Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective To analyze the clinical and imaging features of adrenomyeloneuropathy(AMN).Methods A retrospective analysis was conducted on the clinical data of one patient diagnosed with AMN through genetic testing.Results This patient was a young male with insidious onset,chronic course and progressive aggravation.The main clinical manifestations were speech,choking cough when drinking water,weakness of both lower limbs,unstable walking and urinary incontinence.Physical examination showed dysarthria,bilateral pyramidal tract,sphincter dysfunction,combined with systemic skin blackening,skin and mucosal pigmentation.MRI showed symmetrical abnormal high signal of bilateral corticospinals,significant atrophy of cerebellum,brainstem and cervical and thoracic spinal cord.Lumbar puncture CSF IL-6,IL-8 slightly high,serum myelin oligodendrocyte glycoprotein(MOG)antibody positive(1∶32).The localization diagnosis was adrenal cortex cerebellum bilateral corticospinal tracts peripheral nerve,and the qualitative diagnosis considered hereditary metabolic diseases,MOG antibody-related diseases could not be excluded.But the patient had a chronic course,atrophy of cerebellum,brainstem,cervical and thoracic spinal cord,and considered that the serum MOG antibody might be false positive,so the qualitative diagnosis hereditary metabolic diseases were more likely.Because of the limited technical conditions in our hospital,we could not detect plasma very long-chain fatty acids,while the completion of gene detection showed ABCD1 gene mutation:c.1628C＞T(p.Pro543Leu)variant,so the diagnosis of AMN was clear.Conclusions AMN is an X-linked recessive genetic disorder.Its clinical manifestations primarily include impairment of neural conduction tracts(spastic paraplegia,sphincter dysfunction,and deep sensory disturbances),adrenal cortical insufficiency(skin and mucosal hyperpigmentation,sparse hair),and cerebral symptoms(dysgraphia,visual/hearing impairment,cognitive dysfunction,and personality changes).Imaging findings mainly show demyelination of the brain white matter in the bilateral corticospinal tract regions and degenerative spinal cord atrophy.Elevated levels of very long-chain fatty acids(VLCFAs)and mutations in the ABCD1 gene can confirm the diagnosis of AMN.

Objective To analyze the clinical and imaging features of adrenomyeloneuropathy(AMN).Methods A retrospective analysis was conducted on the clinical data of one patient diagnosed with AMN through genetic testing.Results This patient was a young male with insidious onset,chronic course and progressive aggravation.The main clinical manifestations were speech,choking cough when drinking water,weakness of both lower limbs,unstable walking and urinary incontinence.Physical examination showed dysarthria,bilateral pyramidal tract,sphincter dysfunction,combined with systemic skin blackening,skin and mucosal pigmentation.MRI showed symmetrical abnormal high signal of bilateral corticospinals,significant atrophy of cerebellum,brainstem and cervical and thoracic spinal cord.Lumbar puncture CSF IL-6,IL-8 slightly high,serum myelin oligodendrocyte glycoprotein(MOG)antibody positive(1∶32).The localization diagnosis was adrenal cortex cerebellum bilateral corticospinal tracts peripheral nerve,and the qualitative diagnosis considered hereditary metabolic diseases,MOG antibody-related diseases could not be excluded.But the patient had a chronic course,atrophy of cerebellum,brainstem,cervical and thoracic spinal cord,and considered that the serum MOG antibody might be false positive,so the qualitative diagnosis hereditary metabolic diseases were more likely.Because of the limited technical conditions in our hospital,we could not detect plasma very long-chain fatty acids,while the completion of gene detection showed ABCD1 gene mutation:c.1628C＞T(p.Pro543Leu)variant,so the diagnosis of AMN was clear.Conclusions AMN is an X-linked recessive genetic disorder.Its clinical manifestations primarily include impairment of neural conduction tracts(spastic paraplegia,sphincter dysfunction,and deep sensory disturbances),adrenal cortical insufficiency(skin and mucosal hyperpigmentation,sparse hair),and cerebral symptoms(dysgraphia,visual/hearing impairment,cognitive dysfunction,and personality changes).Imaging findings mainly show demyelination of the brain white matter in the bilateral corticospinal tract regions and degenerative spinal cord atrophy.Elevated levels of very long-chain fatty acids(VLCFAs)and mutations in the ABCD1 gene can confirm the diagnosis of AMN.

