The role and preliminary mechanism of Heparin-binding protein in the develoment of acute pancreatitis / 中华急诊医学杂志

Objective:To explore the role and preliminary mechanism of heparin-binding protein (HBP) in the development of acute pancreatitis (AP) through clinical analysis and animal models.Methods:(1) Clinical research: Blood samples were collected from AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 1 to December 31, 2021 within 30 min of admission, including 20 patients with severe acute pancreatitis (SAP) and 20 patients with non-severe acute pancreatitis (NSAP). Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of HBP, syndecan-1 and hyaluronic acid (HA). Modified CT severity index (MCTSI), another 20 healthy volunteers were selected as controls (HC). Spearman correlation analysis was used to analyze the correlation between HBP and syndecan-1, HA and MCTSI. Receiver operating characteristic (ROC) curve was used to evaluate HBP to predict AP severity. (2)Animal experiment: The rat model of acute pancreatitis was prepared by intraperitoneal injection of L-arginine. In the normal control group (NC, n=8), the low molecular weight heparin (LMWH) intervention group ( n=8), and the acute pancreatitis group ( AP, n=8), the rats were euthanized 12 h later, and peripheral venous blood was collected to detect the levels of HBP, syndecan-1 and HA. Lung tissue and pancreas tissue were collected to observe the pathological damage, and the polysaccharide coating damage of vascular endothelial cells was observed under a fluoroscopy electron microscope. Results:The level of HBP at admission was significantly higher in the AP group than in the HC group, and the increase in the SAP group was more obvious. Correlation analysis showed that HBP was positively correlated with syndecan-1, HA and MCTSI. Animal studies found that the levels of HBP, syndecan-1 and HA in the AP group were significantly higher than those in the NC group. The pancreatic pathological score showed that the AP group was significantly increased, and the fluoroscopy electron microscope showed that the vascular polysaccharide coating was complete in the NC group, and the structure of the AP group was severely damaged. After LMWH intervention, the structure shedding and damage were significantly reduced, and the difference was statistically significant.Conclusions:HBP can promote the progression of AP, which is related to the destruction of the polysaccharide coating structure of endothelial cells and the increase of vascular permeability caused by HBP.

Evaluation of toxin-induced injury and protective effect of triptolide based on a cardiovascular chip model / 药学实践杂志

Objective To construct a cardiovascular chip model for evaluating the damage of vascular glycocalyx induced by four marine toxins: okadaic acid (OA), conotoxin (CTX), tetrodotoxin (TTX) and gymnodimine (GYM), and explore the protective effect of triptolide on toxin-induced injury. Methods Human umbilical vein endothelial cells（HUVEC) were inoculated into a three-channel microfluidic chip. CCK-8 method and immunofluorescence staining were used to analyze the damage of cell viability and glycocalyx tissue induced by low, middle and high concentrations of marine toxin, as well as the protective effect of triptolide on toxin-induced injury. Results The cells in the cardiovascular chip grew well and had structurally intact glycocalyx. Compared with the control group, the activity of HUVEC cells were inhibited in group of the medium and high concentration of OA and high concentration of GYM (P<0.05). The activity of cells had not been inhibited by CTX and TTX significantly , but all the four toxins caused serious damage to the glycocalyx tissue (P<0.01). After pre-protection with triptolide, the toxicity of the four toxins to HUVEC cells and the damage rate of glycocalyx decreased significantly. Conclusion The four marine biotoxins could damage the activity and glycocalyx of HUVEC cells in a dose-dependent manner, while triptolide has a protective effect on HUVEC cells injured by toxin.

Effect of continuous blood purification on immunity and endothelial cell function in patients with sepsis / 中华危重病急救医学

Objective:To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis.Methods:A prospective study was conducted. The patients aged ≥18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL·kg -1·h -1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. Results:Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHEⅡ score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHEⅡ score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×10 9/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (μg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (μg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (μg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). Conclusion:CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.

