ObjectiveTo investigate the efficacy and safety of lenvatinib combined with sintilimab versus atezolizumab combined with bevacizumab in patients with unresectable hepatocellular carcinoma （uHCC）， aims to provide real-world evidence for clinical personalized treatment. MethodsA retrospective analysis was performed for 78 patients with uHCC who were admitted to Beijing Ditan Hospital， Capital Medical University， from January 1， 2023， to May 31， 2025， and according to the treatment modality， they were divided into lenvatinib+sintilimab group （L+S group with 49 patients） and atezolizumab+bevacizumab group （A+T group with 29 patients）. The primary endpoints were progression-free survival （PFS） and overall survival （OS）， and the secondary endpoints included objective response rate （ORR）， disease control rate （DCR）， and the incidence rate of adverse events. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for survival analysis， and the log-rank test was used for comparison between groups. ResultsThe 78 patients had a median PFS of 9 months and a median OS of 15 months. The median PFS was 11 months in the L+S group and 7 months in the A+T group， with no significant difference between the two groups （χ²=0.247， P=0.619）； the median OS was 19 months in the L+S group and 12 months in the A+T group， with a significant difference between the two groups （χ²=6.565， P=0.010）. There were no significant differences between the two groups in complete remission， partial remission， stable disease， disease progression， DCR， and ORR （all P>0.05）. The L+S group had a significantly higher incidence rate of adverse events than the A+T group （95.9% vs 75.9%， P=0.007）， and there was a significant difference in the incidence rate of grade ≥3 adverse events between the L+S group and the A+T group （65.3% vs 34.5%， P=0.008）. ConclusionCompared with atezolizumab combined with bevacizumab， lenvatinib combined with sintilimab can improve the OS of patients with uHCC， while atezolizumab combined with bevacizumab has a better safety profile.

Objective:To investigate the effects of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation on the polarization of Raw264.7 macrophages and to elucidate the underlying mechanisms.Methods:PBS, uninduced BMSCs conditioned medium (CM), and osteogenic induction BMSCs CM for 7 d, 14 d, and 21 d were respectively added to Raw264.7 macrophages. After 48 h of treatment, Western blotting was used to detect and compare the expression of M1 markers of macrophages [inducible nitric oxide synthase (iNOS) and CD86] and M2 markers of macrophages [arginase-1 (ARG-1) and CD163] in each group. In addition, Raw264.7 macrophages were divided into three groups: the PBS group (only PBS added), the BMSCs-exo group (exosomes derived from uninduced BMSCs were added), and 7D-BMSCs-exo (exosomes derived from BMSCs were added after 7 days of osteogenic induction). The absorbance values of Raw264.7 cells in each group at 24 h, 48 h and 72 h were detected by an enzyme-linked immunosorbent assay (ELISA) reader. Western blotting was performed to assess changes of M1 or M2 marker proteins in Raw264.7 macrophages treated by exosome. The supernatants of the three groups of Raw264.7 macrophages were then co-cultured with BMSCs. Alizarin Red staining was used to quantify the formation of mineralized nodules, and alkaline phosphatase (ALP) staining was used to evaluate the osteogenic activity, and the expression levels of osteogenesis-related proteins Runx2, ALP, osteopontin (OPN), and osteocalcin (OCN) were detected. The migration ability of endothelial progenitor cells (EPCs) was detected by scratch assay for migration distance, and the angiogenesis ability was detected by in vitro tube formation assay for the number of vascular rings formed. The expressions of vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) were detected by Western blot. The activation of the MAPK signaling pathway was evaluated by measuring phosphorylated and total P38 and ERK1/2 levels.Results:Western blot analysis showed that CM from BMSCs after 7 days of osteogenic induction (7D-BMSCs-CM) induced the strongest M2 polarization in macrophages. Compared with the PBS group, 7D-BMSCs-CM induced the most significant polarization of Raw264.7 macrophages to the M2 type, and increased ARG-1 and CD163 expression to 1.36±0.09 and 1.69±0.09, respectively ( P<0.05), while decreasing iNOS and CD86 to 0.21±0.03 and 0.29±0.03 ( P<0.05). The absorbance values of macrophages in the 7D-BMSCs-exo group were significantly higher than those in the PBS group at 24 h, 48 h, and 72 h ( P<0.05). Compared with BMSCs-exo group, 7D-BMSCs-exo upregulated the expressions of CD163 and ARG-1 while inhibited the expressions of iNOS and CD86 ( P<0.05). Alizarin red staining showed enhanced mineral deposition and a higher degree of mineralization in the 7D-BMSCs-exo group, the staining intensity of ALP also increased simultaneously, the Western-blot results showed that the protein expressions of Runx2, ALP, OPN and OCN were respectively higher than those in the PBS group ( P<0.05). The results of the scratch assay showed that the relative migration distance of EPCs cells in the 7D-BMSCS-exo group at 24 h reached 2.30±0.05 μm, which was higher than that in the PBS group 1.10±0.02 μm ( P<0.05). The Tube formation experiment showed that the number of vascular rings in the EPCs group was higher than that in the PBS group (30.3±2.5 and 15.0±1.0, P<0.05), and the protein expressions of VEGF-A and PDGF were upregulated. Furthermore, the levels of phosphorylated P38 and ERK1/2 were significantly reduced in the 7D-BMSCs-exo group 0.40±0.06 and 0.25±0.06 compared with the PBS group ( P<0.05). Conclusions:Exosomes secreted by BMSCs during osteogenic differentiation promote the M2 polarization of Raw264.7 macrophages, with the most pronounced effect observed at the 7th day. M2-polarized macrophages, in turn, enhance the osteogenic differentiation of BMSCs and the angiogenic capacity of EPCs. These processes are closely associated with the suppression of the MAPK signaling pathway.