ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Objective To employ three dimensional high-resolution vessel wall magnetic resonance imaging(3D hr-VW-MRI)for analyzing the imaging characteristics of posterior circulation non-stenotic intracranial atherosclerotic plaque and to discuss its diagnostic value in identifying culprit plaques.Methods Ninety-three patients(age[62.94±9.70]years old,67 males,26 females)with non-stenotic atherosclerosis in our hospital from Jan.2019 to Jan.2021 were retrospectively recruited.The imaging features of plaques,including luminal area,maximum wall thickness and minimum wall thickness at the most stenotic site,stenosis rate,plaque burden,remodeling index,eccentricity index,enhancement ratio at the most stenotic site,and intraplaque hemorrhage,were measured based on T1-weighted imaging(T1WI)and contrast-enhanced T1WI.The culprit plaque was defined as a lesion arising from the responsible vascular supply area to a fresh infarction on the diffusion weighted imaging(DWI)and T2 fluid attenuated inversion recovery(T2-FLAIR)images with accompanying ischemic stroke/transient ischemic attack(TIA).A plaque was considered to be a nonculprit plaque when it occurred in patients with presumed ischemic stroke/TIA,but without an infarct on DWI and T2-FLAIR.Results Sixty-one culprit plaques and 32 non-culprit plaques were analyzed.The proportions of patients with hyperlipidemia,National Institutes of Health stroke scale(NIHSS)score,narrowest plaque enhancement rate,and incidence of intraplaque hemorrhage in the culprit plaque group were significantly higher than those in the non-culprit plaque group(all P＜0.05).Multivariate logistic regression analyses showed that NIHSS score(odds ratio[OR]=1.799,95％confidence interval[CI]1.303-2.484,P＜0.001),enhancement ratio(OR=1.076,95％CI 1.027-1.128,P=0.002)and intraplaque hemorrhage(OR=30.708,95％CI 2.563-367.925,P=0.007)were associated with plaque type.Conclusion NIHSS score,enhancement ratio at the most stenotic site,and intraplaque hemorrhage are independent risk factors for culprit plaques in patients with posterior circulation non-stenotic intracranial atherosclerotic disease.These indicators may help identify such culprit plaques and could be used to screen individuals with plaques having these characteristics,thereby providing a basis for early preventive interventions.

Objective To explore the correlation between stroke etiology and clinical and imaging features in patients with acute ischemic stroke(AIS)due to large vessel occlusion treated by intravascular thrombectomy.Methods A total of 213 patients with AIS and endovascular embolectomy in our hospital from Oct.2016 to Jun.2018 were enrolled retrospectively.According to the etiological classification criteria of Trial of Org 10172 in Acute Stroke Treatment(TOAST),there were 116 cases of cardioembolism and 97 cases of non-cardioembolism.Multivariate logistic regression analysis was used to screen the clinical and imaging characteristics for identifying cardioembolism and non-cardioembolism.Results Compared with non-cardioembolism AIS,cardioembolism AIS was associated with higher NIHSS scores(adjusted odds ratio[OR]=1.09,95%confidence interval[95%CI]1.01-1.18,P=0.02),atrial fibrillation(adjusted OR=76.46,95%CI 26.75-218.51,P＜0.01),absence of hypertension(adjusted OR=0.32,95%CI 0.12-0.84,P=0.02),antiplatelet drug use(adjusted OR=5.03,95%CI 1.22-20.63,P=0.03),shorter onset-to-puncture time(adjusted OR=0.998,95%CI 0.996-1.000,P=0.04),and presence of hyperdense artery sign(HAS)(adjusted OR=4.45,95%CI 1.47-13.49,P=0.01).Conclusion There are some differences in clinical and imaging characteristics between patients with cardioembolism and non-cardioembolism AIS.The occurrence of HAS suggests a higher probability of cardioembolism in AIS patients.

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult

OBJECTIVE: To compare clinical effect of Ludloff operation on the clinical efficacy of patients with hallux valgus combined with hammertoe of the second toe. METHODS: The clinical data of 66 patients with hallux valgus treated with Ludloff surgery from July 2015 to July 2022 were retrospectively analyzed. According to exclusion criteria, 33 patients with hallux valgus combined with hammertoe were finally included as case group, and 33 patients with simple hallux valgus were paired as control group. There were 11 males and 22 females in case group, aged from 24 to 62 years old with an average of (33.6±12.7) years old;body mass index (BMI) ranged from 19 to 25 kg·m^-2 with an average of(21.7±3.1) kg·m^-2;17 patients on the left side and 16 patients on the right side;hallux valgus angle (HVA) ranged from 25° to 47° with an average of (36.3±10.2) °;the intermetatarsal angle (IMA) ranged from 13° to 21° with an average of (16.9±3.2) °. There were 12 males and 21 females in control group, aged from 22 to 61 years old with an average of (32.2±10.9) years old;BMI ranged from 18 to 26 kg·m^-2 with an average of (22.0±4.2) kg·m^-2;15 patients on the left side and 18 patients on the right side;HVA ranged from 26° to 46° with an average of (37.2±9.3) °;IMA ranged from 12° to 21° with an average of (17.3±4.7) °. HVA, IMA, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores and visual analogue scale (VAS) were compared at 3, 6 and 12 months after operation between two groups. RESULTS: Both groups were completed 1 year postoperative follow-up. Postoperative cutaneous margin necrosis occurred in 2 patients of case group and incision rupture occurred in 1 patient of control group. There was no significant difference between two groups (χ²=0.058, P>0.05). Both groups were achieved bone union at stageⅠat 12 weeks after opertaion, and no recurrence of bunion was observed during follow-up. Three months after operation, AOFAS forefoot function score of case group was (73.4±8.6), which was lower than that of control group (82.1±10.3), and the difference was statistically significant (P<0.05). There were no significant differences in HVA, IMA, AOFAS and VAS between two groups at 6 and 12 months after operation (P>0.05). CONCLUSION Ludloff surgery for the treatment of bunions with malleform toe of the second toe is slow in the early postoperative functional recovery, but it did not affect the long-term clinical outcome of the patients.
Humans ; Hallux Valgus/physiopathology* ; Male ; Female ; Middle Aged ; Adult ; Retrospective Studies ; Hammer Toe Syndrome/physiopathology* ; Young Adult

