Early diagnosis and treatment of acute ischemic stroke poses a significant challenge due to its suddenness and short therapeutic time window. Human endogenous cells derived biomimetic drug carriers have provided new options for stroke theranostics since these cells have higher biosafety and targeting abilities than artificial carriers. Inspired by natural platelets (PLTs) and their role in targeting adhesion to the damaged blood vessel during thrombus formation, we fabricated a biomimetic nanocarrier comprising a PLT membrane envelope loaded with L-arginine and γ-Fe 2 O 3 magnetic nanoparticles (PAMNs) for thrombus-targeted delivery of L-arginine and in situ generation of nitric oxide (NO). Results demonstrate that the engineered 200 nm PAMNs inherit the natural properties of the PLT membrane and achieve rapid targeting to ischemic stroke lesions under the guidance of an external magnetic field. Subsequent to the release of Larginine at the thrombus site, endothelial cells produce NO, which promotes vasodilation to disrupt the local PLT aggregation. Rapid targeting of PAMNs to stroke lesions as well as in situ generation of NO prompts vasodilation, recovery of blood flow, and reperfusion of the stroke microvascular. Thus, these PLT membrane derived nanocarriers are diagnostically beneficial for localizing stroke lesions and a promising modality for executing therapies.
Uncontrolled hemorrhage leads to high death risk both in military and civilian trauma. Current hemostatic agents still have various limitations and side effects. In this study, natural diatom silica obtained from diatomite and diatom culture was purified and developed for hemorrhage control. To improve the biocompatibility and hemostatic performance of diatom silica, a series of chitosan-coated diatom (CS-diatom) was developed. The composition of CS-diatom prepared was optimized by in vitro hemocompatibility and blood coagulation evaluation for that prepared with 0.5%, 1%, 3%, and 5% chitosan. The results demonstrated that the CS-diatom prepared with 1% chitosan exhibited favorable biocompatibility (hemolysis ratio < 5%, no cytotoxicity to MEFs), great fluid absorbility (24.39 ± 1.53 times the weight of liquid), and desirable hemostasis effect (351 ± 14.73 s at 5 mg/mL, 248 ± 32.42s at 10 mg/mL). Further blood coagulation mechanism study indicated that CS-diatom could provide an ideal interface to induce erythrocyte absorption and aggregation, along with activating the intrinsic coagulation pathway and thus accelerated blood coagulation. Benefitting from the multiple hemostatic performances, CS-diatom showed the shortest clotting time (98.34 ± 26.54 s) and lowest blood loss (0.31 ± 0.11 g) in rat-tail amputation model compare to diatomite and diatom as well as gauze and commercial QuikClot zeolite. The results evidenced that the CS-diatom was a safe and effective hemostatic agent and provided a new understanding of nonsynthetic mesoporous materials for hemorrhage control.
Objective
To evaluate the nutritional risk and therapy in severe and critical patients with COVID-19.
Methods
A total of 523 patients enrolled from four hospitals in Wuhan, China. The inclusion time was from January 2, 2020 to February 15. Clinical characteristics and laboratory values were obtained from electronic medical records, nursing records, and related examinations.
Results
Of these patients, 211 (40.3%) were admitted to the ICU and 115 deaths (22.0%). Patients admitted to the ICU had lower BMI and plasma protein levels. The median Nutrition risk in critically ill (NUTRIC) score of 211 patients in the ICU was 5 (4, 6) and Nutritional Risk Screening (NRS) score was 5 (3, 6). The ratio of parenteral nutrition (PN) therapy in non-survivors was greater than that in survivors, and the time to start nutrition therapy was later than that in survivors. The NUTRIC score can independently predict the risk of death in the hospital (OR = 1.197, 95%CI: 1.091–1.445, p = 0.006) and high NRS score patients have a higher risk of poor outcome in the ICU (OR = 1.880, 95%CI: 1.151–3.070,
p
= 0.012). After adjusted age and sex, for each standard deviation increase in BMI, the risk of in-hospital death was reduced by 13% (HR = 0.871, 95%CI: 0.795–0.955, p = 0.003), and the risk of ICU transfer was reduced by 7% (HR = 0.932, 95%CI:0.885–0.981, p = 0.007). The in-hospital survival time of patients with albumin level ≤35 g/L was significantly decreased (15.9 d, 95% CI: 13.7–16.3, vs 24.2 d, 95% CI: 22.3–29.7, p < 0.001).
Conclusion
Severe and critical patients with COVID-19 have a high risk of malnutrition. Low BMI and protein levels were significantly associated with adverse events. Early nutritional risk screening and therapy for patients with COVID-19 are necessary.
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