ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia. Methods: In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method. Results: Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences. Conclusion The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia. Methods: In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method. Results: Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences. Conclusion The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia. Methods: In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method. Results: Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences. Conclusion The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia. Methods: In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method. Results: Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences. Conclusion The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia. Methods: In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method. Results: Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences. Conclusion The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.

OBJECTIVE: To explore effectiveness of musculoskeletal ultrasound combined with Wide-Awake technique in extensor indicis proprius tendon (EIP) transfer for repairing extensor pollicis longus tendon (EPL) rupture. METHODS: A clinical data of 20 patients with EPL spontaneous rupture, who were admitted between January 2019 and June 2024 and met the selective criteria, was retrospectively analyzed. During EIP transfer surgery, the musculoskeletal ultrasound-guided incision marking combined with Wide-Awake technique was used in combination group (n=10) and the tourniquet-assisted surgery under brachial plexus block anesthesia in the control group. There was no significant difference in the baseline data between groups (P>0.05), including gender, age, affected side, cause and location of tendon rupture, and time from injury to hospitalization. The accuracy of preoperative musculoskeletal ultrasound in predicting the actual tendon rupture site was evaluated in the combination group. The operation time, intraoperative blood loss, visual analogue scale (VAS) scores during operation and at 6 hours after operation, total incision length, and postoperative complications were recorded. Surgical outcomes were assessed at 12 months after operation using the specific EIP-EPL evaluation method (SEEM), which included measurements of thumb elevation loss, thumb flexion loss, index finger dorsiflexion loss, and total score. RESULTS: In the combination group, the incision position marked by preoperative musculoskeletal ultrasound positioning was consistent with the actual tendon rupture position. Compared with the control group, the operation time and total incision length in the combination group were significantly shorter and the VAS score at 6 hours after operation was significantly higher (P<0.05). There was no significant difference in intraoperative blood loss or intraoperative VAS score between groups (P>0.05). All incisions in both groups healed by first intention. Two patients in the control group developed swelling and blisters in the tourniquet area, which subsided spontaneously without special treatment. All patients were followed up 12-14 months, with an average of 12.5 months. The thumb dorsiflexion function of all patients recovered to varying degrees. At last follow-up, the thumb elevation loss in combination group was significantly lower than that in control group, and the total score was significantly higher (P<0.05); there was no significant difference in thumb flexion loss or index finger dorsiflexion loss between groups (P>0.05). CONCLUSION Musculoskeletal ultrasound can accurately locate the site of tendon rupture, assist the Wide-Awake technique in implementing precise anesthesia, and adjust tendon tension while reducing tissue trauma, with satisfactory effectiveness.
Humans ; Male ; Tendon Injuries/diagnostic imaging* ; Tendon Transfer/methods* ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Ultrasonography/methods* ; Rupture/surgery* ; Treatment Outcome ; Operative Time ; Tendons/surgery* ; Young Adult

Objective To investigate the spatiotemporal expression pattern of metabotropic glutamate receptor 4(mGluR4)in the mouse cochlear basilar membrane and its dynamic changes during postnatal development until hair cell synaptic maturation.Methods Ten healthy 3-month-old C57BL/6L wild-type mice(5 males,5 females,25～35 g)were bred to obtain offspring.Cochlear samples from postnatal days 1～30(P1～P30)were analyzed.Frequency-specific auditory brainstem response(ABR)thresholds were measured at 45.2,32.0,22.6,16.0,11.3,8.0,5.6,and 4.0 kHz in P12,P14,P16,P21,and P30 mice.Immunofluorescence assay combined with confocal laser scanning microscopy was used to scan cochlear whole-mount preparations.Spatiotemporal co-localization profiling of mGluR4 and synaptic markers Ctbp2 and Snap25 was observed,and quantitative comparisons of fluorescent puncta density were performed.Results ABR testing revealed undifferentiated waveforms in all P12 mice,while 70%of P14 mice exhibited well-defined Wave I.In P14,P16,P21 and P30,mice undergoing ABR testing,50%failed to exhibit ABR waveforms when stimulated by 45.2 kHz tones,and 87.5%showed no response to 32.0 kHz stimuli.Auditory response thresholds for other frequencies progressively decreased with increasing postnatal age.Immunolocalization demonstrated stronger mGluR4 expression in inner hair cells(IHCs)versus outer hair cells(OHCs).Distinct mGluR4 puncta were observed at IHC presynaptic active zones(co-localized with Snap25)as early as P11,but showed minimal overlap with CtBP2-labeled ribbons.Quantitative analysis revealed significantly higher mGluR4 puncta density at P30 compared to P14 synapses(P<0.05).Conclusion Postnatal upregulation of mGluR4 at IHC synaptic regions correlates with functional maturation.These findings suggest mGluR4 may modulate vesicular exocytosis regulation and exert pharmacological inhibition on glutamate release,potentially influencing synaptic plasticity during auditory pathway refinement.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.