Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Objective To observe the clinical effect of ultrasound-guided nerve block combined with arc edge needle-scalpel in the treatment of cervical spondylotic radiculopathy.Methods 160 cases were randomly divided into 4 groups from A to D,40 cases in each group.Group A was given nerve block,group B was given ultrasound-guided nerve block,group C was given arc edge needle-scalpel,and group D was given ultrasound-guided nerve block combined with arc edge needle-scalpel for 4 weeks.The McGill pain scale,cervical dysfunction index,cervical motion(angle of cervical left and right rotation,anterior flexion,posterior extension and lateral flexion),myoelectric-evoked potentiall(median nerve and ulnar nerve conduction velocity,latency),arterial blood flow velocity(average vertebral artery and basal artery flow velocity,end-diastolic blood flow velocity)were observed.The serum levels of neuron-specific enolase(NSE),β-endorphin(β-EP),lipoprotein-associated phospholipase A2(LpPLA2),6-ketoprostaglandin E1α(6-keto-PGE1α)were measured.The clinical efficacy and safety of each group were observed.Results The response rate in group D was taller than that in group A and group B significantly(χ2=6.605,P=0.013;χ2=4.073,P=0.044).Compared with the other three groups,the McGill pain,NDI,NSE,LpPLA2 and 6-keto-PGE1α in group D decreased significantly(P<0.05),the β-EP increased significantly(P<0.05),and the angles of left and right cervical rotation,anterior flexion,posterior extension and lateral flexion increased significantly(P<0.05),and median nerve and ulnar nerve conduction velocity,vertebral artery and basilar artery average blood flow velocity,end diastolic blood flow velocity increased significantly(P<0.05),and median nerve and ulnar nerve latency decreased significantly(P<0.05).The safety index of group D was higher than that in group A significantly(χ2=5.641,P=0.018).Conclusion Ultrasound-guided nerve block combined with arc edge needle-scalpel can relieve neck and shoulder pain,improve cervical spine function and reduce complications in patients with cervical spondylotic radiculopathy.

ObjectiveTo establish steroid-induced osteonecrosis of the femoral head （SANFH） cell model by using dexamethasone （DEX）-induced bone marrow mesenchymal stem cells （BMSCs） and demonstrate that Gushing Granules （GSNs） exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter （PI3K/Akt/Bad） signalling pathway. MethodsFirstly， SD rats were orally administered with drugs at a dose of 0.9 g·kg^-1 to prepare GSN-containing serum， and CCK-8 screening was used to determine the optimal dosage and duration of action. Then， BMSCs were cultured and treated with 1×10^-6 mol·L^-1 DEX， 10% GSN-containing serum， and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase （ALP） assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene （Bcl-2）， and Bcl-2-associated X protein （Bax）， osteocalcin （OCN）， and Collagen Ⅰ， we used Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%， and the duration of action is 48 hours. After modelling and grouping the cells in each group， the detection results showed that the SANFH model group had significantly lower cell viability， cell proliferation， and ALP expression， as well as protein and mRNA expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased （P<0.05，P<0.01）. After treatment with GSN-containing serum， cell viability， cell proliferation， and ALP expression， as well as expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ nucleic acids and proteins were significantly increased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased（P<0.05，P<0.01）. Compared with the GSN drug-containing serum group， the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically， the cell viability， cell proliferation， ALP expression， and the nucleic acid and protein levels of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ were all significantly decreased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased （P<0.05， P<0.01）. ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway， providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.

Objective To observe the clinical effect of ultrasound-guided nerve block combined with arc edge needle-scalpel in the treatment of cervical spondylotic radiculopathy.Methods 160 cases were randomly divided into 4 groups from A to D,40 cases in each group.Group A was given nerve block,group B was given ultrasound-guided nerve block,group C was given arc edge needle-scalpel,and group D was given ultrasound-guided nerve block combined with arc edge needle-scalpel for 4 weeks.The McGill pain scale,cervical dysfunction index,cervical motion(angle of cervical left and right rotation,anterior flexion,posterior extension and lateral flexion),myoelectric-evoked potentiall(median nerve and ulnar nerve conduction velocity,latency),arterial blood flow velocity(average vertebral artery and basal artery flow velocity,end-diastolic blood flow velocity)were observed.The serum levels of neuron-specific enolase(NSE),β-endorphin(β-EP),lipoprotein-associated phospholipase A2(LpPLA2),6-ketoprostaglandin E1α(6-keto-PGE1α)were measured.The clinical efficacy and safety of each group were observed.Results The response rate in group D was taller than that in group A and group B significantly(χ2=6.605,P=0.013;χ2=4.073,P=0.044).Compared with the other three groups,the McGill pain,NDI,NSE,LpPLA2 and 6-keto-PGE1α in group D decreased significantly(P<0.05),the β-EP increased significantly(P<0.05),and the angles of left and right cervical rotation,anterior flexion,posterior extension and lateral flexion increased significantly(P<0.05),and median nerve and ulnar nerve conduction velocity,vertebral artery and basilar artery average blood flow velocity,end diastolic blood flow velocity increased significantly(P<0.05),and median nerve and ulnar nerve latency decreased significantly(P<0.05).The safety index of group D was higher than that in group A significantly(χ2=5.641,P=0.018).Conclusion Ultrasound-guided nerve block combined with arc edge needle-scalpel can relieve neck and shoulder pain,improve cervical spine function and reduce complications in patients with cervical spondylotic radiculopathy.

