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Pirinixic acid protects against hemorrhagic shock by regulating neutrophil-associated key genes. 吡立酸通过调节中性粒细胞相关关键基因来预防失血性休克。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-26 DOI: 10.1097/SHK.0000000000002763
Xiaowei Zhou, Liyong Zou, Haoyue Deng, Yu Zhu, Jie Zhang, Qinghui Li, Shijie Zhou, Liangming Liu, Li Wang, Tao Li

Background: The uncontrolled inflammatory cascade triggered by hemorrhagic shock (HS) can exacerbate tissue damage and organ dysfunction. Neutrophils, as the most abundant type of leukocytes, are key mediators of the innate immune response in the early stages of injury. There is a lack of suitable treatments targeting neutrophils in HS.

Methods: We used machine learning algorithms to identify neutrophil-associated key genes in patients with HS and assessed the diagnostic efficacy of these genes. Weighted gene co-expression network analysis and consensus clustering analysis were performed based on the key genes to explore their role in HS. Finally, we predicted the binding of key genes to drug candidates using molecular docking and observed effects of drug candidates and expression of key genes in animals with HS.

Results: We screened for key genes with good diagnostic efficacy (ARG1, F2RL1, MPP1, RHOG, UPP1) that activate JAK-STAT3 signaling and apoptotic signaling, leading to poor prognosis. Pirinixic acid screened by CTD database has good affinity with key genes, and it can significantly restore the level of inflammatory factors and coagulation function in HS rats, protect the function of vital organs, and prolong the survival time. It was confirmed that pirinixic acid may improve neutrophil immunity disorders by acting on MPP1, RHOG and F2RL1, and thus protect against HS.

Conclusion: The protective effect of pirinixic acid against hemorrhagic shock-induced immune dysregulation is closely associated with the neutrophil genes MPP1, RHOG, and F2RL1.

背景:失血性休克(HS)引发的不受控制的炎症级联可加重组织损伤和器官功能障碍。中性粒细胞作为最丰富的白细胞类型,是损伤早期先天免疫反应的关键介质。目前尚缺乏针对嗜中性粒细胞的治疗方法。方法:采用机器学习算法识别HS患者中性粒细胞相关关键基因,并评估这些基因的诊断效能。针对关键基因进行加权基因共表达网络分析和共识聚类分析,探讨其在HS中的作用。最后,我们利用分子对接的方法预测了关键基因与候选药物的结合,并观察了候选药物对HS动物的影响和关键基因的表达。结果:我们筛选到诊断效果较好的关键基因(ARG1、F2RL1、MPP1、RHOG、UPP1),这些基因激活JAK-STAT3信号和凋亡信号,导致预后不良。CTD数据库筛选的吡立昔酸与关键基因具有良好的亲和性,可显著恢复HS大鼠炎症因子水平和凝血功能,保护重要脏器功能,延长生存时间。证实吡替尼酸可能通过作用于MPP1、RHOG和F2RL1来改善中性粒细胞免疫紊乱,从而对HS有保护作用。结论:匹立尼克酸对失血性休克免疫失调的保护作用与中性粒细胞基因MPP1、RHOG、F2RL1密切相关。
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引用次数: 0
A new proposed approach to categorize sepsis sub-phenotypes based on combined trajectories of perfusion index and central venous oxygen saturation. 一种基于灌注指数和中心静脉氧饱和度联合轨迹分类脓毒症亚表型的新方法。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-26 DOI: 10.1097/SHK.0000000000002764
Xinchen Wang, Xiaoting Wang, Yan Kang, Xiang Zhou, Wei Du, Yun Long

Background: Circulatory disturbances in sepsis are heterogeneous but often present clinically as a mismatch between peripheral perfusion and tissue oxygenation. Peripheral perfusion index (PI) and central venous oxygen saturation (ScvO₂) have been independently validated as prognostic markers in sepsis; however, their combined utility has not been systematically explored.

Methods: This retrospective cohort study included patients admitted to three intensive care units (ICUs) between January 1, 2015, and December 31, 2021. A novel index, PISO = (PI - 1.1) × ScvO₂, was calculated every 6 hours during the first 72 hours following sepsis onset. Dynamic time warping and hierarchical agglomerative clustering were applied to the 72-hour PISO trajectories to identify sub-phenotypes, with internal validation and sensitivity analysis. Machine learning algorithms were used to predict the sub-phenotypes based on early clinical features. Survival outcomes were assessed using Kaplan-Meier analysis and log-rank tests, with particular focus on the association between 12-hour cumulative fluid balance and 28-day in-hospital survival.

