Background:Sepsis is characterized by profound immune dysregulation, in which myeloid-derived suppressor cells (MDSCs) serve as key regulators of the host immune response. However, the prognostic significance of distinct MDSC subsets during the early phase of sepsis remains incompletely understood.Methods:In this prospective cohort study, flow cytometry was used to quantify circulating MDSC subsets in sepsis patients within 24 hours of intensive care unit (ICU) admission and in healthy control subjects. Patients were followed to establish 90-day survival, and the prognostic significance of MDSC subset frequencies on admission was evaluated using receiver operating characteristic (ROC) curve analysis and Cox regression models. Multivariate Cox models were adjusted for disease severity scores. A murine cecal ligation and puncture (CLP) model of sepsis was also used to investigate temporal and tissue-specific MDSC dynamics and to examine endoplasmic reticulum (ER) stress-related signaling within these cells.Results:Compared with healthy controls, patients with sepsis exhibited the marked expansion of circulating MDSCs, including both polymorphonuclear and monocytic subsets. Among these, the proportion of circulating monocytic MDSCs (M-MDSCs) on ICU admission was significantly higher in 90-day survivors than in non-survivors. After adjusting for disease severity and other clinical variables, higher M-MDSC frequencies were independently associated with lower 90-day mortality. ROC curves confirmed the ability of the M-MDSC proportion to predict 90-day mortality. In the CLP model, MDSC subsets displayed temporal and tissue-specific dynamics that differed between the acute and recovery phases of sepsis. MDSCs isolated from septic mice exhibited ER stress-related pathway activation in the spleen and bone marrow. Collectively, these findings suggest that early M-MDSC expansion represents a distinct immunological phenotype associated with favorable outcomes in sepsis.Conclusions:An early increase in circulating M-MDSCs is associated with improved 90-day survival in patients with sepsis. These findings underscore the dynamic, context-dependent role of M-MDSCs in sepsis, indicating that early immunoregulatory responses, possibly associated with activation of ER stress pathways, may represent an adaptive mechanism leading to favorable clinical outcomes.
Critical care medicine plays a pivotal role in addressing life-threatening conditions; however, its development in China is hindered by resource scarcity and inequitable distribution. Existing studies have mostly focused on ICU bed numbers or selected regions, and have rarely provided a comprehensive, nationwide assessment of ICU beds, staffing and equipment using standardized methods, nor have they systematically quantified population-based equity of ICU resources. To address this evidence gap and describe the current landscape of critical care capacity in China, we conducted a nationwide survey of critical care resources. The survey aimed to describe the current status of resources, quantify population-based equity, and explore regional and hierarchical disparities that may affect access to critical care. This cross-sectional survey was conducted from January 1, 2021, to December 31, 2023, encompassing public comprehensive hospitals, private hospitals, and specialty hospitals across 31 provinces (including municipalities) in China. A total of 4,744 hospitals with a comprehensive ICU provided valid responses and were included in the analysis; the overall response rate among eligible hospitals invited through provincial health authorities was approximately 89.80
Acute respiratory distress syndrome (ARDS) is a highly heterogeneous syndrome with substantial mortality, for which existing subphenotyping strategies based on single-modal data have limited ability to guide targeted therapies. A comprehensive, multimodal framework is urgently needed to decipher its complexity and advance precision care. The BIOWARE study is a prospective, multicenter cohort aiming to enroll 2,000 ARDS patients across nine Chinese centers. The protocol integrates longitudinal data from clinical assessments, ventilator waveforms, advanced imaging (CT, EIT, lung ultrasound), and biospecimen analyses. As of August 2025, 169 patients have been enrolled (median age 62 years, 74
Background:Surfactant protein D (SP-D) has been widely studied in infectious diseases, yet its role in aseptic inflammation remains poorly understood. This study aims to evaluate the clinical and mechanistic relevance of SP-D in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by hypobaric hypoxia. Methods:A hypobaric hypoxia-induced ALI model was established in rats at different time intervals (24, 48, and 72 h). SP-D levels were measured in lung tissue, bronchoalveolar lavage fluid (BALF), and serum, alongside inflammatory markers and hypoxia-inducible factor-1α (Hif-1α) expression. Serum SP-D levels were also compared between ARDS patients and healthy controls. Results:Hypobaric hypoxia-induced dose-dependent lung injury in rats, with elevated inflammatory cytokines, increased Hif-1α expression, reduced SP-D in lung tissue, and increased SP-D in BALF and serum. BALF SP-D positively correlated with lung injury severity, while lung SP-D levels showed a negative correlation. In ARDS patients, serum SP-D levels were significantly elevated and negatively correlated with the oxygenation index. Conclusion:SP-D exhibits dynamic expression changes in response to hypoxia-induced lung injury and holds potential as a biomarker for assessing lung injury severity and predicting outcomes in ARDS.
