Objective:To evaluate the diagnostic value of micro flow imaging (MFI) supported by Image Pro Plus (IPP) software for BI-RADS classification of breast nodules and the correlation between its parameters and Ki-67 expression level.Methods:A total of 205 cases of breast solid nodules with ultrasound BI-RADS classification of 4 categories were enrolled in this study. BI-RADS classification, CDFI score, MFI score, CDFI-IPP score and MFI-IPP score by IPP software were performed for each nodule. Ki-67 immunohistochemical staining of invasive ductal carcinoma was performed to analyze the correlation between MFI-IPP-VI and Ki-67 expression levels.Results:The combined BI-RADS classification for diagnosis of malignant nodules had the largest area under the ROC curve, which was significantly higher than that of BI-RADS, MFI-IPP-VI, MFI score, CDFI-IPP-VI, and CDFI score (all P<0.05). The combined BI-RADS classification had the best diagnostic efficacy for the diagnosis of malignant nodules with a sensitivity of 96.4%, specificity of 65.6% and accuracy of 82.4%. In addition, the agreement between experienced and inexperienced sonographers applying MFI-IPP-VI was higher than MFI (Kappa=0.780 vs. Kappa=0.743). The mean value of Ki-67 in invasive ductal carcinoma was 21.93%±16.37%, and Spearman's correlation analysis showed a positive correlation between MFI-IPP-VI and Ki-67 expression level ( r=0.815, P<0.05). Conclusions:MFI-IPP can assist sonographers to classify breast nodules by BI-RADS, providing an effective basis for puncture biopsy. MFI-IPP-VI offers the possibility of noninvasively predicting the expression level of Ki-67 in invasive ductal carcinoma.

Objective To understand the application effect of early screening scale and behavioral intervention effect in children with autism spectrum disorder (ASD). Methods A total of 348 children with suspected ASD were selected and evaluated using the Modified Checklist for Autism in Toddlers (M-CHAT) and Autism Behavior Checklist (ABC). The evaluation results were compared with those from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Children enrolled were given Early start Denver model (ESDM) intervention. The evaluation results of Gesell Developmental Scale and Autism Treatment Evaluation Checklist (ATEC) scores were compared before and after intervention. Results The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating ASD in children aged 1-3 years were 89.53%, 90.70%, 89.92% and 0.78. The corresponding values of ABC were 78.49%, 81.40%, 79.46% and 0.56. The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating children aged >3-6 years were 87.30%, 77.78%, 84.44% and 0.64. The corresponding values of ABC were 85.71%, 77.78%, 83.33% and 0.62. The sensitivity and accuracy of M-CHAT were higher than ABC for evaluating ASD in children aged 1-3 years (P<0.05). There were no significant differences in sensitivity, specificity and accuracy between M-CHAT and ABC for evaluating ASD in children aged 3-6 years (P>0.05). After intervention, development quotients (DQ) of personal-social aspects, adaptability, language, gross motor, and fine motor of children with ASD were higher than those before intervention (P<0.05). ATEC scores for language, behavior, sensation, and social contact of children with ASD were lower than those before intervention (P<0.05). Conclusion M-CHAT and ABC both can be used for early screening of ASD in children, especially M-CHAT. Early behavioral intervention can effectively improve the condition and developmental level of children with ASD.

Objective:To evaluate the diagnostic value of micro flow imaging (MFI) supported by Image Pro Plus (IPP) software for BI-RADS classification of breast nodules and the correlation between its parameters and Ki-67 expression level.Methods:A total of 205 cases of breast solid nodules with ultrasound BI-RADS classification of 4 categories were enrolled in this study. BI-RADS classification, CDFI score, MFI score, CDFI-IPP score and MFI-IPP score by IPP software were performed for each nodule. Ki-67 immunohistochemical staining of invasive ductal carcinoma was performed to analyze the correlation between MFI-IPP-VI and Ki-67 expression levels.Results:The combined BI-RADS classification for diagnosis of malignant nodules had the largest area under the ROC curve, which was significantly higher than that of BI-RADS, MFI-IPP-VI, MFI score, CDFI-IPP-VI, and CDFI score (all P<0.05). The combined BI-RADS classification had the best diagnostic efficacy for the diagnosis of malignant nodules with a sensitivity of 96.4%, specificity of 65.6% and accuracy of 82.4%. In addition, the agreement between experienced and inexperienced sonographers applying MFI-IPP-VI was higher than MFI (Kappa=0.780 vs. Kappa=0.743). The mean value of Ki-67 in invasive ductal carcinoma was 21.93%±16.37%, and Spearman's correlation analysis showed a positive correlation between MFI-IPP-VI and Ki-67 expression level ( r=0.815, P<0.05). Conclusions:MFI-IPP can assist sonographers to classify breast nodules by BI-RADS, providing an effective basis for puncture biopsy. MFI-IPP-VI offers the possibility of noninvasively predicting the expression level of Ki-67 in invasive ductal carcinoma.