Results: Among 12,975 patients, 5,205 (40.1%) developed sepsis. Of these, 720 patients with complete 6-hourly PI and ScvO₂ data were included. Three distinct PISO sub-phenotypes were identified. Phenotype 3, (n = 190, 33.0%), characterized by a persistently declining trajectory from a negative baseline, was associated with the poorest clinical outcomes. The random forest classifier demonstrated best performance and identified key early clinical features that differentiated each sub-phenotype. Kaplan-Meier analysis revealed that a 12-hour cumulative fluid balance of ≤0 mL was significantly associated with improved 28-day survival in Phenotype 1 (p = 0.038) and Phenotype 2 (p = 0.033).

Conclusions: A persistently negative and declining PISO index within the first 72 hours of sepsis onset identifies a potential-risk sub-phenotype associated with adverse outcomes. Additionally, a non-positive 12-hour cumulative fluid balance post-sepsis onset is associated with improved survival in select phenotypic subgroups.

背景:脓毒症的循环障碍是异质性的,但在临床上经常表现为外周灌注和组织氧合的不匹配。外周灌注指数(PI)和中心静脉氧饱和度(ScvO 2)已被独立验证为脓毒症的预后指标;然而,它们的综合效用尚未得到系统的探讨。方法:本回顾性队列研究纳入2015年1月1日至2021年12月31日期间入住三间重症监护病房(icu)的患者。在脓毒症发作后的前72小时内,每6小时计算一次新的指数PISO = (PI - 1.1) × ScvO 2。动态时间翘曲和分层聚集聚类应用于72小时PISO轨迹来识别亚表型,并进行内部验证和敏感性分析。使用机器学习算法根据早期临床特征预测亚表型。使用Kaplan-Meier分析和log-rank检验评估生存结果,特别关注12小时累积体液平衡与28天住院生存之间的关系。结果:12975例患者中,5205例(40.1%)发生败血症。其中,720例患者有完整的6小时PI和ScvO 2数据。确定了三种不同的PISO亚表型。表型3 (n = 190, 33.0%)的特征是从负基线持续下降,与最差的临床结果相关。随机森林分类器表现出最好的性能,并识别出区分每个亚表型的关键早期临床特征。Kaplan-Meier分析显示,在表型1 (p = 0.038)和表型2 (p = 0.033)患者中,12小时累积体液平衡≤0 mL与28天生存率显著相关。结论:在脓毒症发病的前72小时内,PISO指数持续呈阴性且不断下降,表明存在与不良结局相关的潜在风险亚表型。此外,在某些表型亚组中,脓毒症发病后12小时累积体液平衡非阳性与生存率的提高有关。
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引用次数: 0
Prognostic Impact and Risk Factors of Septic Cardiomyopathy in Patients with Septic Shock: An Observational Study. 感染性休克患者感染性心肌病的预后影响及危险因素:一项观察性研究。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002782
Rui-Ming Xu, Da-Wei Wang, Lei Wang, Jian-Zhong Li, Yan-Yun He, Jing Zhang

Objective: This study aims to identify risk factors associated with septic cardiomyopathy (SCM) in patients diagnosed with septic shock and to assess differences in clinical outcomes between those with septic shock alone and those with concomitant SCM.

Methods: A retrospective observational study was conducted on 108 patients diagnosed with septic shock and admitted to Beijing Tongren Hospital, Capital Medical University, between December 2022 and July 2024. Patients were stratified into two groups based on the presence or absence of SCM: the non-SCM group (n = 90) and the SCM group (n = 18). Baseline characteristics, laboratory markers, cardiac function indices, and clinical outcomes were compared between the two groups. Multivariate logistic regression was employed to identify risk factors for SCM. Within the SCM group, outcomes were further analyzed according to survival status to assess the association between cardiac function recovery and mortality.

Results: The incidence of SCM among patients with septic shock was 16.67%. Compared with the non-SCM group, the SCM group showed a significantly higher prevalence of urinary tract infections and a history of diabetes mellitus (p < 0.05). Higher scores were observed for the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment scales, along with increased levels of admission-day troponin I, interleukin-1 (IL-1), tumor necrosis factor-α, maximum lactic acid (LACmax), maximum brain natriuretic peptide, and peak troponin I (p < 0.05). In contrast, mean arterial pressure at admission, minimum left ventricular ejection fraction (LVEF), and end-point LVEF (LVEFend%) were significantly lower in this group (p < 0.05). Multivariate logistic regression identified elevated IL-1 levels (odds ratio [OR] = 1.14), higher APACHE II scores (OR = 1.13), and increased LACmax (OR = 1.47) as risk factors for SCM (p < 0.05). The presence of SCM was associated with significantly higher in-hospital mortality and increased healthcare costs (p < 0.05). Among patients with SCM, recovery of LVEF and cardiac output was correlated with improved survival outcomes.