Admission HbA1c value as a prognostic marker in patients admitted with COVID-19

Background:Diabetes mellitus has been firmly established as a risk factor for the prognosis of COVID-19. However, the impact of pre-COVID-19 glycemic control on prognosis is yet to be fully understood. Our study aimedto establish the effect of HbA1c at admission on the outcome of patients admitted with COVID-19.Methods:It was a prospective observational study of admitted adult patients with confirmed SARS-CoV-2 infection in a tertiary care centre based on data collected from the medical record section using the patient data registry between April 2021 to June 2021. Information regarding demographic and clinical features, laboratory values, and hospital outcomes was collected and analysed.Results:182 patients admitted to the hospital with COVID-19 during the study period were included, their mean age was 48.75 years, the mean HbA1c was 6.1. Males accounted for 69.8% (127) of the sample population. 41.2% (75) were known diabetics. 44.8% (81) were known hypertensives. The mortality rate overall was 25.3% (46). 63.7% (116) had HbA1c values >6.5.High HbA1c values was associated with longer duration of hospital stay (p=0.032), higher levels of inflammatory markers, increased need for mechanical ventilation (p=0.001), higher mortality rate (p=0.001).Conclusions:Patients with COVID-19 with poor glycemiccontrol as evidenced by admission HbA1c levels were found to have more severe disease course with increased level of inflammatory markers, longer duration of hospital stay and higher risk of mortality

Mechanism of high mobility group protein B1 in lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome / 中华危重病急救医学

Objective:To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS).Methods:① In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). ② In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. Results:① In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. ② In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. Conclusion:HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

Correlação entre níveis de sindecano 1, escore PELOD-2 e mortalidade em sepse pediátrica / Correlation between syndecan-1 level and PELOD-2 score and mortality in pediatric sepsis

RESUMO Objetivo: Analisar a correlação entre a lesão do glicocálix medida pelo nível sérico de sindecano 1 e as disfunções de órgãos avaliadas com o escore PELOD-2, assim como avaliar sua associação com a mortalidade em sepse pediátrica. Métodos: Realizou-se um estudo prospectivo observacional em um hospital terciário público. Sessenta e oito pacientes pediátricos, com diagnóstico de sepse segundo os critérios da International Pediatric Sepsis Consensus Conference, foram consecutivamente recrutados. Nos dias 1 e 5, realizaram-se dosagens dos níveis séricos de sindecano 1 e avaliação dos componentes do escore PELOD-2. Os pacientes foram seguidos por até 28 dias após o diagnóstico de sepse. Resultados: Em geral, o nível de sindecano 1 estava aumentado em todos os participantes, com nível significantemente mais elevado nos pacientes em choque (p = 0,01). O nível de sindecano 1 no dia 1 teve correlação positiva com o escore PELOD-2 no dia 1 e coeficiente de correlação de 0,35 (p = 0,003). Nos primeiros 5 dias após o diagnóstico de sepse, as alterações nos níveis de sindecano 1 tiveram correlação positiva com modificações no escore PELOD-2, com coeficiente de correlação de 0,499 (p < 0,001). Com utilização de um ponto de corte dos níveis de sindecano 1 no dia 1 ≥ 430ng/mL, a disfunção de órgãos (escore PELOD-2 ≥ 8) pôde ser predita com área sob a curva de 74,3%, sensibilidade de 78,6% e especificidade de 68,5% (p = 0,001). Conclusão: O nível de sindecano 1 no dia 1 teve correlação com o escore PELOD-2 no dia 1, porém não se associou com a mortalidade aos 28 dias. A disfunção de órgãos (PELOD-2 ≥ 8) pôde ser predita pelo nível de sindecano 1 nas primeiras 24 horas de sepse, sugerindo seu significante envolvimento na fisiopatologia da disfunção de órgãos associada à sepse.

