation propensity, strict extein sequence dependence, and limited splicing efficiency. Bioinformatic tools have been used to identify aggregation-prone regions in the IntN fragment, and site-directed mutagenesis of hydrophobic residues, relocation of split sites, or removal of misfolding-prone sequences has substantially reduced in vitro aggregation and improved soluble expression and assembly activity. Rational engineering of catalytic residues and adjacent flexible loops has relaxed strict amino acid preferences at extein junctions, enhancing sequence tolerance and reducing the risk of functional impairment in target proteins. Consensus design based on multiple sequence alignments has yielded ultra-fast splicing variants such as Cfa DnaE and Cat-TerL, which exhibit significantly accelerated kinetics and improved tolerance to denaturing conditions. Meanwhile, advances in structural biology have further clarified the conformational dynamics and catalytic mechanisms of splicing, supporting the precise design of high-performance intein modules. On this basis, electrostatic interaction tuning and metagenomic screening have yielded multiple mutually orthogonal split intein pairs, enabling selective multi-fragment protein ligation and providing new routes for the efficient synthesis of large multi-domain functional proteins. With these engineered split inteins offering continuously improved performance and expanded applicability, protein trans-splicing has been widely applied in numerous cutting-edge areas of protein research and biomedicine. In gene delivery, split intein-based systems overcome the packaging limit of adeno-associated viral vectors, enabling the accurate reconstitution of large therapeutic proteins and base editors in target cells, thereby enhancing the efficacy and scope of gene therapy for genetic diseases. In internal protein sequence editing, split inteins mediate precise sequence replacement and modification in flexible regions or loops of target proteins, without the need for complex multi-step ligation and protein refolding involved in traditional protein semisynthesis. In protein-protein interaction studies, intein-mediated splicing covalently captures transient and weak intracellular complexes, enabling sensitive, high-throughput interaction detection and drug screening. In synthetic biology, conditionally controllable splicing systems support the construction of diverse intracellular and cell-surface biological logic gates for the precise regulation of cellular behavior. In mechanistic biochemical research, split inteins enable photocatalytic proximity labeling and site-specific tagging, allowing the preparation of homogeneous protein samples carrying precise post-translational modifications such as ubiquitination and polyglutamylation for chromatin interactome analysis and epigenetic studies. Moreover, covalent trapping strategies using split inteins stabilize transient enzymatic intermediates, providing unprecedented insights into molecular mechanisms such as nucleosome ubiquitination that are difficult to elucidate using conventional methods. This review systematically summarizes key technological advances in split inteins over the past decade, highlighting engineering strategies, mechanistic insights, and the development of orthogonal components. It comprehensively surveys emerging applications at the frontiers of protein research, analyzes current core challenges, and proposes future directions, particularly emphasizing artificial intelligence-driven de novo design and novel splicing pathways to break existing technical bottlenecks. By enabling traceless, efficient, and versatile protein manipulation, split inteins continue to serve as indispensable tools that drive innovation in protein engineering and fundamental life science research.

The surgical management of empyema (excluding those caused by mycobacterium tuberculosis and non-tuberculous mycobacteria) is rapidly evolving towards minimally invasive, precise, and stepwise approaches. The traditional three-stage classification (exudative, fibrinopurulent, and organizing) has limitations in guiding dynamic clinical decision-making. For the first time, this consensus explicitly identifies two critical junctures in the pathological progression of empyema: "early transformation" (stage Ⅰ to Ⅱ) and "late transformation" (stage Ⅱ to Ⅲ), and thereby constructs a corresponding "identification-early warning-intervention" stepwise therapeutic framework. The consensus emphasizes that proactive debridement via video-assisted thoracoscopic surgery should be performed during the early transformation phase to halt disease progression. Conversely, during the late transformation phase, therapeutic goals should be rationally adjusted to prioritize adequate drainage, avoiding futile pleural decortication. Moreover, the consensus underscores the pivotal role of precise perioperative etiological diagnosis (e.g. metagenomic nest-generation sequencing) and standardized anti-infective therapy. Integrating practical experiences from multiple thoracic surgery centers in China and relevant evidence-based literature, this consensus formulates recommendations on the precise definitions of staging, surgical indications for each phase, key technical points, perioperative management, and training systems. It aims to promote the standardized and individualized surgical management of empyema, ultimately optimizing patient prognosis.

