Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

BACKGROUND:With the aging of the population,the incidence of osteoporosis is increasing year by year,and osteoporotic spinal fracture,as one of the common complications,brings great pain and inconvenience to patients.As an effective treatment,percutaneous vertebroplasty has been widely used in clinical practice.However,cement leakage as a potential risk of this procedure has been the focus of researchers.OBJECTIVE:To investigate the causes and management strategies of cement leakage after percutaneous vertebroplasty for osteoporotic vertebral compression fractures.METHODS:A total of 100 osteoporotic vertebral compression fractures patients who underwent percutaneous vertebroplasty in the Department of Orthopedics of Beijing Pinggu District Hospital from March 2017 to February 2021 were selected as the study subjects.According to the 12-month follow-up results,the patients were divided into bone cement leakage group(n=27)and non-bone cement leakage group(n=73).Cox proportional risk regression analysis was used to screen the influencing factors of bone cement leakage after surgery,so as to construct and evaluate the nomogram model for predicting the risk of bone cement leakage after surgery.Visual analog scale score and Oswesry dysfunction index of 27 patients were observed before surgery,3 days and 12 months after surgery following bone cement leakage treatment.RESULTS AND CONCLUSION:(1)Among the 27 patients with bone cement leakage,24 patients had internal leakage of intervertebral disc endplate,no obvious symptoms or discomfort,and no special treatment.Pulmonary embolism occurred in 1 case,and the patient was treated with the help of respiratory department.Two patients with symptoms underwent percutaneous intervertebral foramen endoscopic bone cement removal.(2)CT value,fracture severity,bone cement viscosity,cortical fracture,and injection amount of bone cement were the independent influencing factors for postoperative bone cement leakage(P<0.05).(3)The calibration degree and differentiation degree of the nomogram model were good,and it had good clinical practicability.(4)For 27 patients with external bone cement leakage after surgery,visual analog scale score at 3 days and 12 months after surgery was significantly lower than that before surgery,and the difference was statistically significant(P<0.05).Oswesry dysfunction index score at 12 months after surgery was significantly lower than that at 3 days after surgery,and the difference was statistically significant(P<0.05).(5)The results show that the amount of bone cement injection,bone cement viscosity,cortical fracture,CT value,and fracture severity are the risk factors of bone cement leakage after percutaneous vertebroplasty.

Objective:To explore the effect of preoperative gamma-glutamyl transferase to albumin ratio (GAR) on prognosis of patients with Barcelona clinic liver cancer (BCLC)stage 0-A hepatocellular carcinoma (HCC) after microwave ablation (MWA).Methods:The clinical data of 201 patients with BCLC stage 0 to A who underwent MWA at two centers of Jiaxing Second Hospital and Shengjing Hospital of China Medical University from January 2011 to December 2018 were retrospectively analyzed, including 152 males and 49 females, aged (57.5±9.6) years. X-tile software was used to divide patients into a low GAR group ( n=84, GAR<0.9) and a high GAR group ( n=117, GAR≥0.9). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Univariate and multivariate Cox regression analysis was used to evaluate the relationship between GAR and prognosis. Results:The cumulative survival rates at 1, 3 and 5 years postoperatively were 98.7%, 93.8%, 78.5% for the low GAR group, which were superior to that 97.2%, 87.1%, 70.2% for the high GAR group, and the difference was statistically significant ( χ2=11.89, P=0.001). The recurrence-free survival rates at 1, 3 and 5 years after surgery between the two groups was no significant difference ( χ2=1.70, P=0.192). Multivariate analysis revealed that high GAR ( HR=2.723, 95% CI: 1.508-4.914, P=0.001) was independent risk factors for overall survival after MWA in patients with BCLC stages 0 to A HCC. Male gender ( HR=1.959, 95% CI: 1.127-3.305, P=0.017) and tumor diameter ≥2 cm ( HR=1.547, 95% CI: 1.008-2.373, P=0.046) were independent risk factors for recurrence after MWA in patients with BCLC stages 0 to A HCC. Univariate analysis, GAR≥0.9 was not associated with postoperative recurrence ( HR=1.315, 95% CI: 0.869-1.989, P=0.195). Conclusion:Preoperative GAR (≥0.9) is an independent risk factor affecting overall survival in patients with BCLC stages 0 to A HCC after MWA.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

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.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

The incidence of tumors among the elderly is notably high, presenting significant challenges in terms of harm, complexity, and treatment.The processes of diagnosis and treatment often lack a precise clinical foundation and robust experimental evidence, resulting in numerous difficulties and dilemmas.A collaborative approach that integrates traditional Chinese and Western medicine, leveraging the strengths of both, can substantially alleviate these challenges and ensure that elderly cancer patients can undergo systematic, comprehensive, and intensive cancer treatments.Traditional Chinese medicine can play a vital role throughout the entire continuum of diagnosis and treatment for elderly cancer patients, whether by leading, assisting, or complementing other treatment modalities.This article employs the concepts of ′righteousness′and ′evil′from traditional Chinese medicine, where ′righteousness′signifies the ′state of a person′and ′evil ′denotes the ′state of a tumor′.We systematically explore collaborative diagnosis and treatment strategies that integrate traditional Chinese and Western medicine for tumor management in the elderly, categorizing the approaches into four conditions: strong righteousness with strong evil, strong righteousness with weak evil, weak righteousness with strong evil, and weak righteousness with weak evil.In cases where both righteousness and evil are strong, the treatment strategy is primarily dominated by Western medicine, with support from traditional Chinese medicine.Conversely, when righteousness is strong and evil is weak, the strategy entails a combination of both Chinese and Western medicine.In situations characterized by weak righteousness and strong evil, the treatment approach is largely guided by traditional Chinese medicine, while also considering equal attention to both modalities.Finally, when both righteousness and evil are weak, the coordinated diagnosis and treatment strategy is primarily based on Chinese medicine, with Western medicine adapting to the circumstances and intervening appropriately throughout the process.By accurately assessing the concepts of ′righteousness′and ′evil′and implementing collaborative diagnostic and treatment strategies that integrate both traditional Chinese and Western medicine, we can significantly enhance the physical condition of elderly cancer patients.This comprehensive approach not only boosts immunity and improves organ function but also increases tolerance to tumor treatments, alleviates complications, reduces adverse reactions, and ensures that elderly cancer patients can undergo systemic cancer treatment to its fullest extent.Ultimately, this strategy aims to improve prognosis, enhance quality of life, and extend the effective survival period.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Ischemic stroke is one of the leading causes of mortality and disability,and it particularly inflicts brain damage through various mechanisms.However,there is a significant gap in the availability of specific drugs for the treatment of ischemic stroke.Numerous studies have demonstrated that exercise preconditioning can provide protective ef-fects against ischemic stroke through complex mechanisms.In this review,we aim to summarize the amount of exercise re-quired to induce exercise preconditioning and its potential mechanisms for improving outcomes in ischemic stroke.The fol-lowing benefits of exercise preconditioning have been identified in relation to ischemic stroke:(1)reduction of cerebral edema and infarct size,while promoting angiogenesis;(2)preservation of the integrity of the blood-brain barrier,reduc-tion of apoptosis,and mitigation of neurological damage;(3)inhibition of glutamate overactivation,alleviation of oxida-tive stress,and improvement of the inflammatory response.Ultimately,exercise preconditioning mitigates the damage caused by ischemic stroke through these pathways.