With a global rise in morbidity rates， obesity has become a pressing public health issue. With increased adipocyte number and volume as the main characteristics， obesity is also manifested by metabolic disorders to varying degrees. At the same time， obesity is a risk factor for diabetes， hypertension， stroke， cancer， and cardiovascular diseases， imposing burdens on society and families. Influenced by lifestyle， environment， behavior， and genetics， obesity is caused by the interaction of many factors， and its pathological process is complex， involving inflammation， autophagy， and intestinal dysbiosis. The mitogen-activated protein kinase （MAPK） cascade reaction， a pivotal signaling pathway， plays a crucial role in cellular processes such as proliferation， differentiation， apoptosis， and stress responses. Both Chinese and international studies indicate that the MAPK signaling pathway can effectively regulate obesity through various pathways， including the modulation of adipocyte differentiation and apoptosis， appetite control， and inflammation improvement. Moreover， traditional Chinese medicine （TCM） has demonstrated significant efficacy in preventing and treating obesity， leveraging advantages such as multiple targets， diverse components， and minimal adverse effects. Research indicates that the MAPK signaling pathway is a primary focus of TCM regulation in this context， although a systematic review in this field is currently lacking. Therefore， this paper， by reviewing the latest Chinese and international research， provided a concise overview of the basic structure of the MAPK pathway， with a specific emphasis on recent progress in TCM interventions targeting the MAPK pathway for obesity treatment. The results indicate that regulating adipose tissue formation， differentiation， and thermogenesis， reducing inflammation and oxidative stress levels， and improving insulin sensitivity and metabolic disorders seem to be the main ways for TCM to regulate the MAPK pathway to prevent and treat obesity. However， it is necessary to find more research methods and explore potential mechanisms underlying TCM formulations based on the MAPK pathway for obesity prevention and treatment.

ObjectiveTo explore the possible mechanism of the treatment of dry eye with liver-meridian constraint-heat syndrome by Runmu Xiaoyao Powder （润目逍遥散） by miR-146a-5p and interleukin-1 receptor-associated kinase 1/tumour necrosis factor receptor associated factor 6/nuclear factor-κB （IRAK1/TRAF6/NF-κB） signalling pathway. MethodsEighty C57BL/6J mice were randomly divided into normal group， model group， agonist group， inhibitor group， sodium hyaluronate group， and Runmu Xiaoyao Powder high-， medium-， and low-dose groups， with 10 mice in each group. Except for the normal group， the mice of dry eye with liver-meridian constraint-heat syndrome were modeled by using benzalkonium chloride solution eye drops combined with chronic pain stimulation. Beginning on the 30th day of modelling， mice in Runmu Xiaoyao Powder high-， medium-， and low-dose groups were given 29， 14.5， and 7.25 g/kg of Runmu Xiaoyao Powder respectively twice daily by gavage； mice in sodium hyaluronate group were given 5 μl of sodium hyaluronate drops twice daily； mice in the agonist group were given 2 nmol of agomir-146a-5p drops in each eye at a time， and those in the inhibitor group were given 5 nmol of antagomir-146a-5p drops in each eye， with every other day， 3 times per week； mice in the normal and model groups were gavaged with deionised water at 1 ml/（100 g·d）. The intervention was continued for 14 days in each group， and mice in each group were examined for tear secretion， tear film rupture time， corneal fluorescein staining， and irritability scores on the day following the last intervention； HE staining was used to observe the pathological conditions of the cornea and lacrimal glands in each group； corneal and lacrimal gland inflammatory factors， such as interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， miR-146a-5p expression， were examined； matrix metalloproteinase 3 （MMP-3） and matrix metalloproteinase 9 （MMP-9） expression in cornea， IRAK1， TRAF6， nuclear factor κB p65 （NF-κB p65） protein and mRNA expression in cornea and lacrimal gland， and phosphorylated nuclear factor κB p65 （p-NF-κB p65） protein expression were detected. ResultsCompared with the normal group， mice in the model group showed reduced tear secretion， shorter tear film rupture time， higher irritability score （P＜0.05）， and pathological examination showed staining in the centre of the cornea， obvious corneal damage， increased volume of lacrimal gland follicular cells， disordered arrangement， a large number of inflammatory cell infiltration， and increased neovascularisation； corneal and lacrimal gland tissues showed elevated expression of IL-1β and TNF-α， decreased expression of miR -146a-5p， elevated expression of IRAK1， TRAF6， NF-κB p65， p-NF-κB p65 protein and IRAK1， TRAF6， NF-κB p65 mRNA， and elevated expression of MMP-3， MMP-9 protein in the cornea （P＜0.05）. Compared with the model group， all of the above indexes were significantly improved in high-dose group of Runmu Xiaoyao Powder， while some indexes were improved in the sodium hyaluronate group and the middle- and low-dose Runmu Xiaoyao Powder groups （P＜0.05）. Compared with the model group， corneal and lacrimal IRAK1 and TRAF6 mRNA and IRAK1， TRAF6 and p-NF-κB p65 protein expression decreased in the agonist group； compared with the inhibitor group， IRAK1， TRAF6， NF-κB p65 mRNA and protein expression in the cornea and lacrimal gland in the Runmu Xiaoyao Powder groups decreased （P＜0.05）. ConclusionRunmu Xiaoyao Powder can negatively regulate the IRAK1/TRAF6/NF-κB signalling pathway in the cornea and lacrimal gland of mice with dry eye of liver-meridian constraint-heat syndrome by up-regulation of miR-146a-5p， so as to inhibit inflammatory response and reduce the damage of the ocular surface tissues， and the high doses group showed the best effect.