Introduction: Current education on diabetes self-management is time-consuming as it is conducted face-to-face. This study aimed to evaluate the effectiveness of diabetes education via mobile application on hemoglobin A1c (HbA1c). Methodology: This was a double-blinded randomized controlled study conducted in the Department of Endocrinology, Hospital Pulau Pinang and Hospital Raja Permaisuri Bainun. Participants were stratified randomized according to HbA1c to intervention group (using T-Manis) and control group. The primary objective was to assess the difference in HbA1c between the groups. Secondary objectives were to assess the difference in body weight, hospitalization related to diabetes, diabetes knowledge between groups and usability and satisfaction of T-Manis. Laboratory investigations and questionnaires were conducted at baseline, 4 months and 8 months. Results: A total of 112 participants were randomized into two groups each with 56 participants. Mean age was 51 years with similar diabetes duration of 16 years in both groups. Participants comprised of 61.6% females with ethnic distribution of 49.1% Malay, 30.4% Chinese, 19.6% Indian and 0.9% Siamese. Baseline HbA1c levels were comparable between intervention and control groups (10.04% versus 9.91%; mean difference 0.13%; 95% CI −0.56 to 0.81; p = 0.718). At 4 months, HbA1c of the intervention group demonstrated a significant reduction compared to the control group (8.93% versus 9.80%; mean difference −0.86; 95% CI −1.59 to −0.14; p = 0.02). Sustained reduction of HbA1c in the intervention group was observed at 8 months (mean difference −1.01; 95% CI −1.85 to −0.16; p = 0.02). Baseline body weight was 77 kg, with no betweengroup differences in body weight, hospitalization related to diabetes and diabetes knowledge scores, although diabetes knowledge scores improved at 4 months in the intervention group. 89.3% of participants reported satisfaction with T-Manis Conclusion The T-Manis mobile application aided in significantly improving glycemic control with high user satisfaction, supporting its feasibility as an adjunct to standard diabetes care.
Diabetes Mellitus, Type 2 ; Glycemic Control ; Mobile Applications ; Pangolins

ObjectiveTo observe the effect and therapeutic effect of Kaixuan Jiedu core prescription （KXJD） on skin homing of Th17 cells in the mouse model of imiquimod （IMQ） combined with restraint stress-induced psoriasis-like skin damage， and to explore its potential mechanism from the perspective of neuro-immune axis. MethodsThirty male C57BL/6J mice were randomly allocated into five groups （n=6）： Control， model （IMQ）， restraint stress model （IMQ+RS）， KXJD， and methotrexate （MTX）. The mouse model of psoriasis-like skin damage was established by 5% IMQ combined with restraint stress. At the same time of modeling， each treatment group was treated with corresponding doses of drugs， and the control， IMQ， and IMQ+RS groups were treated with the same amount of normal saline by gavage once a day for 5 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the skin tissue and Baker scoring was performed. Serum levels of interleukin-1β （IL-1β） and angiopoietin-2 （Ang-2） were measured by enzyme-linked immunosorbent assay （ELISA）. The levels of matrix metalloproteinase-9 （MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， C-C motif chemokine ligand 20 （CCL20）， and C-C motif chemokine receptor 6 （CCR6） in the skin tissue were determined. Immunohistochemistry （IHC） was employed to determine the protein expression of cutaneous lymphocyte-associated antigen （CLA）， integrin α_E （CD103）， cytokeratin 10 （CK10）， and nuclear factor-kappa B （NF-κB） in the skin. Immunofluorescence double staining （DIF） was adopted to detect the expression and co-localization of vascular endothelial cadherin （VE-cadherin） and platelet-endothelial cell adhesion molecule （CD31）， CCR6， CD103， substance P （SP）， calcitonin gene-related peptide （CGRP）， and protein gene product 9.5 （PGP9.5） in the skin tissue. Real-time PCR was employed to quantify the mRNA levels of IL-10， IL-17A， and IL-23. ResultsCompared with the control group， the IMQ group and IMQ+RS group showed significant inflammatory cell infiltration， abnormal proliferation of epidermal cells， keratinization and other pathological changes in the skin tissue， and a significant increase in Baker score， elevated levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in the skin lesions， upregulated expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA， and IL-23 mRNA in the skin lesions， and downregulated expression of TIMP-1 and IL-10 mRNA. In addition， the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， SP and PGP9.5 co-localization， and CGRP and PGP9.5 co-localization were increased （P<0.05）. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ+RS group， KXJD and MTX significantly alleviated the pathological damage of skin lesions， significantly decreased the Baker score， lowered the levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in skin lesions， downregulated the expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA and IL-23 mRNA in skin lesions， and upregulated the expression of TIMP-1 and IL-10 mRNA. Furthermore， KXJD and MTX reduced the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， CGRP and PGP9.5 co-localization， and SP and PGP9.5 co-localization （P<0.05）. ConclusionKXJD can significantly ameliorate the psoriasis-like skin damage induced by IMQ combined with restraint stress in mice by regulating the neural-immune axis and inhibiting the skin homing of Th17 cells.

