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Brain edema robustly increases mortality and hinders functional recovery after acute ischemic stroke. However, there are currently no effective therapies available for treating or preventing it. The unchecked opening of the transient receptor potential M4 (TRPM4) channel results in an excessive influx of Na+ and water, which contributes significantly to the formation of brain edema after ischemic stroke. 9‐phenanthrol (9‐Phe), a potent TRPM4 inhibitor, has limited clinical applicability due to its potential cytotoxicity and poor solubility. A brain‐targeting T7 (HAIYPRH)‐modified lipid nanoparticle (LNP) encapsulated 9‐Phe (9‐Phe@T7‐LNP) is designed and synthesized to improve the physicochemical properties and pharmacokinetic properties of 9‐Phe for treating brain edema in vivo. These results demonstrated that 9‐Phe@T7‐LNP can penetrate the intact blood‐brain barrier (BBB) in normal mice and target the brain parenchyma. Moreover, 9‐Phe@T7‐LNP effectively reduced infarct volume and brain edema, prevented neuronal loss and BBB disruption, improved survival, and facilitated neurological function recovery after transient middle cerebral artery occlusion in mice. Additionally, 9‐Phe@T7‐LNP scavenged oxygen‐free radicals and prevented neuronal apoptosis in cultured neurons subjected to oxygen and glucose deprivation/reperfusion. In summary, these findings showed that 9‐Phe@T7‐LNP holds strong potential as a promising targeted therapy for brain edema after stroke, providing superior pharmacological neuroprotection against brain edema. [ABSTRACT FROM AUTHOR]

Acoustic tweezers can control target movement through the momentum interaction between an acoustic wave and an object. This technology has advantages over optical tweezers for in-vivo cell manipulation due to its high tissue penetrability and strong acoustic radiation force. However, normal cells are difficult to acoustically manipulate because of their small size and the similarity between their acoustic impedance and that of the medium. In this study, we use the heterologous expression of gene clusters to generate genetically engineered bacteria that can produce numerous sub-micron gas vesicles in the bacterial cytoplasm. We show that the presence of the gas vesicles significantly enhances the acoustic sensitivity of the engineering bacteria, which can be manipulated by ultrasound. We find that by employing phased-array-based acoustic tweezers, the engineering bacteria can be trapped into clusters and manipulated in vitro and in vivo via electronically steered acoustic beams, enabling the counter flow or on-demand flow of these bacteria in the vasculature of live mice. Furthermore, we demonstrate that the aggregation efficiency of engineering bacteria in a tumour is improved by utilizing this technology. This study provides a platform for the in-vivo manipulation of live cells, which will promote the progress of cell-based biomedical applications. In vivo manipulation of cells has applications in cell-based therapy, tissue engineering and targeted drug delivery. Here the authors demonstrate in vivo programmable acoustic manipulation of genetically engineered bacteria using holographic acoustic tweezers. [ABSTRACT FROM AUTHOR]

This study investigated the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer (OC), as well as its effect on the malignant biological behavior of OC cells. The expression of LINC00665, miR-148b-3p, and Krüppel-like factor 5 (KLF5) in OC tissues and cells were determined by RT-qPCR. Western blot was used to detect the protein expression of KLF5. The expression patterns of LINC00665 in nuclear and cytoplasm fractions were undertaken using RT-qPCR. In addition, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by the luciferase reporter assay, and the correlations among these three genes were analyzed. LINC00665 expression was upregulated both in OC cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion, and migration and induced apoptosis to a certain extent. The subcellular fraction assay revealed LINC00665 to be located mainly in the cytoplasm. miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, the expression of LINC00665 was reversely associated with miR-148b-3p expression but positively correlated with KLF5. Furthermore, miR-148b-3p expression was negatively correlated with KLF5. In addition, si-KLF5 inhibited the malignant biological behavior of OC cells, whereas miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of the miR-148b-3p inhibitor on the malignant biological behavior of OC cells. LINC00665 can be used as an effective prognostic indicator of OC, which has the potential to be a new therapeutic target. [ABSTRACT FROM AUTHOR]

