ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

Objective This study analyzes the optical coherence tomography(OCT)characteristics of patients with symptomatic carotid artery stenosis(CAS)prior to carotid stenting and the influencing factors associated with symptomatic CAS.Methods This study retrospectively included consecutive CAS patients who underwent carotid OCT examination prior to carotid stenting at Department of Nerolgical Intervention and Nerological Intensive Care,Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital)from November 2022 to November 2024.Patients were categorized into symptomatic and asymptomatic CAS groups.General clinical data and laboratory test results were collected and compared between the two groups,including age,sex,body mass index,systolic and diastolic blood pressure(measured on the morning of procedure without antihypertensive medication intervention with patient at resting state for over 30 minutes),medical history(including hypertension,diabetes,atrial fibrillation,coronary heart disease,stroke,and transient ischemic attack),smoking history,alcohol consumption history,and fasting laboratory results obtained on the morning before procedure laboratory results(including,white blood cell count,red blood cell count,monocyte percentage,neutrophil percentage,lymphocyte percentage,platelet count,blood creatinine,blood glucose,international normalized ratio,D-dimer,total cholesterol,triglycerides,homocysteine,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol).Additionally,OCT image parameters were collected and compared between the two groups,including the minimum lumen diameter and minimum lumen area of the target lesion segment,the distal lumen diameter and area of the reference vessel(internal carotid artery),the percentage of lumen area stenosis([reference vessel lumen cross-sectional area-minimum lumen cross-sectional area]/reference vessel lumen cross-sectional area×100%),the lesion length,fibrous cap thickness,lipid arc,and the presence of fibrous plaques,calcified plaques,lipid plaques,white thrombus,cholesterol crystals,macrophage infiltration,microchannels,and plaque rupture.Variables with P＜0.05 from univariate analysis were included in the multivariate Logistic regression analysis to assess the influencing factors of symptomatic CAS.Results A total of 68 patients with CAS were enrolled,comprising 57males and 11females,aged 53 to 84 years with a mean age of(68±7)years.Among them,32 patients were categorized into the symptomatic CAS group and 36 into the asymptomatic CAS group.(1)Compared to the asymptomatic CAS group,patients in the symptomatic CAS group exhibited higher systolic blood pressure([150±23]mmHg vs.[138±21])mmHg,P=0.025).There were no statistically significant differences in general,clinical data,and laboratory test results between the two groups(all P＞0.05).The preoperative OCT imaging parameters comparison between the two groups of CAS patients revealed that the reference vessel distal lumen area was significantly smaller in the symptomatic CAS group([18.67±5.44]mm2 vs.[21.95±5.57]mm2,P=0.017),and the proportion of patients with white thrombus(40.62%[13/32]vs.13.89%[5/36],P=0.013)and microchannels(21.88%[7/32]vs.2.78%[1/36],P=0.014)were higher.(2)A multivariate Logistic regression analysis was conducted using systolic blood pressure,white thrombus,microchannels,and the reference vessel(internal carotid artery)distal lumen area as independent variables.The results indicated that high systolic blood pressure(OR,1.030,95%CI 1.002-1.060,P=0.038),and the presence of white thrombus(OR,3.956,95%CI 1.072-14.600,P=0.039)and microchannels(OR,13.850,95%CI 1.277-150.203,P=0.031)were independent risk factors for symptomatic CAS.Conclusions Compared to patients with asymptomatic CAS,those with symptomatic CAS exhibited higher preoperative(pre-carotid stenting)systolic blood pressure and a smaller distal lumen area of the reference vessel(internal carotid artery),as observed through OCT.Furthermore,a higher proportion of symptomatic CAS patients presented with white thrombus and microchannels.Preoperative systolic blood pressure,along with the presence of white thrombus and microchannels on OCT,are identified as independent risk factors for symptomatic CAS.The conclusions drawn from this study necessitate further validation through large-scale,multicenter,prospective research.

OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi-components by single-marker method(QAMS)to determine the contents of 7 components,so as to provide a scientific basis for their quality control.METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules(No.S1-S10),and similarity evaluation,cluster analysis(CA)and partial least squares-discriminant analysis(PLS-DA)were performed.At the same time,the contents of seven components,including puerarin,daidzin,calycosin-7-O-β-D-glucoside,stilbene glycoside,naringin,icariin and tanshinone ⅡA,were determined by QAMS method,and were compared with the results of external standard method.RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules,namely puerarin(peak 4),daidzin(peak 7),calycosin-7-O-β-D-glucoside(peak 9),stilbene glycoside(peak 10),naringin(peak 12),icariin(peak 17),and tanshinone ⅡA(peak 18);the similarities among them were more than 0.990,and CA and PLS-DA results showed that S4-S5,S8-S10,S1-S3 and S6-S7 were clustered into three categories,respectively.Using naringin as the internal standard,the contents of puerarin,daidzin,calycosin-7-O-β-D-glucoside,stilbene glycoside,icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2,1.709 2-2.374 1,0.285 2-0.326 3,1.024 1-1.523 9,0.140 2-0.290 4,and 0.077 1-0.219 4 mg/g,respectively,by the QAMS.These results showed no significant differences compared to those obtained by the external standard method.CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient,stable and accurate,which can provide a basis for the quality evaluation of Xintong granules.

