Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

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.

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.

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.

Objective:To evaluate the clinical efficacy and prognosis of mechanical lithotripsy, laser lithotripsy under direct peroral cholangioscopy, and their combination in the treatment of difficult common bile duct (CBD) stones.Methods:Clinical data of 345 patients with difficult CBD stones treated at the Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, between January 2020 and December 2024 were retrospectively analyzed, including 176 males and 169 females, aged (71.2±14.2) years. Patients were categorized into three groups based on the lithotripsy technique used: mechanical lithotripsy group ( n=275), laser lithotripsy group under direct peroral cholangioscopy ( n=34), and combined lithotripsy group ( n=35). Operative time, hospitalization costs, stone clearance rate, and postoperative complications were recorded. Follow-ups were conducted through outpatient visits and telephone reviews to monitor stone recurrence. Propensity score matching (PSM) at a 1: 3 nearest-neighbor ratio with a caliper of 0.02 was performed, using lithotripsy method as the dependent variable, and age, sex, stone size, and bile duct diameter as independent variables, resulting in well-balanced mechanical and laser lithotripsy groups. Kaplan-Meier survival analysis was used to assess recurrence-free survival, with comparisons performed using the log-rank test. Results:Before PSM, there were significant differences in age, sex, stone length, and bile duct diameter between the groups (all P<0.05). After PSM, 40 patients were included in the mechanical lithotripsy group, 34 in the laser group, and 35 in the combined group, with no significant differences in baseline or preoperative clinical characteristics (all P>0.05). The combined group had a significantly longer operative time compared to the mechanical group [71.0 (66.0, 92.0) min vs. 50.5 (40.4, 56.5) min, Z=-5.02, P<0.001] and the laser group [71.0 (66.0, 92.0) min vs. 53.0 (26.5, 73.5) min, Z=-2.61, P=0.001]. The laser group also had a longer operative time than the mechanical group [53.0 (26.5, 73.5) min vs. 50.5 (40.4, 56.5) min, Z=-2.27, P=0.023]. Hospitalization costs were significantly higher in the combined group compared to the mechanical group [43 000(33 000, 50 000) yuan vs. 30 000(26 000, 37 000) yuan; Z=-3.43, P<0.001]. The single-session stone clearance rates were 80.0% (32/40) for the mechanical group, 85.3% (29/34) for the laser group, and 62.9% (22/35) for the combined group. Postoperative complication rates were 20.0% (8/40), 11.7% (4/34), and 11.4% (4/35), respectively, with no statistically significant differences among the three groups (all P>0.05). There were also no significant differences in cumulative recurrence-free survival among the groups ( χ2=0.06, P=0.970). Conclusions:For endoscopic management of difficult CBD stones, combined lithotripsy is associated with longer operative time and higher hospitalization costs compared to mechanical and laser lithotripsy alone. Laser lithotripsy also requires more operative time than mechanical lithotripsy. However, the three lithotripsy strategies show no significant differences in postoperative complications or cumulative recurrence-free survival.

Objective:To evaluate the clinical efficacy and prognosis of mechanical lithotripsy, laser lithotripsy under direct peroral cholangioscopy, and their combination in the treatment of difficult common bile duct (CBD) stones.Methods:Clinical data of 345 patients with difficult CBD stones treated at the Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, between January 2020 and December 2024 were retrospectively analyzed, including 176 males and 169 females, aged (71.2±14.2) years. Patients were categorized into three groups based on the lithotripsy technique used: mechanical lithotripsy group ( n=275), laser lithotripsy group under direct peroral cholangioscopy ( n=34), and combined lithotripsy group ( n=35). Operative time, hospitalization costs, stone clearance rate, and postoperative complications were recorded. Follow-ups were conducted through outpatient visits and telephone reviews to monitor stone recurrence. Propensity score matching (PSM) at a 1: 3 nearest-neighbor ratio with a caliper of 0.02 was performed, using lithotripsy method as the dependent variable, and age, sex, stone size, and bile duct diameter as independent variables, resulting in well-balanced mechanical and laser lithotripsy groups. Kaplan-Meier survival analysis was used to assess recurrence-free survival, with comparisons performed using the log-rank test. Results:Before PSM, there were significant differences in age, sex, stone length, and bile duct diameter between the groups (all P<0.05). After PSM, 40 patients were included in the mechanical lithotripsy group, 34 in the laser group, and 35 in the combined group, with no significant differences in baseline or preoperative clinical characteristics (all P>0.05). The combined group had a significantly longer operative time compared to the mechanical group [71.0 (66.0, 92.0) min vs. 50.5 (40.4, 56.5) min, Z=-5.02, P<0.001] and the laser group [71.0 (66.0, 92.0) min vs. 53.0 (26.5, 73.5) min, Z=-2.61, P=0.001]. The laser group also had a longer operative time than the mechanical group [53.0 (26.5, 73.5) min vs. 50.5 (40.4, 56.5) min, Z=-2.27, P=0.023]. Hospitalization costs were significantly higher in the combined group compared to the mechanical group [43 000(33 000, 50 000) yuan vs. 30 000(26 000, 37 000) yuan; Z=-3.43, P<0.001]. The single-session stone clearance rates were 80.0% (32/40) for the mechanical group, 85.3% (29/34) for the laser group, and 62.9% (22/35) for the combined group. Postoperative complication rates were 20.0% (8/40), 11.7% (4/34), and 11.4% (4/35), respectively, with no statistically significant differences among the three groups (all P>0.05). There were also no significant differences in cumulative recurrence-free survival among the groups ( χ2=0.06, P=0.970). Conclusions:For endoscopic management of difficult CBD stones, combined lithotripsy is associated with longer operative time and higher hospitalization costs compared to mechanical and laser lithotripsy alone. Laser lithotripsy also requires more operative time than mechanical lithotripsy. However, the three lithotripsy strategies show no significant differences in postoperative complications or cumulative recurrence-free survival.

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.

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.

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.

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.