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective To explore the activity and mechanism of polymyxin B combined with novel β-lactam/β-lac-tamase inhibitor combinations on biofilm of polymyxin B-resistant Pseudomonas aeruginosa and Klebsiella pneumo-niae.Methods The minimum inhibitory concentration(MIC),minimum biofilm inhibitory concentration(MBIC),and minimum biofilm eradication concentration(MBEC)of all antimicrobial agents were determined by micro-broth dilution method and MBECTM assay.The crystal violet staining method was adopted to evaluate the effect of poly-myxin B combined with cefepime/avibactam,ceftazidime/avibactam,meropenem/avibactam,aztreonam/avibactam,meropenem/vaborbactam,and imipenem/relebactam at sub-MIC doses on inhibition of biofilm formation and eradi-cation of mature biofilm.The best combination scheme for anti-biofilm activity was screened out,and anti-biofilm mechanism of this combination scheme was preliminarily explored with phenol-sulfuric acid method,bacterial motili-ty test,and quorum sensing inhibition test.Results The MBIC and MBEC of all antimicrobial agents were higher than MIC.The combination regimen based on polymyxin B could inhibit the formation of biofilms and eradicate ma-ture biofilm in Pseudomonas aeruginosa and Klebsiella pneumoniae.The combination of polymyxin B with cefepime/avibactam had the highest inhibition and eradication rates,ranging 67.99％-90.16％and 58.26％-63.86％,respectively.The combination of polymyxin B and cefepime/avibactam could inhibit the extracellular poly-saccharides of Klebsiella pneumoniae,with inhibition rates of 34.04％-61.10％,this combination could also re-duce the swimming and twitching motility diameters of bacteria.Cefepime/avibactam monotherapy on quorum sen-sing signaling molecules presented concentration dependent inhibitory effect,and when combined with polymyxin B,the inhibitory effect was consistent with that of monotherapy.Conclusion Polymyxin B and cefepime/avibactam may be potential scheme for clinical treatment for severe biofilm-associated infection caused by polymyxin B-resistant strains,and their mechanisms may be related to the inhibition of bacterial extracellular polysaccharides and motility.

AIM:To explore whether microRNA-30a-3p(miR-30a-3p)is involved in the pathogenesis of non-alcoholic fatty liver disease(NAFLD)by regulating autophagy and promoting lipid deposition.METHODS:Eight-week-old C57BL/6 mice were randomly divided into a normal control group and a high-fat diet(HFD)group.Mice in the HFD group were fed with 60％high fat diet for 10 weeks to induce the NAFLD phenotype.Some mice were injected with adeno-virus overexpressing miR-30a-3p via the tail vein and subsequently fed with high-fat diet for 4 weeks.Glucose tolerance and insulin resistance tests were performed at the end of the treatments.In addition,the concentrations of hepatic alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were mea-sured.Hematoxylin-eosin staining and oil red O staining were conducted to examine morphological changes and lipid depo-sition in the liver tissue.The expression levels of microtubule-associated protein light chain 3(LC3),autophagy-related protein 5(ATG5),beclin-1 and p62 were quantified through Western blot.In addition,NAFLD models were established in AML12 hepatocytes by incubating the cells with palmitic acid and oleic acid(PO).The AML12 cells were transfected with miR-30a-3p shRNA to knock down miR-30a-3p expression.The concentration levels of TG and TC after miR-30a-3p knockdown were measured by the kits.Nile red staining was performed to examine lipid droplet aggregation and dual fluo-rescent recombinant adenovirus Ad-mCherry-GFP-LC3B was transfected into AML12 cells to observe changes in autopha-gic flow.RESULTS:HFD-fed mice exhibited significant insulin resistance and reduced glucose tolerance,significant lip-id deposition in the liver tissue,coupled with increased hepatic ALT,AST,TG and TC levels.The expression levels of au-tophagy-related proteins LC3-Ⅱ,beclin-1,and ATG5 were decreased,while that of p62 was increased(P<0.01).More-over,miR-30a-3p overexpression significantly increased blood glucose and insulin resistance in HFD-fed mice.However,it aggravated lipid droplets deposition in liver tissue and enhanced hepatic TG,TC,AST and ALT levels.Western blot re-vealed that the expression levels of LC3-Ⅱ,beclin-1 and ATG5 were further reduced,while that of p62 was significantly in-creased(P<0.01).In vitro,we observed that the TG and TC levels,as well as lipid accumulation in PO-treated AML12 cells were increased significantly.Similarly,the expression levels of LC3-Ⅱ,beclin-1 and ATG5 were decreased,whereas that of p62 increased in PO-treated AML12 cells(P<0.01).Notably,knockdown of miR-30a-3p resulted in a significant reduction in the TG content in PO-treated AML12 cells and lipid droplet aggregation was significantly suppressed.Further-more,the expression of LC3-Ⅱ,beclin-1 and ATG5 proteins was increased,while that of p62 was decreased significantly and the autophagy flow was improved(P<0.01).CONCLUSION:The miR-30a-3p exacerbates hepatic lipid deposi-tion,inducing severe hepatic steatosis and liver damage,to promote the occurrence and development of NAFLD in mice.Mechanistically,its effects involve inhibition of hepatic autophagy level.