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective:To investigate the effects of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation on the polarization of Raw264.7 macrophages and to elucidate the underlying mechanisms.Methods:PBS, uninduced BMSCs conditioned medium (CM), and osteogenic induction BMSCs CM for 7 d, 14 d, and 21 d were respectively added to Raw264.7 macrophages. After 48 h of treatment, Western blotting was used to detect and compare the expression of M1 markers of macrophages [inducible nitric oxide synthase (iNOS) and CD86] and M2 markers of macrophages [arginase-1 (ARG-1) and CD163] in each group. In addition, Raw264.7 macrophages were divided into three groups: the PBS group (only PBS added), the BMSCs-exo group (exosomes derived from uninduced BMSCs were added), and 7D-BMSCs-exo (exosomes derived from BMSCs were added after 7 days of osteogenic induction). The absorbance values of Raw264.7 cells in each group at 24 h, 48 h and 72 h were detected by an enzyme-linked immunosorbent assay (ELISA) reader. Western blotting was performed to assess changes of M1 or M2 marker proteins in Raw264.7 macrophages treated by exosome. The supernatants of the three groups of Raw264.7 macrophages were then co-cultured with BMSCs. Alizarin Red staining was used to quantify the formation of mineralized nodules, and alkaline phosphatase (ALP) staining was used to evaluate the osteogenic activity, and the expression levels of osteogenesis-related proteins Runx2, ALP, osteopontin (OPN), and osteocalcin (OCN) were detected. The migration ability of endothelial progenitor cells (EPCs) was detected by scratch assay for migration distance, and the angiogenesis ability was detected by in vitro tube formation assay for the number of vascular rings formed. The expressions of vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) were detected by Western blot. The activation of the MAPK signaling pathway was evaluated by measuring phosphorylated and total P38 and ERK1/2 levels.Results:Western blot analysis showed that CM from BMSCs after 7 days of osteogenic induction (7D-BMSCs-CM) induced the strongest M2 polarization in macrophages. Compared with the PBS group, 7D-BMSCs-CM induced the most significant polarization of Raw264.7 macrophages to the M2 type, and increased ARG-1 and CD163 expression to 1.36±0.09 and 1.69±0.09, respectively ( P<0.05), while decreasing iNOS and CD86 to 0.21±0.03 and 0.29±0.03 ( P<0.05). The absorbance values of macrophages in the 7D-BMSCs-exo group were significantly higher than those in the PBS group at 24 h, 48 h, and 72 h ( P<0.05). Compared with BMSCs-exo group, 7D-BMSCs-exo upregulated the expressions of CD163 and ARG-1 while inhibited the expressions of iNOS and CD86 ( P<0.05). Alizarin red staining showed enhanced mineral deposition and a higher degree of mineralization in the 7D-BMSCs-exo group, the staining intensity of ALP also increased simultaneously, the Western-blot results showed that the protein expressions of Runx2, ALP, OPN and OCN were respectively higher than those in the PBS group ( P<0.05). The results of the scratch assay showed that the relative migration distance of EPCs cells in the 7D-BMSCS-exo group at 24 h reached 2.30±0.05 μm, which was higher than that in the PBS group 1.10±0.02 μm ( P<0.05). The Tube formation experiment showed that the number of vascular rings in the EPCs group was higher than that in the PBS group (30.3±2.5 and 15.0±1.0, P<0.05), and the protein expressions of VEGF-A and PDGF were upregulated. Furthermore, the levels of phosphorylated P38 and ERK1/2 were significantly reduced in the 7D-BMSCs-exo group 0.40±0.06 and 0.25±0.06 compared with the PBS group ( P<0.05). Conclusions:Exosomes secreted by BMSCs during osteogenic differentiation promote the M2 polarization of Raw264.7 macrophages, with the most pronounced effect observed at the 7th day. M2-polarized macrophages, in turn, enhance the osteogenic differentiation of BMSCs and the angiogenic capacity of EPCs. These processes are closely associated with the suppression of the MAPK signaling pathway.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Objective To investigate the efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) previously treated with tyrosine kinase inhibitor (TKI). Methods A retrospective analysis was performed for the clinical data of 76 patients with unresectable HCC who were treated with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 2019 to January 2020, and according to the treatment method, they were divided into TKI previously untreated group with 49 patients and TKI treatment-experienced group with 27 patients. The patients were observed till one year after enrollment, adjustment of treatment regimen, tumor progression, or death. The two groups were compared in terms of progression-free survival (PFS) time, objective response rate (ORR), disease control rate (DCR), and incidence rate of adverse events. The t -test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Wilcoxon rank-sum test was used for comparison of categorical data between two groups; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison between groups. Results There were no significant differences between the TKI previously untreated group and the TKI treatment-experienced group in median PFS time (115 days vs 72 days, P =0.148), ORR (36.7% vs 18.5%, P =0.098), DCR (65.3% vs 55.6%, P =0.402), and incidence rates of grade ≥3 adverse events (24.5% vs 18.5%, P =0.550). Conclusion Patients with unresectable HCC previously treated with TKI can benefit from lenvatinib and have good safety, with similar results to those treated with TKI for the first time.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.