ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.

Voice biomarkers， as an emerging smart medical technology， are now being used in applications such as assisting in the diagnosis and treatment of diseases， facilitating accurate and personalized medical services for patients. However， it also raises many ethical issues， including informed consent， privacy protection， accuracy and reliability， data security， legal risks， and other issues. This paper systematically sorted out the ethical issues in the applications of voice biomarkers in the medical field， summarized these issues， such as informed consent， privacy protection， accuracy and reliability， data security， and legal risks， as well as explored the corresponding coping strategies. These countermeasures encompassed utilizing new media platforms to raise public awareness of voice biomarkers， strengthening supervision and management to promote the privacy protection of voice biomarkers， reducing algorithm biases to promote the general benefits of voice biomarkers to the public， establishing multidisciplinary teams to protect the data security of voice biomarkers， and encouraging medical professionals and researchers to participate in policy research， with a view to providing references for promoting and regulating the applications of voice biomarkers in the medical field.

Objective To investigate the expression of α7 nicotinic acetylcholine receptor (α7nAChR) in thymic T follicular helper cells (TFH) and its significance in patients with myasthenia gravis (MG). Methods Fifteen MG patients who underwent surgical treatment at the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People’s Hospital from June 2022 to June 2023 were selected as a MG group, including 7 males and 8 females, aged 12-30 years. Twelve patients who underwent partial thymectomy to optimize surgical field exposure during cardiac surgery at Fuwai Central China Cardiovascular Hospital from June 2022 to June 2023 were selected as a control group, including 5 males and 7 females aged 20-35 years. Thymus single cell suspension was obtained by grinding the thymus tissue, and flow cytometry was used to detect the expression of α7nAChR in TFH cells. The thymus cell suspension was purified using density gradient centrifugation, followed by immunomagnetic bead separation to obtain CD4+T cells. CXCR5 antibody and coupled magnetic beads were added to isolate TFH cells. Real-time fluorescent polymerase chain reaction and Western blotting were performed to further investigate the expression of α7nAChR in TFH cells. Results Compared with the control group, the proportion of thymic TFH cells in the MG group was significantly increased (P<0.05), along with significantly decreased mRNA and protein expression levels of α7nAChR within these cells (P<0.01). Conclusion The findings suggest that there is a reduced expression of α7nAChR within thymic TFH cells in MG patients, leading to weakened immunosuppressive function which may indirectly contribute to disease onset and progression.

The existing epilepsy seizure detection algorithms have problems such as overfitting and poor generalization ability due to high reliance on manual labeling of electroencephalogram's data and data imbalance between seizure and interictal periods. An unsupervised learning detection method for epileptic seizure that jointed graph attention network (GAT) and Transformer framework (GAT-T) was proposed. In this method, channel correlations were adaptively learned by GAT encoder. Temporal information was captured by one-dimensional convolution decoder. Combining outputs of the two mentioned above, predicted values for electroencephalogram were generated. The collective anomaly score was calculated and the detection threshold was determined. The results demonstrated that GAT-T achieved the average performance exceeding 90% (or 99%) with a 0.25 s (or 2 s) time segment length, which could effectively detect epileptic seizures. Moreover, the channel association probability matrix was expected to assist clinicians in the initial screening of the epileptogenic zone, and ablation experiments also reflected the significance of each module in GAT-T. This study may assist clinicians in making more accurate diagnostic and therapeutic decisions for epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Algorithms ; Seizures/physiopathology* ; Neural Networks, Computer ; Signal Processing, Computer-Assisted