Objective:To evaluate the body composition of ulcerative colitis (UC) patients by bioelectrical impedance analysis (BIA) and explore the correlation between body composition indices and disease activity, laboratory indices, and readmission.Methods:Patients with active UC hospitalized in the Department of Gastroenterology of Peking Union Medical College Hospital were enrolled continuously, and age and sex ratio-matched healthy volunteers were recruited through recruitment posters. Body composition was measured via BIA. Appendicular skeletal muscle index (ASMI) and trunk skeletal muscle index (TSMI) were calculated and adjusted for height (m 2). Muscle function was evaluated via handgrip strength. Moreover, patients were followed up after discharge and the readmissions due to recurrence or aggravation of UC were recorded. Results:This study enrolled 62 UC patients and 38 healthy volunteers. TSMI decreased significantly ( P<0.001) while ASMI showed no significant difference in male patients compared with healthy controls. ASMI ( P<0.001) and TSMI ( P=0.002) in female patients were significantly lower than those in healthy controls. Compared with patients with normal TSMI, a larger proportion of patients with low TSMI tended to show severe disease activity ( P=0.075), while no such trend was observed in patients with low ASMI. Handgrip strength and phase angle were significantly positively correlated with ALB in UC patients ( P<0.05). The proportion of patients with readmission was significantly higher in the low phase angle group than that in the normal phase angle group (58.3% vs. 22.0%, P=0.040). Conclusions:There were abnormal body composition and gender differences in UC patients. TSMI correlated better with clinical characteristics than ASMI in UC patients. Low phase angle might be predictive for readmission in UC patients.

Objective To investigate the difference of electrocardiographic(ECG)features between total left main artery(LM)occlusion and subtotal occlusion,and analyze risk factors of in-hospital mortality.Methods A total of 94 patients with left main complete occlusion and 99 patients with subtotal occlusion were included.ECG characteristics,coronary angiography and other clinical data were compared,and factors of hospital death were analyzed.The receiver operating characteristics(ROC)curve was used to analyze the predictive value of ECG characteristics in hospital death risk in patients with LM occlusion.The relationship between ECG characteristics,shock and collateral circulation were analyzed in patients with LM occlusion.Results Compared with the subtotal occlusion group,patients with LM occlusion presented with more ST-segment elevation(STE)in Ⅰ,avL,V2-V5,more STE in avR and avL,more left anterior fascicular block+right bundle branch block,prolonged QRS duration,less STE in avR and less STE in avR+V1.The in-hospital mortality was 46.8%(44/94)in LM occlusion and 14.1%(14/99)in LM subtotal occlusion.STE in avR+avL predicted total LM occlusion with a specificity of 0.97,and left anterior branch+right bundle branch block predicted total LM occlusion with a specificity of 1.00.In patients with total LM occlusion,STE in Ⅰ,avL,V2-V5,prolongation of QRS duration,shock,no collateral circulation,STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block,and STE in Ⅰ,avL,V2-V5 combined with shock predicted in-hospital mortality,with the area under the curve of 0.716,0.619,0.766,0.688,0.572,0.785,respectively.The diagnostic specificity of STE in Ⅰ,avL,V2-V5 combined with shock was 0.82,and the sensitivity was 0.75.STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block predicted in-hospital death in LM occlusion with a specificity of 0.94.The proportion of shock was higher in patients with STE in Ⅰ,avL,V2-V5,left anterior fascicular block+right bundle branch block and collateral flow absence(P＜0.05).In patients with total occlusion,no collateral flow was observed in patients with STE in Ⅰ,avL,V2-V5.In patients with STE in avR(including avR+V1),82.4%of patients presented with right coronary collateral circulation supplying the left anterior descending coronary artery and left circumflex artery territory.In patients with STE in avR+avL,69.2%of patients presented with right coronary collateral circulation supplying left anterior descending coronary artery territory.Conclusion Total LM occlusion presents with different ECG features compared with subtotal occlusion.In LM total occlusion,the ECG features predict in-hospital mortality and are associated with different collateral circulation.

