Relationship between thrombus composition and prognosis in patients with acute ischemic stroke undergoing mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy has emerged as the primary endovascular treatment for acute ischemic stroke. Numerous studies have investigated the relationship between thrombus composition and factors such as pharmacological thrombolysis, stroke etiology, mechanical thrombectomy, and radiological imaging. However, limited research has explored the association between thrombus composition and clinical outcomes. METHODS: This retrospective analysis examined the histopathological examination of thrombi retrieved from 50 patients with acute ischemic stroke between May 2020 and May 2023. The composition of the retrieved thrombi was assessed using HE staining to quantify the proportions of red blood cells, white blood cells, platelets, and fibrin. Based on the predominant composition of the thrombus, the patients were divided into two groups: erythrocyte-rich and fibrin-rich. Demographics, clinical characteristics, and clinical outcomes assessed by the National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) scores were collected retrospectively. RESULT: Of the 50 patients, 23 were classified in the erythrocyte-rich group, and 27 were classified in the fibrin-rich group. There were no significant differences between the two groups in terms of age, sex, stroke subtype, history of hypertension and diabetes, thrombus location, NIHSS scores, mRS scores on admission, the time interval from symptom onset to hospitalization and reperfusion, or the rate of successful reperfusion. However, erythrocyte-rich thrombi were associated with a shorter time interval from puncture to reperfusion. No significant differences were found in the red blood cell fraction and fibrin/platelet fraction between large artery atherosclerosis and cardioembolism. At the 90-day follow-up, patients with erythrocyte-rich thrombi exhibited lower NIHSS scores and more favorable functional outcomes (mRS scores of 0-2) compared to those with fibrin-rich thrombi. CONCLUSION: Erythrocyte-rich thrombi were linked to shorter time intervals from puncture to reperfusion and favorable clinical outcomes in patients with acute ischemic stroke. The composition of the thrombus may influence the thrombectomy strategy for endovascular therapy.

Correction to: Construction of Medical Equipment-Based Doctor Health Monitoring System.

The original version of this article unfortunately contained a mistake. Corrections in equations which were highlighted in a doc file were not carried out. The original version has been corrected.

Construction of medical equipment-based doctor health monitoring system.

The health status of doctors has been overlooked by the society and even the doctors themselves, especially those doctors who work long hours. Their attention is always on patients, so they are more likely to ignore their own health problems. Therefore, in this paper, we propose a medical equipment-based doctor health monitoring system (hereinafter referred to as Doc-care). Doc-care can be used as a private health manager for doctors, and doctors can monitor their health indicators in real time while using medical equipment to aid diagnosis and treatment. When the doctor's health status is neglected, Doc-care can protect the doctor's health; combining with the convolutional neural network method to detect and grade the doctor's health indicators, to assess the doctor's real-time health status. After referring to the doctor's past health data in the cloud server, giving appropriate advice and predictions about the doctor's health status.

Protein disulfide isomerase increases in myocardial endothelial cells in mice exposed to chronic hypoxia: a stimulatory role in angiogenesis.

Previous studies have shown that exposure to chronic hypoxia protects against myocardial infarction, but little is known about the cellular and molecular mechanisms involved. Here we observed that chronic hypoxia for 3 wk resulted in improved survival of mice (from 64% to 83%), reduced infarction size (from 45 +/- 4% to 32 +/- 4%, P < 0.05), increased cardiac ejection fraction (from 19 +/- 4% to 35 +/- 5%, P < 0.05), coronary flow velocity under adenosine-induced hyperemia (from 58 +/- 2 to 75 +/- 5 cm/s, P < 0.05), myocardial capillary density (from 3,772 +/- 162 to 4,760 +/- 197 capillaries/mm(2), P < 0.01), and arteriolar density (from 8.04 +/- 0.76 to 10.34 +/- 0.69 arterioles/mm(2), P < 0.05) 3 wk after myocardial infarction. With two-dimensional gel electrophoresis, we identified that protein disulfide isomerase (PDI) was highly upregulated in hypoxic myocardial capillary endothelial cells. The loss of PDI function in endothelial cells by small interfering RNA significantly increased the number of apoptotic cells (by 3.4-fold at hypoxia, P < 0.01) and reduced migration (by 52% at hypoxia, P < 0.001) and adhesion to collagen I (by 42% at hypoxia, P < 0.01). In addition, the specific inhibition of PDI by PDI small interfering RNA (by 46%, P < 0.01) and bacitracin (by 72%, P < 0.001) reduced the formation of tubular structures by endothelial cells. Our data indicate that chronic hypoxic exposure improves coronary blood flow and protects the myocardium against infarction. These beneficial effects may be partly explained by the increased endothelial expression of PDI, which protects cells against apoptosis and increases cellular migration, adhesion, and tubular formation. The increased PDI expression in endothelial cells may be a novel mechanism to protect the myocardium against myocardial ischemic diseases.