Conclusion: Elevated IL-1 levels, increased peak lactic acid concentration, and higher APACHE II scores were associated with the development of SCM in patients with septic shock. SCM was further associated with increased mortality and greater healthcare resource utilization. Restoration of cardiac function, particularly improvements in LVEF and cardiac output, was correlated with improved prognosis and may serve as a valuable indicator of clinical outcomes.

目的:本研究旨在确定诊断为脓毒性休克的患者脓毒性心肌病(SCM)的相关危险因素,并评估单独脓毒性休克和合并SCM患者临床结局的差异。方法:对2022年12月至2024年7月首都医科大学附属北京同仁医院收治的108例脓毒性休克患者进行回顾性观察研究。根据是否存在SCM将患者分为两组:非SCM组(n = 90)和SCM组(n = 18)。比较两组患者的基线特征、实验室指标、心功能指标和临床结果。采用多因素logistic回归来确定SCM的危险因素。在SCM组中,根据生存状态进一步分析结果,以评估心功能恢复与死亡率之间的关系。结果:感染性休克患者中SCM的发生率为16.67%。与非SCM组相比,SCM组尿路感染患病率和糖尿病史明显高于非SCM组(p < 0.05)。急性生理和慢性健康评估II (APACHE II)和序事性器官衰竭评估量表得分较高,入院日肌钙蛋白I、白细胞介素-1 (IL-1)、肿瘤坏死因子-α、最大乳酸(LACmax)、最大脑钠肽和肌钙蛋白I峰值水平均升高(p < 0.05)。相比之下,入院时平均动脉压、最小左室射血分数(LVEF)和终点LVEF (lvefind %)均显著低于对照组(p < 0.05)。多因素logistic回归发现IL-1水平升高(比值比[OR] = 1.14)、APACHE II评分升高(OR = 1.13)和LACmax升高(OR = 1.47)是SCM的危险因素(p < 0.05)。SCM的存在与更高的住院死亡率和增加的医疗费用相关(p < 0.05)。在SCM患者中,LVEF和心输出量的恢复与生存结果的改善相关。结论:IL-1水平升高、乳酸峰值浓度升高、APACHE II评分升高与感染性休克患者发生SCM相关。SCM与死亡率增加和医疗资源利用率增加进一步相关。心功能的恢复,特别是LVEF和心输出量的改善,与预后的改善相关,可能是临床结果的一个有价值的指标。
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引用次数: 0
Epidemiological Assessment of Blood and Blood-Borne Pathogen Exposure Among Neurosurgical Health Care Workers in a Chinese Tertiary Hospital (2008-2024). 2008-2024年三级医院神经外科医护人员血液及血源性病原体暴露的流行病学评价
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002788
Liyi Wang, Bing Gao, Chi Zhang, Huifang Zhao, Yongwan Chang, Yating Wang, Xiangyu Zhou, Xuhua Cao

Objective: This study aimed to examine the prevalence of occupational exposure to blood-borne pathogens (BBPs) and assess the associated psychological impact among health care workers (HCWs) in a neurosurgery department.

Methods: (1) A retrospective cross-sectional survey was conducted to assess BBP exposure trends among neurosurgical HCWs from 2008 to 2024. (2) A questionnaire-based survey was administered to HCWs with documented BBP exposure between 2022 and 2024 to assess occupational protection practices and psychological responses.

Results: (1) The cross-sectional survey identified needlestick injuries (NSIs) to the hand were the most frequent type of exposure, primarily occurring in operating rooms and among physicians with 2 to 10 years of work experience. Emergency treatment was universally administered following exposure, however, follow-up examination rates varied widely (0.00%-76.92%). Compared to the control group, HCWs with multiple BBP exposures were more likely to be formally employed, vaccinated against hepatitis B, over 24 years old, and involved in a broader range of exposure-related procedures (p < 0.05). Formal employment status emerged as an independent risk factor for repeated exposures. (2) The questionnaire survey indicated low utilization of personal protective equipment (6.25%-18.75%) and limited participation in occupational safety training (37.50%), with pre-employment training being the most common (43.75%). Risk perception varied by gender and occupation, with males demonstrating lower risk perception and nurses exhibiting the highest awareness (p < 0.05). Most respondents (68.75%) considered departmental protective equipment adequate for routine clinical operations. Following exposure, 96.88% of HCWs reported psychological distress, with moderate to severe anxiety particularly prevalent among associate chief physicians and other HCWs exposed to syphilis-positive sources.