急性呼吸窘迫综合征(ARDS)是常见的呼吸系统危重症,发病率和死亡率都很高.高原气压低、氧含量低、干燥寒冷、强辐射及气候多变的环境对人体健康有巨大的影响.高海拔地区急慢性缺氧可诱发多种疾病,ARDS的发病率也显著增加,为16.70% ~20.72%.低氧是高原ARDS的诱发及加重因素.高原ARDS尽管与平原地区的ARDS有许多相似之处,但高原低压低氧的环境,造成高原ARDS独特的病理生理特征,因此其诊断标准和低海拔地区不完全相同.海拔氧合指数校正的柏林标准可以区分高原ARDS的严重程度,但仍存在争议,对于高原ARDS诊断目前仍没有统一可行的标准.本文就高原ARDS诊断方面的相关研究进展进行综述.
Objectives: This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow alteration and outcome in critically ill patients. Design: Prospective, observational, pilot study. Setting: ICU in a university hospital. Patients: Two hundred eighty-two critically ill adult patients admitted to the ICU. Interventions: None. Measurements and Main Results: All patients underwent simultaneous measurements by CRT and sidestream dark field imaging within 24 hours of ICU admission. Other clinical data such as demographic characteristics, hemodynamics, laboratory values, treatment, and physiologic parameters were also included simultaneously. Microcirculatory measurements were performed at 10.2 ± 5.7 hours after ICU admission. Of the 282 included patients, 106 (37.6%) were female, the median (interquartile range) age was 63 years (53–74 yr), and the median Sequential Organ Failure Assessment (SOFA) score was 5 (2–7). The primary finding was the association between CRT and simultaneous the condition of peripheral circulation (microvascular flow index [MFI]: r = –0.4430, p < 0.001; proportion of perfused vessels: r = –0.3708, p < 0.001; heterogeneity index: r = 0.4378, p < 0.001; perfused vessel density: r = –0.1835, p = 0.0020; except total vessel density: p = 0.9641; and De Backer score: p = 0.5202) in critically ill patients. In addition, this relationship was also maintained in subgroups. Microcirculatory flow abnormalities, 28-day mortality, and SOFA score appeared to be more severe for increasing CRT. In a multivariable analysis, prolonged CRT was independently associated with microvascular flow abnormalities (MFI < 2.6; odds ratio [OR], 1.608; 95% CI, 2.1–10.2; p < 0.001). Similarly, multivariable analysis identified CRT as an independent predictor of 28-day mortality (OR, 1.296; 95% CI, 1.078–1.558; p = 0.006). Conclusions: In our ICU population, a single-spot prolonged CRT was independently associated with abnormal microcirculation and increased mortality.
