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Background Sepsis‐associated encephalopathy (SAE) always manifests with severe inflammatory symptoms and cognitive impairment. High mobility group box 1 (HMGB1) is a pro‐inflammatory cytokine. In this study we investigated the role of HMGB1 in SAE. Methods An SAE mouse model was established through cecal ligation and puncture surgery and then injected with adenovirus short hairpin RNA (Ad‐sh)‐HMGB1 or Ad‐sh‐myeloid differentiation protein (MD‐2). The cognitive impairment and pathological injury in mice of different groups were evaluated using the Morris water maze experiment, Y‐maze test, tail suspension test, fear conditioning test, and haematoxylin‐eosin staining. The expressions of HMGB1 (fully reduced and disulfide (ds)HMGB1), MD‐2, and NLRP3 in SAE mice were determined. Then, levels of inflammatory cytokines were measured. The binding relation between HMGB1 and MD‐2 was predicted and certified. Additionally, MD‐2 was downregulated to verify the role of the binding of HMGB1 and MD‐2 in neuroinflammation and cognitive impairment in SAE. Results Expressions of HMGB1, MD‐2, NLRP3, and inflammatory cytokines were enhanced in the SAE mouse model, which were in parallel with impaired cognitive function. HMGB1 silencing resulted in downregulated NLRP3 expression and alleviated neuroinflammation and cognitive impairment in SAE mice. Mechanically, dsHMGB1 bound to MD‐2 to activate NLRP3, thereby exacerbating neuroinflammation and cognitive impairment in SAE mice. The limited binding of HMGB1 and MD‐2 downregulated NLRP3 expression to alleviate neuroinflammation and cognitive impairment in SAE mice. Conclusion HMGB1 was overexpressed in SAE, and dsHMGB1 bound to MD‐2 to activate NLRP3 inflammasome, inducing neuroinflammation and cognitive impairment in SAE.

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Introduction: In clinical practice, it has been observed that patients with severe infections show changes to their hematocrit (HCT) and serum albumin (ALB) levels. This study aimed to evaluate whether the difference of HCT and ALB (HCT-ALB) levels can be used as an additional biomarker for fast diagnosis of severe infections. Material and methods: This was a retrospective case-control study which included adult patients with severe infections, patients with non-infective conditions and healthy individuals. A total of 7,117 individuals were recruited in Yunnan Province, China, from January 2012 to January 2018, and were divided into three groups: 1,033 patients with severe infections (group 1); 1,081 patients with non-infective conditions (group 2); and 5,003 healthy individuals from the general population (group 3). The potential diagnostic threshold of HCT-ALB for severe infectious patients was determined by the receiver operating characteristic (ROC) curve analysis. Group 3 was used as the reference to draw the ROC curves of the HCT-ALB value in group 1 or group 2. Results: HCT-ALB values in each group were significantly different. We found that the area under the ROC curve (AUC) of group 1 reached 0.87 (95% CI: 0.86-0.89), whereas the AUC of group 2 was 0.60 (95% CI: 0.58-0.62). To reach a higher specificity of 99.0% (95% CI: 98.8-99.3%, and with sensitivity of 37.5%, 95% CI: 34.5-40.5%), a HCT-ALB value of 10.25 was recommended as the standard for diagnosis of severe infection. Conclusions: The HCT-ALB value was increased in patients with infectious disease. The measurement of the HCT-ALB value (> 10.25) might be useful in the fast diagnosis of infectious disease.