Objective This study analyzes the optical coherence tomography(OCT)characteristics of patients with symptomatic carotid artery stenosis(CAS)prior to carotid stenting and the influencing factors associated with symptomatic CAS.Methods This study retrospectively included consecutive CAS patients who underwent carotid OCT examination prior to carotid stenting at Department of Nerolgical Intervention and Nerological Intensive Care,Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital)from November 2022 to November 2024.Patients were categorized into symptomatic and asymptomatic CAS groups.General clinical data and laboratory test results were collected and compared between the two groups,including age,sex,body mass index,systolic and diastolic blood pressure(measured on the morning of procedure without antihypertensive medication intervention with patient at resting state for over 30 minutes),medical history(including hypertension,diabetes,atrial fibrillation,coronary heart disease,stroke,and transient ischemic attack),smoking history,alcohol consumption history,and fasting laboratory results obtained on the morning before procedure laboratory results(including,white blood cell count,red blood cell count,monocyte percentage,neutrophil percentage,lymphocyte percentage,platelet count,blood creatinine,blood glucose,international normalized ratio,D-dimer,total cholesterol,triglycerides,homocysteine,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol).Additionally,OCT image parameters were collected and compared between the two groups,including the minimum lumen diameter and minimum lumen area of the target lesion segment,the distal lumen diameter and area of the reference vessel(internal carotid artery),the percentage of lumen area stenosis([reference vessel lumen cross-sectional area-minimum lumen cross-sectional area]/reference vessel lumen cross-sectional area×100%),the lesion length,fibrous cap thickness,lipid arc,and the presence of fibrous plaques,calcified plaques,lipid plaques,white thrombus,cholesterol crystals,macrophage infiltration,microchannels,and plaque rupture.Variables with P＜0.05 from univariate analysis were included in the multivariate Logistic regression analysis to assess the influencing factors of symptomatic CAS.Results A total of 68 patients with CAS were enrolled,comprising 57males and 11females,aged 53 to 84 years with a mean age of(68±7)years.Among them,32 patients were categorized into the symptomatic CAS group and 36 into the asymptomatic CAS group.(1)Compared to the asymptomatic CAS group,patients in the symptomatic CAS group exhibited higher systolic blood pressure([150±23]mmHg vs.[138±21])mmHg,P=0.025).There were no statistically significant differences in general,clinical data,and laboratory test results between the two groups(all P＞0.05).The preoperative OCT imaging parameters comparison between the two groups of CAS patients revealed that the reference vessel distal lumen area was significantly smaller in the symptomatic CAS group([18.67±5.44]mm2 vs.[21.95±5.57]mm2,P=0.017),and the proportion of patients with white thrombus(40.62%[13/32]vs.13.89%[5/36],P=0.013)and microchannels(21.88%[7/32]vs.2.78%[1/36],P=0.014)were higher.(2)A multivariate Logistic regression analysis was conducted using systolic blood pressure,white thrombus,microchannels,and the reference vessel(internal carotid artery)distal lumen area as independent variables.The results indicated that high systolic blood pressure(OR,1.030,95%CI 1.002-1.060,P=0.038),and the presence of white thrombus(OR,3.956,95%CI 1.072-14.600,P=0.039)and microchannels(OR,13.850,95%CI 1.277-150.203,P=0.031)were independent risk factors for symptomatic CAS.Conclusions Compared to patients with asymptomatic CAS,those with symptomatic CAS exhibited higher preoperative(pre-carotid stenting)systolic blood pressure and a smaller distal lumen area of the reference vessel(internal carotid artery),as observed through OCT.Furthermore,a higher proportion of symptomatic CAS patients presented with white thrombus and microchannels.Preoperative systolic blood pressure,along with the presence of white thrombus and microchannels on OCT,are identified as independent risk factors for symptomatic CAS.The conclusions drawn from this study necessitate further validation through large-scale,multicenter,prospective research.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

