Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques.Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.Results Regimen 1,featuring B-cell depletion,T-cell inhibition,and C3 complement suppression,reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration.Regimen 2,adding C5 complement inhibition and interleukin-6 inhibition to Regimen 1,more effectively lowered lymphocyte levels,inhibited acute humoral rejection and complement activation,and decreased antibody deposition.However,a late-phase cytokine storm and residual T cells emerged.Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention.Yet,it requires balancing medication complexity and safety.This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.

Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques.Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.Results Regimen 1,featuring B-cell depletion,T-cell inhibition,and C3 complement suppression,reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration.Regimen 2,adding C5 complement inhibition and interleukin-6 inhibition to Regimen 1,more effectively lowered lymphocyte levels,inhibited acute humoral rejection and complement activation,and decreased antibody deposition.However,a late-phase cytokine storm and residual T cells emerged.Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention.Yet,it requires balancing medication complexity and safety.This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.

In many neurodegenerative diseases,eye movement is disrupted,which is a common and early characteris-tic of neurodegenerative diseases.Characterizing eye movement is important for the diagnosis of neurodegenerative disea-ses,helping to track disease progression and response to treatment.In recent years,eye tracking technology has been ap-plied to the assessment of cognitive function in patients with neurodegenerative diseases.Compared to traditional cognitive assessment methods,the technology has higher temporal and spatial resolution for sensitive quantification.Eye tracking da-ta confirms that executive dysfunction is common in Parkinson's disease and amyotrophic lateral sclerosis,while attention deficit is a characteristic of Alzheimer's disease and multiple sclerosis.Research using eye tracking to evaluate the cogni-tive function of epilepsy patients is still in its early stages,but this method has shown advantages.In this article,the appli-cation of eye tracking technology in neurodegenerative diseases is reviewed.

Objective:To analyze evaluation outcomes and influential indexes of 116 continuing medical education (CME) programs, and to offer references for ascertaining the quality evaluation focuses of CME programs.Methods:Chi-Square test and Fisher exact test were adopted to perform univariate analysis on evaluation outcomes of 28 indexes, and logistic regression was used for multivariate analysis.Results:Logistic regression showed that the indexes influencing the evaluation outcomes of programs qualified or not included consistency of basic information [ OR=6.712, 95%CI (1.314, 34.275)], whether textbooks provided by host institutions [ OR=109.386, 95%CI (2.577, 4 642.659)], whether the number of people in the meeting room equaled with the signature list [ OR=13.296, 95%CI (2.440, 72.456)], feedback of learners examination materials [ OR=19.069, 95%CI (3.713, 97.929)], feedback of teachers evaluation materials [ OR=13.497, 95%CI (2.672, 68.181)] and whether submit learners' credits according to regulations or not [ OR=51.326, 95%CI (4.999, 526.996)]. Conclusion:The administrative departments of CME should complete program evaluation regulations, adjust and perfect evaluation indexes based on research outcomes, emphasize on influential indexes of evaluation outcomes, and give full play of the guiding role of evaluation indexes.

This study investigated the effect of arctigenin (Arc) on the cell activation, cytokines expression, proliferation, and cell-cycle distribution of mouse T lymphocytes. Mouse lymphocytes were prepared from lymph node and treated with Phorbol-12-myristate-13-acetate (PMA)/Ionimycin (Ion) and/or Arc. CD69, CD25, cytokines, proliferation and cell cycle were assayed by flow cytometry. The results showed that, at concentrations of less than 1.00 micromol x L(-1), Arc expressed non-obvious cell damage to cultured lymphocytes, however, it could significantly down-regulate the expression of CD69 and CD25, as well as TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6 and IL-10 on PMA/Ion stimulated lymphocytes. At the same time, Arc could also inhibit the proliferation of PMA/Ion-activated lymphocytes and exhibited lymphocyte G 0/G1 phase cycle arrest. These results suggest that Arc possesses significant anti-inflammatory effects that may be mediated through the regulation of cell activation, cytokines expression and cell proliferation.

