This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

Among numerous medical imaging modalities, diffusion weighted imaging (DWI) is extremely sensitive to acute ischemic stroke lesions, especially small infarcts. However, magnetic resonance imaging is time-consuming and expensive, and it is also prone to interference from metal implants. Therefore, the aim of this study is to design a medical image synthesis method based on generative adversarial network, Stroke-p2pHD, for synthesizing DWI images from computed tomography (CT). Stroke-p2pHD consisted of a generator that effectively fused local image features and global context information (Global_to_Local) and a multi-scale discriminator (M ²Dis). Specifically, in the Global_to_Local generator, a fully convolutional Transformer (FCT) and a local attention module (LAM) were integrated to achieve the synthesis of detailed information such as textures and lesions in DWI images. In the M ²Dis discriminator, a multi-scale convolutional network was adopted to perform the discrimination function of the input images. Meanwhile, an optimization balance with the Global_to_Local generator was ensured and the consistency of features in each layer of the M ²Dis discriminator was constrained. In this study, the public Acute Ischemic Stroke Dataset (AISD) and the acute cerebral infarction dataset from Yantaishan Hospital were used to verify the performance of the Stroke-p2pHD model in synthesizing DWI based on CT. Compared with other methods, the Stroke-p2pHD model showed excellent quantitative results (mean-square error = 0.008, peak signal-to-noise ratio = 23.766, structural similarity = 0.743). At the same time, relevant experimental analyses such as computational efficiency verify that the Stroke-p2pHD model has great potential for clinical applications.
Humans ; Tomography, X-Ray Computed/methods* ; Diffusion Magnetic Resonance Imaging/methods* ; Cerebral Infarction/diagnostic imaging* ; Stroke/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Algorithms

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

OBJECTIVE: To compare the therapeutic effect of Fu's subcutaneous needling combined with scalp acupuncture and simple scalp acupuncture for shoulder-hand syndrome phase Ⅰ after cerebral infarction. METHODS: A total of 68 patients with shoulder-hand syndrome phase Ⅰ after cerebral infarction were randomized into a combination group (34 cases, 1 case dropped out) and a scalp acupuncture group (34 cases). Internal medicine treatment and conventional rehabilitation training were adopted in both groups. In the scalp acupuncture group, acupuncture was applied at parietal area and anterior parietal area of Yu's scalp acupuncture, electroacupuncture was connected for 30 min, with disperse-dense wave, in frequency of 2 Hz/100 Hz and in electric current of 1 mA, and the needles were retained for 6 h, once a day for continuous 14 days. On the basis of the treatment in the scalp acupuncture group, Fu's subcutaneous needling was applied at the affected muscles during needle retaining in the combination group, once a day in the first 3 days, once every other day in left days, 2-day interval was taken after 4-time treatment, for 14 days totally. Before and after treatment, the scores of the short form of McGill pain questionnaire (SF-MPQ), edema degree, guides to evaluation of permanent impairment (GEPI), and disabilities of the arm, shoulder and hand (DASH) were observed in the two groups, respectively, and the therapeutic effect was evaluated after treatment. RESULTS: After treatment, the scores of pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI), as well as the total scores of SF-MPQ were decreased compared with those before treatment in the two groups (P<0.05), and the above indexes in the combination group were lower than those in the scalp acupuncture group (P<0.05). After treatment, the scores of edema degree and DASH were decreased compared with those before treatment (P<0.05), while the GEPI scores were increased compared with those before treatment (P<0.05) in the two groups; in the combination group, the scores of edema degree and DASH were lower (P<0.05) while the GEPI score was higher (P<0.05) than those in the scalp acupuncture group. The total effective rate was 97.0% (32/33) in the combination group, which was superior to 91.2% (31/34) in the scalp acupuncture group (P<0.05). CONCLUSION Both Fu's subcutaneous needling combined with scalp acupuncture and simple scalp acupuncture can effectively relieve the shoulder joint pain and edema degree of hand, improve the upper limb function in patients with shoulder-hand syndrome phase Ⅰ after cerebral infarction, and the combination therapy has better therapeutic effect than simple scalp acupuncture.
Humans ; Male ; Female ; Acupuncture Therapy/instrumentation* ; Middle Aged ; Cerebral Infarction/therapy* ; Aged ; Treatment Outcome ; Scalp ; Reflex Sympathetic Dystrophy/therapy* ; Acupuncture Points ; Adult

