Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.

Objective:To explore whether tryptophan metabolism is related to bone growth by comparing the differences in tryptophan metabolism after rotator cuff tear (RCT) repair between rats with normal bone remodeling capability and those with defective bone remodeling capability.Methods:Of the 50 adult female Sprague Dawley (SD) rats used for this study, 18 were randomly selected to undergo bilateral ovariectomy (OVX) (OVX group), and the remaining 32 underwent bilateral OVX sham surgery (sham surgery group). All rats were maintained in standard conditions. Three months after surgery, 4 rats were randomly selected from OVX group and the sham surgery group, respectively, for Micro CT identification of bone loss at the rat humeral head. The remaining rats in OVX group underwent RCT modeling and surgical repair of acute supraspinatus muscle transection (OVX+RCT group) ( n=14); the remaining rats in the sham surgery group were subjected to either surgical repair of acute supraspinatus muscle transection (RCT group, n=14) or RCT sham surgery (SO group, n=14). The grip power of the rats was tested 2 weeks after surgery. The supraspinatus tendon-bone complex was harvested for evaluation of new bone formation and growth through real-time fluorescence quantitative polymerase chain reaction (qPCR), hematoxylin eosin (HE) staining, and immunohistochemistry (IHC) staining. The tryptophan metabolism was analyzed using ultra high performance liquid chromatography (UPLC). Results:The grip power test showed that SO group had the greatest grip power, followed by RCT group and OVX+RCT group, with statistically significant differences between the 3 groups ( P<0.05). The qPCR showed that the relative expression of osteosclerosis in the tendon-bone complex in SO group was significantly higher than that in OVX+RCT group and RCT group; IHC staining showed that the relative expression of osteocalcin in RCT group was significantly higher than that in SO group and OVX+RCT group ( P<0.05). The UPLC showed that the content of tryptophan in the rotator cuff tendon-bone complex was similar among SO, RCT, and OVX+RCT groups, showing no significant difference ( P>0.05). The qPCR showed that the expression of indoleamine 2, 3-dioxygenase 2 in the Kynurenic acid metabolism pathway showed an increasing trend from SO group to RCT group to OVX+RCT group, with OVX+RCT group significantly higher than SO group ( P<0.05). The expression of 3-hydroxybenzoate 3, 4-dioxygenase in OVX+RCT group was significantly higher than that in RCT group and in SO group ( P<0.001). The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased from SO group to RCT group to OVX+RCT group. The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased among SO, RCT, and OVX+RCT groups( P<0.001). The expression of dopamine decarboxylase in the indole metabolism pathway in OVX+RCT group was significantly higher than that in SO group ( P<0.01). The expression of cytochrome P450 oxidoreductase increased from SO group to RCT group to OVX+RCT group ( P<0.001). Conclusions:The tryptophan metabolism in the supraspinatus tendon-bone complex after RCT in rats is mainly dominated by kynurenic acid metabolism, followed by 5-hydroxytryptamine metabolism. In RCT bone remodeling, the 5-hydroxytryptamine metabolic pathway changes the most, followed by the indole pathway. The contents of niacin and xanthurenic acid in the kynurenic acid metabolism pathway are related to bone growth; the 5-hydroxytryptamine, hydroxyindoleacetic acid, and melatonin in the 5-hydroxytryptophan metabolic pathway are related to bone growth; the tryptophan and indole lactate in the indole metabolism pathway are related to bone growth. Therefore, tryptophan metabolism is related to bone growth, providing potential therapeutic targets for RCT repair.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective:To comparative investigate the HPV16 virus-specific immune characteristics of HPV vaccinees, cervical precancerous lesions patients and cervical cancer patients.Methods:Six female HPV vaccinees, five patients with cervical precancerous lesions or cervical cancer and 8 healthy female volunteers from Beijing were recruited as subjects. Peripheral anticoagulated blood specimens were collected from these subjects and the peripheral blood mononuclear cells (PBMCs) and plasma were isolated. After culturing in vitro with the stimulation of L1 protein peptide pool derived from HPV16 for 9-10 days, the percentage of CD4 + and CD8 + -T lymphocytes secreting cytokines IFN-γ, IL-2 and TNF-α in the PBMCs were detected by flow cytometry. The level of HPV16 IgG antibody in plasma was determined by ELISA. Results:The IgG levels of vaccinees were significantly higher than those of healthy donors as well as patients with cervical precancerous lesions or cervical cancer. Moreover, the specific CD4 + T cell immune level of vaccinees against HPV16 was significantly higher than that of healthy controls. Furthermore, there was a positive correlation between the level of specific T cell immunity and the level of antibody against HPV16 in all the donors (Pearson, r>0.4, p<0.05). Conclusions:The virus-specific immune responses, i. e. humoral responses as well as cellular immune responses are presenting diversely among different HPV-related subjects. HPV vaccinees possess robust humoral immunity and CD4 + T cell responses.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.