Conclusion: Targeted interventions are warranted to mitigate occupational BBP exposure, including enhanced safety training, emergency response drills, and departmental inspections. Ensuring access to adequate protective equipment and reinforcing procedural compliance are essential. Psychological support services and post-exposure follow-up should be prioritized for at-risk subgroups, particularly HCWs with higher professional ranks and those exposed to high-risk pathogens, to safeguard both physical and mental health.

目的:本研究旨在调查职业接触血源性病原体(BBPs)的流行情况,并评估其对神经外科医护人员(HCWs)的相关心理影响。方法:(1)采用回顾性横断面调查方法,评估2008 - 2024年神经外科医护人员BBP暴露趋势。(2)对2022 - 2024年间有BBP暴露记录的医护人员进行问卷调查,评估职业防护措施和心理反应。结果:(1)横断面调查发现手部针刺损伤(nsi)是最常见的暴露类型,主要发生在手术室和具有2至10年工作经验的医生中。暴露后普遍给予急诊治疗,但随访检查率差异很大(0.00%-76.92%)。与对照组相比,多次接触BBP的医护人员更有可能被正式聘用,接种过乙型肝炎疫苗,年龄超过24岁,并参与了更广泛的接触相关程序(p < 0.05)。正式就业状况成为重复暴露的独立风险因素。(2)问卷调查显示,个人防护用品使用率低(6.25% ~ 18.75%),职业安全培训参与率低(37.50%),其中以岗前培训最为常见(43.75%)。风险认知因性别和职业而异,男性风险认知较低,护士风险认知最高(p < 0.05)。大多数应答者(68.75%)认为部门防护装备足以应付常规临床操作。暴露后,96.88%的医护人员报告了心理困扰,中度至重度焦虑在副主任医师和其他接触梅毒阳性源的医护人员中尤为普遍。结论:有针对性的干预措施是必要的,以减轻职业BBP暴露,包括加强安全培训,应急响应演习和部门检查。确保获得足够的防护设备和加强程序遵守是至关重要的。应优先为高危亚群体,特别是职级较高的卫生保健工作者和高危病原体接触者提供心理支持服务和接触后随访,以保障身心健康。
{"title":"Epidemiological Assessment of Blood and Blood-Borne Pathogen Exposure Among Neurosurgical Health Care Workers in a Chinese Tertiary Hospital (2008-2024).","authors":"Liyi Wang, Bing Gao, Chi Zhang, Huifang Zhao, Yongwan Chang, Yating Wang, Xiangyu Zhou, Xuhua Cao","doi":"10.1097/SHK.0000000000002788","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002788","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to examine the prevalence of occupational exposure to blood-borne pathogens (BBPs) and assess the associated psychological impact among health care workers (HCWs) in a neurosurgery department.</p><p><strong>Methods: </strong>(1) A retrospective cross-sectional survey was conducted to assess BBP exposure trends among neurosurgical HCWs from 2008 to 2024. (2) A questionnaire-based survey was administered to HCWs with documented BBP exposure between 2022 and 2024 to assess occupational protection practices and psychological responses.</p><p><strong>Results: </strong>(1) The cross-sectional survey identified needlestick injuries (NSIs) to the hand were the most frequent type of exposure, primarily occurring in operating rooms and among physicians with 2 to 10 years of work experience. Emergency treatment was universally administered following exposure, however, follow-up examination rates varied widely (0.00%-76.92%). Compared to the control group, HCWs with multiple BBP exposures were more likely to be formally employed, vaccinated against hepatitis B, over 24 years old, and involved in a broader range of exposure-related procedures (p < 0.05). Formal employment status emerged as an independent risk factor for repeated exposures. (2) The questionnaire survey indicated low utilization of personal protective equipment (6.25%-18.75%) and limited participation in occupational safety training (37.50%), with pre-employment training being the most common (43.75%). Risk perception varied by gender and occupation, with males demonstrating lower risk perception and nurses exhibiting the highest awareness (p < 0.05). Most respondents (68.75%) considered departmental protective equipment adequate for routine clinical operations. Following exposure, 96.88% of HCWs reported psychological distress, with moderate to severe anxiety particularly prevalent among associate chief physicians and other HCWs exposed to syphilis-positive sources.</p><p><strong>Conclusion: </strong>Targeted interventions are warranted to mitigate occupational BBP exposure, including enhanced safety training, emergency response drills, and departmental inspections. Ensuring access to adequate protective equipment and reinforcing procedural compliance are essential. Psychological support services and post-exposure follow-up should be prioritized for at-risk subgroups, particularly HCWs with higher professional ranks and those exposed to high-risk pathogens, to safeguard both physical and mental health.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Urinary oxygen partial pressure as a potential biomarker for acute kidney injury: a narrative review. 尿氧分压作为急性肾损伤的潜在生物标志物:一项叙述性综述。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002783
Jing Wen, Kefan Duan, Yuhang Ma, Ge Dai, Fengfeng Mo, Jiafeng Wang

