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.

Objective:To develop and assess a three-class machine learning model for predicting wild-type, 19 del, and 21 L858R mutations of the epidermal growth factor receptor (EGFR) in lung adenocarcinoma using 18F-FDG PET/CT radiomic features and clinical features. Methods:The retrospective data was collected from 703 patients (346 males, 357 females; age (64.3±9.0) years) with lung adenocarcinoma at the First People′s Hospital of Changzhou from January 2018 to June 2023. Patients were divided into the training set (563 cases) and test set (140 cases) at the ratio of 8∶2. Clinical features were selected using recursive feature elimination (RFE). Radiomic features were extracted from PET and CT images, and the optimal feature sets were selected using minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) methods. Base models were constructed by using random forest (RF), logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), and multi-layer perceptron (MLP), and the stacking method was applied to establish the CT and PET ensemble models. Delong test was used to compare the AUC differences between the PET/CT combined model and the clinical + PET/CT integrated model.Results:Among 703 patients, 273 were with EGFR wild-type, 202 were with 19 del mutation, and 228 were with 21 L858R mutation. In the single-modal analysis, the AUCs of CT ensemble model in the training and test sets were 0.893 and 0.667, respectively, while the AUCs of PET ensemble model were 0.692 and 0.660. The AUC of PET/CT combined model were 0.897 in training set and 0.672 in test set. The AUC of clinical + PET/CT integrated model showed further improvement, with AUCs of 0.902 and 0.721 in training and test sets, respectively. Notably, the clinical + PET/CT integrated model outperformed PET/CT combined model in predicting wild-type EGFR (test set AUC: 0.784 vs 0.707; Z=3.28, P=0.001). Conclusion:The three-class model (clinical + PET/CT integrated model) based on 18F-FDG PET/CT radiomics and clinical features effectively predicts EGFR mutation subtypes in lung adenocarcinoma.

With the rapid development of generative adversarial networks (GAN), learning the mapping between CT and PET images enables cross-modality generation. This not only integrates anatomical and functional information to improve image quality, but also helps reduce the radiation exposure to some extent. Based on a review of representative GAN architectures such as conditional GAN and CycleGAN, this paper discusses their research progress and limitations in various application scenarios, including initial tumor diagnosis and staging, treatment evaluation and follow-up, as well as methods for reducing PET/CT radiation dose. Additionally, challenges related to small-sample learning, model interpretability, and cross-institutional standardization are highlighted, and the clinical application prospects of GAN-based cross-modality generation technology are explored.

Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

OBJECTIVE: To observe the effects of enhanced rehabilitation on the prognosis of critically ill patients in the intensive care unit (ICU). METHODS: A single-center retrospective historical controlled study was conducted, patients admitted to the ICU of Peking University First Hospital from May 1, 2020, to April 30, 2021, and from October 1, 2021, to September 30, 2022 were enrolled. According to the different rehabilitation treatment strategies during different periods, patients were divided into the conventional rehabilitation group (patients receiving conventional rehabilitation treatment from May 1, 2020, to April 30, 2021) and the enhanced rehabilitation group (patients receiving the therapy of multidisciplinary team, ie medical care-rehabilitation-nursing care from October 1, 2021, to September 30, 2022). General data, acute physiology and chronic health evaluation II (APACHE II), and study endpoints were collected. Primary endpoints included rehabilitation-therapy rate, intervention time for rehabilitation, rehabilitation-related adverse events, and prognostic indicators such as (length of stay in hospital, length of stay in the ICU, and duration of mechanical ventilation). Secondary endpoints included incidence of deep vein thrombosis and hospital mortality. Kaplan-Meier curves were used to analyze cumulative discharge rates within 50 days. RESULTS: A total of 539 ICU patients were enrolled, with 245 in the conventional rehabilitation group and 294 in the enhanced rehabilitation group; 322 patients had an APACHE II score ≤ 15, while 217 patients had an APACHE II score > 15. Compared to the conventional rehabilitation group, the enhanced rehabilitation group demonstrated significantly higher rehabilitation-therapy rate [51.70% (152/294) vs. 11.43% (28/245)], earlier intervention time for rehabilitation [days: 2.00 (1.00, 3.00) vs. 4.00 (3.00, 7.00)]; shorter length of stay in hospital [days: 18.00 (12.00, 30.00) vs. 21.00 (13.00, 36.00)] and lower incidence of DVT [17.01% (50/294) vs. 24.08% (59/245)]. The differences were all statistically significant (all P < 0.05). There were no rehabilitation-related adverse events occurred in either group. Kaplan-Meier analysis demonstrated a significantly higher cumulative discharge rate within 50 days in the enhanced rehabilitation group compared to the conventional rehabilitation group [86.7% (255/294) vs. 82.9% (203/245); Log-Rank test: χ² = 4.262, P = 0.039]. Subgroup analysis showed that for patients with APACHE II score ≤ 15, the enhanced rehabilitation subgroup had higher rehabilitation-therapy rate [44.32% (78/176) vs. 6.16% (9/146), P < 0.05]. For patients with APACHE II score > 15, compared to the conventional rehabilitation group, the enhanced subgroup demonstrated higher rehabilitation-therapy rate [62.71% (74/118) vs. 19.19% (19/99), P < 0.05] and shorter length of stay in hospital [days: 20.50 (12.00, 31.25) vs. 26.00 (16.00, 43.00), P < 0.05]. CONCLUSIONS Enhanced rehabilitation therapy with medical care, rehabilitation and nursing care, improved rehabilitation-therapy rate, advanced time of rehabilitation treatment, reduced length of stay in hospital and incidence of deep vein thrombosis in critically ill patients, particularly benefited those with APACHE II score > 15. The enhanced rehabilitation was beneficial to the patient in the intensive care unit with safety and worth more investigation.
Humans ; Retrospective Studies ; Critical Illness/rehabilitation* ; Intensive Care Units ; Prognosis ; Length of Stay ; APACHE ; Historically Controlled Study ; Male ; Female ; Middle Aged ; Aged

Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences.An effective way to obtain a single enantiomer is through racemates resolution.Recent literature shows that chiral metal-organic frameworks(CMOFs)have many applications in various fields because of their diverse topologies and functionalities.This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs.It highlights key advances and issues in the separation domain.In conclusion,the review provides perspectives on the challenges and prospective advance-ments of CMOFs materials and CMOFs-based separation technologies.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Sepsis is a life-threatening acute organ dysfunction syndrome caused by a dys-regulated host response to infection.As a regenerative medicine therapy with broad clinical prospects,stem cells have attracted significant at-tention due to their multifaceted biological capabilities,including anti-inflammatory,antioxidant,and anti-apoptotic effects,as well as immunomodulatory properties and tissue/organ repair potential.Mesenchymal stem cells(MSCs)function through mechanisms such as modulating macrophage polarization and suppressing excessive inflammation responses,thereby promoting tissue regeneration.Pre-clinical studies demonstrate that MSCs significantly reduce sepsis mortality and decrease sepsis-associated complications including acute kidney injury(AKI),acute respiratory distress syndrome(ARDS)and sepsis associated myopathy.Furthermore,perinatal-derived stem cells and genetically modified stem cells have shown therapeutic promise in sepsis management.Current challenges in stem cell-based sepsis therapy cover optimizing delivery strategies,standardizing cell preparation protocols and de-veloping biomarker-guided personalized therapeutic regimens.

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.