Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1 ^+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity-collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

Objective To investigate the protective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on the pulmonary arterial hypertension(PAH)model induced by monocrotaline(MCT)/monocrotaline pyrrole(MCTP)in SD rats/human pulmonary artery endothelial cell(HPAEC).Methods In vivo experiment,60 male SD rats were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(20 mg/kg)group,AS-Ⅳ medium-dose(40 mg/kg)group,AS-Ⅳ high-dose(80 mg/kg)group,or sildenafil(Sil,100 mg/kg)group,with 10 rats in each group;except for the control group,PAH rat models were established by single intraperitoneal injection of MCT(60 mg/kg)in other groups.In vitro experiment,HPAECs were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(10 μmol/L)group,AS-Ⅳ medium-dose(20 μmol/L)group,MCTP+AS-Ⅳ high-dose(40 μmnol/L)group,or p38 mitogen-activated protein kinase(MAPK)signaling pathway inhibitor(SB203580,5 μmol/L)group;except for the control group,in vitro PAH cell models were established by MCTP(60 μg/mL)induction for 24 h in other groups.In vivo experiments,after 4 weeks of drug intervention,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)of rats were measured by hemodynamic methods,the right ventricle hypertrophy index was measured by weighing methods,the percentage of pulmonary arteriole wall thickness to outer diameter(WT％)and percentage of the wall area to total vascular area(WA％)were observed by hematoxylin-eosin staining,the expression of cysteine aspartic acid specific protease 3(caspase 3)protein in lung tissue was observed by immunohistochemistry(IHC),and the apoptosis of lung tissue cells was detected by TUNEL assay.In vitro experiments,JC-1 staining was used to detect the mitochondrial membrane potential in cells,and immunofluorescence was used to detect caspase 3 protein expression.In vitro and in vivo experiments,Western blotting was used to detect the expression of caspase 3,B-cell lymphoma gene 2(Bcl-2),Bcl-2 associated X protein(Bax),p38 MAPK,and phosphorylated p38 MAPK proteins in lung tissue and HPAECs.Results In vivo experiments,the RVSP,mPAP,and right ventricle hypertrophy index were decreased in the Sil group and each dose group of AS-Ⅳ(all P＜0.01);the WA％and WT％of each dose group of AS-Ⅳ were decreased(all P＜0.01),the expression of caspase 3 protein in lung tissue was decreased(all P＜0.01),and the apoptosis of lung tissue cells was decreased(all P＜0.01).In vitro experiments showed that after intervention with each dose of AS-Ⅳ and SB203580,the mitochondrial membrane potential of HPAEC was increased(all P＜0.01)and the expression of caspase 3 was decreased(all P＜0.01).In vivo and in vitro experiments,each dose of AS-Ⅳand SB203580 reduced the expression of Bax and phosphorylated p38 MAPK proteins,and increased the expression of Bcl-2 protein(all P＜0.01).Conclusion AS-Ⅳ reduces apoptosis by inhibiting p38 MAPK signaling pathway,improving PAH in SD rats.

Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We un-covered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Objective To investigate the clinical features of spinocerebellar ataxia 12(SCA12).Methods The clinical data of a family with SC A1 2 diagnosed by gene detection were retrospectively analyzed,and the literature was reviewed.Results Three patients in this family were diagnosed as SCA12.Among them,2 patients with clinical symptoms were＞45 years old,the clinical symptoms were head tremor,upper limb tremor,voice tremor,dystonia and ataxia.Another one case was 31 years old,did not have relevant clinical manifestations yet.Cranial MRI showed that cerebral cortex atrophy was more serious than cerebellar atrophy in 2 patients.Conclusion SCA12 typically presents with upper limb tremor,with head tremor being less common,as the disease progresses,symptoms such as ataxia,dystonia,Parkinsonism,and cognitive impairment may develop,due to its highly heterogeneous clinical features,genetic testing can be helpful for diagnosis.