Acute kidney injury (AKI) remains a crucial condition associated with poor prognosis in critically ill patients. Renal oxygenation resulting from renal ischemia is a significant contributor to AKI, wherein urine oxygen partial pressure partially indicates renal medullary oxygenation. The partial pressure of oxygen in urine may serve as a potential biomarker for the prediction and prognosis of AKI. Advances in technology have rendered novel non-invasive and real-time method for urinary oxygen detection. This review examines the significance, detecting method and potential clinical utility of urinary oxygen partial pressure to predict AKI.

急性肾损伤(AKI)仍然是危重症患者预后不良的关键疾病。肾缺血引起的肾氧合是AKI的一个重要因素,其中尿氧分压部分指示肾髓质氧合。尿氧分压可作为AKI预测和预后的潜在生物标志物。随着技术的进步,尿氧检测已成为一种新颖的、无创的、实时的方法。本文就尿氧分压预测AKI的意义、检测方法及潜在临床应用进行综述。
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引用次数: 0
Impact of Intensivist-Performed Transesophageal Echocardiogram Program on Patient Management- A Five-Year Single Center Experience. 强化医师执行的经食管超声心动图程序对患者管理的影响-一个五年的单中心经验。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002789
Andrew A Alberter, Taylor Miller, William A Teeter, Daniel J Haase, Justin E Richards, Samuel M Galvagno, Thomas M Scalea, Elizabeth K Powell

Purpose: Transesophageal echocardiography (TEE) has been slow to be incorporated in intensivist practice despite several studies showing how this diagnostic modality can change clinical management with improved reliability and clinical certainty. This study aimed to explore the feasibility of an intensivist-performed TEE program and its potential impact on management of critically ill patients.

Materials and methods: This single-center, retrospective cohort study used data from a multidisciplinary intensivist-performed TEE database at a quaternary care academic hospital. Consecutive TEE studies performed between January 1, 2020 and March 31, 2025 were reviewed.

Results: A total of 120 examinations were reviewed. Intensivist-performed TEE altered clinical management in 83% of cases (99 of 120 patients). The most frequent abnormalities identified were right ventricular dysfunction (23%), reduced left ventricular ejection fraction (21%), and valvular pathologies (19%). The most common changes in management included fluid administration (23%), inotrope initiation (17%), and ECMO cannula repositioning or confirmation (13%). There was one minor complication of TEE (0.8%) without any incidence of bleeding or esophageal perforation.

Conclusions: Our results support that an intensivist-performed TEE program is feasible, safe, and clinically useful in changing management in a diverse population of critically ill medical and surgical patients in a variety of clinical environments.

目的:经食管超声心动图(TEE)在强化医生的实践中一直进展缓慢,尽管有几项研究表明这种诊断方式如何改变临床管理,提高了可靠性和临床确定性。本研究旨在探讨重症医师执行TEE计划的可行性及其对危重病人管理的潜在影响。材料和方法:这项单中心、回顾性队列研究使用的数据来自一家四级护理学术医院的多学科重症医师TEE数据库。回顾了2020年1月1日至2025年3月31日期间进行的连续TEE研究。结果:共回顾检查120例。强化治疗的TEE改变了83%的病例(120例患者中的99例)的临床管理。最常见的异常是右心室功能障碍(23%),左心室射血分数降低(21%)和瓣膜病变(19%)。最常见的治疗改变包括液体给药(23%)、肌力启动(17%)和ECMO插管重新定位或确认(13%)。TEE有1例轻微并发症(0.8%),未发生出血或食管穿孔。结论:我们的研究结果支持强化医师实施TEE方案是可行的、安全的,并且在改变各种临床环境中危重医学和外科患者的管理方面具有临床价值。
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引用次数: 0
Bioengineered M13 Bacteriophage-GelMA Construct Modulates Immune Responses in a Preclinical Model of Sepsis. 生物工程M13噬菌体-凝胶蛋白构建在败血症临床前模型中调节免疫反应。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002787
Arezou Rahimi, Sara Soudi, Saeid Vakilian, Fatemeh Jamshidi-Adegani, Majid Sadeghizadeh, Ali Hazrati, Khamis Al-Riyami, Zohreh Safari, Reza Alimohammadi, Sulaiman Al-Hashmi

