Sepsis is a systemic inflammatory condition triggered by severe infection, frequently resulting in multi-organ dysfunction. Vascular dysfunction, as its core pathological mechanism, involves a vicious cycle of inflammation, coagulation, and endothelial injury. The mechanism of vascular damage caused by sepsis is widely studied, and neutrophils play a significant role in this process. Neutrophil extracellular traps (NETs) are an important mechanism. While NETs are designed to entrap pathogens, their excessive formation or impaired degradation directly drives vascular injury. NETs contribute to the exacerbation of vascular dysfunction through mechanisms including the induction of endothelial injury, the promotion of coagulation abnormalities, and the enhancement of vascular permeability. Nonetheless, the precise signaling pathways and regulatory networks governing these processes remain incompletely understood. This article seeks to systematically review the fundamental mechanisms through which NETs contribute to sepsis-associated vascular dysfunction, in addition to evaluating their potential utility as biomarkers and therapeutic targets. This review seeks to elucidate novel insights into the mechanisms underpinning vascular dysfunction in sepsis and associated clinical interventions, thereby contributing a theoretical foundation for the development of targeted therapeutic strategies to mitigate related pathophysiological damage.
ABSTRACT:Sepsis-induced cardiomyopathy ( SIC ) is a distinct form of myocardial injury that disrupts tissue perfusion and stands as the significant cause of mortality among sepsis patients. Currently, effective preventive or treatment strategies for SIC are lacking. YiQiFuMai injection (YQFM), composed of Panax ginseng C.A. Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., is widely used in China to treat cardiovascular diseases, such as coronary heart disease, heart failure, and SIC . Research has shown that YQFM can improve cardiac function and alleviate heart failure through multiple pathways. Nevertheless, the mechanisms through which YQFM exerts its effects on SIC remain to be fully elucidated. In this study, we firstly investigated the therapeutic effects of YQFM on a SIC rat model and explored its effects on myocardial ferroptosis in vivo. Then, LPS-induced myocardial cell death model was used to evaluate the effects of YQFM on ferroptosis and xCT/GPX4 axis in vitro . Furthermore, using GPX4 inhibitors, we aimed to verify whether YQFM improved cardiomyocyte ferroptosis through the xCT/GPX4 axis. The results showed that YQFM was effective in alleviating myocardial injury in septic model rats. Besides, the concentrations of iron and the levels of lipid peroxidation-related factors (ROS, MDA, and 4-HNE) were significantly decreased and the expression of xCT/GPX4 axis was upregulated in SIC rats after YQFM treatment. In vitro studies also showed that YQFM alleviated iron overload and lipid peroxidation and activated xCT/GPX4 axis in LPS-induced myocardial cell death model. Moreover, GPX4 inhibitor could abolish the effects above. In summary, the study highlights the regulatory effect of YQFM in mitigating myocardial injury. It probably achieves this ameliorative effect by enhancing xCT/GPX4 axis and further reducing ferroptosis.
本病例在本院伦理委员会备案(伦理审批编号BL202303),患者已签署知情同意书。
Brucellosis can lead to pathological changes of multiple systems. Capillary leak syndrome (CLS) is a clinical syndrome caused by different reasons, mainly characterized by hypotension, hypoproteinemia and systemic edema. The condition is critical and the clinical manifestations are complex, and multiple organ dysfunction syndrome (MODS) may occur in severe cases. CLS caused by brucellosis is extremely rare. The diagnosis and treatment of a patient with brucellosis complicated with CLS and MODS was analyzed in this paper, in order to improve the knowledge of clinicians about brucellosis and its complications.
