ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant

ObjectiveTo explore the effects of transmembrane protein 16B （TMEM16B） on brain edema and blood-brain barrier after cerebral ischemia-reperfusion injury in rats. MethodsTMEM16B overexpression and knockdown was performed by adeno-associated virus （AAV）， and then adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion （MCAO）. Rats were randomly divided into Sham group， MCAO group， AAV no-load group， TMEM16B overexpression group and TMEM16B knockdown group. Modified neurological severity scores， adhesive removal test and cylinder test were used to evaluate neurologic function. The ultrastructure of ischemic brain tissue was observed by transmission electron microscope. Brain water content was reflected by dry wet weight ratio of brain tissue. The expressions of TMEM16B， aquaporin4 （AQP4）， Claudin5 and zonula occludens-1 （ZO-1） were investigated by immunofluorescence and Western blot. ResultsCompared with the AAV no-load group， the sensory and motor functions of rats in TMEM16B overexpression group were significantly impaired. Mitochondria were swollen； mitochondrial cristae and tight junctions disappeared. The brain water content was higher in overexpression group. The expression of TMEM16B and AQP4 increased while the expression of Claudin5 and ZO-1 decreased （all P<0.05）. Compared with the AAV no-load group， the rats in TMEM16B knockdown group showed some recovery in motor function. The mitochondrial cristae and structure were clear， and the basement membrane was partially blurred. The brain water content was lower in knockdown group. The protein levels of TMEM16B and AQP4 were lower while the levels of Claudin5 and ZO-1 were higher in TMEM16B knockdown group than in AAV no-load group （all P<0.05）. ConclusionAn increase in TMEM16B expression aggravates brain edema and blood-brain barrier damage in rats after cerebral ischemia-reperfusion injury， while a decrease in TMEM16B expression alleviates brain edema and protects the blood-brain barrier.

OBJECTIVE To investigate the mechanism of Shenling baizhu san （SLBZS） in ameliorating ulcerative colitis （UC）. METHODS Mice were randomly divided into normal group， model group， and low-， medium-， high-dose SLBZS groups （3， 6， 12 g/kg）， with 10 mice in each group. Except for the normal group， mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously， mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration， the histopathological morphology of colon tissues was observed； the serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-18 were detected； the total bile acid contents in liver， gallbladder and colon tissues were determined； the expression level of NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41（GPR41），GPR43，farnesoid X receptor （FXR）， G protein-coupled bile acid receptor 1 （TGR5）， flavin-containing monooxygenase 3 （FMO3）， cytochrome P450 family 27 subfamily A member 1 （CYP27A1）， CYP7A1] in liver or colon tissues， as well as the proteins related to Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3 inflammatory axis [TLR4， NF-κB， phosphorylated NF-κB （p-NF-κB）， myeloid differentiation factor 88 （MyD88）， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， caspase-1] in colon tissues were measured. RESULTS Compared with the model group， the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α， IL-1β and IL-18， total bile acid contents in liver and colon tissues， as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues， TLR4， p-NF-κB， NF-κB， MyD88， NLRP3， ASC and caspase-1 in colon tissues were significantly decreased （P＜0.05）. Meanwhile， the total bile acid content in gallbladder， the protein expression levels of GPR41 and GPR43 in colon tissues， along with CYP27A1， FXR and TGR5 in liver tissues were significantly increased （P＜0.05）. CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.

Objective:To explore the prominent manifestations and internal associations of the overuse of short-form videos,inattention,and school refusal behavior in junior high school students.Methods:A survey was conducted among 1 106 junior high school students,utilizing the Short-form Video APP Overuse Scale,the Inatten-tion subscale of the Swanson,Nolan,and Pelham Rating Scale(SNAP-Ⅳ),and the School Refusal Behavior Ques-tionnaire to assess the extent of short-form video overuse,inattention,and school refusal behavior.By using the R language for network analysis,the core nodes of individual networks and the bridge nodes connecting the combined networks were analyzed,and the structural differences in networks across genders and grades were compared.Re-sults:The core nodes of the network pertaining to overuse of short-form video,inattention,and school refusal behav-ior were"Using short videos enhances connection with others"(expected influence value=1.03),"easily distract-ed"(expected influence value=1.99),and"school alienation"(expected influence value=0.83).The bridge nodes in the combined network were"defiant behavior"(bridge expected influence value=0.69)and"difficulty sustaining mental activities"(bridge expected influence value=0.47).Analysis of network structure differences i-dentified that the core nodes within the combined networks of the first,second,and third grades of junior high school students were respectively"prioritizing short videos over other activities","defiant behavior",and"academic aptitude".Conclusion:Junior high school students exhibiting overuse of short videos,inattention,or school refusal behavior are characterized by enhanced social connectivity through platforms such as short video apps,a propensity for distraction,and feelings of school alienation,respectively.When these three behaviors coexist,the most salient related factor is oppositional behavior,coupled with difficulties in sustaining cognitive tasks and maintaining con-centration.

Parkinson's disease(PD)is a common progressive neurodegenerative disease mainly affecting the motor system.Various genetic factors and cellular mechanisms underlying PD have recently been discovered.Emerging evidence suggests that epigenetic modifications play a very important role in the pathogenesis,prevention,and treatment of PD.Epigenetic modification mediates genetic and environmental interactions mainly through complex interactions of DNA methylation,histone modification,and non-coding RNA,thereby affecting expression in the absence of changes in DNA sequence.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.Recent studies have found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modifications in the treatment of PD.Traditional Chinese medicine benefits from its multi-level and multi-target regulatory effects,and various traditional Chinese medicine monomers,compound prescriptions,and techniques have been evaluated,confirming that this is a promising approach for improving symptoms in PD.This review summarizes the mechanisms by which epigenetic modifications contribute to P D,explores the role of traditional Chinese medicine,and provides new ideas for clinical treatment and drug development in PD through epigenetic intervention.

