Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

OBJECTIVES: This study aimed to investigate the influence of the dimensional stability of 3D printed resin master model on the replication accuracy of implant replicas. METHODS: Ten digital impressions of patients undergoing continuous crowns or fixed bridge restoration supported by two implants were obtained, and resin models with implant replicas were 3D printed. Scanning rods were fixed on the replicas 3, 7, and 14 days after printing. The 3D, linear, and angular deviations of the scanning rods at different times were analyzed through Geomagic Wrap 2021 software. RESULTS: The position of the replicas shifted mesiolingually, in the same direction as the shrinkage of the model. From day 7 onward, the 3D, distance linear, and angular deviations of the replicas (scanning rod) significantly increased compared with those on the 3rd day (P<0.05). On the 14th day, the changes were even more pronounced, with the above deviations showing statistical significance (P<0.05) compared with those for the 3-day and 7-day groups. No statistical difference in height linear deviation was observed among the groups. CONCLUSIONS The insufficient dimensional stability of 3D printed resin models can lead to changes in the relative position and angle of the replicas, thereby affecting the accuracy of the replicas in recreating the implant's position. Complete manufacturing of prosthesis is recommended within 7 days after the model is printed.
Printing, Three-Dimensional ; Humans ; Dental Implants ; Models, Dental ; Dental Impression Technique ; Crowns

ObjectiveTo observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis （NASH） and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin （IL）-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group， with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules， while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0， 12， and 24， the traditional Chinese medicine （TCM） syndrome score， body mass index （BMI）， liver fat content assessed by Fibroscan （CAP value）， the level of alanine transaminase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transferase （GGT）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acid （FFA）， and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% （23/37） in the control group and 85.71% （30/35） in the treatment group， with a statistically significant difference （χ² = 5.14， P<0.05）. At weeks 12 and 24 after treatment， the TCM syndrome score， BMI， CAP value， TC， TG， LDL-C， and FFA were all significantly lower in both groups compared to pre-treatment levels， while the HDL-C level significantly increased （P<0.05）. The effect was better at week 24 （P<0.05） than at week 12 （P<0.05）， and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment （P<0.05）. After 24 weeks of treatment， both groups exhibited significant reductions in IL-18 and IL-1β levels （P<0.05）. The treatment group demonstrated superior efficacy compared to the control group after treatment （P<0.05）. Both groups experienced decreases in ALT， AST， and GGT levels after treatment （P<0.05）. However， there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group， nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia， exhibiting hepatoprotective， anti-inflammatory， lipid-regulating， and weight-reducing effects.