Objective: To investigate the mechanism of interleukin-6 (IL-6) /signal transducers and activators of transcriptional 3 (STAT3) /helper T cell 17 (Th17) signaling pathway in lung injury of rats with sepsis intervened by forsythia, with a view to provide experimental basis for the role and mechanism of forsythia in the treatment of sepsis. Methods: In July 2021, 30 healthy Wistar male rats were selected and randomly divided into sham operation group, model group and treatment group, with 10 rats in each group. The rat model of sepsis was established by cecal ligation and puncture. 2 h after recovery, the rats were given traditional Chinese medicine forsythia orally, twice a day at an interval of 12 h. The wet/dry mass ratio (W/D) of lung tissue was detected 24 h after surgery. The morphological changes of lung tissue were detected by HE staining. Flow cytometry was used to detect Th17 population in peripheral blood. The expression levels of IL-6 and interleukin-17A (IL-17A) in serum were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of IL-17A and IL-6 in lung tissues were detected by reverse transcription-polymerase chain reaction. The expression levels of STAT3 and IL-17A in lung tissue were determined by Western blotting. Results: Compared with model group, the W/D of lung tissue in treatment group was decreased, and the difference was statistically significant (P<0.05). HE staining of lung tissue showed that compared with the model group, the degree of lung lesion and injury was reduced in the treatment group. Compared with sham operation group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in model group was significantly increased (P<0.05). Compared with model group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in treatment group was significantly decreased (P<0.05). Compared with sham operation group, peripheral blood serum IL-6 and IL-17 of rats in model group were significantly increased (P<0.05). Compared with model group, IL-6 and IL-17 in peripheral blood serum of rats in treatment group were decreased (P<0.05). Compared with sham operation group, the expressions of IL-17A and IL-6 mRNA in lung tissue of model group were significantly increased (P<0.05). Compared with model group, the expressions of IL-17A and IL-6 mRNA in lung tissue of rats in treatment group were significantly decreased (P<0.05). Compared with sham operation group, the protein expressions of STAT3 and IL-17A in lung tissue in model group were significantly increased (P<0.05). Compared with model group, the pritein expressions of STAT3 and IL-17A in lung tissue in treatment group were significantly decreased (P<0.05) . Conclusion: Forsythia plays a role in alleviating lung injury by down-regulating the expressions of the signaling pathway IL-6/STAT3/Th17, which providing a new target for the treatment of sepsis induced lung injury.
老年多器官功能障碍综合征(MODSE)是老年危重症患者死亡的重要病因,常表现为心、肺、肾等主要脏器的衰竭,中医药在辨证论治及整体观念思想的指导下,对于MODSE的治疗有一定的优势,五苓升陷汤为升陷汤与五苓散的合方,具有益气升陷、温阳利水的作用,现介绍五苓升陷汤治疗MODSE心肾衰竭验案1例并文献回顾.
Caroli病又称先天性肝内胆管扩张症,是一种罕见的先天性胆道疾病,临床表现缺乏特异性,极易误诊漏诊。Caroli病好发于儿童及青少年,80%的患者在30岁前发病。现报告1例73岁老年发热待查患者最终诊断为Caroli病的诊治过程,以期提高临床医师对老年患者发热待查的罕见原因-Caroli病的认识。
葡萄糖是一种重要的营养物质,在维持机体正常生理活动过程中起重要作用.当机体由于糖代谢紊乱或限制碳水化合物摄入而处于高血糖或低血糖状态时,可影响细胞自噬.自噬有益或有害,细胞在不利环境压力下通过适度自噬维持稳态,但超过自噬阈值细胞会发生损伤甚至死亡.近年来,葡萄糖影响自噬具体机制的研究取得了一定成果,同时靶向自噬治疗疾病也成为一种有前景的发展方向.因此,全面总结葡萄糖水平影响自噬的相关文献不仅可为自噬机制研究提供新的理论依据,也可为临床治疗疾病提供新思路.