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with tenecteplase in the treatment of CWS.Methods A prospective study was conducted on 136 CWS patients consecutively admitted in Department of Neurology of Zhengzhou People's Hospital from March 2019 to March 2024.They were randomly divided into a tenecteplase group(67 cases)and a control group(69 cases).NIHSS was used to evaluate the recovery of neurological function after treatment.mRS was employed to assess long-term prognosis.Results Significantly larger proportion of white matter lesions and higher baseline SBP level were observed in the tenecteplase group than the control group(P＜0.05).The tenecteplase group obtained obviously greater ratio of overall recovery than the control group,with notably lower NIHSS score,incidence of new CWS attacks and proportion of new acute cerebral infarction at 24 and 72 h and 7 d after treat-ment(P＜0.05,P＜0.01).Moreover,the proportion of mRS score of 0-2 was notably greater,while that of the score of 3-6 was lower in the tenecteplase group than the Control group(P＜0.05).Intravenous thrombolysis with tenecteplase was an influencing factors for 90-day mRS score of 0-2 and of 3-6 in the CWS patients(OR=0.264,95％CI:0.089-0.813;OR=4.144,95％CI:1.184-14.506,P＜0.05).Conclusion Intravenous thrombolysis with tenecteplase for CWS significantly improves the proportion of patients with good prognosis.

Objective To investigate the effects of different timing of initiation of rivaroxaban anti-coagulation therapy on the efficacy and bleeding risk of atrial fibrillation patients after stroke.Methods A total of 336 patients with atrial fibrillation and stroke admitted in our hospital be-tween January 2021 and December 2023 were consecutively enrolled,and randomly divided into an experimental group(165 cases)and a control group(171 cases).The experimental group received rivaroxaban treatment within 48 h of symptom onset,whereas the control group initiated oral ri-varoxaban treatment on the 3rd,6th,and 12th day post-stroke onset,respectively,depending on stroke severity(mild,moderate,and severe).Their baseline clinical data were collected,and all of them were followed up till 90 d after stroke.The incidences of recurrent ischemic stroke,symp-tomatic intracranial hemorrhage and extracranial hemorrhage,mortality,and proportion of pa-tients with mRS score≤ 2 and distribution of the score were observed and analyzed in the two groups.Results During a 90-day follow-up period,the patients with moderate stroke from the ex-perimental group of patients exhibited a significantly lower rate of recurrent ischemic stroke than those in the control group(5.4％vs 15.9％,P=0.037).However,for patients with mild and se-vere stroke,no obvious difference was observed in the primary endpoint of recurrent ischemic stroke between the experimental and control groups(3.0％vs 3.2％,12.5％vs 14.8％,P＞0.05).Though no statistical differences were observed,lower rates of symptomatic intracranial hemor-rhage(1.5％vs 3.2％,5.4％vs 9.8％),reduced incidence of extracranial hemorrhage(9.0％vs 14.5％,12.2％vs 15.9％),and lower mRS score[1(0,2)vs 1(1,2),3(1,4)vs 3(2,4)]were seen in the patients with mild and moderate stroke from the experimental group when compared with the control group(P＞0.05).Similarly,there were no statistically differences for the severe stroke patients between the experimental and control groups(P＞0.05)in the incidence of extracranial hemorrhage(20.8％vs 22.2％),rate of symptomatic intracranial hemorrhage(20.8％vs 7.4％),mortality(8.3％vs 3.7％),and mRS score[4(3,4)vs 3(3,4)].Two patients from the experimen-tal group died,with one case due to secondary pulmonary infection and the other due to brainstem hemorrhage.In the control group,only one death occurred due to brainstem hemorrhage.Conclu-sion For atrial fibrillation patients,anticoagulation with rivaroxaban within 48 h after stroke has no significant increase in the risk of bleeding,reduces the proportion of recurrent ischemic stroke in patients with moderate stroke,and may improve the prognosis of patients.