Flexible manipulation techniques for living cells and organisms are extremely useful tools for fundamental biomedical and life science research. Acoustic tweezers, which permit non-contact, label-free manipulation, are particularly suited to micromanipulation tasks as they provide a large acoustic radiation force and can be applied in various media. Here, we describe the design and fabrication of a 3 MHz, 64-element (8 × 8), 2D planar ultrasound array that realizes the multidimensional translation, rotation, orientation, and levitation of living cells and organisms. The focusing vortex and twin fields are generated using the holographic acoustic elements framework method. We demonstrate that the eggs and larvae of brine shrimp can be translated along a preset trajectory by controlling the central position of the vortex. By multiplexing counterclockwise vortices, clockwise vortices, and twin trap fields in a time sequence, the rotation direction of the shrimp eggs can be switched in real time, while non-spherical larvae can be reoriented. Moreover, the reflection of the acoustic beam can lift eggs and larvae from the bottom of the culture dish and further manipulate them in the vertical and horizontal directions. Additionally, we present quantitative analyses of the shrimp-egg rotation frequency with respect to the focal depths, topological charges of the vortex, and excitation voltages. These results indicate that acoustic tweezers based on 2D matrix arrays can realize complex and selective manipulation of living cells and organisms, thereby demonstrating their value for advancing research in the fields of cell assembly, tissue engineering, and micro-robot driving. [ABSTRACT FROM AUTHOR]

High-frequency convex array transducer, featuring both high spatial resolution and wide field of view, has been successfully developed for ophthalmic imaging. To further expand its application range to small animals’ imaging, this work develops a high-frequency microconvex array transducer possessing smaller aperture size and wider scanning angle. This transducer featured 128 array elements arranged in a curvilinear 2–2 piezoelectric composite configuration, yielding a maximum view angle of 97.8°. The array was composed of two front matching layers, a nonconductive backing layer, and a customized flexible circuit that electrically connected array elements to coaxial cables. The center frequency and the −6-dB fractional bandwidth were about 18.14 MHz and 69.15%, respectively. The image of a tungsten wire phantom resulted in approximately 62.9- $ {\mu } \text{m}$ axial resolution and 121.3- $ {\mu }\text{m}$ lateral resolution. The image of the whole kidney of a rat as well as its internal arteries was acquired in vivo, demonstrating the imaging capability of the proposed high-frequency microconvex array transducers for small animals’ imaging applications. [ABSTRACT FROM AUTHOR]

Conventional ultrasound probes have inherent limitations in some application scenarios. Because of their fixed shapes and sizes, they can hardly pass through small orifices to examine the target closely. With the recent development of microelectromechanical systems and flexible electronic technologies, collapsible and self-assembling devices are being considered as a potential approach to address this problem. This article presents an innovative transformable ultrasonic transducer (TUT), which can transform between a one-dimensional (1-D) linear array and a 2-D planar array with the ability of switching between different functions including 2-D/3-D imaging and high-intensity focused ultrasound beamforming. The transforming process is accomplished with a specially designed flexible printed circuit board inspired by a paper-folding mechanism. The electrical and acoustic properties of the developed transducer along with the acoustic field distribution in its different forms have been characterized. The 2-D/3-D imaging performances of the TUT have been also evaluated under 1-D and 2-D configurations, respectively. In addition, the performance of a focused concave transforming mode has been also discussed. The evaluation results suggest that TUT can maintain its performance under different structures with precise transforming control. The TUT device has the potential to considerably expand the applications of industrial and clinical ultrasound. [ABSTRACT FROM AUTHOR]

