Microglial inflammation, involved in the occurrence and development of sepsis-associated encephalopathy, exhibits upregulation of proinflammatory cytokine and proinflammatory enzyme expression, leading to inflammation-induced neuronal cell apoptosis. TIR domain containing adaptor molecule-2 (TICAM-2) participates in lipopolysaccharide (LPS) mediated BV2 cell inflammation. SET8 plays a crucial role in a variety of cellular signal pathways. In this study, we hypothesize that SET8 participates in LPS-mediated microglial inflammation via modulation of TICAM-2 expression. Our data indicated that LPS induced BV2 inflammation via upregulation of TICAM-2 expression. Moreover, LPS treatment inhibited SET8 expression, while it increased activating transcription factor 2 (ATF2) expression. The effects of sh-SET8 and ATF2 overexpression were similar to that of LPS treatments. Inhibition of TICAM-2 expression counteracted sh-SET8-mediated and ATF2 overexpression mediated BV2 cell inflammation. Further, SET8 was found to interact with ATF2. A mechanistic study found that H4K20me1, a downstream target of SET8, and ATF2 enriched at the TICAM-2 promoter region. Luciferase reporter assays indicated that sh-SET8 increased TICAM-2 promoter activity but augmented the effect of ATF2 overexpression on TICAM-2 promoter activity as well. Co-transfection of sh-SET8 with ATF2 overexpression more dramatically increased TICAM-2 expression in BV2 cells. The present study indicated that SET8 interacted with ATF2 to modulate TICAM-2 expression, which participated in LPS-mediated BV2 cell inflammation.
A simple, colorimetric 'turn on' sensor for ultrasensitive detection of thrombin has been developed using fibrinogen-modified gold nanoparticles (Fib-Au NPs). The assay was based on the thrombin-fibrinogen interaction which is part of the physiological process of blood clotting. The fibrinogen was immobilized on the surface of 96-well plate offering reactive N-oxysuccinimide esters (referred to as NOS group) surface. Introducing thrombin and Fib-Au NPs into the fibrinogen-bound 96-well plate induced the immobilization of Fib-Au NPs on the surface of 96-well plate through the thrombin mediated conversion of soluble fibrinogen to insoluble cross-linked fibrin. Such process could be detected visually post HAuCl(4)-NH(2)OH redox reaction catalyzed by the Au NPs. The parameters governing the performance of the assay have been optimized. The detection limit was 3.2 fM, corresponding to 0.16 amol thrombin in 50 μL of sample. Other proteins, such as bovine serum albumin (BSA), pepsin, trypsin, hemoglobin, lysozyme, and cytochrome c did not show interference with the assay of thrombin. In addition, the work demonstrates the feasibility of thrombin detection in a complex matrix, showing potential for rapid medical diagnostics.
Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.目的： 探讨机械循环支持联合免疫调节治疗对暴发性心肌炎患者预后的影响。 方法： 本研究为回顾性研究，入选2008年8月至2020年12月东莞康华医院收治的暴发性心肌炎患者88例。收集纳入患者住院期间的病史资料、实验室检查结果、治疗方案、临床结局等资料。根据治疗方式将其分为机械循环支持+免疫调节组（38例）、机械循环支持组（20例）和传统治疗组（30例）。机械循环支持+免疫调节组采用机械循环支持［主动脉内球囊反搏（IABP）或IABP+体外膜肺氧合（ECMO）］及免疫调节治疗（免疫球蛋白和糖皮质激素）；机械循环支持组仅采用机械循环支持；传统治疗组未接受机械循环支持及免疫调节治疗，仅使用血管活性药和强心药等。比较3组患者的院内病死率及住院时间。 结果： 本研究共纳入88例暴发性心肌炎患者，年龄（35.0±10.8）岁，男性46例（52.3%）。机械循环支持+免疫调节组［7.9%（3/38）比56.7%（17/30），P=0.001 2］和机械循环支持组［30.0%（6/20）比56.7%（17/30），P=0.002 8］病死率均低于传统治疗组；机械循环支持+免疫调节组与机械循环支持组相比，院内病死率更低（P=0.005 4）。最常见的死亡原因为多脏器功能障碍综合征（MODS），其在机械循环支持+免疫调节组、机械循环支持组和传统治疗组中的死因构成比分别为3/3、4/6和12/17。MODS在机械循环支持组［20.0%（4/20）］和传统治疗组［40.0%（12/30）］的发生率明显高于机械循环支持+免疫调节组［7.9%（3/38）］（P均<0.01）。在痊愈出院患者中，机械循环支持+免疫调节组患者的住院时间［（13.4±5.5）d］短于传统治疗组［（18.5±7.4）d，P<0.05］和机械循环支持组［（16.9±8.5）d，P<0.05］。 结论： 机械循环支持联合免疫调节治疗与暴发性心肌炎患者住院死亡率降低和住院时间缩短相关。.