Forsythiaside B (FTB) is one of the main components of Forsythia suspensa (Thunb.) Vahl and exerts anti-inflammatory and anti-oxidative effects. However, its mechanism of action as a treatment for sepsis remains unclear. In this study, we developed a rat model of sepsis using cecal ligation and puncture (CLP) to investigate the effects of FTB on sepsis-associated coagulopathies. Using rats with sepsis, we investigated the effects of FTB on neutrophil extracellular trap (NETs) formation and peptidylarginine deiminase 4 (PAD4) expression in neutrophils. NET (DNase1) and PAD4 (Cl-amidine) inhibitors were used to further investigate whether FTB mitigates sepsis-associated coagulopathies by inhibiting PAD4-dependent NETs production. Our results showed that treatment with FTB increased the survival rate, ameliorated the CLP-induced inflammatory response and multiple organ dysfunction, and reduced CLP-induced pathological changes. FTB also alleviated the associated coagulopathies. Additionally, we demonstrated that treatment with FTB inhibited NETs formation and downregulated PAD4 expression in peripheral neutrophils. The effects of FTB on coagulopathies were similar to those of monotherapy with NET or PAD4 inhibitors. In conclusion, our study confirmed that FTB can alleviate coagulopathies in rats with sepsis. The underlying mechanism of FTB’s effect consists in inhibition of PAD4-dependent NETs formation.
全球范围内甲状腺癌的发病率呈快速增长态势,随着社会经济的发展、诊断技术的不断提高、全民对健康关注度的增加以及健康体检的普及,甲状腺癌的检出率不断提高。电离辐射与甲状腺癌的发生相关,本文通过分析1例甲状腺癌患者(放射科医师)的临床资料,旨在提高放射作业人员对辐射防护的认识,减少医疗辐射暴露,对提高职业暴露人员健康水平具有重要意义。
目的 探讨胱天蛋白酶募集域蛋白9(CARD9)在重症急性胰腺炎(SAP)大鼠中的早期表达,并探讨柴芩承气汤对其的调控机制.方法 将SD大鼠分为假手术组(SHAM组)、SAP组和柴芩承气汤组(CQCQD组),每组20只.检测血清淀粉酶(AMY)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β水平及CARD9 mRNA表达;术后3、6、12 h分批处死大鼠,开腹观察胰腺组织的病理学变化;采用Western blot法检测3、6、12 h各组胰腺组织中CARD9蛋白磷酸化水平.结果 SAP组AMP、TNF-α、IL-1β、CARD9 mRNA水平随造模时间延长而逐渐升高.与SHAM组比较,SAP组炎性因子水平明显升高(P<0.05);同时间点CQC-QD组AMP、TNF-α、IL-1β、CARD9 mRNA水平较SAP组明显降低,差异有统计学意义(P<0.05).3、6、12 h CQCQD组蛋白磷酸化水平较SAP组明显下降,较SHAM组有所升高(P<0.05).CARD9 mRNA表达的曲线下面积(AUC)为0.923,灵敏度和特异度分别为89.9%、94.8%,有较高的诊断准确性.结论 柴芩承气汤可降低血清CARD9 mRNA水平,从而减轻SAP时胰腺的炎症损伤.
老年系统性红斑狼疮(SLE)多隐匿起病,早期临床表现不典型,且老年患者常伴发多种基础病,故其临床表现复杂多变,现报道1例老年SLE患者并发脓毒症的诊治过程,以期提高临床医师对老年SLE及其严重并发症的认识。
神经性耳鸣是以患者主观感受为主,耳科常见病症之一,发病部位虽在耳,但与肝、脾、肾等脏腑密切相关,主要责之于脾胃,以脾胃运化失常、升降失调为主要病机,导致脾胃虚弱,生化无源、痰浊内蕴,上扰清窍、脾壅肝郁,气机失调、脾虚及肾,清窍失养,使精微无法上荣耳窍、气血痰湿阻滞耳窍,发为耳鸣,治疗以调和脾胃为主,在治疗过程中以脾胃的气机升降功能为核心,运用辛开苦降作为调和脾胃的基本治疗之法,选用《伤寒论》中其法的代表方半夏泻心汤作为底方进行加减,调达脾胃的气机升降功能,在遣方用药中坚持"平衡用药观"的原则,灵活配伍,本文从脾胃论治,形成以脾胃为中心,使各脏腑之间的功能得以恢复、气血得生、痰湿得运,耳鸣自消,通过上述的治疗之法及原则,以期为该病的中医诊疗提供思路,后附验案一则.
