Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

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.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Objective To investigate mitochondrial function mediated by phospholipase D1(PLD1)in the lungs of mice with bronchopulmonary dysplasia.Methods Wild-type(WT)and PLD1 knockout(PLD1-KO)newborn mice were assigned to four groups:normoxic+WT,normoxic+PLD1-KO,hyperoxic+WT,and hyperoxic+PLD1-KO,with nine mice in each group.Mice in the hyperoxia groups were exposed to hyperoxia(85％ O2)for 14 days.Mice in the normoxic groups were exposed to normoxic conditions(21％ O2)for 14 days.On the 14th day,the levels of oxidative stress,apoptosis,and fibrosis in lungs were evaluated using commercial kits for malondialdehyde(MDA)and superoxide dismutase(SOD),Western blot for BAX,BCL-2,and Cleaved Caspase-3,and immunohistochemistry for α-SMA and AIF.The following MLE-12 cell groups were prepared,normoxic+si-NC,hyperoxic+si-NC,normoxic+si-PLD1,and hyperoxic+si-PLD1.After transient transfection,the cells were exposed to normoxia or hyperoxia for 24 h.Mitochondrial reactive oxygen species(mtROS)and function were measured using MitoSOX Red and the hippocampus mitochondrial stress test.Results The levels of α-SMA and AIF staining,MDA,Cleaved Caspase 3,and BAX in lung tissue were significantly increased in the hyperoxic groups compared with the normoxic groups(P＜0.05),while SOD activity and BCL-2 levels were significantly decreased(P＜0.05).α-SMA and AIF staining,and the abundance of Cleaved Caspase-3 and BAX in lung tissue were lower in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05),while SOD activity and BCL-2 abundance were higher in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic groups was significantly lower than that in the normoxic groups(P＜0.05);however,the level of AIF was increased significantly in the cytoplasm of the hyperoxic groups compared with the normoxic groups(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic+si-PLD1 group was significantly increased compared with that in the hyperoxic+si-NC group(P＜0.05).The abundance of mtROS in hyperoxia MLE-12 cell groups was higher than that in the normoxia groups(P＜0.05),and the abundance of mtROS in the hyperoxia+si-PLD1 group was lower than that in the hyperoxia+si-NC group(P＜0.05).Compared with the normoxic+si-NC group,basic respiration,ATP production,maximum respiration,and spare respiratory capacity was significantly decreased in the hyperoxic+si-NC group(P＜0.05).Compared with the hyperoxic+si-NC group,the hyperoxic+si-PLD1 group had significantly increased basic respiration,ATP production,maximum respiration,and spare respiratory capacity(P＜0.05).Conclusions PLD1 is involved in hyperoxia-induced injury of mouse BPD and MLE-12 cells.Deletion of the PLD1 gene may alleviate hyperoxia-induced lung injury by inhibiting mitochondrial-dependent apoptosis.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Objective To investigate mitochondrial function mediated by phospholipase D1(PLD1)in the lungs of mice with bronchopulmonary dysplasia.Methods Wild-type(WT)and PLD1 knockout(PLD1-KO)newborn mice were assigned to four groups:normoxic+WT,normoxic+PLD1-KO,hyperoxic+WT,and hyperoxic+PLD1-KO,with nine mice in each group.Mice in the hyperoxia groups were exposed to hyperoxia(85％ O2)for 14 days.Mice in the normoxic groups were exposed to normoxic conditions(21％ O2)for 14 days.On the 14th day,the levels of oxidative stress,apoptosis,and fibrosis in lungs were evaluated using commercial kits for malondialdehyde(MDA)and superoxide dismutase(SOD),Western blot for BAX,BCL-2,and Cleaved Caspase-3,and immunohistochemistry for α-SMA and AIF.The following MLE-12 cell groups were prepared,normoxic+si-NC,hyperoxic+si-NC,normoxic+si-PLD1,and hyperoxic+si-PLD1.After transient transfection,the cells were exposed to normoxia or hyperoxia for 24 h.Mitochondrial reactive oxygen species(mtROS)and function were measured using MitoSOX Red and the hippocampus mitochondrial stress test.Results The levels of α-SMA and AIF staining,MDA,Cleaved Caspase 3,and BAX in lung tissue were significantly increased in the hyperoxic groups compared with the normoxic groups(P＜0.05),while SOD activity and BCL-2 levels were significantly decreased(P＜0.05).α-SMA and AIF staining,and the abundance of Cleaved Caspase-3 and BAX in lung tissue were lower in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05),while SOD activity and BCL-2 abundance were higher in the hyperoxia+PLD1-KO group than in the hyperoxia+WT group(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic groups was significantly lower than that in the normoxic groups(P＜0.05);however,the level of AIF was increased significantly in the cytoplasm of the hyperoxic groups compared with the normoxic groups(P＜0.05).The level of AIF in MLE-12 cell mitochondria in the hyperoxic+si-PLD1 group was significantly increased compared with that in the hyperoxic+si-NC group(P＜0.05).The abundance of mtROS in hyperoxia MLE-12 cell groups was higher than that in the normoxia groups(P＜0.05),and the abundance of mtROS in the hyperoxia+si-PLD1 group was lower than that in the hyperoxia+si-NC group(P＜0.05).Compared with the normoxic+si-NC group,basic respiration,ATP production,maximum respiration,and spare respiratory capacity was significantly decreased in the hyperoxic+si-NC group(P＜0.05).Compared with the hyperoxic+si-NC group,the hyperoxic+si-PLD1 group had significantly increased basic respiration,ATP production,maximum respiration,and spare respiratory capacity(P＜0.05).Conclusions PLD1 is involved in hyperoxia-induced injury of mouse BPD and MLE-12 cells.Deletion of the PLD1 gene may alleviate hyperoxia-induced lung injury by inhibiting mitochondrial-dependent apoptosis.

Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.