Objective To investigate the susceptibility and infection characteristics of dengue virus(DENV)in cells derived from diverse tissues of tree shrews and to provide a basis for expanding the repertoire of DENV-permissive cell models in this species.Methods DENV was inoculated at a multiplicity of infection(MOI)of 0.02 into tree shrew skin fibroblasts(TSFs),primary tree shrew renal epithelial cells(pTRECs),tree shrew aortic endothelial cells(TAECs),tree shrew aortic smooth muscle cells(TASMCs),tree shrew hepatocytes(THs),tree shrew corneal stromal cells(TCSCs),tree shrew brain microvascular endothelial cells(TBMECs),and tree shrew retinal microvascular endothelial cells(TRMECs).C6/36,Vero,A549,and BHK-21 cells(commonly used for DENV propagation)were used as positive controls.Over 6 days post-infection,cellular cytopathic effects were monitored at 12-hour intervals using an inverted microscope,viral RNA loads in cell lysates were quantified by real-time fluorescent quantitative PCR to generate proliferation curves,and viral titers were determined by plaque assay.Results Seven types of tree shrew cells,except TRMECs,were susceptible to DENV.Prolonged infection induced pronounced cytopathic effects,including cell rounding,detachment,necrosis,and lysis,across all susceptible cells.The viral RNA loads detected in lysates of pTRECs,TBMECs,TASMCs,TAECs and THs,approached those of positive controls(≥4×107 copies/μL).Infectious progeny viruses were produced by these five cell types,with three(TAECs,3.13×105 PFU/mL;THs,2.03×105 PFU/mL;pTRECs,1.58×105 PFU/mL)exhibiting titers comparable to C6/36(3.85×10 5 PFU/mL)and earlier viral harvests.Conclusion DENV exhibits broad susceptibility to tree shrew cells of multiple tissue origins,with proliferation rates surpassing those of conventional cell lines sourced from other species.TAECs,THs,and pTRECs are particularly suitable for large-scale DENV proliferation,suggesting their potential involvement in in vivo infection.

Objective:To gain an in-depth understanding of the willingness and needs of rural residents for emergency rescue training, so as to provide reference for improving their participation in emergency rescue training and the training effectiveness.Methods:Purposive sampling was used to select 16 rural residents in different streets of two townships in Binzhou City, Shandong Province from April to May 2024 as study subjects. Information was collected using face-to-face semi-structured in-depth interviews. After the interview, timely transcription and verification were conducted, and the Colaizzi 7-step analysis method was used to analyze and summarize the data.Results:The majority of residents had a strong willingness to participate in emergency rescue training, and some had a negative willingness. Rural residents' needs for emergency rescue training focused on five main areas of targeted, content, specialization, continuity, and implementation needs.Conclusions:The motivating factors for rural residents' willingness to participate in emergency rescue training are complex. The relevant departments and organizations should give full consideration to the actual needs of the residents and provide them with active and substantive guidance and assistance.

Objective To investigate the susceptibility and infection characteristics of dengue virus(DENV)in cells derived from diverse tissues of tree shrews and to provide a basis for expanding the repertoire of DENV-permissive cell models in this species.Methods DENV was inoculated at a multiplicity of infection(MOI)of 0.02 into tree shrew skin fibroblasts(TSFs),primary tree shrew renal epithelial cells(pTRECs),tree shrew aortic endothelial cells(TAECs),tree shrew aortic smooth muscle cells(TASMCs),tree shrew hepatocytes(THs),tree shrew corneal stromal cells(TCSCs),tree shrew brain microvascular endothelial cells(TBMECs),and tree shrew retinal microvascular endothelial cells(TRMECs).C6/36,Vero,A549,and BHK-21 cells(commonly used for DENV propagation)were used as positive controls.Over 6 days post-infection,cellular cytopathic effects were monitored at 12-hour intervals using an inverted microscope,viral RNA loads in cell lysates were quantified by real-time fluorescent quantitative PCR to generate proliferation curves,and viral titers were determined by plaque assay.Results Seven types of tree shrew cells,except TRMECs,were susceptible to DENV.Prolonged infection induced pronounced cytopathic effects,including cell rounding,detachment,necrosis,and lysis,across all susceptible cells.The viral RNA loads detected in lysates of pTRECs,TBMECs,TASMCs,TAECs and THs,approached those of positive controls(≥4×107 copies/μL).Infectious progeny viruses were produced by these five cell types,with three(TAECs,3.13×105 PFU/mL;THs,2.03×105 PFU/mL;pTRECs,1.58×105 PFU/mL)exhibiting titers comparable to C6/36(3.85×10 5 PFU/mL)and earlier viral harvests.Conclusion DENV exhibits broad susceptibility to tree shrew cells of multiple tissue origins,with proliferation rates surpassing those of conventional cell lines sourced from other species.TAECs,THs,and pTRECs are particularly suitable for large-scale DENV proliferation,suggesting their potential involvement in in vivo infection.

Objective To investigate the clinical features of spinocerebellar ataxia 12(SCA12).Methods The clinical data of a family with SC A1 2 diagnosed by gene detection were retrospectively analyzed,and the literature was reviewed.Results Three patients in this family were diagnosed as SCA12.Among them,2 patients with clinical symptoms were＞45 years old,the clinical symptoms were head tremor,upper limb tremor,voice tremor,dystonia and ataxia.Another one case was 31 years old,did not have relevant clinical manifestations yet.Cranial MRI showed that cerebral cortex atrophy was more serious than cerebellar atrophy in 2 patients.Conclusion SCA12 typically presents with upper limb tremor,with head tremor being less common,as the disease progresses,symptoms such as ataxia,dystonia,Parkinsonism,and cognitive impairment may develop,due to its highly heterogeneous clinical features,genetic testing can be helpful for diagnosis.