BACKGROUND:Finite element modeling,as an important engineering analysis technique,has been widely used in various fields of bioengineering research.However,there is little literature on what material properties should be selected for each anatomical structure of the knee joint finite element modeling at different ages for different research purposes.OBJECTIVE:To summarize the material properties of knee joint finite element models at different ages based on previous knee joint finite element studies.METHODS:The search terms were"knee,finite element,material selection,ligament injury,osteoarthritis,elderly,children,young people"in Chinese and English.Articles were searched on CNKI and PubMed,with a timeframe of 1950 to 2024.According to inclusion and exclusion criteria,108 articles were finally included for summary.RESULTS AND CONCLUSION:Children's knee bone density will increase with age,reaching peaks in adulthood.From middle-aged to the age,the elastic modulus of knee joint femur,tibia,fibula,and patella will decrease with age,and then return to the elastic modulus of childhood.The elastic modulus of children and adult cartilage is basically the same,and the elastic modulus of the elderly increases.With the increase of age,the elastic modulus of the knee ligament will decrease to a certain extent,but there is no significant difference in the elastic modulus of the knee ligament of young people and the elderly.With the increase of age,the loss of mechanical integrity of the knee meniscus will damage the biomechanical function of the tissue and disturb the various anisotropic biomechanical responses that are effectively carried and transmitted by the tissue.Knee joint finite element modeling can be used to deeply understand the biomechanical characteristics of the knee joints,develop new implanted materials,predict knee joint diseases,improve surgical technology,and guide patients to rehabilitate exercise.

BACKGROUND:Finite element modeling,as an important engineering analysis technique,has been widely used in various fields of bioengineering research.However,there is little literature on what material properties should be selected for each anatomical structure of the knee joint finite element modeling at different ages for different research purposes.OBJECTIVE:To summarize the material properties of knee joint finite element models at different ages based on previous knee joint finite element studies.METHODS:The search terms were"knee,finite element,material selection,ligament injury,osteoarthritis,elderly,children,young people"in Chinese and English.Articles were searched on CNKI and PubMed,with a timeframe of 1950 to 2024.According to inclusion and exclusion criteria,108 articles were finally included for summary.RESULTS AND CONCLUSION:Children's knee bone density will increase with age,reaching peaks in adulthood.From middle-aged to the age,the elastic modulus of knee joint femur,tibia,fibula,and patella will decrease with age,and then return to the elastic modulus of childhood.The elastic modulus of children and adult cartilage is basically the same,and the elastic modulus of the elderly increases.With the increase of age,the elastic modulus of the knee ligament will decrease to a certain extent,but there is no significant difference in the elastic modulus of the knee ligament of young people and the elderly.With the increase of age,the loss of mechanical integrity of the knee meniscus will damage the biomechanical function of the tissue and disturb the various anisotropic biomechanical responses that are effectively carried and transmitted by the tissue.Knee joint finite element modeling can be used to deeply understand the biomechanical characteristics of the knee joints,develop new implanted materials,predict knee joint diseases,improve surgical technology,and guide patients to rehabilitate exercise.

To investigate the association between neutrophil to lymphocyte ratio (NLR) andestimated glomerular filtration rate (eGFR) in patients with diabetes using large-scale data.

Objective:To investigate the risk factors for postoperative venous thromboembolism(VTE)in patients with non-small cell lung cancer(NSCLC),and establish a nomogram model for the accurate prediction of high-risk individuals.Methods:A total of 472 patients with NSCLC who underwent radical surgical resection in The First Affiliated Hospital of Anhui Medical University from June 2019 to December 2023 were included in the study.All patients were randomly assigned to the modeling group(n=332)or the internal validation group(n=140)at a ratio of 7∶3.In addition,200 patients with NSCLC admitted to Fuyang Hospital Affiliated with Anhui Medical University during the same period were randomly selected as the external validation group.To analyze the risk factors for post-operative VTE,patients in the modeling group were further assigned to the VTE group(n=58)or the non-VTE group(n=274),and the demographic data,clinicopathological features,and laboratory test results of the two groups were compared.Multivariate Logistic regression analysis was used to identify independent risk factors for VTE and to construct a nomogram model to predict VTE risk.The predictive ability of the model was evaluated using receiver op-erating characteristic(ROC)and calibration curves.Results:The incidence of post-operative VTE in patients with NSCLC was 16.9%.Patients in the VTE group were older(P=0.006),had a more advanced TNM stage(P<0.001),had more frequent vascular invasion(P=0.001),and had a longer duration of surgery(P=0.033)than patients in the non-VTE group.In addition,there were significant differences between patients in the VTE and non-VTE groups for pre-operative activated partial thromboplastin time(APTT)(P=0.003),D-dimer level(P<0.001),and serum carcinoembryonic antigen(CEA)level(P=0.029).Age,TNM stage,and pre-operative D-dimer level were independent risk factors for VTE in patients with NSCLC.Based on these four variables,a nomogram model was developed to predict the risk of post-operative VTE.The areas under the ROC curves for the modeling,internal validation,and external validation groups were 0.836,0.871,and 0.864,respectively.The calibration curve indicates a high degree of consistency between the predicted risks of the model and the actual risks that occur.Conclu-sions:The nomogram model based on age,TNM stage,operative time,and pre-operative D-dimer level can effectively identify individuals at risk of VTE,and it promises to be a valuable tool for risk assessment.