Objectives This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU). Design Clinical retrospective cross-sectional study. Setting A comprehensive teaching tertiary hospital in China. Participants Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU. Main outcome measures HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded. Results Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p<0.001). The area under the curve (AUC) value of HBP for diagnosing sepsis was 0.733, which was lower than those corresponding to PCT, CRP and SOFA but higher than those of IL-6, LAC and APACHE II. Multivariate logistic regression analysis identified HBP, PCT, CRP, IL-6 and SOFA as valuable indicators for diagnosing sepsis. A sepsis diagnostic model was constructed based on these indicators, with an AUC of 0.901, a sensitivity of 79.7% and a specificity of 86.9%. Conclusions HBP could serve as a biomarker for the diagnosis of sepsis in the ICU. Compared with single indicators, the sepsis diagnostic model constructed using HBP, PCT, CRP, IL-6 and SOFA further enhanced the diagnostic performance of sepsis.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE’s influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

To investigate the protective effect of biliary tract external drainage on cytokine expression and pathomorphism of intestine, liver, and lung in rats with hemorrhagic shock. Randomized, control animal study. This study was conducted at The Institution Digestive Surgery Research Laboratory of Shanghai Jiao Tong University. Sprague-Dawley rats. Biliary tract external drainage was performed by inserting a cannula into the bile duct. Hemorrhagic shock was induced by drawing blood from the carotid artery. Twenty-four Sprague-Dawley rats were randomized to three equal groups of eight: sham shock; hemorrhagic shock; and hemorrhagic shock plus bile duct drainage. The messenger RNA expression of tumor necrosis factor-alpha, interleukin-6 in the intestine, liver, and lung tissue from the three groups were analyzed by reverse transcription-polymerase chain reaction. Tumor necrosis factor-alpha was analyzed in the bile of the rats by enzyme-linked immunosorbent assay. Histology of intestine, liver, and lung was performed in all groups by hematoxylin and eosin staining. The messenger RNA expression of tumor necrosis factor-alpha was significantly increased in the hemorrhagic shock group compared with the sham shock group (intestine 0.54 +/- 0.07 vs. 0.37 +/- 0.05, liver 1.01 +/- 0.06 vs. 0.56 +/- 0.07, lung 0.94 +/- 0.07 vs. 0.62 +/- 0.06). The messenger RNA expression of interleukin-6 was also significantly increased in the hemorrhagic shock group compared with the sham shock group (intestine 0.89 +/- 0.12 vs. 0.50 +/- 0.09, liver 1.07 +/- 0.10 vs. 0.57 +/- 0.12, lung 1.09 +/- 0.09 vs. 0.67 +/- 0.06). Biliary tract external drainage reduced significantly the messenger RNA expression of tumor necrosis factor-alpha (intestine 0.43 +/- 0.06 vs. 0.54 +/- 0.07, liver 0.74 +/- 0.18 vs. 1.01 +/- 0.06, lung 0.87 +/- 0.15 vs. 0.94 +/- 0.07) and interleukin-6 (intestine 0.60 +/- 0.11 vs. 0.89 +/- 0.12, liver 0.71 +/- 0.16 vs. 1.07 +/- 0.10, lung 0.88 +/- 0.25 vs. 1.09 +/- 0.09). The concentration of tumor necrosis factor-alpha in bile was significantly higher in the hemorrhagic shock group compared with the sham shock group (31.22 +/- 6.44 ng/mL vs. 15.49 +/- 3.64 ng/mL, p < .01). The histologic observation of the intestine, liver, and lung showed that the biliary tract external drainage significantly attenuate the putrescence and exfoliation of intestinal villi, denaturation and putrescence of hepatocytes, edema, and inflammatory cells infiltration of lung. Biliary tract external drainage decreases the messenger RNA expression of tumor necrosis factor-alpha, interleukin-6 and attenuate the tissue injury of the intestine, liver, and lung in rats model of hemorrhagic shock. The gut-liver axis was implicated to play a crucial role in hemorrhagic shock-induced multiple organ dysfunction syndrome.

The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups: control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF‐α, IL‐1β, and IL‐6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF‐α, IL‐1β, IL‐6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats.