Background:The benefits of early use of norepinephrine in endotoxemic shock remain unknown. We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model.Methods:Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs. Treatment included fluid resuscitation and administration of different doses of norepinephrine, to induce return to baseline mean arterial pressure (MAP). Fluid management, hemodynamic, microcirculation, inflammation, and organ function variables were monitored. All animals were supported for 6 h after endotoxemic shock.Results:Infused fluid volume decreased with increasing norepinephrine dose. Return to baseline MAP was achieved more frequently with doses of 0.8 µg/kg/min and 1.6 µg/kg/min (P <0.01). At the end of the shock resuscitation period, cardiac index was higher in pigs treated with 0.8 µg/kg/min norepinephrine (P <0.01), while systemic vascular resistance was higher in those receiving 0.4 µg/kg/min (P <0.01). Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2 µg/kg/min norepinephrine (P <0.01), while the percentage of perfused small vessel density (PSVD) was higher in those receiving 0.8 µg/kg/min (P <0.05) and serum lactate was higher in the groups administered no and 1.6 µg/kg/min norepinephrine (P <0.01).Conclusions:The impact of norepinephrine on the macro- and micro-circulation in early-stage endotoxemic shock is dose-dependent, with very low and very high doses resulting in detrimental effects. Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.
Objective Combined with domestic and foreign guidelines,to explore the individualized treatment strategy of urosepsis,and to provide reference for standardized diagnosis and treatment of urosepsis patient.Methods To analyze the diagnosis and treatment process of a patient with urogenic sepsis who was admitted to the department of critical care medicine of the First Affiliated Hospital of Xi'an Jiaotong University in April 15,2021.During the diagnosis and treatment process,we performed puncture drainage fluid and urine culture as soon as possible to confirm the diagnosis from the perspective of etiology.Considering the possible pathogenic bacteria at the infection site,the drug resistance of pathogenic bacteria in medical units,and drug safety,imipenem and cilastatin was chosen for anti-infective therapy.A two-step approach was used for drug administration based on drug pharmacokinetics/pharmacodynamic(PK/PD)characteristics,and drug concentration monitoring.The patients were followed up after discharge.Results The patient was critically ill on admission and was diagnosed with urosepsis.We optimize the empirical use of antimicrobials based on their PK/PD characteristics.Ultrasound-guided percutaneous nephrostomy of the left renal pelvis was performed to adequately drain the infection.Urine culture returned as extended-spectrum β-lactamase(ESBL)-producing Escherichia coli,confirming the etiological diagnosis.After 7 days of treatment,the patient's condition improved,the antibacterial drugs were downgraded to piperacillin-tazobactam,and the total course of anti-infection was 14 days.The patient was in good condition 2 months after discharge,and underwent left ureteral calculus and lithotripsy in the local hospital,and the left nephrostomy tube was removed.After discharge,the patient's condition was stable,no recurrence was found after 7 months of follow-up,and daily life was not affected.Conclusions Management of infection foci in urosepsis patient is critical.Diagnosis and treatment should refer to domestic and foreign guidelines,and formulate treatment strategies based on the distribution of local pathogens,drug resistance,and the actual clinical conditions of patients.Optimize the use of antibiotics based on drug PK/PD characteristics,monitor the concentration of therapeutic drugs,and realize individualized treatment.
Approximately 2% of the global population lives above 1500 m, where low atmospheric pressure, decreased oxygen levels, harsh cold and dry conditions, strong radiation, and the effects of climate change present significant health challenges. Residents of these high-altitude areas display physiological adaptions, including smaller body size, enlarged ribs, improved oxygen delivery in hypoxic conditions, and adjustments in oxygen utilization and metabolism. Both acute and chronic hypoxia prevalent in such regions can trigger various diseases by stimulating hypoxia-inducible factors, boosting inflammatory responses, and impairing mitochondrial function.Acute Respiratory Distress Syndrome (ARDS) - a critical respiratory condition associated with high morbidity and mortality - occurs more frequently among the health risks in these environments. Hypoxia is a critical predisposing and aggravating factor for high-altitude ARDS. Despite similarities with its low-altitude counterpart, ARDS in high-altitude areas displays unique pathophysiology and clinical manifestations due to the specific environmental conditions.This review aims to shed light on how high-altitude environments influence the diagnosis and treatment of ARDS, providing a comprehensive understanding of the distinct challenges inherent to these regions.