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with tenecteplase in the treatment of CWS.Methods A prospective study was conducted on 136 CWS patients consecutively admitted in Department of Neurology of Zhengzhou People's Hospital from March 2019 to March 2024.They were randomly divided into a tenecteplase group(67 cases)and a control group(69 cases).NIHSS was used to evaluate the recovery of neurological function after treatment.mRS was employed to assess long-term prognosis.Results Significantly larger proportion of white matter lesions and higher baseline SBP level were observed in the tenecteplase group than the control group(P＜0.05).The tenecteplase group obtained obviously greater ratio of overall recovery than the control group,with notably lower NIHSS score,incidence of new CWS attacks and proportion of new acute cerebral infarction at 24 and 72 h and 7 d after treat-ment(P＜0.05,P＜0.01).Moreover,the proportion of mRS score of 0-2 was notably greater,while that of the score of 3-6 was lower in the tenecteplase group than the Control group(P＜0.05).Intravenous thrombolysis with tenecteplase was an influencing factors for 90-day mRS score of 0-2 and of 3-6 in the CWS patients(OR=0.264,95％CI:0.089-0.813;OR=4.144,95％CI:1.184-14.506,P＜0.05).Conclusion Intravenous thrombolysis with tenecteplase for CWS significantly improves the proportion of patients with good prognosis.

Objective To investigate the effects of different timing of initiation of rivaroxaban anti-coagulation therapy on the efficacy and bleeding risk of atrial fibrillation patients after stroke.Methods A total of 336 patients with atrial fibrillation and stroke admitted in our hospital be-tween January 2021 and December 2023 were consecutively enrolled,and randomly divided into an experimental group(165 cases)and a control group(171 cases).The experimental group received rivaroxaban treatment within 48 h of symptom onset,whereas the control group initiated oral ri-varoxaban treatment on the 3rd,6th,and 12th day post-stroke onset,respectively,depending on stroke severity(mild,moderate,and severe).Their baseline clinical data were collected,and all of them were followed up till 90 d after stroke.The incidences of recurrent ischemic stroke,symp-tomatic intracranial hemorrhage and extracranial hemorrhage,mortality,and proportion of pa-tients with mRS score≤ 2 and distribution of the score were observed and analyzed in the two groups.Results During a 90-day follow-up period,the patients with moderate stroke from the ex-perimental group of patients exhibited a significantly lower rate of recurrent ischemic stroke than those in the control group(5.4％vs 15.9％,P=0.037).However,for patients with mild and se-vere stroke,no obvious difference was observed in the primary endpoint of recurrent ischemic stroke between the experimental and control groups(3.0％vs 3.2％,12.5％vs 14.8％,P＞0.05).Though no statistical differences were observed,lower rates of symptomatic intracranial hemor-rhage(1.5％vs 3.2％,5.4％vs 9.8％),reduced incidence of extracranial hemorrhage(9.0％vs 14.5％,12.2％vs 15.9％),and lower mRS score[1(0,2)vs 1(1,2),3(1,4)vs 3(2,4)]were seen in the patients with mild and moderate stroke from the experimental group when compared with the control group(P＞0.05).Similarly,there were no statistically differences for the severe stroke patients between the experimental and control groups(P＞0.05)in the incidence of extracranial hemorrhage(20.8％vs 22.2％),rate of symptomatic intracranial hemorrhage(20.8％vs 7.4％),mortality(8.3％vs 3.7％),and mRS score[4(3,4)vs 3(3,4)].Two patients from the experimen-tal group died,with one case due to secondary pulmonary infection and the other due to brainstem hemorrhage.In the control group,only one death occurred due to brainstem hemorrhage.Conclu-sion For atrial fibrillation patients,anticoagulation with rivaroxaban within 48 h after stroke has no significant increase in the risk of bleeding,reduces the proportion of recurrent ischemic stroke in patients with moderate stroke,and may improve the prognosis of patients.

Objective:To investigate the efficacy and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) who are currently using direct oral anticoagulants (DOACs).Methods:Patients with AIS admitted to the Stroke Center of Zhengzhou People's Hospital from January 2021 to December 2024 and had taken DOACs within 48 hours prior to onset were included retrospectively. The demographic characteristics, vascular risk factors, laboratory test results, baseline National Institutes of Health Stroke Scale (NIHSS) scores, and other clinical data were collected. The main outcome measure was the functional outcome evaluated using the modified Rankin Scale at 90 days after onset, with a score of 0-2 defined as good outcome. The secondary outcome measures were symptomatic intracranial hemorrhage (sICH) and any bleeding in any location occurring within 36 hours after onset. Multivariate logistic regression analysis was used to determine the independent influencing factors of the outcome. Results:A total of 153 patients were included, with 87 males (56.9%), aged (71.261±6.983) years. Seventy-four patients (48.4%) underwent IVT, and 59 (38.6%) had poor outcome. The good outcome rate in the IVT group was significantly higher than that in the non-IVT group (71.6% vs. 51.9%; χ2=6.274, P=0.012), but there was no significant difference in the incidence of sICH and any bleeding in any location. The baseline NIHSS score of the good outcome group was significantly lower than that of the poor outcome group (8.817±3.677 vs. 11.203±5.060; t=3.361, P<0.001), and the proportion of IVT was significantly higher than that of the poor outcome group (56.4% vs. 35.6%; χ2=6.274, P=0.012). Multivariate logistic regression analysis showed that previous history of stroke or transient ischemic attack (odds ratio [ OR] 3.964, 95% confidence interval [ CI] 1.611-9.753; P=0.003) and high baseline NIHSS score ( OR 1.129, 95% CI 1.034-1.233; P=0.007) were independently associated with the poor outcome, while IVT was independently associated with the good outcome ( OR 0.166, 95% CI 0.068-0.410; P<0.001). Conclusion:For patients with AIS who had taken DOACs within 48 hours before onset, IVT can significantly improve the outcome without increasing the risk of sICH.