Objective To discuss the correlation between noninvasive hemodynamic parameters and major adverse cardiovascular events(MACE)in patients with acute anterior wall myocardial infarction after receiving percutaneous coronary intervention(PCI).Methods A total of 132 patients with acute anterior wall myocardial infarction,who received PCI at the Affiliated People's Hospital of Shandong First Medical University of China between October 2021 and February 2024,were collected.At 24 h and 7 d after surgery,the hemodynamic parameters,including mean arterial pressure(MAP),cardiac index(CI),cardiac output(CO),stroke volume(SV),peripheral vascular resistance index(SVRI),were recorded.Spearman correlation analysis was used to analyze the relationship between Killip grade of cardiac function and hemodynamic parameters.According to the presence or absence of MACE within 6 months after PCI,the patients were divided into MACE group and non-MACE group.The predictive value of hemodynamic parameters for MACE was analyzed by receiver operating characteristic(ROC)curves.Results The postoperative 7-day levels of CO,CI and SV were higher than their postoperative one-day levels,while the postoperative 7-day level of SVRI was lower than its postoperative one-day level(P＜0.05).Of the 132 patients,Killip classification of grade Ⅰ was seen in 39,grade Ⅱ in 62,grade Ⅲin 23 and grade Ⅳ in 8.The postoperative 7-day levels of CO,CI and SV in the patients with Killip gradeⅢ-Ⅳ were lower than those in the patients with Killip grade Ⅰ-Ⅱ,while the level of SVRI in the patients with Killip grade Ⅲ-Ⅳ was higher than that in the patients with Killip grade Ⅰ-Ⅱ(P＜0.05).The results of Spearman correlation analysis showed that Killip grade of cardiac function was negatively correlated with the postoperative 7-day levels of CO,CI and SV,while positively correlated with the postoperative 7-day level of SVRI after PCI(r=-0.518,r=-0.480,r=-0.416 and r=0.493 respectively,all P＜0.05).Six months after PCI,34 patients developed MACE.The levels of CO,CI and SV in MACE group were lower than those in the non-MACE group,while the level of SVRI in MACE group was higher than that in the non-MACE group(P＜0.05).The area under the ROC curve(AUC)of MAP,CO,CI,SV,SVRI and combination of the five indicators for predicting MACE was 0.620,0.687,0.676,0.649,0.710 and 0.860 respectively,and the AUC value of the combination of the five indicators was the greatest one.Conclusion In patients with acute anterior wall myocardial infarction after receiving PCI,the changes in the levels of MAP,CO,CI,SV and SVRI can reflect cardiac function level to a certain extent and can predict the occurrence of MACE events in the short term.

Objective To address the limitations of conventional physics-informed neural network(PINN)in handling hemodynamic boundary constraints,an improved hard boundary-constrained PINN(HBC-PINN)framework was proposed to achieve precise prediction of blood flow fields within stenotic arteries.Methods An idealized stenosed vessel geometry model was established and computational fluid dynamic simulation was performed to obtain a validation dataset.Appropriate boundary dependent trial functions were designed according to the hard constraint method to embed the flow boundary conditions into the network output.Thus,an HBC-PINN model with the hard boundary constraint method was constructed to predict the velocity field and pressure field of stenosed blood flow.Meanwhile,an original PINN model with the soft constraint method was also built for comparison.By evaluating the accuracy of the two models on the validation dataset,the capability of the HBC-PINN model to simulate hemodynamics without using any labeled data for training was verified.Results The effectiveness of the HBC-PINN method in predicting hemodynamic parameters in stenosed blood flow tasks was validated.The relative L2 errors of the flow velocity and pressure predicted by the HBC-PINN in two different stenosis scenarios were both lower than 0.5％,representing an improvement of over 48.8％in accuracy compared to the original PINN model.Additionally,the prediction accuracy of the transverse velocity also increased by more than 35.4％.Conclusions Implementing hard constraints on boundary conditions in the PINN modeling process can effectively improve the prediction accuracy of hemodynamic parameters and the efficiency of model solving.

Objective To address the limitations of conventional physics-informed neural network(PINN)in handling hemodynamic boundary constraints,an improved hard boundary-constrained PINN(HBC-PINN)framework was proposed to achieve precise prediction of blood flow fields within stenotic arteries.Methods An idealized stenosed vessel geometry model was established and computational fluid dynamic simulation was performed to obtain a validation dataset.Appropriate boundary dependent trial functions were designed according to the hard constraint method to embed the flow boundary conditions into the network output.Thus,an HBC-PINN model with the hard boundary constraint method was constructed to predict the velocity field and pressure field of stenosed blood flow.Meanwhile,an original PINN model with the soft constraint method was also built for comparison.By evaluating the accuracy of the two models on the validation dataset,the capability of the HBC-PINN model to simulate hemodynamics without using any labeled data for training was verified.Results The effectiveness of the HBC-PINN method in predicting hemodynamic parameters in stenosed blood flow tasks was validated.The relative L2 errors of the flow velocity and pressure predicted by the HBC-PINN in two different stenosis scenarios were both lower than 0.5％,representing an improvement of over 48.8％in accuracy compared to the original PINN model.Additionally,the prediction accuracy of the transverse velocity also increased by more than 35.4％.Conclusions Implementing hard constraints on boundary conditions in the PINN modeling process can effectively improve the prediction accuracy of hemodynamic parameters and the efficiency of model solving.