The association between thiamine use and clinical outcomes among patients with sepsis and alcohol use disorder (AUD) is unclear. In this retrospective cohort study of patients from Medical Information Mart for Intensive Care III (MIMIC-III, version 1.4), we evaluated the association of thiamine use with clinical outcomes in patients with AUD and sepsis. The primary outcome was 28-day survival, and secondary outcomes included ICU, in-hospital, and 90-day mortality, ICU and hospital length of stay, duration of vasopressor use, need and duration of continuous renal replacement therapy (CRRT), and dynamic changes for variables up to day 7 after ICU admission. A total of 944 patients with sepsis and AUD were included in this cohort [median age, 53.1 years; women, 26.0% (245 of 944)]. Among all patients, 24.6% (233 of 944) received thiamine with a dose of 200 mg (IQR 100–345 mg). The 28-day mortality was 11.2% (26 of 233) in the thiamine use group compared with 18.6% (132 of 711) in the no thiamine use group (P = 0.009). After adjustment for a series of confounders, the mixed-effects Cox proportional hazards models showed that administration of thiamine was associated with a lower risk of 28-day mortality compared with no administration of thiamine. In critically ill patients with alcohol use disorder admitted for sepsis, treatment with thiamine may be associated with a decreased risk of death. However, the present results should be interpreted with caution due to the limitations of retrospective design. Additional larger, multicenter randomized controlled trials are needed to confirm our findings.
Abstract Background: Recent studies demonstrate the advantage of peripheral perfusion-targeted resuscitation protocols based on capillary refill time (CRT) assessment in critically ill patients. Additionally, sidestream dark field (SDF) imaging could direct visualize sublingual microcirculation of critically ill patients. This study aimed to determine the association between the sublingual microcirculation and CRT in critically ill patients in the early phase of intensive care unit (ICU) admission. Methods: This prospective, observational, pilot study included 282 patients in the ICU of Zhongnan Hospital of Wuhan University between October 2021 and January 2022. All patients underwent simultaneous measurements by CRT and SDF imaging within 24 hours of ICU admission. Additionally, other clinical data such as demographic variables, hemodynamics, laboratory values, treatment, and physiological parameters were also included. The primary outcome was the association between CRT and simultaneous sublingual microcirculation parameters in critically ill patients.Results: Of the 282 included patients, 106 (37.6%) were female, the median (IQR) age was 63 (53-74) years, and the median (IQR) SOFA score was 5 (2-7). Microcirculatory measurements (CRT and SDF imaging) were performed at 10.2 ± 5.7 hours after ICU admission. Significant relationships were observed between the CRT and MFI (r = -0.4430, p < 0.001), PPV (r = -0.3708, p < 0.001), PVD (r = -0.1835, p = 0.0020), and HI (r = 0.4378, p < 0.001). Neither TVD (p = 0.9641) nor De Backer score (p = 0.5202) were related to the CRT. Compare to CRT< 3s group, MFI (2.60 vs. 2.88, p < 0.001), PPV (91.35% vs. 99.10%, p < 0.001), PVD (13.36 mm/mm2 vs. 14.55 mm/mm2, p = 0.002), and HI (0.46 vs. 0.15, p < 0.001) were significantly worse in the CRT ≥ 3s group. The similar results were also found in the sepsis subgroup and the hyperlactatemia subgroup. Prolonged CRT was an independent predictor of 28-days mortality (OR = 1.296; (95%CI, 1.078-1.558); p = 0.006).Conclusions: Our findings suggested that there was a significant and moderate association between CRT and some sublingual microcirculation parameters more related to perfusion (MFI, PPV, and HI) in heterogeneous ICU patients at the early phase of admission.Trial registration: The study was retrospectively registered on November 7, 2021, ChiCTR2100052999.
Acute respiratory distress syndrome (ARDS) is a common cause of critical illness and high mortality from respiratory failure. Increased dead space fraction (VD/VT) was independently associated with lung injury and mortality of ARDS. VD/VT is readily obtained by bedside measurements of arterial blood gas and end-tidal carbon dioxide. Early attention and application of VD/VT as an indicator will help to better understand the pathophysiological of ARDS, guide clinical treatment, and better assess the severity and clinical prognosis of the disease.