Background: A life-threatening condition, sepsis is defined by dysregulated immune system responses and multi-organ dysfunction. There is still no drug or treatment that can completely and guarantee to cure this condition; available treatments mainly focus on controlling the infection with antibiotics, supporting organ function, and managing symptoms. Although artificial lymphoid tissues (ALTs) have potential for localized immunomodulation, their application is often limited by inadequate biological function and poor structural integrity. To address these issues, we developed a novel bioink that combines gelatin methacryloyl (GelMA) with M13 bacteriophage, a filamentous, non-lytic virus recognized for its immunomodulatory activity, self-assembling capacity, and biocompatibility. Male C57BL/6 mice (8-10 weeks, 22-25 g) were randomly assigned to six groups: sham + normal saline (NS), CLP + NS, CLP + M13, 3D-M13, 3D+M13, and 3D+M13 + CLP. The cecal ligation and puncture (CLP) procedure was applied to induce polymicrobial sepsis. Cell-laden, three-dimensional (3D) bioprinted GelMA scaffolds with or without M13 bacteriophage were surgically implanted on the spleen 35 days prior to sepsis induction. Subsequently, immune, histological, and biochemical parameters were assessed. Compared with GelMA-only scaffolds, M13-containing scaffolds demonstrated improved printability, mechanical stability, cellularity, and angiogenesis. Mice implanted with 3D+M13 scaffolds exhibited significantly reduced levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), as well as higher levels of anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor beta (TGF-β). Additionally, the bacterial load was reduced, and organ injury in the liver, lungs, and kidneys was reduced. Circulating liver enzyme levels were also reduced, suggesting precautionary measures against sepsis-induced hepatic dysfunction. The integration of M13 bacteriophage into GelMA bioink is a distinctive approach that simultaneously enhances the stability of ALT and stimulates anti-inflammatory immune modulation. This dual structural-immunological effect defines a new paradigm for the development of multifunctional biomaterials in the fields of immune regulation and tissue engineering.

背景:脓毒症是一种危及生命的疾病,由免疫系统反应失调和多器官功能障碍所定义。目前还没有药物或治疗方法可以完全治愈这种疾病;现有的治疗方法主要集中在用抗生素控制感染、支持器官功能和控制症状。虽然人工淋巴组织(ALTs)具有局部免疫调节的潜力,但其应用往往受到生物功能不足和结构完整性差的限制。为了解决这些问题,我们开发了一种新的生物链接,将明胶甲基丙烯酰(GelMA)与M13噬菌体结合在一起,M13噬菌体是一种丝状的非溶性病毒,以其免疫调节活性、自组装能力和生物相容性而闻名。雄性C57BL/6小鼠(8 ~ 10周,22 ~ 25 g)随机分为假药+生理盐水(NS)组、CLP + NS组、CLP +M13组、3D-M13组、3D+M13组和3D+M13 + CLP组。采用盲肠结扎穿刺(CLP)方法诱导多微生物脓毒症。在脓毒症诱导前35天,将带有或不带有M13噬菌体的承载细胞的三维(3D)生物打印GelMA支架手术植入脾脏。随后,评估免疫、组织学和生化参数。与仅gelma支架相比,含有m13的支架显示出更好的打印性、机械稳定性、细胞结构和血管生成。3D+M13支架小鼠的促炎细胞因子、肿瘤坏死因子α (TNF-α)和白细胞介素-6 (IL-6)水平显著降低,抗炎细胞因子白介素-10 (IL-10)和转化生长因子β (TGF-β)水平升高。此外,细菌负荷减少,肝脏、肺和肾脏的器官损伤减少。循环肝酶水平也降低,提示对败血症引起的肝功能障碍采取预防措施。将M13噬菌体整合到GelMA生物链接中是一种独特的方法,可以同时增强ALT的稳定性并刺激抗炎免疫调节。这种双重结构-免疫效应定义了在免疫调节和组织工程领域开发多功能生物材料的新范式。
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引用次数: 0
Activation of the Cerebrospinal Fluid-Contacting Nucleus Mitigates Systemic Inflammation Induced by Sepsis. 脑脊液接触核的激活减轻败血症引起的全身炎症。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002665
Peng-Fei Liu, Yu-Han Ding, Ying Li, Yao Yan, Yi-Jun Zhang, Jing Zhao, Bin Gui, Su-Ming Zhang, Qing-Qing Zhang, Rui Wang, Zhi-Ping Wang, Li-Cai Zhang

