1.Effect of heparin-binding protein on vascular permeability in patients with sepsis
China Modern Doctor 2024;62(10):32-35
Objective To investigate the correlation between heparin-binding protein(HBP)and vascular permeability in patients with sepsis.Methods Four hundred infected patients admitted to Affiliated Jinhua Hospital Zhejiang University School of Medicine from November 2019 to November 2022 were retrospectively selected and divided into sepsis group(n=190)and non-sepsis group(n=210)according to whether they were diagnosed with sepsis or not.HBP,the difference between hematocrit(HCT)and serum albumin(ALB)(HCT-ALB)and percentage of fluid overload were compared between two groups.Pearson method was used to analyze the correlation between HBP,HCT-ALB and percentage of liquid overload.Results HBP,HCT-ALB and percentages of fluid overload in sepsis group were significantly higher than those in non-sepsis group(P<0.05).Pearson correlation analysis showed that serum HBP level was positively correlated with HCT-ALB and percentage of fluid overload 24h after admission(P<0.05).Conclusion Increased vascular permeability in patients with sepsis may be related to the high level of HBP released by neutrophils stimulated by bacterial toxins.
2.A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.
Tao HE ; Mingxing HU ; Shunyao ZHU ; Meiling SHEN ; Xiaorong KOU ; Xiuqi LIANG ; Lu LI ; Xinchao LI ; Miaomiao ZHANG ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2023;13(2):804-818
Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

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