OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

Differentiated thyroid carcinoma(DTC)generally has a favorable prognosis.Most patients with DTC achieve good outcomes with surgery combined with radioactive iodine(RAI)therapy,with a 10-year survival rate exceeding 90%.However,about 5%-10%of patients develop unresectable local disease or distant metastases during the course of treatment,and may even gradually progress to a radioiodine-refractory(RAIR)state.For these advanced and inoperable patients,traditional treatments are difficult to control disease progression,making systemic drug therapy the mainstay of treatment.Over the past decade,significant advances in molecular targeted therapy and immunotherapy have transformed the landscape of advanced DTC.The2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer(abbreviation ATA guideline)propose a precision treatment model centered on molecular subtyping.This article compares the main differences in systemic therapy for advanced DTC between the 2015 and 2025 ATA guidelines,and,by integrating key clinical trials and real-world data,analyzes the evolution of treatment strategies over the past ten years and future directions.

Objective:To construct the risk prediction model for early-onset peritoneal dialysis-associated peritonitis (PDAP) in peritoneal dialysis patients based on six machine learning algorithms.Methods:This study was retrospective. Convenience sampling was used to select peritoneal dialysis patients who were regularly followed up in the Department of Nephrology of Guizhou Provincial People's Hospital from December 2009 to August 2023 to collect general information, primary diseases, and laboratory indicators of the study population. It was randomly divided into a modeling set and validation set in the ratio of 7∶3. With the occurrence of early-onset PDAP as the dependent variable, the risk prediction model of early-onset PDAP in peritoneal dialysis patients was constructed based on six machine learning algorithms, namely, Logistic regression, decision tree, support vector machine, random forest, extreme gradient boosting, and artificial neural network, respectively. Model performance was evaluated based on the area under the receiver operating characteristic curve ( AUC) , accuracy, and F1 score to select the optimal model. Results:The final data of 890 peritoneal dialysis patients were analyzed, of which 86 patients developed early-onset PDAP, and the incidence of early-onset PDAP was 9.66%. The four prediction models, Logistic regression, support vector machine, extreme gradient boosting, and random forest, had high accuracy with AUC values of 0.703, 0.729, 0.782, and 0.814, respectively, with the random forest model having higher AUC value, accuracy, and F1 score. Further ranking of the importance of risk factors for early-onset PDAP based on the random forest model showed that the top five characteristic variables were C-reactive protein, triglycerides, platelet, ferritin, and leukocyte, in that order. Conclusions:The risk prediction model for early-onset PDAP in peritoneal dialysis patients constructed based on the random forest model has optimal performance, which can help medical and nursing staff assess and prevent early-onset PDAP at an early stage.

The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

Differentiated thyroid carcinoma(DTC)generally has a favorable prognosis.Most patients with DTC achieve good outcomes with surgery combined with radioactive iodine(RAI)therapy,with a 10-year survival rate exceeding 90%.However,about 5%-10%of patients develop unresectable local disease or distant metastases during the course of treatment,and may even gradually progress to a radioiodine-refractory(RAIR)state.For these advanced and inoperable patients,traditional treatments are difficult to control disease progression,making systemic drug therapy the mainstay of treatment.Over the past decade,significant advances in molecular targeted therapy and immunotherapy have transformed the landscape of advanced DTC.The2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer(abbreviation ATA guideline)propose a precision treatment model centered on molecular subtyping.This article compares the main differences in systemic therapy for advanced DTC between the 2015 and 2025 ATA guidelines,and,by integrating key clinical trials and real-world data,analyzes the evolution of treatment strategies over the past ten years and future directions.

Objective:To construct the risk prediction model for early-onset peritoneal dialysis-associated peritonitis (PDAP) in peritoneal dialysis patients based on six machine learning algorithms.Methods:This study was retrospective. Convenience sampling was used to select peritoneal dialysis patients who were regularly followed up in the Department of Nephrology of Guizhou Provincial People's Hospital from December 2009 to August 2023 to collect general information, primary diseases, and laboratory indicators of the study population. It was randomly divided into a modeling set and validation set in the ratio of 7∶3. With the occurrence of early-onset PDAP as the dependent variable, the risk prediction model of early-onset PDAP in peritoneal dialysis patients was constructed based on six machine learning algorithms, namely, Logistic regression, decision tree, support vector machine, random forest, extreme gradient boosting, and artificial neural network, respectively. Model performance was evaluated based on the area under the receiver operating characteristic curve ( AUC) , accuracy, and F1 score to select the optimal model. Results:The final data of 890 peritoneal dialysis patients were analyzed, of which 86 patients developed early-onset PDAP, and the incidence of early-onset PDAP was 9.66%. The four prediction models, Logistic regression, support vector machine, extreme gradient boosting, and random forest, had high accuracy with AUC values of 0.703, 0.729, 0.782, and 0.814, respectively, with the random forest model having higher AUC value, accuracy, and F1 score. Further ranking of the importance of risk factors for early-onset PDAP based on the random forest model showed that the top five characteristic variables were C-reactive protein, triglycerides, platelet, ferritin, and leukocyte, in that order. Conclusions:The risk prediction model for early-onset PDAP in peritoneal dialysis patients constructed based on the random forest model has optimal performance, which can help medical and nursing staff assess and prevent early-onset PDAP at an early stage.

The gut microbiota is a vast microbial ecosystem,specifically present in the organism and plays an important regulatory role in the body's health or disease state together with its metabolites.After spinal cord injury,the complex pathophysiology at the site of trauma makes axonal regeneration difficult,and the autonomic motor dysfunction induced by spinal cord injury disrupts gastrointestinal function and causes gut microbiota imbalance.The previous clinical outcomes of neurorepair strategies after spinal cord injury have not been ideal.The dysregulated gut microbiota and neuroinflammation after spinal cord injury are closely associated with the prognosis of the patients.The potential mechanisms by which the gut microbiota may influence the neuroinflammation after spinal cord injury may include the activation of gut-associated lymphoid tissue and disruption of the intestinal barrier by the imbalanced microbiota,and gut microbiota and its metabolites such as lipopolysaccharides(LPS),short chain fatty acids(SCFAs),5-hydroxytryptamine(5-HT),and tryptophan,as well as immune cells,inflammatory factors,and neurotransmitters the local inflammatory response in the spinal cord through the circulatory system.This paper revews the studies on the changes in gut microbiota after spinal cord injury and their effects on the spinal cord neuroinflammation,providing new targets and new ideas for improving the neuroinflammation after spinal cord injury.