Objective:To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison.Methods:The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis.Results:Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 ( n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 ( n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 ( n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 ( n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion:CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

Objective:To observe the expression of adenosine kinase (ADK) in the hippocampus of patients with refractory epilepsy, and to explore the role of ADK in the pathogenesis of refractory epilepsy.Methods:Thirteen patients with intractable epilepsy who underwent surgical resection of hippocampal tissue at the First Affiliated Hospital of Harbin Medical University were collected as the epilepsy group; At the same time, 4 cases of relatively normal temporal lobe brain tissue from patients with traumatic brain injury undergoing debridement surgery (without previous history of epileptic seizures) were collected, and these 4 patients served as the control group. The expression of ADK in two groups of specimens was detected at the tissue, gene, and protein levels using methods such as dual fluorescence immunohistochemistry, real-time quantitative polymerase chain reaction (RT Real time PCR), and Western blotting.Results:In the human brain, ADK was mainly expressed in the nucleus of astrocytes. Through histological observation, ADK was weakly expressed in normal brain tissue, while there is significant proliferation of glial cells and excessive expression of ADK in the brain tissue of patients with refractory epilepsy. The percentage of ADK positive glial cells in the epilepsy group was (53.90±17.59)%, and the control group was (23.82±4.18)%, with a statistically significant difference ( P<0.01). At the genetic level, using RT Real time PCR, it was found that the expression level of ADK mRNA in the epilepsy group was higher than that in the control group, with a 2 -△△Cp of 13.36, which was 13.36 times higher than that in the control group. At the protein level, the expression of ADK protein in the epilepsy group was found to be higher than that in the control group using protein immunoblotting ( P<0.01). Conclusions:ADK is weakly expressed in the nucleus of astrocytes in normal human brain tissue. In the brain tissue of patients with refractory epilepsy, astrocytes significantly proliferate and there is excessive expression of ADK. ADK may play an important role in the occurrence and development of refractory epilepsy in humans.

Objective:To investigate the prediction of National Institute of Healthy (NIH) risk stratification of gastrointestinal stromal tumor(GIST) based on clinical ultrasound model, ultrasonographic radiomics model and combined model by oral contrast enhanced ultrasonography.Methods:The clinical and ultrasound imaging data of 204 gastric GIST patients attending Tianjin Medical University Cancer Institute and Hospital from June 2021 to June 2022 were retrospectively analyzed, among whom a total of 101 patients with high and moderate NIH risk stratification GIST confirmed by postoperative pathology were included in the high risk group, and a total of 103 patients with low and extremely low NIH risk stratification GIST were in the low risk group. The ultrasound images of the largest diameter of the GIST were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from the ROI segmented images. The patients were randomly divided into training and validation sets in the ratio of 7∶3. The XGBoost of Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and combined model. Then the area under ROC curve (AUC), sensitivity, specificity, and accuracy were evaluated; the predictive ability of the three models was compared by Delong test. Calibration Curve was applied to evaluate the model performance, and the clinical Decision Curve Analysis was applied to determine the net benefit to patients.Results:A total of 578 ultrasonographic radiomics features were extracted from ROI, and 8 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. Finally, test results showed that AUC, sensitivity, specificity and accuracy of clinical ultrasound imaging model, ultrasonographic radiomics model and combined model were 0.75, 69.3%, 68.9%, 69.1%; 0.87, 79.2%, 81.6%, 80.4%; 0.91, 80.2%, 83.5%, 81.9%, respectively. Delong test showed that the difference of AUC between ultrasonographic radiomics model and clinical ultrasound imaging model was statistically significant ( Z=2.698, P<0.001), and the combined model was significantly better than clinical ultrasound imaging model ( Z=4.062, P<0.001) and ultrasonographic radiomics model ( Z=2.225, P=0.026). Calibration Curve showed the high performance of combined model, and Decision Curve Analysis showed the superior clinical usefulness of combined model. Conclusions:It is feasible to construct an ultrasonographic radiomics model for GIST NIH risk stratification based on oral contrast enhanced ultrasonography images, and the combined model has more advantageous diagnostic performance, which can identify high risk NIH GIST objectively and stably for clinical purposes.