This narrative review examines the challenges, strategies, and future directions in the development of young teachers within the pathophysiology departments of Chinese medical colleges. A thorough review of 49 studies published between 2013 and 2024 was carried out using PubMed, Web of Science, and various Chinese databases. The primary challenges identified include teaching innovation (cited in 84.2% of the studies), research pressure (91.2%), disciplinary characteristics (87.7%), and career development (80.7%). Medical schools have responded by enhancing training systems (94.7%), innovating teaching methods (93.0%), and bolstering research support (96.5%). Looking ahead, trends are shifting toward the application of new technologies, interdisciplinary integration, and international collaboration. The focus on cultivating young teachers is increasingly geared towards personalization and diversification, which are essential for advancing education in pathophysiology. High-quality young teachers are pivotal in raising teaching standards, fostering research innovation, and facilitating interdisciplinary exchanges. Based on these insights, we recommend several practical measures to enhance the quality of pathophysiology education in China. These include establishing comprehensive training programs that integrate teaching innovation and research skills; developing structured mentorship systems with clear pathways for career advancement; creating platforms that support technology-enhanced teaching and international collaboration; and implementing systematic evaluation mechanisms to assess teaching effectiveness. These targeted interventions will require a coordinated effort from department heads, educational institutions, and policymakers to ensure a sustained improvement in the quality of pathophysiology education.

This narrative review examines the challenges, strategies, and future directions in the development of young teachers within the pathophysiology departments of Chinese medical colleges. A thorough review of 49 studies published between 2013 and 2024 was carried out using PubMed, Web of Science, and various Chinese databases. The primary challenges identified include teaching innovation (cited in 84.2% of the studies), research pressure (91.2%), disciplinary characteristics (87.7%), and career development (80.7%). Medical schools have responded by enhancing training systems (94.7%), innovating teaching methods (93.0%), and bolstering research support (96.5%). Looking ahead, trends are shifting toward the application of new technologies, interdisciplinary integration, and international collaboration. The focus on cultivating young teachers is increasingly geared towards personalization and diversification, which are essential for advancing education in pathophysiology. High-quality young teachers are pivotal in raising teaching standards, fostering research innovation, and facilitating interdisciplinary exchanges. Based on these insights, we recommend several practical measures to enhance the quality of pathophysiology education in China. These include establishing comprehensive training programs that integrate teaching innovation and research skills; developing structured mentorship systems with clear pathways for career advancement; creating platforms that support technology-enhanced teaching and international collaboration; and implementing systematic evaluation mechanisms to assess teaching effectiveness. These targeted interventions will require a coordinated effort from department heads, educational institutions, and policymakers to ensure a sustained improvement in the quality of pathophysiology education.

This narrative review examines the challenges, strategies, and future directions in the development of young teachers within the pathophysiology departments of Chinese medical colleges. A thorough review of 49 studies published between 2013 and 2024 was carried out using PubMed, Web of Science, and various Chinese databases. The primary challenges identified include teaching innovation (cited in 84.2% of the studies), research pressure (91.2%), disciplinary characteristics (87.7%), and career development (80.7%). Medical schools have responded by enhancing training systems (94.7%), innovating teaching methods (93.0%), and bolstering research support (96.5%). Looking ahead, trends are shifting toward the application of new technologies, interdisciplinary integration, and international collaboration. The focus on cultivating young teachers is increasingly geared towards personalization and diversification, which are essential for advancing education in pathophysiology. High-quality young teachers are pivotal in raising teaching standards, fostering research innovation, and facilitating interdisciplinary exchanges. Based on these insights, we recommend several practical measures to enhance the quality of pathophysiology education in China. These include establishing comprehensive training programs that integrate teaching innovation and research skills; developing structured mentorship systems with clear pathways for career advancement; creating platforms that support technology-enhanced teaching and international collaboration; and implementing systematic evaluation mechanisms to assess teaching effectiveness. These targeted interventions will require a coordinated effort from department heads, educational institutions, and policymakers to ensure a sustained improvement in the quality of pathophysiology education.

Metal-organic frameworks(MOFs)are porous materials composed of metal ions or metal clusters and organic ligands by coordination,which have the advantages of large specific surface area,good thermal stability and adjustable pore size,and have a promising application in gas chromatographic separation.In recent years,MOFs materials have been used as stationary phases for gas chromatography mainly including ZIF,MIL,UiO-66,HKUST-1,IRMOFs,etc.Based on the molecular sieve effect,van der Waals forces,hydrogen bonding and π-π interactions,the pore size,pore microenvironment,unsaturated metal site and special functional group of the MOFs stationary phase materials can be specifically designed and regulated.MOFs materials as stationary phases have unique separation performance for n-alkanes and their isomers,aromatic compounds and their isomers,alcohols/ketones/aldehydes and their isomers,and chiral compounds.The combination of organic polymers and novel nanomaterials with MOFs materials can improve the separation performance and stability of MOFs.Therefore,MOFs materials are expected to be the promising stationary phase that can be applied to gas separation in complex environments.In this article,the research advances of various stationary phases based on MOFs for gas chromatography in recent years were reviewed.The separation performance and separation mechanism of MOFs stationary phases for mixed gas samples were discussed,and the development trends in the future were prospected.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.