Filamins in cardiovascular development.

Filamins are classically recognized as large cytoplasmic proteins that cross-link cortical actin into dynamic 3-dimensional structures and transmit extracellular signals through integrin receptors into the cytoplasm. However, recent reports indicate that filamins interact with a large number of other proteins with diverse functions, including transcriptional factors and cellular molecules involved in signaling, adhesion, and cellular motility, and are also present in the cell nucleus. In addition, genetic mutations in filamins have been linked to a wide range of human genetic disorders, including skeletal, central nervous system, and cardiovascular malformations, highlighting distinct filamin interactions. Here, we update the cardiovascular phenotypes of patients with mutations in filamin genes and mice deficient in filamins and filamin-interacting proteins.

Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development.

Mutations in filamin B (FLNB), a gene encoding a cytoplasmic actin-binding protein, have been found in human skeletal disorders, including boomerang dysplasia, spondylocarpotarsal syndrome, Larsen syndrome, and atelosteogenesis phenotypes I and III. To examine the role of FLNB in vivo, we generated mice with a targeted disruption of Flnb. Fewer than 3% of homozygous embryos reached term, indicating that Flnb is important in embryonic development. Heterozygous mutant mice were indistinguishable from their wild-type siblings. Flnb was ubiquitously expressed; strong expression was found in endothelial cells and chondrocytes. Flnb-deficient fibroblasts exhibited more disorganized formation of actin filaments and reduced ability to migrate compared with wild-type controls. Flnb-deficient embryos exhibited impaired development of the microvasculature and skeletal system. The few Flnb-deficient mice that were born were very small and had severe skeletal malformations, including scoliotic and kyphotic spines, lack of intervertebral discs, fusion of vertebral bodies, and reduced hyaline matrix in extremities, thorax, and vertebrae. These mice died or had to be euthanized before 4 weeks of age. Thus, the phenotypes of Flnb-deficient mice closely resemble those of human skeletal disorders with mutations in FLNB.

Antagonizing reactive oxygen by treatment with a manganese (III) metalloporphyrin-based superoxide dismutase mimetic in cardiac transplants.

OBJECTIVE: Oxidative stress might be an important factor contributing to injury during alloimmune activation. Herein, we evaluated the efficacy of a superoxide dismutase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTmPyP), on cytokine gene expression and apoptotic signaling in a rat model of cardiac transplantation. METHODS: Lewis-->Lewis (isografts) or Wistar-Furth-->Lewis (allografts) heterotopic rat transplants without and with treatment with MnTmPyP were used. Reactive oxygen formation was determined on the basis of dihydroethidine fluorescence and lucigenin-enhanced chemiluminescence. In situ graft function was determined by means of sonomicrometry. Inflammatory cytokine, proapoptotic, and antiapoptotic gene expression at either postoperative day 4 (early rejection) or postoperative day 6 (late rejection) was determined by means of reverse transcriptase polymerase chain reaction. RESULTS: An increased production of reactive oxygen in allografts was inhibited to isograft control levels by MnTmPyP. MnTmPyP restored either the percentage of fractional shortening, the distended diastolic and systolic myocardial segment lengths, or both in allografts. Of the increases in cytokine and proapoptotic gene expression in allografts, only interleukin 6 was decreased by MnTmPyP. MnTmPyP inhibited antiapoptotic gene expression (Bcl-2 and Bcl-xL) during early rejection but restored expression at later stages. The increase in activated caspase-3 levels in allografts was inhibited by MnTmPyP. CONCLUSIONS: The mechanism of the beneficial effect of MnTmPyP on graft function appear related, in part, to scavenging O2*- and by decreasing apoptotic signaling rather than an effect on inflammatory cytokine gene expression.

Hierarchical change in antioxidant enzyme gene expression and activity in acute cardiac rejection: role of inducible nitric oxide synthase.