ObjectiveTo observe the effects of Youguiwan on bone metabolism and bone morphogenetic protein-2 （BMP-2）/Smad signaling pathway in ovaries-removed rats with osteoporosis and study the mechanism of Youguiwan in the prevention and treatment of osteoporosis. MethodA postmenopausal rat model of osteoporosis was prepared by bilateral ovariectomy. The 40 female SD rats were randomly divided into five groups， including sham operation group， model group， alendronate sodium group （0.1 mg·kg^-1）， and high-dose and low-dose （5.36 and 2.68 g·kg^-1） groups of Youguiwan. The drug was given seven days after modeling， once a day for 12 weeks. After the treatment， the changes in femur tissue structure were observed by micro-CT， including bone mineral density （BMD）， bone volume/total volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone surface/bone volume （BS/BV）， and trabecular separation （Tb.Sp）. Ossification was observed by saffrane-solid green staining， and serum levels of bone metabolism markers， including bone alkaline phosphatase （BALP）， osteocalcin （BGP）， type Ⅰ procollagen amino terminal propeptide （PINP）， and tartrate-resistant acid phosphatase 5b （TRACP-5b）， were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of Runx2， BMP-2， and Smad1 in rat femur were detected by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham operation group， bone trabecula in the model group was sparse. BMD， BV/TV， Tb.N， and Tb.Th were decreased （P<0.05， P<0.01）. BS/BV （P<0.05） and Tb.Sp were increased. The content of BGP， BALP， PINP， and TRACP-5b in serum was significantly increased （P<0.01）. The mRNA and protein expressions of Runx2， BMP-2， and Smad1 in rat femur were significantly decreased （P<0.05， P<0.01）. Compared with the model group， the number of bone trabeculae in the high-dose and low-dose groups of Youguiwan was increased， and the bone microstructure was improved. BMD， BV/TV， Tb.N， and Tb.Th were increased significantly （P<0.05， P<0.01）， and BS/BV and Tb.Sp were increased. The content of bone metabolic markers decreased （P<0.05， P<0.01）. ConclusionYouguiwan has certain preventive and therapeutic effects on postmenopausal osteoporosis， and its mechanism may be related to promoting bone formation by regulating the BMP-2/Smad signaling pathway.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

Objective:To explore the comparative study of video laryngoscopy combined with bronchial blocker and video laryngoscopy combined with double-lumen tube in the teaching of endotracheal intubation in thoracic surgery in the standardized residency training of anesthesia.Methods:The trainees of the standardized residency training were randomly divided into control group and experimental group for clinical teaching, with 25 ones in each group. The experimental group was treated with visual laryngoscopy combined with bronchial blocker, while the control group was treated with visual laryngoscopy combined with double-lumen tube group. The intubation time, intubation success rate, positioning time, hemodynamic changes, and complication incidence during intubation, as well as student assessment results were recorded. GraphPad Prism 6.0 was used for t test and Chi-square test. Results:The time of endotracheal intubation [(95.3±10.1) vs. (137.5±13.5)] and positioning time [(100.8±11.7) vs. (155.4±15.3)] in the experimental group were both shorter than those of the control group ( P< 0.001), the hemodynamic changes in patients with immediate intubation were smaller ( P<0.001), the success rate of intubation was higher (92% vs. 68%) ( P<0.001), the complication incidence was lower ( P<0.001) and the students' performance was higher ( P<0.001). Conclusion:In the anesthesia teaching of thoracic surgery, bronchial blocker can reduce the time of endotracheal intubation, lower the hemodynamic changes during intubation, cut down the incidence of complications, improve the success rate of endotracheal intubation and enhance the confidence of students.