Regional citrate anticoagulation (RCA) is recommended for critically ill patients at high bleeding risk undergoing continuous renal replacement therapy (CRRT). Nafamostat mesylate (NM), a short-half-life serine protease inhibitor, is a popular alternative in East Asia. Direct comparisons of their efficacy and safety are limited. This retrospective single-center study included 81 critically ill patients receiving CRRT with either NM (n = 31) or RCA (n = 50) from January 2022 to January 2023. The primary outcome was filter lifespan. Secondary outcomes included circuit patency, bleeding events, and metabolic complications. The median filter lifespan was significantly shorter in the NM group compared to the RCA group (23.4 vs. 29.6 h, p = 0.02). The NM group also had a higher rate of unplanned circuit discontinuation (52.3 vs. 39.1%, p = 0.03). Multivariable analysis confirmed RCA was independently associated with a lower risk of circuit failure (HR = 0.44, p = 0.03). Although not statistically significant, trends favored NM regarding metabolic safety, with lower incidences of severe metabolic alkalosis (16.1 vs. 36.0%, p = 0.09) and hypocalcemia (9.7 vs. 26.0%, p = 0.13). RCA demonstrated superior anticoagulation efficacy in prolonging filter survival, while NM may offer a more favorable metabolic safety profile. The choice of anticoagulant should be individualized based on efficacy priorities and metabolic risk.

Objective: To investigate the protective effect of biliary tract external drainage on cytokine expression and pathomorphism of intestine, liver, and lung in rats with hemorrhagic shock. Design: Randomized, control animal study. Setting: This study was conducted at The Institution Digestive Surgery Research Laboratory of Shanghai Jiao Tong University. Subjects: Sprague-Dawley rats. Interventions: Biliary tract external drainage was performed by inserting a cannula into the bile duct. Hemorrhagic shock was induced by drawing blood from the carotid artery. Measurements and Main Results: Twenty-four Sprague-Dawley rats were randomized to three equal groups of eight: sham shock; hemorrhagic shock; and hemorrhagic shock plus bile duct drainage. The messenger RNA expression of tumor necrosis factor-[alpha], interleukin-6 in the intestine, liver, and lung tissue from the three groups were analyzed by reverse transcription-polymerase chain reaction. Tumor necrosis factor-[alpha] was analyzed in the bile of the rats by enzyme-linked immunosorbent assay. Histology of intestine, liver, and lung was performed in all groups by hematoxylin and eosin staining. The messenger RNA expression of tumor necrosis factor-[alpha] was significantly increased in the hemorrhagic shock group compared with the sham shock group (intestine 0.54 ± 0.07 vs. 0.37 ± 0.05, liver 1.01 ± 0.06 vs. 0.56 ± 0.07, lung 0.94 ± 0.07 vs. 0.62 ± 0.06). The messenger RNA expression of interleukin-6 was also significantly increased in the hemorrhagic shock group compared with the sham shock group (intestine 0.89 ± 0.12 vs. 0.50 ± 0.09, liver 1.07 ± 0.10 vs. 0.57 ± 0.12, lung 1.09 ± 0.09 vs. 0.67 ± 0.06). Biliary tract external drainage reduced significantly the messenger RNA expression of tumor necrosis factor-[alpha] (intestine 0.43 ± 0.06 vs. 0.54 ± 0.07, liver 0.74 ± 0.18 vs. 1.01 ± 0.06, lung 0.87 ± 0.15 vs. 0.94 ± 0.07) and interleukin-6 (intestine 0.60 ± 0.11 vs. 0.89 ± 0.12, liver 0.71 ± 0.16 vs. 1.07 ± 0.10, lung 0.88 ± 0.25 vs. 1.09 ± 0.09). The concentration of tumor necrosis factor-[alpha] in bile was significantly higher in the hemorrhagic shock group compared with the sham shock group (31.22 ± 6.44 ng/mL vs. 15.49 ± 3.64 ng/mL,p< .01). The histologic observation of the intestine, liver, and lung showed that the biliary tract external drainage significantly attenuate the putrescence and exfoliation of intestinal villi, denaturation and putrescence of hepatocytes, edema, and inflammatory cells infiltration of lung. Conclusions: Biliary tract external drainage decreases the messenger RNA expression of tumor necrosis factor-[alpha], interleukin-6 and attenuate the tissue injury of the intestine, liver, and lung in rats model of hemorrhagic shock. The gut-liver axis was implicated to play a crucial role in hemorrhagic shock-induced multiple organ dysfunction syndrome.