Objective:To characterize the molecular evolution of coxsackievirus A10 (CVA10) strains in Anhui Province.Methods:The nucleic acids of CVA10 isolates in Anhui Province were extracted for whole-genome PCR amplification. One-generation sequencing was performed and the complete whole-genome sequences of 10 isolates were obtained. Nucleotide and amino acid sequence similarity analysis of CVA10 isolates and reference strains was performed using MegAlign in DNAStar software. MEGA 11.0 was used to classify the genotypes of CVA10 isolates and representative strains based on phylogenetic analysis of the VP1 region, and the average evolutionary differences between genotypes were calculated. BioEdit 7.2 was used to calculate the entropy of amino acid substitution in the P1-P3 region of the isolates and analyze the amino acid non-synonymous substitution sites. Recombination signals associated with the Anhui isolates were detected using RDP4 and further verified using Simplot 3.5. DnaSp6 software was selected to analyze the selection pressure of CVA10 isolates and prototype strains.Results:Based on the VP1 region, CVA10 isolates and CVA10 representative strains were categorized into A-F genotypes, and most of the CVA10 prevalent in mainland China belonged to the F genotype, with some isolates in Anhui Province being more closely related to the Yunnan isolates. The average rate of evolutionary difference in nucleotides among genotypes ranged from 18.70% to 33.70%. The isolates shared 17 non-synonymous amino acid mutation sites in the VP1 region, and amino acid substitutions in the VP1, 3A and 3C regions might affect the pathogenicity of the strains. The isolates frequently recombined with a variety of other EVA strains in the 5′UTR, 2C, 3C, 3D, and 3′UTR regions. Selection pressure analysis of the isolates showed that the isolate genes were affected by negative selection pressure.Conclusions:Genetic evolutionary analysis of CVA10 suggests that mutations and recombination with other types of EVA strains are prevalent, affecting the molecular epidemiological trend of CVA10, and that molecular surveillance of CVA10 strains in Anhui Province should continue to be strengthened.

With the rapid development of artificial intelligence(AI)technology and its extensive application in the medical field,Al has gradually been applied to all aspects of cerebrovascular disease diagnosis and treatment,including but not limited to prevention,prediction,diagnosis,treatment,and prognosis assessment.This article reviewed the current application of Al technology in the field of cerebrovascular disease diagnosis and treatment and discussed the improvement of the diagnostic and therapeutic process with AI technology application.It provides novel insights and strategies for the clinical management of cerebrovascular diseases.

With the rapid development of artificial intelligence(AI)technology and its extensive application in the medical field,Al has gradually been applied to all aspects of cerebrovascular disease diagnosis and treatment,including but not limited to prevention,prediction,diagnosis,treatment,and prognosis assessment.This article reviewed the current application of Al technology in the field of cerebrovascular disease diagnosis and treatment and discussed the improvement of the diagnostic and therapeutic process with AI technology application.It provides novel insights and strategies for the clinical management of cerebrovascular diseases.

Objective:To characterize the molecular evolution of coxsackievirus A10 (CVA10) strains in Anhui Province.Methods:The nucleic acids of CVA10 isolates in Anhui Province were extracted for whole-genome PCR amplification. One-generation sequencing was performed and the complete whole-genome sequences of 10 isolates were obtained. Nucleotide and amino acid sequence similarity analysis of CVA10 isolates and reference strains was performed using MegAlign in DNAStar software. MEGA 11.0 was used to classify the genotypes of CVA10 isolates and representative strains based on phylogenetic analysis of the VP1 region, and the average evolutionary differences between genotypes were calculated. BioEdit 7.2 was used to calculate the entropy of amino acid substitution in the P1-P3 region of the isolates and analyze the amino acid non-synonymous substitution sites. Recombination signals associated with the Anhui isolates were detected using RDP4 and further verified using Simplot 3.5. DnaSp6 software was selected to analyze the selection pressure of CVA10 isolates and prototype strains.Results:Based on the VP1 region, CVA10 isolates and CVA10 representative strains were categorized into A-F genotypes, and most of the CVA10 prevalent in mainland China belonged to the F genotype, with some isolates in Anhui Province being more closely related to the Yunnan isolates. The average rate of evolutionary difference in nucleotides among genotypes ranged from 18.70% to 33.70%. The isolates shared 17 non-synonymous amino acid mutation sites in the VP1 region, and amino acid substitutions in the VP1, 3A and 3C regions might affect the pathogenicity of the strains. The isolates frequently recombined with a variety of other EVA strains in the 5′UTR, 2C, 3C, 3D, and 3′UTR regions. Selection pressure analysis of the isolates showed that the isolate genes were affected by negative selection pressure.Conclusions:Genetic evolutionary analysis of CVA10 suggests that mutations and recombination with other types of EVA strains are prevalent, affecting the molecular epidemiological trend of CVA10, and that molecular surveillance of CVA10 strains in Anhui Province should continue to be strengthened.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg^-1） and Captopril group （0.002 57 g·kg^-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.

Diffuse large B-cell lymphoma (DLBCL) can be caused by multiple factors, including virus and autoimmune function, which in turn trigger persistent activation of the B-cell receptor (BCR) signaling pathway and other related signaling pathways, which collectively promote malignant B-cell proliferation and lead to tumor formation. Studies have shown significant progress in the treatment of primary and relapsed/refractory DLBCL with Bruton tyrosine kinase inhibitor (BTKi) in combination with chemotherapy, immunotherapy and small molecule inhibitors in the setting of poor outcome with BTKi monotherapy. This article reviews the progress of BTKi combined regimens in DLBCL.

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.