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.

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 clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis （NASH） combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1）. MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen， Stomach， and Hepatobiliary Diseases， the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method， patients were randomly divided into an observation group （62 cases） and a control group （62 cases）. The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally， while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， traditional Chinese medicine （TCM） syndrome scores （discomfort/dull pain/distending pain in liver region， fatigue， etc.）， body mass index （BMI）， waist-to-height ratio （WHtR）， high-density lipoprotein cholesterol （HDL-C）， total cholesterol （TC）， triglycerides （TG）， homeostatic model assessment for insulin resistance （HOMA-IR） ［including fasting blood glucose （FBG） and fasting insulin level （INS）］， free fatty acids （FFA）， IL-6， and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment， the total effective rate in the observation group was 92.3% （48/52）， while that in the control group was 75.5% （39/49）. The total effective rate in the observation group was higher than that in the control group （χ²=5.339， P<0.05）. After treatment， the TCM syndrome scores in both groups were significantly reduced （P<0.05）， and the post-treatment scores in the observation group were better than those in the control group （P<0.05）. After treatment， the levels of ALT， AST， TC， FFA， fasting insulin （FINS）， HOMA-IR， MCP-1， IL-6， CAP， LSM， BMI， and WHtR were decreased （P<0.05） significantly in both groups， and the observation group showed superior improvement in the above indicators compared to the control group （P<0.05）. The observation group exhibited significant reductions in TG and FBG （P<0.05） and an increase in HDL-C （P<0.05）， while no significant changes were observed in the control group. The observation group was superior to the control group after treatment （P<0.05）. No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis， lowers liver stiffness， inhibits the expression of serum inflammatory factors， and alleviates liver inflammation. No obvious adverse reactions occur， suggesting it is suitable for clinical application.

ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis （NASH） combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1）. MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen， Stomach， and Hepatobiliary Diseases， the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method， patients were randomly divided into an observation group （62 cases） and a control group （62 cases）. The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally， while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， traditional Chinese medicine （TCM） syndrome scores （discomfort/dull pain/distending pain in liver region， fatigue， etc.）， body mass index （BMI）， waist-to-height ratio （WHtR）， high-density lipoprotein cholesterol （HDL-C）， total cholesterol （TC）， triglycerides （TG）， homeostatic model assessment for insulin resistance （HOMA-IR） ［including fasting blood glucose （FBG） and fasting insulin level （INS）］， free fatty acids （FFA）， IL-6， and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment， the total effective rate in the observation group was 92.3% （48/52）， while that in the control group was 75.5% （39/49）. The total effective rate in the observation group was higher than that in the control group （χ²=5.339， P<0.05）. After treatment， the TCM syndrome scores in both groups were significantly reduced （P<0.05）， and the post-treatment scores in the observation group were better than those in the control group （P<0.05）. After treatment， the levels of ALT， AST， TC， FFA， fasting insulin （FINS）， HOMA-IR， MCP-1， IL-6， CAP， LSM， BMI， and WHtR were decreased （P<0.05） significantly in both groups， and the observation group showed superior improvement in the above indicators compared to the control group （P<0.05）. The observation group exhibited significant reductions in TG and FBG （P<0.05） and an increase in HDL-C （P<0.05）， while no significant changes were observed in the control group. The observation group was superior to the control group after treatment （P<0.05）. No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis， lowers liver stiffness， inhibits the expression of serum inflammatory factors， and alleviates liver inflammation. No obvious adverse reactions occur， suggesting it is suitable for clinical application.

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 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.

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.