ABSTRACT Objective: To analyze the correlation between glycocalyx disruption measured via the serum syndecan-1 level and organ dysfunctions assessed by the PELOD-2 score and to evaluate its association with mortality in pediatric sepsis. Methods: We performed a prospective observational study in a tertiary public hospital. Sixty-eight pediatric patients diagnosed with sepsis according to International Pediatric Sepsis Consensus Conference criteria were consecutively recruited. We performed measurements of day 1 and day 5 serum syndecan-1 levels and PELOD-2 score components. Patients were followed up to 28 days following sepsis diagnosis. Results: Overall, the syndecan-1 level was increased in all subjects, with a significantly higher level among septic shock patients (p = 0.01). The day 1 syndecan-1 level was positively correlated with the day 1 PELOD-2 score with a correlation coefficient of 0.35 (p = 0.003). Changes in syndecan-1 were positively correlated with changes in the PELOD-2 score, with a correlation coefficient of 0.499 (p < 0.001) during the first five days. Using the cutoff point of day 1 syndecan-1 ≥ 430ng/mL, organ dysfunction (PELOD-2 score of ≥ 8) could be predicted with an AUC of 74.3%, sensitivity of 78.6%, and specificity of 68.5% (p = 0.001). Conclusion: The day 1 syndecan-1 level was correlated with the day 1 PELOD-2 score but not 28-day mortality. Organ dysfunction (PELOD-2 ≥ 8) could be predicted by the syndecan-1 level in the first 24 hours of sepsis, suggesting its significant pathophysiological involvement in sepsis-associated organ dysfunction.

A hiperemia reativa correlaciona-se com presença de sepse e degradação de glicocálix na unidade de terapia intensiva: um estudo de coorte prospectiva / Reactive hyperemia correlates with the presence of sepsis and glycocalyx degradation in the intensive care unit: a prospective cohort study

RESUMO Objetivo: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. Métodos: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. Resultados: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. Conclusão: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.

Abstract Objective: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. Methods: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. Results: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. Conclusion: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.

The glycocalyx barrier function in ocular surface and its alteration in dry eye disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Some studies have shown that the glycocalyx barrier formed by highly glycosylated mucin and galectin-3 in the epithelial cells of the eyeball is important for the maintenance of moisturization and lubrication of the surface of the eye. The decrease in the wettability of the eye surface and the shortening of the tear film breakup time in dry eye patients are closely related to the damage of the glycocalyx barrier. This article outlines the composition of the glycocalyx barrier on ocular surface and its changes in the dry eye patients. It will also introduce a new method for assessing the damage of the glycocalyx barrier in dry eye patients. Finally, two ophthalmological drugs, which target regulating the abnoemality of transmembrane mucins in dry eye disease will be mentioned.

Influence of in vitro capacitation time on structural and functional human sperm parameters / 亚洲男科学杂志(英文版)

A cascade of dramatic physiological events is linked to the sperm acrosome reaction and binding to the oocyte's zona pellucida during human sperm capacitation. However, structural and functional sperm changes during capacitation currently remain poorly defined. Here, we performed a multibiomarker approach based on the utilization of sperm concentration, motility, viability, morphology, acrosome reaction, tyrosine phosphorylation, DNA fragmentation, and lectin-binding sites to analyze the impact caused by swim-up selection times (uncapacitated, 1 h capacitated, and 4 h capacitated) on sperm function and structure in normozoospermic samples. We found that a 4 h swim-up capacitation increased sperm quality, because a large number of cells with normal morphology and lower DNA fragmentation rates were recovered. Furthermore, the long-term capacitation induced a higher percentage of cells with tyrosine phosphorylation of the principal piece as well as a redistribution of lectin-binding sites. Overall, the multivariate biomarkers analyzed showed a less variable distribution on spermatozoa recovered after 4 h capacitation than that with the shorter capacitation time. These findings stress the importance of capacitation time as a relevant factor in sperm quality with potential biological reproductive implications both for basic research and in assisted reproduction techniques.

Revisión Bibliográfica: Glicocálix Endotelial como Blanco de Agresión del Fenómeno Isquemia Reperfusión / Bibliographic Review: Endothelial Glycocalyx as Target of Aggression of the Ischemia-Reperfusion Injury

El glicocálix endotelial es una estructura rica en glucosaminoglicanos, proteoglicanos y glucoproteínas que recubre el endotelio vascular; además de ser una estructura de protección, al estar en contacto directo con la sangre se convierte en el blanco de agresión de diversos mecanismos fisiopatológicos. El fenómeno isquemia-reperfusión se presenta comúnmente en varias entidades del paciente crítico, incluyendo: eventos cerebro vasculares isquémicos, síndrome coronario agudo, sepsis y choque en sus distintos tipos, traumatismos mayores, cirugía y trasplante. Las complicaciones derivadas de este fenómeno son múltiples y dependientes del sitio de presentación; el común denominador es la disfunción microvascular que potencialmente podría desencadenar un fallo multisistémico. El objetivo de esta revisión bibliográfica fue realizar una actualización de los conocimientos en relación a la injuria del glicocálix endotelial durante el fenómeno isquemia-reperfusión.(au)