Objective To investigate the value of the Changsha version of the Montreal Cognitive Assessment Scale (MoCA) in the assessment of vascular cognitive impairment after cerebral infarction .Methods 112 cases of clinically diagnosed cerebral infarc-tion were selected and divided into the normal cognition (NC) group and vascular cognitive impairment(VCI) group .The Changsha version of MoCA and the mini-mental state examination(MMSE) were adopted to detect the cognitive function ,the correlation of two scales was analyzed and the cutoff values of the Changsha version of MoCA were preliminarily studied .Results The total scores of the Changsha version of MoCA and MMSE in the VCI group were 15 .12 ± 4 .60 and 20 .44 ± 3 .22 respectively ,which were lower than 22 .75 ± 1 .79 and 25 .21 ± 1 .74 in the NC group ,the difference had statistical significance (P< 0 .05);the total scores of the Changsha version of MoCA was positively correlated with the total scores of MMSE (r=0 .84 ,P<0 .01);the best cut-off value of the Changsha version of MoCA was 20/21 ,the sensitivity and specificity were 92% and 95% respectively .Conclusion The Changsha version of MoCA can screen VCI well and has a high screening value ,and its optimal cutoff value is 20/21 .

OBJECTIVE: At present the function of Fas and Bcl-2 gene in the pathogenesis of myasthenia gravis has gained more attention and more studies have been extensively made inside and outside, to investigate the modulation of Fas and Bcl-2 gene expression is of extremely significance for exploring the pathogenesis and treatment of myasthenia gravis.DATA SOURCE: The related articles published in English from January 1990 to December 2004 were computer searched in Medline database using the terms of "Fas", "Bcl-2", "Myasthenia Gravis" and "gene".STUDY SELECTION: The data were identified preliminarily and literatures on the relationship between Fas and Bcl-2 gene and myasthenia gravis, as well as on Fas and Bcl-2 gene and genotherapy were remained for searching the full content.DATA EXTRACTION: A great deal of literatures about Fas and Bcl-2 gene were searched, 21 of which were studies on Fas and Bcl-2 gene and myasthenia gravis, and 32 on myasthenia gravis related genotherapy. A total of 20 representative articles were selected for analysis in this study.DATA SYNTHESIS: Eight out of 20 literatures were about the relationship between Fas gene and myasthenia gravis, 5 about the Bcl-2 gene and myasthenia gravis, 7 about the genotherapy in the treatment of myasthenia gravis and immune diseases.CONCLUSION: Abnormal Fas and Bcl-2 gene modulation and uncontrollable expression were closely associated with apoptosis defect of T lymphocyte and thymocytes, and even closely related to the pathogenesis of myasthenia gravis. To explore pathogenesis of myasthenia gravis at gene level by inducing cell apoptosis and depressing self-antibody production, would provide new means for the treatment of myasthenia gravis.

Objective To investigate the change and its clinical significance of serum erythropoietin(EPO) content in the patients with acute cerebral stroke.Methods The serum EPO content in 60 patients with acute cerebral infarction(ACI),45 patients with cerebral hemorrhage(CH) and 40 patients with other nervous system diseases(control group) were detected by radio-immunity means.The patients with acute cerebral stroke were evaluated by National Institute of Health Stroke Scale(NIHSS).Results The serum EPO content in ACI group and CH group [(1.64?0.41)ng/ml,(1.59?0.54)ng/ml] were significant higher than that in the control group [(1.17?0.86)ng/ml](all P

Objective To explore the changes of serum sFas levels and its clinical significance in patients with myasthenia gravis(MG).Methods T cell subsets and sFas levels in serum of 45 MG patients and 40 controls were measured by using flow cytometry and enzyme-linked immunosorbent assay each.Besides,the sFas levels variety of 24 MG patients using glucocorticoid(GC) were observed.Results(1) The percentage of CD~+_8T cells was much decreased in MG group[(21.50?2.21)%] compared with control group[(27.75?3.00)%]((P