目的:探讨苦参碱对大鼠慢性萎缩性胃炎(CAG)的影响及其作用机制.方法:采用多因素复合法建立CAG模型,将大鼠分为正常组、模型组、阳性对照组(维酶素300 mg·kg-1)、苦参碱高剂量组(200 mg·kg-1)、苦参碱低剂量组(100 mg·kg-1),每组10只.灌胃给药,连续治疗8周后,于光镜下观察胃黏膜组织病理学并进行病理程度分级;放射免疫法测定血清胃泌素(GAS)和血浆生长抑素(SS)含量;酶联免疫吸附法测定胃黏膜匀浆液中白细胞介素1β(1L-1β)、IL-6、肿瘤坏死因子α(TNF-α)浓度,实时定量聚合酶链反应法测定胃黏膜Toll样受体4(TLR4)、髄样分化因子88(MyD88)、核因子κB(NF-κB)基因表达.结果:各给药组大鼠胃黏膜病变有显著减轻,炎性细胞浸润程度和固有腺体萎缩程度的组间差异均有统计学意义(P<0.01);与模型组相比,苦参碱高、低剂量组大鼠血清GAS含量显著升高(P<0.01),血浆SS含量则出现显著降低(P<0.01);苦参碱高、低剂量组大鼠胃黏膜IL-1β、IL-6和TNF-a水平均有显著降低,与模型组相比组间差异均有统计学意义(P<0.01);与模型组相比,苦参碱高剂量组大鼠胃黏膜TLR4、MyD88和NF-κB mRNA相对表达量均有显著降低(P<0.05或P<0.01),苦参碱低剂量组TLR4和NF-κB mRNA相对表达量均有显著降低(P<0.05或P<0.01).结论:苦参碱可通过抑制TLR4/MyD88/NF-KB信号转导通路的持续活化及相关炎症细胞因子的高表达,减轻CAG炎症反应,阻止炎症细胞对胃黏膜造成的损伤,发挥对胃黏膜的保护作用.
Background: Sepsis is the main aetiology of acute kidney injury (AKI) in critically ill patients, with high morbidity and mortality. The early identification of septic patients at high risk for AKI, followed by the timely implementation of appropriate interventions, is crucial for improving patient outcomes. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]) are promising biomarkers for AKI. Furthermore, the Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN) is a tool for evaluating and treating acute illness in a timely manner based on best practices. We hypothesized that the use of this biomarker-guided point-of-care tool would improve the prognosis of patients with sepsis-associated acute kidney injury (SA-AKI).Methods: This was a single-centre prospective before-and-after study in the ICU of a comprehensive tertiary hospital. From June 2015 to December 2020, we assessed and managed patients with septic shock based on the biomarker-guided CERTAIN checklist. A checklist based on the Sepsis 3.0 bundle and urinary [TIMP-2] × [IGFBP7]>0.3(ng/mL) 2 /1000 within 12 hours were used as the inclusion criteria. The CERTAIN checklist includes the care bundles recommended in the Sepsis 3.0 bundle and Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines. The primary outcome was the incidence of moderate-to-severe AKI on the first day and within seven days after enrolment and mortality at 90 days after discharge from the hospital. The secondary outcomes were the ICU length of stay, non-mechanical ventilation duration, and the proportions of patients with the recovery of renal function and major adverse kidney events (MAKEs) at 90 days after exposure to events initiating AKI.Results: At the end of the study, 124 patients had been treated based on the checklist. When compared to a cohort of 112 patients matched for disease, the CERTAIN group had a lower proportion of patients needing mechanical ventilation, a lower proportion of patients needing vasoactive agents, a shorter ICU length of stay, and a higher proportion of patients with recovered kidney function. Furthermore, there was a trend towards a higher 90-day survival rate in the CERTAIN group.Conclusions: Implementation of the CERTAIN checklist was associated with improvements in the short-term recovery of kidney function, airway and haemodynamic management and mortality in patients with SA-AKI.Trial registration: NCT01973829; Date of registration: November 1, 2013.