The endothelial glycocalyx is a structure rich in glycosaminoglycans, proteoglycans and glycoproteins that cover vascular endothelium; in addition of being a protective structure, the direct contact with blood turns it the target of aggression of multiple physiopathological mechanisms. The ischemia-reperfusion injury commonly presents in several critical care entities, including: ischemic stroke, acute coronary syndrome, sepsis and shock, major trauma, surgery and transplantation. Complications are multiple and dependent of the site of presentation; the common denominator is microvascular dysfunction that could potentially trigger multiple organ dysfunction syndrome. The aim of this bibliographic review was to update the knowledge regarding endothelial glycocalyx damage and ischemia-reperfusion injury.(au)

Dexamethasone protects the glycocalyx on the kidney microvascular endothelium during severe acute pancreatitis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation. Methods: Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. Results: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. Conclusions: Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.

Comparison of effects of sevoflurane and propofol anesthesia on endothelial glycocalyx degradation in patients undergoing abdominal surgery / 中华麻醉学杂志

Objective To compare the effects of sevoflurane and propofol anesthesia on endothelial glycocalyx degradation in the patients undergoing abdominal surgery.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 25-75 yr,weigbing 45-80 kg,scheduled for elective open colon or rectal surgery,were divided into 2 groups (n =30 each) using a random number table method:sevoflurane anesthesia group (group S) and propofol anesthesia group (group P).In group S,1.5％-2.5％ sevoflurane was inhaled for maintenance of anesthesia.In group P,propofol was intravenously infused at 50-150 μg · kg-1 · m-1 to maintain the bispectral index value at 40-60.The concentrations of heparan sulfate (HS),syndecan-1 and vascular cell adhesion molecule-1 (VCAM-1) in serum were determined after tracheal intubation (T0),at 1 h after skin incision (T1),at 2 h after skin incision (T2),at the end of operation (T3) and at 24 h after operation (T4).Blood gas analysis and blood biochemical test were performed at T0 and T4,and strong ion gap (SIG) was calculated.Results Compared with the baseline at T0,the concentrations of serum HS at T2-4 and syndecan-1 at T3-4 and SIG at T4 were significantly increased,and the concentrations of serum ALB at T4 were decreased in S and P groups (P＜0.05).Compared with group P,the concentrations of serum HS at T3,4 and syndecan-1 at T4 and SIG at T4 were significantly decreased,the concentrations of serum ALB at T4 were increased (P＜0.05),and no significant change was found in the serum concentrations of VACM-1 and lactate in group S (P＞0.05).Conclusion Compared with propofol anesthesia,sevoflurane anesthesia is more helpful in decreasing endothelial glycocalyx degradation and in reducing vascular endothelial damage in the patients undergoing abdominal surgery.

Dose and timing of normal saline resuscitation on endothelial glycocalyx in early septic shock / 中华危重病急救医学