Objective:To explore the classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography and its impact on their donor sites.Methods:A retrospective analysis was conducted of the data of 67 patients with large soft tissue defects who had been repaired with anterolateral thigh perforator flaps at Department of Orthopaedics, The Hospital Affiliated to The Second Medical University of Shandong, Department of Orthopaedics, The 80th Group Army Hospital of the People's Liberation Army, and Department of Orthopaedics, Weifang Traditional Chinese Medicine Hospital. The patients were divided into 2 groups according to their flaps used: a unilobar group and a bilobar group. In the unilobar group, 36 cases [25 males and 11 females with an age of (40.3±8.3) years] were repaired with a unilobar anterolateral thigh perforator flap from March 2015 to April 2019. In the bilobar group, 31 cases [22 males and 9 females with an age of (38.9±7.4) years] were repaired with a bilobar anterolateral thigh perforator flap from May 2019 to August 2023. Color Doppler ultrasonography was used to classify the bilobar flaps into 4 types according to the different distributions of perforating vessels: common trunk type, separate trunks type, fascia dependent type, and composite mixed type. The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were compared with the intraoperative findings in the bilobar group. One year after operation, recovery rate of donor muscle strength, rate of skin paresthesia, scar length at the donor site, the widest scar width and motor function were compared between the 2 groups.Results:The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were consistent with the intraoperative findings ( P<0.05). There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). One year after operation in the bilobar group, the recovery rate of donor muscle strength was 96.8% (30/31), significantly higher than that in the unilobar group [77.8% (28/36)], the rate of skin paresthesia 6.5% (2/31), significantly lower than that in the unilobar group [27.8% (10/36)], the scar length at the donor site (22.18±5.02) cm, significantly longer than that in unilobar group [(17.35±3.11) cm], the widest scar width (7.26±1.58) mm, significantly narrower than that in the unilobar group [(43.72±9.81) mm], and the scores of Vancouver Scar Assessment Scale and Fugl-Meyer lower limb motor function scale were (1.95±0.57) points and (8.39±2.17) points, respectively, significantly lower than those in the unilobar group [(6.38±1.72) points and (14.02±3.54) points] ( P<0.05). Conclusions:Preoperative classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography may provide guidance for flap harvesting and lobe layout of the flap. Compared to traditional unilobar flaps, bilobar ones may minimize tissue damage at a donor site.

Objective:To explore the classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography and its impact on their donor sites.Methods:A retrospective analysis was conducted of the data of 67 patients with large soft tissue defects who had been repaired with anterolateral thigh perforator flaps at Department of Orthopaedics, The Hospital Affiliated to The Second Medical University of Shandong, Department of Orthopaedics, The 80th Group Army Hospital of the People's Liberation Army, and Department of Orthopaedics, Weifang Traditional Chinese Medicine Hospital. The patients were divided into 2 groups according to their flaps used: a unilobar group and a bilobar group. In the unilobar group, 36 cases [25 males and 11 females with an age of (40.3±8.3) years] were repaired with a unilobar anterolateral thigh perforator flap from March 2015 to April 2019. In the bilobar group, 31 cases [22 males and 9 females with an age of (38.9±7.4) years] were repaired with a bilobar anterolateral thigh perforator flap from May 2019 to August 2023. Color Doppler ultrasonography was used to classify the bilobar flaps into 4 types according to the different distributions of perforating vessels: common trunk type, separate trunks type, fascia dependent type, and composite mixed type. The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were compared with the intraoperative findings in the bilobar group. One year after operation, recovery rate of donor muscle strength, rate of skin paresthesia, scar length at the donor site, the widest scar width and motor function were compared between the 2 groups.Results:The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were consistent with the intraoperative findings ( P<0.05). There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). One year after operation in the bilobar group, the recovery rate of donor muscle strength was 96.8% (30/31), significantly higher than that in the unilobar group [77.8% (28/36)], the rate of skin paresthesia 6.5% (2/31), significantly lower than that in the unilobar group [27.8% (10/36)], the scar length at the donor site (22.18±5.02) cm, significantly longer than that in unilobar group [(17.35±3.11) cm], the widest scar width (7.26±1.58) mm, significantly narrower than that in the unilobar group [(43.72±9.81) mm], and the scores of Vancouver Scar Assessment Scale and Fugl-Meyer lower limb motor function scale were (1.95±0.57) points and (8.39±2.17) points, respectively, significantly lower than those in the unilobar group [(6.38±1.72) points and (14.02±3.54) points] ( P<0.05). Conclusions:Preoperative classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography may provide guidance for flap harvesting and lobe layout of the flap. Compared to traditional unilobar flaps, bilobar ones may minimize tissue damage at a donor site.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.