Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation.

Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

[Yin-yang penetrating acupuncture with elongated needle for spastic limb dysfunction after stroke: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect between yin-yang penetrating acupuncture with elongated needle and routine acupuncture for spastic limb dysfunction after stroke. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each group. Both groups received basic treatment, yin-yang penetrating acupuncture with elongated needle was applied from Yanglingquan (GB 34) to Xuanzhong (GB 39), Quchi (LI 11) to Wenliu (LI 7), Huantiao (GB 30) to Fengshi (GB 31), Jianyu (LI 15) to Quchi (LI 11), etc. on the affected side in the observation group; routine acupuncture was applied at Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Jiquan (HT 1), Chize (LU 5), Weizhong (BL 40), Jianyu (LI 15), etc. on the affected side in the control group. Once a day, 5 times a week, 2 weeks as a course, 2 courses were required in the two groups. Before and after treatment，the modified Ashworth scale (MAS) grade, Fugl-Meyer assessment scale (FMA) score, activity of daily living scale (ADL) (Barthel index) score were observed, and the clinical effect was evaluated in the two groups. RESULTS: Compared before treatment, the MAS grade after treatment was improved in the two groups (P<0.05), that in the observation group was superior to the control group (P<0.05). Compared before treatment, the FMA and ADL scores after treatment were increased in the two groups (P<0.05), the changes in the observation group were larger than the control group (P<0.05). The total effective rate in the observation group was 80.0% (24/30), which was superior to 70.0% (21/30) in the control group (P<0.05). CONCLUSION: Yin-yang penetrating acupuncture with elongated needle could improve muscle tension, spasm grade and motor function in patients with spastic limb dysfunction after stroke, enhance the activity of daily living, its clinical effect is superior to routine acupuncture.

Metal-Organic Framework/Ag-Based Hybrid Nanoagents for Rapid and Synergistic Bacterial Eradication.

Recent emerged metal-organic frameworks (MOFs), as superior drug carriers, provide novel strategies to combat pathogenic bacterial infections. Although various antibacterial metal ions can be easily introduced in MOFs for chemical bacterial ablation, such a single-model bactericidal method suffers from high-dose use, limited antibacterial efficiency, and slow sterilization rate. Hence, developing a dual bactericidal system is urgently required. Herein, we report an MOF/Ag-derived nanocomposite with efficient metal-ion-releasing capability and robust photo-to-thermal conversion effect for synergistic sterilization. The MOF-derived nanocarbon consisting of metallic zinc and a graphitic-like carbon framework is first synthesized, and then Ag nanoparticles (AgNPs) are evenly introduced via the displacement reaction between Zn and Ag+. Upon near-infrared irradiation, the fabricated nanoagents can generate massive heat to destroy bacterial membranes. Meanwhile, abundant Zn2+ and Ag+ ions are released to make chemical damage to bacterial intracellular substances. Systematic antibacterial experiments reveal that such dual-antibacterial effort can endow the nanoagents with nearly 100% bactericidal ratio for highly concentrated bacteria at a very low dosage (0.16 mg/mL). Furthermore, the nanoagents exhibit less cytotoxicity, which provides potential possibilities for the applications in the biological field. In vivo assessment indicates that the nanocomposites can realize rapid and safe wound sterilization and are expected to be an alternative to antibiotics. Overall, we present an easily fabricated structure-engineered nanocomposite with chemical and photothermal effects for broad-spectrum bacterial sterilization.

Biocompatible graphene-based nanoagent with NIR and magnetism dual-responses for effective bacterial killing and removal.

Antibiotics have been widely used in clinical applications to treat pathogenic infections at present, but the problem of drug-resistance associated with the abuse of antibiotics has become a large threat to human beings. Herein, we developed an antibacterial nanoagent by coating quaternized chitosan (QCS) on the surface of Fe3O4 nanoparticles-anchored graphene oxide (GO), which enabled QCS and GO to achieve synergistic effects on killing the drug-resistant bacteria. Systematical antibacterial experiments showed that the prepared nanoagent had antibacterial ability, which was significantly enhanced after the introduction of near-infrared (NIR). Importantly, the nanoagent could be easily recycled and reused without the reduction of the antibacterial ability. During the test time, this nanoagent exhibited no obviously toxic side effect to cells. Given the above advantages, we anticipate that the nanoagent has a promising future in various applications such as wound disinfection, water purification, and surface sterilization of medical devices.

Design of Carrageenan-Based Heparin-Mimetic Gel Beads as Self-Anticoagulant Hemoperfusion Adsorbents.

The currently used hemoperfusion adsorbents such as activated carbon and ion-exchange resin show dissatisfactory hemocompatibility, and a large dose of injected heparin leads to the increasing cost and the risk of systematic bleeding. Natural polysaccharide adsorbents commonly have good biocompatibility, but their application is restricted by the poor mechanical strength and low content of functional groups. Herein, we developed an efficient, self-anticoagulant and blood compatible hemoperfusion adsorbent by imitating the structure and functional groups of heparin. Carrageenan and poly(acrylic acid) (PAA) cross-linked networks were built up by the combination of phase inversion of carrageenan and post-cross-linking of AA, and the formed dual-network structure endowed the beads with improved mechanical properties and controlled swelling ratios. The beads exhibited low protein adsorption amounts, low hemolysis ratios, low cytotoxicity, and suppressed complement activation and contact activation levels. Especially, the activated partial thromboplastin time, prothrombin time, and thrombin time of the gel beads were prolonged over 13, 18, and 4 times than those of the control. The self-anticoagulant and biocompatible beads showed good adsorption capacities toward exogenous toxins (560.34 mg/g for heavy metal ions) and endogenous toxins (14.83 mg/g for creatinine, 228.16 mg/g for bilirubin, and 18.15 mg/g for low density lipoprotein (LDL)), thus, highlighting their potential usage for safe and efficient blood purification.

Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats.

BACKGROUND: The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and immunohistochemical techniques to determine the role of the hypothalamus in glyco-regulation during disturbances in carbohydrate metabolism. METHODS: The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats (age 14 months), which included 24 normal weight rats (weighing (365 +/- 76.5) g) and 24 overweight rats (weighing (714 +/- 83.5) g). Then, 12 rats (6 normal, 6 overweight) underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion. fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI, the expression of neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted. RESULTS: There was a transient, but significant, decrease in fMRI signal intensity in all rats (mean (3.12 +/- 0.78)%) in the hypothalamus within 19.5 - 25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats ((2.2 +/- 1.5)% vs (4.2 +/- 0.7)% inhibition, t = 2.12, P < 0.05). There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group (21% vs 23%, t = 0.71, P > 0.05); but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than those in the control group (22% vs 31%, t = 3.25, P < 0.01). CONCLUSIONS: There is a transient, but significant, decrease in BOLD signal intensity in the hypothalamus following glucose ingestion, which is similar to that observed in humans. The response of the hypothalamus to glucose ingestion was different in overweight and normal weight rats. The percentage of NPY positive cells in obese rats were lower than those in the control group, although this difference was not statistically significant. The percentage of 5-HT positive cells in obese rats was significantly lower than those in the control group.