Objective@#To observe the effect of different doses and timing of normal saline (NS) resuscitation combined with norepinephrine (NE) on endothelial glycocalyx in rabbits with early septic shock.@*Methods@#Thirty New Zealand male rabbits were randomly divided into sham group, model group, 30 mL and 60 mL timely resuscitation groups (30 mL and 60 mL timely group), and 30 mL delayed resuscitation group (30 mL delayed group) with 6 rabbits in each group. The rabbit model of septic shock was reproduced by cecal ligation and puncture (CLP). The rabbits in sham group were only received abdominal cavity open without cecal and ligation. The rabbits in 30 mL and 60 mL timely groups and 30 mL delayed group were intravenous infused with 30 mL/kg or 60 mL/kg NS immediately or 1 hour after model reproduction for 1 hour, and the mean arterial pressure (MAP) was maintained over 75 mmHg (1 mmHg = 0.133 kPa) compared with intravenous pumping of 0.02-0.05 μg·kg-1·min-1 NE followed by 5 mL/h NS infusion till the end of the experiment. The rabbits in sham and model groups were only given 5 mL/h NS. The changes in arterial blood gas before and immediately after resuscitation were observed in three fluid resuscitation groups. The internal jugular vein blood was collected at 0, 3, 6 hours after model reproduction. The levels of syndecan-1 (polysaccharide envelope marker) in plasma were determined by enzyme linked immunosorbent assay (ELISA). The rabbits were sacrificed at 6 hours after model reproduction, and the lung tissue was harvested. Western Blot was used to determine the protein expressions of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 2 (MMP-2) and syndecan-1. The positive expression of syndecan-1 in lung tissue was observed by immunohistochemical method.@*Results@#① Blood gas analysis: compared with the results before resuscitation, the levels of lactic acid (Lac) after resuscitation in three fluid resuscitation groups were significantly decreased, especially in 30 mL timely group; the central venous blood oxygen saturation (ScvO2) was significantly increased, especially in 30 mL delayed group. Oxygenation index (PaO2/FiO2) was improved in 30 mL timely and 30 mL delayed resuscitation groups, which was decreased in 60 mL delayed group. ② Plasma marker: compared with sham group, plasma syndecan-1 level in model group was significantly increased with a time-dependent manner. Plasma syndecan-1 levels at 3 hours in 30 mL timely and 30 mL delayed groups were significantly decreased as compared with those of model group (ng/L: 138.0±2.4, 139.7±15.7 vs. 161.5±4.1, both P < 0.05), but it was significantly increased at 6 hours in 30 mL delayed group (ng/L: 213.1±19.4 vs. 206.4±15.5, P < 0.05). The plasma syndecan-1 levels at 3 hours and 6 hours in 60 mL timely group were significantly higher than those in model group (ng/L: 233.0±28.9 vs. 161.5±4.1, 252.3±27.2 vs. 206.4±15.5, both P < 0.05). ③ Protein expression in lung tissue: compared with sham group, the protein expressions of ICAM-1 and MMP-2 in lung tissue of model group were significantly increased, and syndecan-1 protein expression was significantly decreased. After 30 mL timely or 30 mL delayed resuscitation, the protein expressions of ICAM-1 and MMP-2 in lung tissue were significantly decreased, and syndecan-1 protein expression was significantly increased, especially in 30 mL timely group, which showed statistical differences as compared with those of model group (ICAM-1 protein: 0.56±0.09 vs. 1.04±0.05, MMP-2 protein: 0.83±0.15 vs. 1.06±0.06, syndecan-1 protein: 2.09±0.08 vs. 0.99±0.03, all P < 0.05). The change tendency of protein expressions in 60 mL timely group was opposite to the other two resuscitation groups. ④ Immunohistochemistry: the positive expression of syndecan-1 in lung tissues was significant in the sham group, and it was lowered in model group. The positive expression of syndecan-1 was increased after 30 mL timely or 30 mL delayed resuscitation, but further weakened in 60 mL timely group.@*Conclusions@#The dose and timing of resuscitation with NS in septic shock can affect pulmonary vascular endothelial glycocalyx function. The timely resuscitation with 30 mL NS in combination with NE plays a protective effect on endothelial cell and glycocalyx. However, NS resuscitation which was not timely or excessive infusion can make the glycocalyx degradation more obvious, resulting in increased endothelial permeability, microcirculation damaged, thus aggravate lung injury.

Vascular Endothelial Glycocalyx and Lipoproteins / 医用生物力学

Vascular endothelial cell glycocalyx is a layer of glycoprotein complex located on the surface of endothelial cells, forming a selective permeation barrier on the surface of endothelial cells. In the present review, after a brief introduction of glycocalyx, the relationship between glycocalyx and mass transport under fluid sheer stress (FSS), especially the relationship between glycocalyx and macromolecules such as low density lipoprotein (LDL) has been discussed. This relationship was reflected as following: on the one hand, the thickness and integrity of the glycocalyx affects the concentration polarization of LDL and its transendothelial transport and heparan sulfate proteoglycan (HSPG) participates in the whole process of residual lipoproteins metabolism. On the other hand, ox-LDL, an oxidized product of LDL, destroys heparan sulfate (HS) which is a major component of the endothelial cell glycocalyx. The study on relationship between vascular endothelial glycocalyx and lipoproteins will provide a new clue to elucidate the pathogenesis of atherosclerosis and provide more evidence to view the glycocalyx as a new control target.

