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Thermal ablation is an exciting new minimally invasive treatment that destroys liver tumors without removing them. It uses image guidance to place a needle through the skin into a liver tumor, which is highly dependent on surgeons’ experience. With the development of digital medicine, augmented reality (AR) has become a more intuitive and safer way to achieve real-time navigation. However, the technology is still in its infancy due to its limited accuracy and real-time performance. To address these problems, we syncretized the holographic AR with the digital twin technique to track the dynamic surgical scene and provide the 3-D navigation of heterogeneous target regions via internal motion prediction. To tackle the dilemma of real-time performance and precise internal motion estimation, a dynamic adaptation scheme is proposed to compensate for the time cost induced by the external/internal correlation model and data transmission. We carried out a series of experiments to validate our methods. With the proposed external/internal correlation model, the average estimation errors of the tumor and vessels are 2.18 and 2.79 mm, respectively. Besides, we performed in vivo experiments on two beagle dogs with an artificial lesion in their liver, respectively, and the puncture accuracy of our method are 2.5 and 2.17 mm. The results show that on one hand, our method can fulfill the real-time requirement of AR via using the intraoperative data, which is also more precise than that with preoperative data. On the other hand, our method can provide more 3-D information for surgeons, such as vessels, which can well ensure the safety of operation.

Acute ischemic stroke has become the major cause of mortality and disability worldwide. Following ischemic stroke, the reperfusion injury is mainly mediated by the burst of reactive oxygen and nitrogen species (RONS). Therefore, blocking the excessive production or removing RONS holds great promise as a potential therapeutic strategy. Herein, we developed a Co-doped Fe3O4nanozyme that is capable of scavenging H2O2, O2•–, •NO, and ONOO– in vitro and in vivo and provides neuroprotection against ischemic stroke. In vitro experiments showed that pre-incubation with the Co-Fe3O4nanozyme could prevent neurotoxicity and neuroinflammation induced by H2O2or lipopolysaccharide, respectively, in HT22 cells. After intravenous administration, the Co-Fe3O4nanozyme showed no signs of toxicity in peripheral organs of C57BL/6J mice, even after prolonged delivery for 4 weeks. In permanent photothrombotic stroke model and transient middle cerebral artery occlusion stroke model, the Co-Fe3O4nanozyme specifically accumulated in the infarct rim at 72 h post-stroke and was endocytosed by neurons, astrocytes, microglia, and endothelial cells. Importantly, the Co-Fe3O4nanozyme delivery reduced the infarct volume in both stroke models. The observation that the Co-Fe3O4nanozyme was efficacious in two well-characterized ischemic stroke models provides strong evidence that it represents a powerful tool for targeting oxidative and nitrosative stress in the ischemic brain.

Ischemic stroke (IS) is one of most common causes of disability in adults worldwide. However, there is still a lack of effective and reliable diagnostic markers and therapeutic targets in IS. Furthermore, immune cell dysfunction plays an important role in the pathogenesis of IS. Hence, in-depth research on immune-related targets in progressive IS is urgently needed.

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:Stroke is prevalent in hypertensive population. It has been suggested that unsaturated fatty acids (USFA) have protective effect on stroke. The effect of saturated fatty acids (SFAs) on stroke is still unclear. Therefore, we studied the relationship between circulating fatty acids and acute ischemic stroke (AIS) in hypertensive patients.

BackgroundIschaemic stroke and transient ischaemic attack (TIA) share a common cause. We aim to develop and validate a concise prognostic nomogram for patients with minor stroke and TIA.MethodsA total of 994 patients with minor stroke and TIA were included. They were split into a derivation (n=746) and validation (n=248) cohort. The modified Rankin Scale (mRS) scores 3 months after onset were used to assess the prognosis as unfavourable outcome (mRS≥2) or favourable outcome (mRS<2).ResultThe final model included seven independent predictors: gender, age, baseline National Institute of Health Stroke Scale (NIHSS), hypertension, diabetes mellitus, white blood cell and serum uric acid. The Harrell’s concordance index (C-index) of the nomogram for predicting the outcome was 0.775 (95% CI 0.735 to 0.814), which was confirmed by the validation cohort (C-index=0.787 (95% CI 0.722 to 0.853)). The calibration curve showed that the nomogram-based predictions were consistent with actual observation in both derivation cohort and validation cohort.ConclusionThe proposed nomogram showed favourable predictive accuracy for minor stroke and TIA. This has the potential to contribute to clinical decision-making.

Supplemental Digital Content is available in the text.

Early detection and drug intervention with the appropriate timing and dosage are the main clinical challenges for ischemic stroke (IS) treatment. The conventional therapeutic agents relay fluorescent signals, which require real-time external light excitation, thereby leading to inevitable autofluorescence and poor tissue penetration. Herein, we report endogenous peroxynitrite (ONOO–)-activated BDP-4/Cur-CLNPs that release NIR afterglow signals (λmax697 nm) for real-time monitoring of the progression of ischemia reperfusion (I/R) brain injury while releasing curcumin for the safe treatment of IS. The BDP-4/Cur-CLNPs exhibited bright NIR afterglow luminescence (maximum 732-fold increase), superb sensitivity (LOD = 82.67 nM), high energy-transfer efficiency (94.6%), deep tissue penetration (20 mm), outstanding antiapoptosis, and anti-inflammatory effects. The activated NIR afterglow signal obtained in mice with middle cerebral artery occlusion (MCAO) showed three functions: (i) the BDP-4/Cur-CLNPs are rapidly activated by endogenous ONOO–, instantly illuminating the lesion area, distinguishing I/R damage from normal areas, which can be successfully used for endogenous ONOO–detection in the early stage of IS; (ii) real-time reporting of in situgeneration and dynamic fluctuations of endogenous ONOO–levels in the lesion area, which is of great value in monitoring the evolutionary mechanisms of IS; and (iii) dynamic monitoring of the release of curcumin drug for safe treatment. Indeed, the released curcumin effectively decreased apoptosis, enhanced survival, alleviated neuroinflammation, reduced brain tissue loss, and improved the cognition of MCAO stroke mice. This work is the first example of afterglow luminescence for early diagnosis, real-time reporting, drug tracing, and treatment for IS.