Objective:To evaluate the image quality and radiation dose in contrast-enhanced thoracic-abdominal-pelvic CT using automatic tube voltage modulation (ATVM) coupled with artificial intelligence iterative reconstruction (AIIR) versus routine tube voltage combined with Karl-3D iterative reconstruction (Karl-3D IR), and to determine the optimal noise level for AIIR in contrast-enhanced thoracic-abdominal-pelvic CT.Methods:A total of 100 patients who underwent contrast-enhanced thoracic-abdominal-pelvic CT examination in the Affiliated Hospital of Hebei University from April to October, 2023 were randomly divided into group A and group B using a random number table, with 50 patients in each group. Group A was scanned using ATVM, and images were reconstructed using AIIR with 1-5 noise levels. Group B was scanned using tube voltage 120 kVp and images were reconstructed with Karl-3D IR and noise level 5. The single-to-noise ratio (SNR), contrast-to-noise ratio (CNR), effective dose (E), and size-specific dose estimate (SSDE) were recorded or calculated for all patients or images. Subjective evaluations of all images were performed. The quality of the reconstructed images using AIIR with 1-5 noise levels were compared and the optimal noise level of AIIR for image reconstruction was determined. Image quality and radiation dose were statistically analyzed for Group A (image reconstruction with optimal AIIR noise level) and Group B.Results:The mean SNR and mean CNR of the reconstructed images using AIIR with noise levels 1, 2, and 3 in group A were higher than those using AIIR with noise levels 4 and 5. The images reconstructed using AIIR with noise levels 3 and 4 scored higher in subjective assessment than those reconstructed using AIIR with noise levels 1, 2, and 5. Therefore, noise level 3 was optimal for AIIR in reconstruction of contrast-enhanced thoracic-abdominal-pelvic CT images. The mean SNR, mean CNR, and subjective evaluation score of group A using AIIR with noise level 3 were higher than those of group B using Karl-3D IR with noise level 5 ( P<0.001). The mean SSDE and the mean E of group A were reduced by 46% and 41%, respectively, compared with those of group B. Conclusions:ATVM technology combined with the AIIR algorithm can improve image quality and reduced patient radiation dose in contrast-enhanced thoracic-abdominal-pelvic CT. Noise level 3 is optimal for AIIR in the reconstruction of arterial-phase and venous-phase contrast-enhanced thoracic-abdominal-pelvic CT images.

Purpose To explore deep transfer learning(DTL)based on multi-parameter MRI for joint prediction of uterine endometrial cancer microsatellite expression with clinical parameters.Materials and Methods Retrospective analysis was conducted on 262 patients with uterine endometrial cancer in the Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University from January 2020 to December 2022,who were randomly divided into a training cohort(n=183)and a validation cohort(n=79)in a 7∶3 ratio.DTL features were extracted from T2WI and diffusion-weighted imaging(DWI)using a 50-layer residual neural network(ResNet50).Subsequently,T2-net,DWI-net,multi-sequence fusion and a combined model were constructed.A combined model was constructed via incorporating multiparametric fusion DTL features and clinically independent prognostic factors identified through both univariate and multivariate Logistic regression analysis.Model performance was assessed using the area under the curve,calibration curve and decision curve.Grad-CAM was used for model visualization analysis.Results Compared with single-sequence models,the multi-sequence fusion models exhibited superior performance,with area under the curve value of 0.898 for the validation cohort,accuracy of 0.823,sensitivity of 0.812,specificity of 0.825,respectively,and F1 score was 0.650.Univariate and multivariate Logistic regression analyses revealed that serum human epididymis protein 4 levels and the presence of uterine fibroids were clinically independent risk factors.Ultimately,the combined model demonstrated the best predictive performance in the validation cohort,with area under the curve value of 0.924,accuracy of 0.835,sensitivity of 0.875,specificity of 0.825,respectively,and F1 score was 0.683.Conclusion The multi-parameter fusion model based on DTL features can effectively and non-invasively predict the microsatellite status of endometrial cancer patients.

Objective To explore the prescription and preparation technology of compound Bupleurum suppository and draft its quality standard.Methods The volatile oil of Bupleurum was extracted by steam distillation,and the compound Bupleurum-based suppository was prepared by mixing the volatile oil with taurine using the melting method.The quality standard of the preparation was formulated according to the quality inspection items of the general rule 0107 of the Pharmacopoeia of the People's Republic of China(2020 Edition,Volume IV);The contents of n-hexanoic acid and n-heptanoic acid in the preparation were determined by gas chromatography-mass spectrometry(GC-MS).The content of taurine in the preparation was determined by high-performance liquid chromatography(HPLC).Results The optimized distillation time of the volatile oil was 1.5 h,The linear ranges of n-hexanoic acid,n-heptanoic acid and taurine are 23.175 0-115.875 0 μg·mL-1(R2=0.999 4),4.590 0-68.850 0 μg·mL-1(R2=0.998 9)and 15-125 μg·mL-1(R2=0.999 6),respectively.The average recoveries are 99.83%,101.96%,98.89%with RSDs of 2.84%,1.36%,2.88%,respectively.The RSDs of precision,stability,and repeatability tests are less than 5%.The properties,mass difference,melting time,microbial limit,and stability assessment of the preparationwere all in accordance with the Pharmacopoeia of the People's Republic of China.Conclusion Compound Bupleurum suppository preparation technology is reasonable and feasible,which meets the quality standard.