Effect of goal-directed fluid therapy guided by different goals on endothelial glycocalyx in patients undergoing high-risk abdominal surgery: a prospective randomized controlled clinical study / 中华麻醉学杂志

Objective To evaluate the effect of goal-directed fluid therapy (GDFT) guided by different goals on endothelial glycocalyx,inflammatory cytokines and postoperative complications in patients undergoing high-risk abdominal surgery.Methods Eighty patients of both sexes,aged 18-64 yr,with body mass index of 18-30 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective retroperitoneal tumor resection,were divided into 2 groups (n =40 each) by a random number table method:stroke volume variation (SVV) 9％-14％ group (L group,n=40) and SVV＜9％ group (H group,n =40).SVV 9％-14％ and SVV＜9％ were used as the target and GDFT was performed though combing with cardiac index and mean arterial pressure.The concentrations of syndecan 1,hyaluronic acid,heparan sulfate,tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were determined at 5 min before skin incision (T0),1 h after skin incision (T1),4 h after skin incision (T2) and 24 and 72 h after operation (T3,4).The intraoperative urine volume,blood loss,volume of liquid infused,volume of blood infused,amount of norepinephrine consumed,operation time,extubation time and length of postoperative hospital stay were recorded.Results Compared with the baseline value at T0,the concentrations of syndecan 1,hyaluronic acid,heparan sulfate,TNF-α and IL-6 in serum were significantly increased at T1-4 in H group,and the concentrations of syndecan 1,heparan sulfate,TNF-α and IL-6 in serum at T1-4 and concentrations of hyaluronic acid at T1-3 were significantly increased in L group (P＜0.05).Compared with H group,the volume of liquid infused was significantly reduced,the amount of norepinephrine consumed was increased,the concentrations of syndecan 1,IL-6 and TNF-α in serum were decreased at T1-4,the concentrations of hyaluronic acid were decreased at T2,3,and the concentrations of heparan sulfate were decreased at T1-3 in group L (P＜0.05).Conclusion Compared with GDFT with the target of SVV＜9％,GDFT with the target of SVV 9％-14％ is more helpful in decreasing degradation of endothelial glycocalyx during the perioperative period and in reducing damage to endothelial barrier,and the mechanism may be related to inhibiting inflammatory responses of patients undergoing high-risk abdominal surgery.

Research progress of glycocalyx on endothelium in sepsis / 中华实用儿科临床杂志

The mortality of sepsis remains high,and it is still a major cause of death in critically ill patients.But its pathophysiological mechanism remains a mystery,not yet fully clear.Endothelium play an important role in the development of sepsis.Maintaining the integrity of its surface glycocalyx to a certain extent reduces sepsis damage;and its destruction mediates a series of pathophysiological responses,including increasing vascular permeability by cell pathway or intracellular pathways,increasing the adhesion of white blood cells to endothelial cejls and a variety of cytokines to promote inflammatory response,activating of thrombin to coagulation dysfunction,promoting synthesis of nitric oxide to change vascular tension.The damage of glycocalyx as a first step in endothelial cell injury can be used as early diagnosis and prognosis of sepsis,which provides new ideas for the diagnosis and treatment of sepsis.

Perioperative implication of the endothelial glycocalyx / 대한마취과학회지

The endothelial glycocalyx (EG) is a gel-like layer lining the luminal surface of healthy vascular endothelium. Recently, the EG has gained extensive interest as a crucial regulator of endothelial funtction, including vascular permeability, mechanotransduction, and the interaction between endothelial and circulating blood cells. The EG is degraded by various enzymes and reactive oxygen species upon pro-inflammatory stimulus. Ischemia-reperfusion injury, oxidative stress, hypervolemia, and systemic inflammatory response are responsible for perioperative EG degradation. Perioperative damage of the EG has also been demonstrated, especially in cardiac surgery. However, the protection of the EG and its association with perioperative morbidity needs to be elucidated in future studies. In this review, the present knowledge about EG and its perioperative implication is discussed from an anesthesiologist's perspective.