肺性脑病是慢性肺部疾病、肺源性心脏病等疾病晚期常见并发症,病死率高,是常见的内科急危重症之一.运用中西医结合方法诊治肺性脑病可降低病死率.临床上安宫牛黄丸治疗肺性脑病多有应用,且取得了良好的疗效.本文通过总结中医古籍和西医对肺、肠、脑关系的认识以及安宫牛黄丸治疗肺性脑病的机制,从肺、肠、脑三者的关系进一步阐释肺性脑病的发病机制和演变过程,以期对临床诊治肺性脑病起到指导作用,具有科学性与实际意义.
脓毒症是危重患者常见的死亡原因,脓毒症胃肠功能障碍发病率及病死率居高不下,是影响患者预后的独立危险因素.中医药在治疗脓毒症胃肠功能障碍方面积累了大量临床研究资料,取得了一定的成果.文章对中医药治疗脓毒症胃肠功能障碍研究进行了梳理和总结,以期为脓毒症胃肠功能障碍的治疗提供新思路.
乙型流行性感冒(乙型流感)并发横纹肌溶解综合征(RM)的病例较为罕见,且大多数为儿童.天津市第一中心医院2019年5月20日收治1例成人乙型流感口服布洛芬后并发RM患者,患者以全身肌肉疼痛、乏力、纳差为主要表现,肌酸激酶(CK)、肌红蛋白(MYO)等心肌酶学指标显著升高,并随着时间延长动态改变.患者入院后立即给予了抗病毒、保肝、碱化尿液、大量补液及营养支持治疗,体温降至正常,乏力及肌肉疼痛症状有所好转;入院2?d患者CK、MYO等血清酶学指标逐渐下降,复查尿常规正常;入院9?d患者症状及各项实验室指标明显好转出院.1个月后门诊复查,患者各项生化指标完全恢复正常.
中医基础理论包括五运六气学说,该学说起源于《黄帝内经·素问》,书中描写运气学说的文章有七篇,这七篇论述,有着"运气七篇"的称号.在运气学说中,其主要核心是人和天地的宏观整体思想,其认为气化是五运六气的基础原理,而气化理论的主要内容是,标本中气与开阖枢理论.张仲景对五运六气理论亦有研究,《伤寒杂病论》序中言:"夫天布五行,以运万类."书中对于疾病的认识、发生、转归上又以太阳、阳明、少阳、太阴、少阴、厥阴,三阴三阳理论为基础,后世更有"六经钤百病"之说.可见伤寒六经与六气之间有着千丝万缕的联系,而标本中气和开阖枢理论的应用亦可在《伤寒论》的行文中找到线索.
Cervical vertigo is a common clinical disease. In this study, we investigated the clinical efficacy of adding the treatment protocol of Gui Zhi Ge Gen Tang and electroacupuncture to the Western medical treatment in cervical vertigo. The results showed that the total effective rate of the study group was higher than that of the control group (P<0.05). After treatment, the vertigo, headache, neck and shoulder pain, daily life and work, and psychological and social adjustment scores were higher in the study group than in the control group (P<0.05). LVA, RVA, and VB were higher in the study group than in the control group after treatment (P<0.05). The whole blood viscosity high cut, whole blood viscosity low cut, and plasma viscosity levels were lower in the study group than in the control group after treatment (P<0.05). After treatment, PF, RF, RE, BP, GH, VT, SF, MH, and HT were higher in the study group than those before treatment (P<0.05). The incidence of adverse reactions was not statistically significant in the study group compared with the control group (P>0.05). This means that electroacupuncture combined with Gui Zhi Ge Gen Tang can effectively increase the blood flow velocity of the vertebrobasilar artery in patients with cervical vertigo and improve their blood rheology and quality of life with definite efficacy and high safety.