Reciprocal interactions between the central nervous system and immune are now recognized as critical components of the host response in sepsis. However, the precise mechanism by which the central nervous system modulates immune function remains largely elusive. The cerebrospinal fluid (CSF)-contacting nucleus (CSF-contacting nucleus) is a unique nucleus, with its neurons located in the brain parenchyma and processes extending into the CSF. Here, we demonstrate that the CSF-contacting nucleus plays a protective role in sepsis. We observed a significant Fos high expression within the CSF-contacting nucleus in response to sepsis with immunofluorescence assays. Ablation of the CSF-contacting nucleus exacerbated sepsis severity, result in levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) elevated. Conversely, chemogenetic activation of the CSF-contacting nucleus resulted in a reduction in pro-inflammatory cytokine (IL-1β, IL-6, and TNFα) levels while simultaneously increasing the levels of IL-10. Inhibition of the CSF-contacting nucleus specifically elevated IL-6 levels. Notably, single-cell RNA sequencing was employed to identify key components within the CSF-contacting nucleus that regulate systemic inflammation in septic mice. Our findings indicate an upregulation of immune-related genes in the CSF-contacting nucleus during sepsis. Collectively, our study underscores a significant role of the CSF-contacting nucleus in neuro-immune interactions and suggests its potential as a novel therapeutic target for immune-mediated diseases.

中枢神经系统和免疫系统之间的相互作用现在被认为是败血症中宿主反应的关键组成部分。然而,中枢神经系统调节免疫功能的确切机制在很大程度上仍然难以捉摸。脑脊液接触核(CSF-contact nucleus)是一种独特的核,其神经元位于脑实质,突起延伸至脑脊液。在这里,我们证明了csf接触核在脓毒症中起保护作用。我们用免疫荧光法观察到,在脓毒症的反应中,Fos在接触csf的细胞核中有显著的高表达。消融与csf接触的细胞核会加重脓毒症的严重程度,导致促炎细胞因子(IL-1β、IL-6和TNFα)水平升高。相反,与csf接触的细胞核的化学发生激活导致促炎细胞因子(IL-1β、IL-6和TNFα)水平降低,同时IL-10水平升高。抑制与csf接触的细胞核特异性地提高IL-6水平。值得注意的是,单细胞RNA测序被用来鉴定与csf接触的细胞核内调节脓毒症小鼠全身炎症的关键成分。我们的研究结果表明,在败血症期间,与csf接触的细胞核中免疫相关基因的上调。总的来说,我们的研究强调了接触csf的细胞核在神经免疫相互作用中的重要作用,并表明其作为免疫介导疾病的新治疗靶点的潜力。
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引用次数: 0
VASOACTIVE AGENT THERAPY IN SEPTIC SHOCK: FROM MONOTHERAPY BATTLES TO TAILORED HEMODYNAMIC OPTIMIZATION. 感染性休克的血管活性药物治疗:从单一治疗战斗到量身定制的血流动力学优化。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-23 DOI: 10.1097/SHK.0000000000002781
Mingyang Zhu, Yuxiang Zhang, Wenming Liu

Hemodynamic stabilization and preservation of organ perfusion are central elements in the management of septic shock. This is achieved by fluid resuscitation and by administration of vasoactive agents to secure a time window for definitive cause-directed therapy. Guided by the Surviving Sepsis Campaign, the optimization of vasoactive agent strategies, namely protective hemodynamic management, has become a central focus. Tracing key research over the past 25 years reveals a paradigm shift in vasopressor therapy, from empiricism to goal-directed strategy. This evolution has deepened our understanding of the benefit-risk profile of vasoactive agents and fostered a new conceptual framework regarding organ perfusion and protection. Under this framework, management strategies have advanced from the mere pursuit of hemodynamic parameters to care bundles that integrate the monitoring of organ perfusion, microcirculation, and oxygen metabolism. These advances have optimized agent selection, established safe dosing ranges, and ultimately promoted the widespread adoption of combined and multimodal therapy concepts. This review delineates this transformative journey, synthesizing evidence on the reappraisal of traditional agents and exploring "de-catecholaminization" strategies, thereby aiming to broaden the therapeutic landscape. The integration of artificial intelligence and genomic medicine is expected to further advance personalized management strategies for septic shock.