Objective To investigate the correlation between scattered infarction in the radial coronary area of the lenticulostriate artery(LSA)and early neurological deterioration(END).Methods A total of 164 patients diagnosed with LSA infarction who were hospitalized in the Stroke Center of Zhengzhou People's Hospital from January 2018 to September 2023 were retrospectively included.According to the location of infarct lesions,the cases were divided into single lesions at the origin of the LSA(n=103)and multiple scattered lesions originating from the LSA(n=61).The clinical features,risk factors and prognosis analysis of the two groups were observed and compared.Results Among 164 patients,END occurred in 49 cases,and 115 cases did not have END.Univariate analysis results showed that compared to a single lesion,the incidence of END was significantly higher in cases where the infarction originated from the LSA and presented as multiple scattered lesions[27(55.1％)vs.22(44.9％),P＜0.05].Compared to anterior infarctions,the incidence of END was significantly higher in patients with posterior infarctions[39(79.6％)vs.10(20.4％),P＜0.05].Multivariate Logistic regression analysis,adjusted for confounding factors,indicated that infarctions originating from the LSA with multiple scattered lesions(OR=3.669,95％CI:1.696-7.939,P=0.001)and posterior infarctions(OR=2.303,95％CI:1.005-5.279,P=0.049)were independently associated with the occurrence of END.After 3 months of follow-up,compared with the single lesion,the proportion of patients with infarction originating from LSA and dispersed in multiple places had a significantly reduced prognosis(45.9％vs.91.3％),and the clinical outcomes were poor.Conclusions Scattered infarcts in the radiate crown area of the LSA and posterior infarctions are independent risk factors for the occurrence of END in LSA infarctions.Patients with scattered infarcts in the radiate crown area are more likely to develop END,leading to poor prognosis.

Objective To investigate the correlation between scattered infarction in the radial coronary area of the lenticulostriate artery(LSA)and early neurological deterioration(END).Methods A total of 164 patients diagnosed with LSA infarction who were hospitalized in the Stroke Center of Zhengzhou People's Hospital from January 2018 to September 2023 were retrospectively included.According to the location of infarct lesions,the cases were divided into single lesions at the origin of the LSA(n=103)and multiple scattered lesions originating from the LSA(n=61).The clinical features,risk factors and prognosis analysis of the two groups were observed and compared.Results Among 164 patients,END occurred in 49 cases,and 115 cases did not have END.Univariate analysis results showed that compared to a single lesion,the incidence of END was significantly higher in cases where the infarction originated from the LSA and presented as multiple scattered lesions[27(55.1％)vs.22(44.9％),P＜0.05].Compared to anterior infarctions,the incidence of END was significantly higher in patients with posterior infarctions[39(79.6％)vs.10(20.4％),P＜0.05].Multivariate Logistic regression analysis,adjusted for confounding factors,indicated that infarctions originating from the LSA with multiple scattered lesions(OR=3.669,95％CI:1.696-7.939,P=0.001)and posterior infarctions(OR=2.303,95％CI:1.005-5.279,P=0.049)were independently associated with the occurrence of END.After 3 months of follow-up,compared with the single lesion,the proportion of patients with infarction originating from LSA and dispersed in multiple places had a significantly reduced prognosis(45.9％vs.91.3％),and the clinical outcomes were poor.Conclusions Scattered infarcts in the radiate crown area of the LSA and posterior infarctions are independent risk factors for the occurrence of END in LSA infarctions.Patients with scattered infarcts in the radiate crown area are more likely to develop END,leading to poor prognosis.