Visinin-like protein 1 (VILIP-1), a myristoylated calcium sensor protein of the EF-hand Ca2+-binding protein superfamily, plays multiple physiological roles in the central nervous system and peripheral organs. In present study, the cDNA encoding VILIP-1 was identified from the brain and spinal cord cDNA library of Gekko japonicus. It contains a 573 bp open reading frame corresponding to a deduced protein of 191 amino acids. Gecko VILIP-1 shares more than 95.3% identity with vertebrate VILIP-1 proteins, and structurally consists of conserved four EF-hand Ca2+-binding motifs and one dsRNA-binding domain, suggesting that selective pressure must have been extremely high for the conservation of VILIP-1 during vertebrate evolution. Northern blot and RT-PCR showed that gecko VILIP-1 was ubiquitously expressed in all tissues examined. In situ hybridization revealed that the VILIP-1 transcript mainly appeared in the gray matter of the spinal cord, with less distribution in the white matter. Semiquantitative RT-PCR also showed that VILIP-1 expression in spinal cord after tail amputation remained stable at 1 day and 1 week, but decreased at 2 weeks, a time coinciding with regeneration bud formation. This suggests that VILIP-1 may function as a regeneration-associated factor in the form of a monomer or/and RNA-binding complex.

China has the largest stroke population and at-risk population in the world. However, it has a lower thrombolytic therapy rate and longer onset-to-needle time/door-to-needle time for patients who had an acute stroke compared with developed countries, which might be due to redundant procedures or inefficient systems. Things are changing due to some new initiatives. Two years ago, a new emergency system in China, Stroke Emergency Map, was first launched as a regional emergency system in Shenzhen, the bustling metropolis just north of Hong Kong. As a result of the Stroke Emergency Map in Shenzhen, the number of thrombolytic cases increased in the last 2 years, from 568 to 809 annually. The Stroke Emergency Map, first pioneered in Shenzhen and now spreading to the rest of China, is a comprehensive and interdisciplinary system. The benefits are not just the immediate improvements in the acute stroke care because the continuous data collection and audit allows for improvements in logistics and future strategies.

Supplemental Digital Content is available in the text

No relevant conflicts of interest to declare.

The phosphatidylinositol 3' –kinase (PI3K)-Aktsignaling pathway has been shown to be critical in modulating platelet function and increasing number of studies have been focusing on the development of PI3K inhibitors to modulate platelet function. We recently identified a novel small molecule compound S14161, namely 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene, displaying potent antileukemia and antimyeloma activity via inhibition of the PI3K pathway (Mao et al, Blood, 2011, 117:1986). In the present study, we evaluated the effect of S14161 on platelet activation and the underlying mechanisms. Gel-filtered human platelets were isolated from venous blood of healthy adults and the effect of S14161 on platelet aggregation in response to agonists was determined. Results showed that S14161 inhibited platelet aggregation induced by collagen, convulxin, thrombin, PAR1 agonist peptide SFLLRN, and U46619 in a dose dependent manner (2.5-10μM) with the most striking inhibition for collagen by 89.8% (P<0.001, n=3) and for U46619 by 94.3% (P<0.001, n=3), respectively compared to vehicle-treated samples when 10μM S14161 was used. Flow cytometry studies showed that S14161 inhibits convulxin- or thrombin-induced P-selectin expression and fibrinogen binding of single platelet. S14161 also inhibited platelet spreading on fibrinogen and clot retraction, processes mediated by outside-in signaling. Using a microfluidic chamber we demonstrated that incubation of S14161 decreases platelet adhesion on collagen-coated surface by about 80% at various time points of blood flow in the chambers. Western blot showed that similar to LY294002, the classic PI3K inhibitor, S14161 inhibited phosphorylation of Akt Ser473 and Akt Thr308 in response to collagen, thrombin, or U46619, implying the involvement of PI3K pathway. Additionally, S14161 inhibited MAPK/ERK1/2 phosphorylation. Finally, the effects of S14161 on thrombus formation in vivo were measured using a ferric chloride-induced carotid artery injury model in mice. The intraperitoneal injection of S14161 (2mg/kg) to male C57BL6/J mice significantly extended the first occlusion time (5.05±0.99 min, N=9) compared to the vehicle controls (3.72±0.95 min, N=8) (P<0.05), but did not increase the bleeding time (P>0.05). Taken together, our data showed that S14161 inhibits platelet activation and thrombus formation, and may be developed as a novel therapeutic agent for the prevention of thrombotic disorders. (This study was supported by National Natural Science Foundation of China 81170132 to Li Zhu)

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

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Abstract 3249