血流动力学的稳定和器官灌注的保存是处理感染性休克的核心要素。这是通过液体复苏和血管活性药物的管理来实现的,以确保最终病因导向治疗的时间窗口。在生存败血症运动的指导下,血管活性药物策略的优化,即保护性血流动力学管理,已成为中心焦点。追踪过去25年的关键研究揭示了血管加压治疗的范式转变,从经验主义到目标导向的策略。这一演变加深了我们对血管活性药物的获益-风险概况的理解,并培养了一个关于器官灌注和保护的新概念框架。在这个框架下,管理策略已经从单纯追求血流动力学参数发展到结合器官灌注、微循环和氧代谢监测的护理包。这些进展优化了药物选择,建立了安全给药范围,并最终促进了联合和多模式治疗概念的广泛采用。这篇综述描述了这一变革之旅,综合了对传统药物重新评估的证据,并探索了“去儿茶酚胺化”策略,从而旨在拓宽治疗前景。人工智能与基因组医学的结合有望进一步推进感染性休克的个性化治疗策略。
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引用次数: 0
Risk model based on neutrophil-related genes constructs to assess prognosis and immune landscape in sepsis. 基于中性粒细胞相关基因的风险模型构建评估败血症的预后和免疫景观。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2025-12-11 DOI: 10.1097/SHK.0000000000002768
Fan Sun, Min Shi, Xiaodong Li, Xueyun Liu, Xiaowei Wang

Background: Sepsis is a persistent systemic inflammatory disease involving multiple organ failure caused by a dysregulated immune response to infection. As primary effector cells in innate immunity, neutrophils significantly contribute to combating infections and mediating inflammatory responses. The aim of this study was to evaluate the prognostic significance of neutrophil-related genes (NRGs) in sepsis and their relationship with the immune microenvironment.

Methods: This study was drawing on transcriptomic data and clinical characterization of sepsis patients from the GEO database. Sepsis prognostic genes were discovered through a combination of differential analysis, weighted gene co-expression network analysis (WGCNA), and univariate cox regression analysis. Molecular subtypes of sepsis were identified by consensus clustering methods, survival differences between subtypes were compared and gene enrichment analysis was performed. Further univariate cox regression analysis and LASSO combined were performed to identify sepsis feature genes. Utilizing multivariate cox regression analysis, a prognostic model was developed, and its predictive capability was subsequently examined through receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analyses. Subsequently, immune cell infiltration and gene enrichment were assessed in the various risk groups.

Results: This study identified the presence of two molecular subtypes in sepsis, with Cluster1 patients having significantly better survival than Cluster2. The prognostic model based on NRGs (RCBTB2, KRT23, KLF9, GIMAP4 and CD84) in this study significantly differentiated the survival prognosis of high risk and low risk patients. The low risk patient group showed significant enrichment in immune related pathways (T cell receptor signaling and primary immunodeficiency), while the high risk group primarily exhibited significant enrichment in metabolism related pathways (glycine serine and threonine metabolism).

Conclusion: Risk models constructed on the basis of NRGs are effective in predicting survival outcomes and immune profiles of sepsis patients, providing a new perspective on the link between NRGs and sepsis.

背景:脓毒症是一种持续的全身性炎症性疾病,涉及多器官功能衰竭,由对感染的免疫反应失调引起。作为先天免疫的主要效应细胞,中性粒细胞在对抗感染和介导炎症反应中发挥着重要作用。本研究的目的是评估中性粒细胞相关基因(NRGs)在脓毒症中的预后意义及其与免疫微环境的关系。方法:本研究利用GEO数据库中脓毒症患者的转录组学数据和临床特征。通过差异分析、加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)和单因素cox回归分析相结合,发现脓毒症预后基因。采用一致聚类方法鉴定脓毒症的分子亚型,比较不同亚型的生存差异,并进行基因富集分析。进一步进行单因素cox回归分析和LASSO联合鉴定脓毒症特征基因。采用多变量cox回归分析建立预后模型,并通过受试者工作特征(ROC)曲线和Kaplan-Meier (K-M)生存分析检验其预测能力。随后,对不同风险组的免疫细胞浸润和基因富集进行了评估。结果:本研究发现脓毒症中存在两种分子亚型,Cluster1患者的生存率明显高于Cluster2。本研究中基于NRGs (RCBTB2、KRT23、KLF9、GIMAP4和CD84)的预后模型可明显区分高危和低危患者的生存预后。低危患者组免疫相关通路(T细胞受体信号和原发性免疫缺陷)显著富集,高危患者组代谢相关通路(甘氨酸丝氨酸和苏氨酸代谢)显著富集。结论:基于NRGs构建的风险模型可有效预测脓毒症患者的生存结局和免疫特征,为NRGs与脓毒症的联系提供了新的视角。
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引用次数: 0
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