Previous studies have suggested that matrix metalloproteinase (MMP) inhibitor uptake may offer a precise estimation of MMP activity in atherosclerotic lesions. In this study, we explored the feasibility of noninvasive detection of MMP-9 activity using technetium-99m-labeled matrix metalloproteinase-9 antibody (Tc-McAb) in vivo.ApoE-deficient (ApoE) atherosclerosis mice models (n=10) were induced through a high-cholesterol diet following ligation of their left common carotid artery. After 4 weeks, the models were verified through proton density-weighted and T2-weighted images obtained by MRI. C57BL/6 sham mice (n=8) were used as controls. In addition, normal mice (n=20) were used to characterize blood clearance. After radiolabeled McAb administration, single-photon emission computed tomography (SPECT) was performed. Subsequently, left common carotid arteries were harvested for ex-vivo autoradiograph imaging. Then, morphology and activity assays of MMP-9 were histologically and immunohistochemically examined.MRI showed higher signal intensities in the left common carotid arteries with irregular stenoses in the lumen of blood vessels in atherosclerosis mice models in vivo. Atherosclerotic lesions on left common carotid artery specimens were also clearly visualized using SPECT 2 h after Tc-McAb administration in vivo. Note that the radiochemistry purity of the Tc-McAb used was 85-95%. Biodistribution studies have shown that the clearance of Tc-McAb from blood was rapid. In addition, atherosclerotic lesions were clearly visualized on radioautography film shadows ex vivo.MMP-9 activities within the atherosclerotic lesions were noninvasively detected using Tc-labeled SPECT in vivo.
Perioperative hyperglycemia is a common metabolic disorder in the clinic. Hyperglycemia, via upregulation of E74-like ETS transcription factor 3 (ELF3), induces cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) expressions, thus leading to endothelial apoptosis and vascular endothelial injury. Propofol is a widely used anesthetic. In the present study, we explored whether and how propofol protects against high glucose-induced COX2 and iNOS expressions in human umbilical vein endothelial cells (HUVECs). We found that high glucose level decreases cell viability and increases COX2 and iNOS expressions in HUVECs. Our data also indicated that ELF3 overexpression participates in high glucose-mediated cell viability reduction and high glucose-induced COX2 and iNOS expressions. Moreover, propofol treatment improves high glucose-mediated reduction in cell viability and decreases COX2 and iNOS expressions via inhibition of ELF3 expressions. Furthermore, specificity protein 1 (SP1) was found to regulate ELF3 expression, thus mediating endothelial injury. Propofol inhibits high glucose-induced SP1 expression. High glucose increases the abundance of SP1 bound to the ELF3 promoter, which can be reversed by propofol treatment. The protective effect of propofol is reversed by SP1 overexpression. In conclusion, propofol downregulates high glucose-induced SP1 expression, thus attenuating high glucose-induced ELF3 expression, inhibiting high glucose-induced COX2 and iNOS expressions, and improving high glucose-mediated cell viability reduction in HUVECs.
Objective
To evaluate the diagnostic value of 99Tcm-MDP SPECT/CT in the diagnosis of lumbar spondylolysis.
Methods
A total of 58 patients (28 males, 30 females, average age 61.3 years) who underwent bone scan and SPECT/CT because of low back pain from January 2012 to May 2014 were retrospectively evaluated. The final diagnosis was based on comprehensive results of SPECT/CT and follow-up. The diagnostic sensitivity and accuracy of SPECT, CT and SPECT/CT images were calculated and χ2 test was performed to analyze the data.
Results
Twenty-eight patients were diagnosed as lumbar spondylolysis. The diagnostic sensitivities of SPECT, CT and SPECT/CT were 53.6%(15/28), 78.6%(22/28) and 100%(28/28). The diagnostic accuracies of SPECT, CT and SPECT/CT were 48.3%(28/58), 89.7%(52/58) and 93.1%(54/58). SPECT/CT was proved to be more accurate than SPECT(χ2=28.13, P<0.05).
Conclusion
SPECT/CT bone scan may detect lumbar spondylolysis in early stage.
Key words:
Spondylolysis; Lumbar vertebrae; Tomography, emission-computed, single-photon; Tomography, X-ray computed; Radionuclide imaging; MDP
Objective
To investigate the value of CT in detecting incidental extracardiac findings (IEFs) when used for attenuation correction during SPECT/CT myocardial perfusion imaging (MPI).
Methods
A total of 520 patients (288 males, 232 females, average age 65.8 years) who underwent SPECT/CT MPI between July 2014 and February 2016 were retrospectively analyzed. Low dose CT attenuation correction was used during MPI. IEFs of lung, mediastinum and chest wall, large blood vessels, spine, and part of upper abdomen were recorded independently. All findings were divided into three categories: IEFs requiring further examination and treatment measures taken immediately (group A), IEFs requiring follow-up or further examination (group B), IEFs need no further treatment (group C).
Results
IEFs (n=356) were observed in 52.31%(272/520) of the patients, with 24 cases in group A (4.62%, 24/520), 105 cases in group B (20.19%, 105/520) and 143 cases in group C (27.50%, 143/520). There were 158 clinically significant IEFs in 129 patients (24.81%, 129/520), including 5(0.96%, 5/520) with newly diagnosed malignancy.
Conclusion
IEFs detected by CT used for attenuation correction during SPECT/CT MPI are not uncommon, including a few cases with clinically significant findings.
Key words:
Myocardial perfusion imaging; Tomography, emission-computed, single-photon; Tomography, X-ray computed
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