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Background: Gout is the most prevalent form of inflammatory arthritis in the world. Total hip arthroplasty (THA) has emerged as a widely sought-after and highly effective surgical procedure for advanced hip diseases. However, there is a lack of research on the impact of gout on primary THA outcomes in large cohorts. This study aimed to address this gap by primarily investigating complications following THA in patients with or without gout. Methods: Patients with records of gout in the 2 years leading up to their primary THA and who also have at least 2 years of follow-up were identified using a national insurance database and compared to a 5:1 matched control. A total of 32,466 patients with gout and 161,514 patients without gout undergoing THA were identified. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. In addition, 90-day emergency department (ED) visits and inpatient readmission were also documented. Results: Patients with gout demonstrated higher rates of medical complications including deep vein thrombosis, transfusion, acute kidney injury, and urinary tract infection than non-gout patients (p < 0.001). Gout patients also showed higher rates of pulmonary embolism (p = 0.017). Increased incidences of surgical complications were identified in gout patients, specifically wound complications and periprosthetic joint infection (p < 0.001). There was an increased risk of revision for gout patients up to 90 days (p = 0.003), 1 year (p = 0.027), and 2 years (p = 0.039). There was also an increased risk of dislocation for gout patients up to 90 days (p = 0.022) and 1 year (p = 0.047), but not at 2 years. No significant difference was observed in aseptic loosening or periprosthetic fracture. Additionally, gout patients also demonstrated a higher likelihood of 90-day ED visits and readmission (p < 0.001). Conclusions Primary THA in gout patients is associated with increased risks of multiple medical and surgical complications. Our findings provide insights into the planning and expectation of THA for patients with gout. These insights have the potential to benefit the decision-making process for gout patients considering THA.

Objective Metabolomics was used to analyze the changes of metabolites in the plasma of Fenpropathrin-contaminated rats to find potential biomarkers for forensic identification of Fenpropathrin poisoning.Methods SD rats in the two experimental groups were given 20.5 mg/kg and 41 mg/kg doses of fenpropathrin respectively by gavage.The rats in the control group were given equivalent volume of normal saline.The angular vein blood of rats was collected 24 hours after gavage,and endogenous small molecule metabolites in plasma were investigated by ultra-performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).The data was processed by SIMCA14.1.The differential metabolites in plasma of fenpropathrin-infected rats were screened out according to the Variable Importance in Projection(VIP)and p<0.05 in the OPLS-DA model.Finally,the pathways were analyzed.Results There were significant differences in plasma metabolite levels between the control group and the experimental group,and 17 biomarkers were selected to identify whether the rats had received fenpropathrin,which mainly affected purine metabolism,Alanine,aspartate and glutamate metabolism,arginine biosynthesis,biosynthesis of unsaturated fatty acids and pyrimidine metabolism.Conclusion Fenpropathrin can change the composition of metabolites in rats,and the differential markers screened can provide supportive forensic evidence for cases related to deltamethrin poisoning.

Objective:To determine the efficacy and influencing factors of thymectomy for bulbar myasthenia gravis.Methods:The clinical data of 120 patients with bulbar myasthenia gravis admitted to the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People's Hospital from March 2018 to June 2023 were collected, with 61 males and 59 females. There were 66 patients with thymoma and 54 patients with non-thymoma. The duration of bulbar muscle involvement before operation ranged from 11 days to 108 months. Preoperative AChR-Ab was positive in 105 cases and negative in 15 cases. There were 28 cases with bulbar muscle involvement as the initial symptom and 92 cases as the non-initial symptom. There were 7 cases with crisis and 113 cases without crisis in the past. The postoperative efficacy was evaluated according to the Myasthenia Gravis post-treatment status evaluation program of the American Myasthenia Gravis Society. Univariate analysis and logistic regression analysis were used to analyze the factors that may affect the surgical efficacy. Results:All 120 patients successfully underwent extended thymectomy, there was no perioperative death. The follow-up time was 3-57 months, with a median of 24 months. Twenty-two patients (18.33%) achieved complete durable remission, 1 patient (0.83%) maintained remission, 65 patients (54.17%) had minimal symptoms, and 20 patients (16.70%) improved. No change in 8 cases (6.67%), no aggravation cases (0), deterioration in 2 cases (1.67%), and death in 2 cases (1.67%). 23 cases(19.17%) achieved clinical remission and 85 cases (70.83%) achieved partial remission. Univariate analysis showed that positive AChR-Ab before operation and duration of bulbar muscle involvement before operation were the influencing factors of surgical efficacy in patients with bulbar MG, and the difference was statistically significant ( P<0.05). Logistic regression analysis showed that positive AChR-Ab before operation and the duration of bulbar muscle involvement before operation were independent influencing factors of surgical efficacy. Conclusion:Thymectomy can effectively relieve the symptoms of bulbar myasthenia gravis. Patients with positive AChR-Ab before surgery and shorter duration of bulbar muscle involvement may benefit more from thymectomy.