Association between endothelial injury and organ dysfunction in sepsis / 中华实用儿科临床杂志

The definition of sepsis has been updated as life-threatening organ dysfunction caused by a dysregulated host response to infection according to the Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3).Sepsis affects functions of endothelial cell (EC) which include vasoregulation,barrier function,inflammation,hemostasis,and is thought to be the key factor in the progression from sepsis to organ failure.Recent studies also demonstrated the mechanism of endothelial dysfunction in sepsis is mediated by glycocalyx shedding.This review covers the current insight in sepsis-associated endothelial dysfunction in different organ systems,as well as the clinical assessmeut and clinical trial aiming at the system of endothelium.

Association between endothelial injury and organ dysfunction in sepsis / 中华实用儿科临床杂志

The definition of sepsis has been updated as life-threatening organ dysfunction caused by a dysregulated host response to infection according to the Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3).Sepsis affects functions of endothelial cell (EC) which include vasoregulation,barrier function,inflammation,hemostasis,and is thought to be the key factor in the progression from sepsis to organ failure.Recent studies also demonstrated the mechanism of endothelial dysfunction in sepsis is mediated by glycocalyx shedding.This review covers the current insight in sepsis-associated endothelial dysfunction in different organ systems,as well as the clinical assessmeut and clinical trial aiming at the system of endothelium.

Variation and clinical value of endothelial glycocalyx in the patients with septic shock / 中华危重病急救医学

Objective To explore the variation and clinical value of the degradation of endothelial glycocalyx in the patients with septic shock. Methods A prospective case control study was conducted. Patients of 18 years or older diagnosed with septic shock and admitted to Department of Critical Care Medicine of Affiliated Hospital of Binzhou Medical University from June 2014 to May 2015 were enrolled. The levels of degradation products, including hyaluronic acid (HA) and heparin sulfate (HS), at 0, 6, 12, 24, 48 hours were determined, while 20 healthy people were enrolled and served as controls. The changes of HA and HS were analyzed in the patients with septic shock. The differences of HA and HS between survival group and death group after 28 days were also analyzed. The relationships between HA, HS and tumor necrosis factor-α (TNF-α), sequential organ failure assessment (SOFA) score, arterial blood lactate (Lac), platelet, albumin were analyzed by Pearson correlation analysis. The receiver-operating characteristic (ROC) curve was plotted to assess the prognostic value of HA and HS for patients with septic shock. Results Thirty-one patients diagnosed as septic shock were enrolled, among whom 17 patients died after 28 days, with a mortality of 54.8%. The levels of HA and HS in patients with septic shock were increased significantly as compared with those of health control group, peaked at 48 hours, and the levels of HA and HS at 48 hours were significantly higher than those at 0 hour [HA (μg/L): 119.47±32.44 vs. 94.84±23.63, HS (μg/L): 72.83±19.03 vs. 58.83±16.63, both P < 0.05]. The levels of HA and HS at 0 hour and 48 hours in death group were significantly higher than those of the survival group [HA (μg/L): 130.42±27.67 vs. 93.29±29.80, 105.14±19.18 vs. 70.82±13.24; HS (μg/L): 67.23±25.01 vs. 39.23±14.58, 79.74±19.84 vs. 56.17±14.53, all P < 0.05]. The levels of HA and HS in patients with septic shock were remarkably positively correlated with the levels of TNF-α, SOFA score, Lac, and platelet, but were remarkably negatively correlated with albumin levels (r value of HA was 0.595, 0.462, 0.545, 0.466, -0.534, respectively; r value of HS was 0.607, 0.468, 0.563, 0.547, -0.455, respectively; all P < 0.05). It was demonstrated by ROC curves that the areas under ROC curve (AUC) of HA and HS at 0 hour and 48 hours for predicting the prognosis of patients with septic shock were 0.881, 0.940 and 0.833, 0.821, respectively, the sensitivities of HA and HS were 87.5%, 100.0% and 83.3%, 81.3%, respectively, and the specificities of HA and HS were 82.6%, 78.3% and 91.3%, 78.3%, respectively. Conclusions The concentrations of degradation products generated by endothelial glycocalyx in the blood of the patients with septic shock are remarkably increased. The elevated levels of the degradation products are closely associated with the severity of septic shock, microcirculation disturbance, and the levels of inflammatory factors.