Reactive oxygen and nitrogen may mediate inflammation injury, but the status of the antioxidant defense system that might influence this process is unknown. In the present study, we examined the expression profile of the antioxidant enzymes, manganese superoxide dismutase (MnSOD), catalase and glutathione peroxidase (GPX) in acutely rejecting cardiac allografts and the potential role of inducible nitric oxide synthase (iNOS) in modulating antioxidant gene expression and activity. Donor hearts from Lewis (isograft) or Wistar-Furth (allograft) rats were transplanted into Lewis recipient rats. A subset of the allografts received L-N6-(1-imino-ethyl) lysine (L-NIL), a specific iNOS inhibitor, beginning the day of surgery until the day of harvesting. Catalase and glutathione peroxidase (GPX) protein levels were significantly decreased by postoperative day 4 (POD4) and postoperative day 5 (POD5), respectively, in allografts compared to isografts. While CuZn superoxide dismutase (CuZn SOD) levels were unchanged, there was a 50% decrease in MnSOD protein in allografts at postoperative day 6 (POD6). The sequential loss in antioxidant protein levels was not due to transcriptional regulation since there was no change in RNA levels for any of the genes tested. L-NIL did not alter catalase protein; however, the loss of MnSOD protein at POD6 was prevented by L-NIL. Consistent with a decrease in antioxidant protein levels, there was a sequential loss in enzyme activity for MnSOD, catalase and GPX. L-NIL however, restored MnSOD and GPX activities but not catalase activity. Treatment with CsA restored both protein and enzyme activities of GPX and MnSOD but not catalase. These results indicate that the loss in MnSOD and GPX protein and activity in allografts occurs via an iNOS-dependent mechanism whereas the decrease in catalase appears to be iNOS-independent. This suggests a differential role for iNOS in regulating post-translational modification of individual antioxidant enzymes in acute cardiac transplantation.

Treatment with {alpha}-phenyl-N-tert-butylnitrone, a free radical-trapping agent, abrogates inflammatory cytokine gene expression during alloimmune activation in rat cardiac allografts.

Spin-trapping nitrones such as alpha-phenyl-N-tert-butylnitrone (PBN) have traditionally been used to trap and stabilize free radicals for detection by electron paramagnetic resonance (EPR) spectroscopy. Unlike classical antioxidants, these agents have never been evaluated therapeutically in allograft transplantation. In the present study, we examined potential mechanisms of action of treatment with PBN in a rat model of acute cardiac allograft transplantation. Graft rejection was determined by histological examination and graft function determined by in situ sonomicrometry. DNA binding for nuclear factor (NF)-kappaB and activator protein (AP-1) were determined by gel shift assays. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for inducible nitric-oxide synthase (iNOS) and inflammatory cytokines. Histological rejection scores were elevated in untreated allografts and decreased by treatment with PBN. In situ sonomicrometry revealed decreased heart rate and distended end diastolic and end systolic segment lengths with rejection. Although PBN did not alter heart rate, it did normalize the distention of both diastolic and systolic cardiac dimension. EPR spectroscopy revealed nitrosylation of myocardial heme protein in untreated allografts that was decreased by treatment with PBN. PBN also decreased iNOS protein and iNOS mRNA. RT-PCR analysis revealed enhanced cytokine gene expression for interferon-gamma, interleukin-6, and interleukin-10 in untreated allografts. Expression for these genes was potently inhibited or abolished in recipients treated with PBN. PBN treatment also decreased DNA binding of transcription factors, NF-kappaB and AP-1. Thus, PBN retains significant anti-inflammatory properties through its action to down-regulate cytokine gene expression that contribute to protection against acute alloimmune activation in cardiac allografts.

Variable efficacy of N6-(1-iminoethyl)-L-lysine in acute cardiac transplant rejection.

We examined the efficacy and mechanism of action of N(6)-(1-iminoethyl)-L-lysine (L-NIL), a highly selective inhibitor of inducible nitric oxide (NO) synthase (iNOS), on acute cardiac transplant rejection. L-NIL produced a concentration-dependent attenuation of plasma NO by-products and a decrease in nitrosylation of heme protein without altering protein levels of iNOS. At postoperative day 4, L-NIL did not alter the increased binding activities for transcription factors nuclear factor-kappaB and activator protein-1. Whereas L-NIL decreased inflammatory cell infiltration, graft survival was only prolonged at the dose of 1.0 microg/ml that incompletely blocked NO production. Higher L-NIL concentrations (30 and 60 microg/ml) ablated the increased NO production but failed to improve graft survival and even potentiated NF-kappaB binding activity examined at day 6. Alloimmune activation indicated by increased cytokine gene expression for interferon-gamma, interleukin-6, and interleukin-10 was inhibited in grafts only by treatment with 1.0 microg/ml L-NIL. These findings suggest a complex role of NO in acute cardiac allograft rejection. Partial inhibition of iNOS is beneficial to graft survival, whereas total ablation may oppose any benefits to graft survival. These studies have important implications in understanding the dual role of NO in acute rejection and help to reconcile discrepancies in the literature.