Abstract Prone position ventilation improves oxygenation and reduces the mortality rate in patients with acute respiratory distress syndrome (ARDS). However, conventional prone ventilation is not sufficient for patients with ARDS living at high altitudes. Accordingly, this report proposes the concept of continuous lateral prone ventilation, which achieves lung protection by improving arterial oxygen and lung compliance as well as reducing the driving pressure while applying positive end-expiratory pressure, in patients with ARDS living at plateaus.
Long-term chronic hypoxia can promote microangiogenesis through a variety of mechanisms to enhance the effective exchange of blood and tissue fluid and ensure oxygen transport, which is a physiological mechanism for the body to adapt to hypoxic environment. However, when the body suffers from various stresses such as severe trauma, infection, and hypoxia, microvascular hyperplasia may play adverse roles, and hypovolemic shock may occur in the early stage of the disease. With the development of the disease and inappropriate medical intervention, it is easy to develop capillary leakage and organ and tissue edema, thus aggravating the disease. At this time, the body may have special pathophysiology. This paper describes the physiological mechanism of microangiogenesis in chronic hypoxic environment and discusses its possible pathophysiological and clinical characteristics, which is beneficial to the accurate implementation of clinical treatment.
Objective:To virtually screen out the potential targets improving brain microcirculation of the Tibetan medicine Rhodiola, based on chemical similarity target prediction and network topology analysis methods.Methods:The active ingredients of Rhodiola based on chemical composition database and related literatures, were selected by pharmacokinetic parameters (ADME). The swiss online target prediction platform was used to predict potential targets of active components of Rhodioal sachalinensis by chemical similarity method. Obtaining brain microcirculation-related targets through the GeneCards database, and obtaining the Rhodiola active components and brain microcirculation common target. Common target proteins were linked to the STRING database. Construction of a protein-protein interaction (PPI) network model using Cytoscape software. Obtaining core targets (core target) based on network topology algorithm. For KEGG analysis of the common targets, to clarify which signaling pathways are potential targets of Rhodiola to improve brain microcirculation.Results:Seventy-six active components and 660 targets were selected from Tibetan medicine Rhodiola to obtain 526 brain microcirculation related targets, 141 intersection targets, core targets AKT1, TNF, VEGFA, GAPDH, MAPK3, EGFR, SRC, Casp 3, and reverse find core target related components to obtain 25 key active components. The KEGG analysis selected 150 pathways (P<0.01), and the main signaling pathways include: HIF-1 signaling pathway, Rap1 signaling pathway, focal adhesion plaque, relaxin signaling pathway, Ras signaling pathway, and PI3K-Akt signaling pathway, TNF signaling pathway, and ErbB signaling pathway.Conclusion:Tibetan medicine Rhodiola can improve the role of brain microcirculation through multi-component, multi-target and multi-pathway coordination. This study has preliminarily screened out the potential targets and signal pathway of regulating cerebral microcirculation, which provides a rich theoretical basis for further expanding the application of Tibetan medicine Rhodiola brain protection and pharmacology.
Lung surfactant protein D (SP-D) is a glycoprotein of the lectin family. In lungs it is synthesized and secreted mainly in the alveolar type Ⅱ epithelial cells and non-ciliated bronchiole epithelial cells, and are stored in secretory granules of Clara cells. SP-D is one of the surfactant binding proteins and is also a part of the pulmonary surfactant system. In addition to contributing to the homeostasis of surfactant pools in alveolar space, SP-D also exhibits functions of host defense and immunoregulation. This paper summarizes some relevant studies on SP-D in acute lung diseases in recent years, providing important theoretical basis for the potential treatment of many lung diseases, especially in inflammatory lung diseases.