The "brain electric field" therapy is a novel electroacupuncture method created by Professor GAO Weibin to treat cerebral infarction in the recovery period. This therapy is suitable for the treatment of motor disorders, sensory disorders, cognitive disorders, hemianopsia and bulbar paralysis during the recovery period of cerebral infarction. Based on the different symptoms, the corresponding brain functional areas are selected, supplemented with Taiyang 2, Tunyan 2, Tiyan, Gongxue and Xiatianzhu. These points are attached to electric acupuncture apparatus, and stimulated with dense wave, at frequency of 50 Hz and tolerable intensity. This therapy presents a remarkable effect on cerebral infarction in the recovery period, providing the new approach to the treatment of this disease.
Humans ; Cerebral Infarction/therapy* ; Electroacupuncture ; Acupuncture Points ; Brain/physiopathology* ; Male ; Middle Aged ; Female

OBJECTIVE: To establish a predictive model for severe swallowing disorder after acute ischemic stroke based on nomogram model, and evaluate its effectiveness. METHODS: A prospective study was conducted. The patients with acute ischemic stroke admitted to Mianyang Central Hospital from October 2018 to October 2021 were enrolled. Patients were divided into severe swallowing disorder group and non-severe swallowing disorder group according to whether severe swallowing disorder occurred within 72 hours after admission. The differences in general information, personal history, past medical history, and clinical characteristics of patients between the two groups were compared. The risk factors of severe swallowing disorder were analyzed by multivariate Logistic regression analysis, and the relevant nomogram model was established. The bootstrap method was used to perform self-sampling internal validation on the model, and consistency index, calibration curve, receiver operator characteristic curve (ROC curve), and decision curve were used to evaluate the predictive performance of the model. RESULTS: A total of 264 patients with acute ischemic stroke were enrolled, and the incidence of severe swallowing disorder within 72 hours after admission was 19.3% (51/264). Compared with the non-severe swallowing disorder group, the severe swallowing disorder group had a higher proportion of patients aged of ≥ 60 years old, with severe neurological deficits [National Institutes of Health stroke scale (NIHSS) score ≥ 7], severe functional impairments [Barthel index, an activity of daily living functional status assessment index, < 40], brainstem infarction and lesions ≥ 40 mm (78.43% vs. 56.81%, 52.94% vs. 28.64%, 39.22% vs. 12.21%, 31.37% vs. 13.62%, 54.90% vs. 24.41%), and the differences were statistically significant (all P < 0.01). Multivariate Logistic regression analysis showed that age ≥ 60 years old [odds ratio (OR) = 3.542, 95% confidence interval (95%CI) was 1.527-8.215], NIHSS score ≥ 7 (OR = 2.741, 95%CI was 1.337-5.619), Barthel index < 40 (OR = 4.517, 95%CI was 2.013-10.136), brain stem infarction (OR = 2.498, 95%CI was 1.078-5.790) and lesion ≥ 40 mm (OR = 2.283, 95%CI was 1.485-3.508) were independent risk factors for severe swallowing disorder after acute ischemic stroke (all P < 0.05). The results of model validation showed that the consistency index was 0.805, and the trend of the calibration curve was basically consistent with the ideal curve, indicating that the model had good prediction accuracy. ROC curve analysis showed that the area under the ROC curve (AUC) predicted by nomogram model for severe swallowing disorder after acute ischemic stroke was 0.817 (95%CI was 0.788-0.852), indicating that the model had good discrimination. The decision curve showed that within the range of 5% to 90%, the nomogram model had a higher net benefit value for predicting the risk of severe swallowing disorder after acute ischemic stroke, indicating that the model had good clinical predictive performance. CONCLUSIONS The independent risk factors of severe swallowing disorder after acute ischemic stroke include age ≥ 60 years old, NIHSS score ≥ 7, Barthel index < 40, brainstem infarction and lesion size ≥ 40 mm. The nomogram model established based on these factors can effectively predict the occurrence of severe swallowing disorder after acute ischemic stroke.
United States ; Humans ; Aged ; Middle Aged ; Ischemic Stroke ; Deglutition Disorders ; Models, Statistical ; Nomograms ; Prognosis ; Prospective Studies ; Brain Stem Infarctions

Humans ; Infarction, Middle Cerebral Artery/surgery* ; Thrombectomy ; Thrombosis/etiology* ; Stents/adverse effects* ; Treatment Outcome