Objective: To investigate the feature and treatment of atrial tachycardia (AT) originated from right atrial appendage (RAA) in children. Methods: The data of 42 children with AT originated from RAA, who were admitted the First Hospital of Tsinghua University from January 2010 to September 2022 were analyzed retrospectively.The clinical characteristics, treatment and efficacy were analyzed. The children were divided into tachycardia cardiomyopathy group and normal cardiac function group. The differences in the ablation age and the heart rate during AT between two groups were compared by independent sample t-test. Results: Among 42 children, there were 20 males and 22 females. The age of onset was 2.7 (0.6, 5.1) years. Their age at radiofrequency ablation was (6.5±3.6) years, and the weight was (23.4±10.0) kg. Thirty-two children (76%) had sustained AT. The incidence of tachycardia cardiomyopathy was 43% (18/42). Compared to that of the normal cardiac function group, the ablation age and the heart rate at atrial tachycardia of the tachycardia cardiomyopathy group were higher ((8.1±3.8) vs. (5.3±3.1) years, t=-2.63, P=0.012; (173±41) vs. (150±30) beats per minute, t=-2.05, P=0.047. Thirty-eight children (90%) responded poorly to two or more antiarrhythmic drugs. The immediate success rate of radiofrequency ablation (RFCA) was 57% (24/42), and the AT recurrence rate was 17% (4/24). Twenty-two children underwent RAA resection, and their AT were all converted to sinus rhythm after the surgery. During the RAA resection, 10 cases of right atrial appendage aneurysm were found, 9/18 of which failed the RFCA. Conclusions: The AT originated from the RAA in children tend to present with sustained AT, respond poorly to antiarrhythmic drugs, and has a low success rate of RFCA as well as high recurrence rate. Resection of the RAA is a safe and effective complementary treatment.
Male ; Female ; Humans ; Child ; Atrial Appendage/surgery* ; Anti-Arrhythmia Agents/therapeutic use* ; Retrospective Studies ; Catheter Ablation ; Tachycardia/surgery* ; Treatment Outcome ; Cardiomyopathies

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

ObjectiveTo study the efficacy of Aclasta combined with Liuwei Dihuangwan on osteoporosis and the effect on quality of life. MethodA total of 126 patients with osteoporosis who were treated in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from September 2019 to September 2020 were classified into the observation group and the control group with the randomized double-blind method. The observation group consisted of 60 patients （26 males and 34 females） with the age of 59-85 years old ［mean： （72.0 ± 6.5） years old］. The control group was composed of 66 patients （31 males and 35 females）， with the age of 62-82 years old ［mean： （73.0±8.2） years old］. The control group was treated with Aclasta， and the observation group Aclasta combined with Liuwei Dihuangwan. After treatment， the effective rate of each group was calculated. Bone mineral density （BMD） was measured in both groups before and after treatment， and serological parameters calcium （Ca）， total 25 （OH） vitamin D₃ （VITD-T）， osteocalcin （OC）， serum alkaline phosphatase （ALP）， parathyroid hormone （PTH）， β-collagen special sequence （β-CTX）， and total procollagen 1 N-terminal propeptide （T-P1NP） were also measured. Visual Analogue Scale （VAS） score， Japanese Orthopaedic Association （JOA） score， and Oswestry Disability Index （ODI） score were evaluated. On this basis， the effect was compared between the two groups. ResultThe indexes were insignificantly different between the two groups before treatment. After 6 months of treatment， the two groups showed decrease in VAS score and ODI score （P<0.01）， increase in JOA score （P<0.01）， BMD of lumbar spine and hip joint， elevation of Ca， VITD-T， OC， ALP， and PTH （P<0.05， P<0.01）， and decrease of β-CTX （P<0.01） as compared with before treatment. The level of T-P1NP dropped in the observation group after treatment （P<0.01）.After treatment， the total effective rate of the observation group was 88.3% （53/60）， as compared with the 74.2% （49/66） in the control group （χ²=4.047， P<0.05）. Moreover， after treatment， the observation group demonstrated higher levels of BMD， Ca， VITD-T， OC， and PTH （P<0.05）， lower levels of T-P1NP （P<0.05）， lower VAS score （P<0.01）， and higher JOA score （P<0.05） than the control group， but the ODI score was insignificantly different from that in the control group. ConclusionAclasta combined with Liuwei Dihuangwan is effective on osteoporosis， without increasing the incidence of adverse reactions. In addition， the combination can alleviate pain and improve the quality of life of osteoporosis patients.