Objective:To analyze the status of targeted surveillance of nosocomial infection in intensive care unit (ICU) of Qinghai Provincial People′s Hospital to provide a basis for nosocomial infection prevention strategy in hospitals at high altitude.Methods:By means of retrospective survey, the data of targeted surveillance of nosocomial infection and device-related infection in ICU of Qinghai Provincial People′s Hospital from January 2017 to December 2020 were collected.Results:Totally 6283 patients were enrolled in the study. The incidence of nosocomial infection was 6.20%, and the case-time infection rate was 6.94%. The patients with respiratory system infection were dominant among the patients with nosocomial infection, accounting for 58.68%, followed by urinary system infection, accounting for 17.58%. Among the patients with device-related infection, the incidence of ventilator-related pneumonia (VAP) was 8.88‰, the incidence of catheter associated urinary tract infection (CAUTI) was 2.53‰, and the incidence of catheter-related bloodstream infection (CRBSI) was 0. The daily VAP rate was 15.09‰ in 2017 and 8.38‰ in 2020.Conclusion:The incidence of ICU device-associated infection shows an overall downward trend. The incidence of nosocomial infection in ICU can be effectively reduced by carrying out the targeted monitoring of nosocomial infection in ICU, discovering the risk factors in time, and taking intervention measures.
There are two techniques of airway suction during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS): open airway suction and enclosed airway suction. To do the former, patients are disconnected from ventilators in the airway suction, and suction tubes are put into the endotracheal tubes to suck; to do the latter, patients will not be disconnected from ventilators. Positive end-expiratory pressure (PEEP) ventilation is one of the main measures to improve oxygenation. When open endotracheal suction is performed, disconnection of PEEP leads to alveolar collapse. It may increase shunt effect, dead cavity ventilation, and ventilation/perfusion mismatch, and further aggravate lung injury. In this paper, we analyze the shunt, dead cavity, ventilator-related lung injury, and hemodynamics, and explore the endotracheal suction technique for lung protection in ARDS.
急性呼吸窘迫综合征(ARDS)时肺血管收缩、肺血管阻力增加、肺动脉高压,导致患者右心后负荷过高,继而并发急性肺心病(ACP),加重右心功能损害,出现严重肺水肿及低氧血症.长期暴露在高原慢性低氧环境的健康人,极易出现生理性肺动脉高压及血液黏滞度改变等,这些因素会加重高原ARDS的严重程度.因此,高原ARDS与平原ARDS的病理生理变化有所不同,诊断标准、临床表现、病情严重程度也不一致.本文从高原ARDS的病理生理机制出发,探讨右心功能损害的影响因素,提出高原慢性低氧暴露下的ARDS更应关注右心功能的监测与保护,优化呼吸支持治疗、肺血管扩张治疗、抗凝治疗等,以减少治疗中的再损伤,提高ARDS救治的存活率.
Objective:To investigate the expression and effect of pulmonary surfactant protein-D (SP-D) in the occurrence and development of high altitude pulmonary edema.Methods:64 male Wistar rats were randomly divided into four groups: normal control group (n=16, 586 m altitude with room temperature feeding), low-pressure hypoxia 24 h, 48 h and 72 h group (n=16, feeding in a simulated altitude 6000 m with low-pressure hypoxia chamber for 24 h, 48 h and 72 h, respectively). The right lung tissue was used for HE staining to observe the lung tissue injury. The alveolar lavage fluid of the left lung was taken to measure the SP-D, IL-1β, IL-6, CRP and TNF-α by enzyme-linked immunosorbent assay.Results:The animal model of high-altitude pulmonary edema was successfully established. Compared with the control group, the pathological scores of lung tissue in the 24, 48 and 72 h hypoxia groups were increased. The protein expression of SP-D was decreased while IL-1β, IL-6, CRP and TNF-α were increased significantly (P<0.05). SP-D in alveolar lavage fluid was negatively correlated with lung histopathological score (r=-0.687, P<0.05). Inflammatory factors IL-1β, IL-6, CRP and TNF-were positively correlated with lung histopathological score (r=0.705, P<0.05; r=0.728, P<0.05; r=0.733, P<0.05; r=0.737, P<0.05).Conclusion:SP-D plays a important role in the occurrence and development of high altitude pulmonary edema, which may be a new target for the prevention and treatment.