Acoustic vortex beams, which have both linear and angular momentum, can be used to make precise acoustic tweezers. Limited by the symmetry of a normal vortex beam, these tweezers are usually used for trapping or rotating particles in two dimensions. Here, the three-dimensional spiral motion of two soft particles of different sizes was realized using a vortex beam with a twisted focus, which was synthesized by a silicone binary-phase logarithmic-spiral zone plate. Numerical simulations and experimental measurements demonstrated that the beam had anisotropic focuses of crescent transverse intensity profiles and a screw phase dislocation with a singularity at the center. Experiments showed that a small particle (k0r ≈ 1.3) can follow the twisted intensity of the beam, but a large particle (k0r ≈ 4.7) spirals up away from the twisted field pattern. This is attributed to the dominant gradient force for the small particle, whereas the scattering effect induced a scattering force combined with a gradient force for the large particle. This focused twisted beam, which was generated with a structured silicone plate, and the three-dimensional spiral motion of microparticles, advance the development of simple, compact, and disposable acoustic devices for the precise and diverse manipulation of microparticles. [ABSTRACT FROM AUTHOR]

Objective: Traditional endoscopic ultrasonography (EUS), which uses one-dimensional (1-D) curvilinear or radial/circular transducers, cannot achieve dynamic elevational focusing, and the slice thickness is not sufficient. The purpose of this study was to design and fabricate a 1.5-dimensional (1.5-D) circular array transducer to achieve dynamic elevational focusing in EUS in vivo. Methods: An 84 × 5 element 1.5-D circular array transducer was successfully developed and characterized in this study. It was fabricated with PZT-5H 1-3 composite that attained a high-electromechanical coupling factor and low-acoustic impedance. The acoustic field distribution was measured with different transmission modes to validate the 1.5-D elevational beam focusing capability. The imaging performance of the 84 × 5 element 1.5-D circular array transducer was evaluated by two wire phantoms, an agar-based cyst phantom, an ex vivo swine pancreas, and an in vivo rhesus macaque rectum based on multifocal ray-line imaging method with five-row elevational beam steering. Results: It was demonstrated that the transducer exhibited a central frequency of 6.47 MHz with an average bandwidth of 50%, a two-way insertion loss of 23 dB, and crosstalk of <−26 dB around the center frequency. Conclusion: Dynamic elevational focusing and the enhancement of the slice thickness in EUS were obtained with a 1.5-D circular array transducer. Significance: This study promotes the development of multirow and two-dimensional array EUS probes for a more precise clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Multisource data are captured from different sensors or generated with different generation mechanisms. Ground camera images (images taken from ground-based camera) and rendered images (synthesized by the position information from 3-D image-based point cloud) are different-source geospatial data, called cross-domain images. Particularly, in outdoor environments, the registration relationship between the above cross-domain images is available to establish the spatial relationship between 2-D and 3-D space, which is an indirect solution for virtual–real registration of augmented reality (AR). However, the traditional handcrafted feature descriptors cannot match the above cross-domain images because of the low quality of rendered images and the domain gap between cross-domain images. In this article, inspired by the success achieved by deep learning in computer vision, we first propose an end-to-end network, DIFD-Net, to learn domain invariant feature descriptors (DIFDs) for cross-domain image patches. The DIFDs are used for cross-domain image patch retrieval to the registration of ground camera and rendered images. Second, we construct a domain-kept consistent loss function, which balances the feature descriptors for narrowing the gap in different domains, to optimize DIFD-Net. Specially, the negative samples are generated from positive during training, and the introduced constraint of intermediate feature maps increases extra supervision information to learn feature descriptors. Finally, experiments show the superiority of DIFDs for the retrieval of cross-domain image patches, which achieves state-of-the-art retrieval performance. Additionally, we use DIFDs to match ground camera images and rendered images, and verify the feasibility of the derived AR virtual–real registration in open outdoor environments [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS), an interventional imaging technology, utilizes a circular array to delineate the cross-sectional morphology of internal organs through the gastrointestinal (GI) track. However, the performance of conventional EUS transducers has scope for improvement because of the ordinary piezoelectric parameters of Pb(Zr, Ti) $\text{O}_{{3}}$ (PZT) bulk ceramic as well as its inferior mechanical flexibility which can cause material cracks during the circular shaping process. To achieve both prominent imaging capabilities and high device reliability, a 128-element 6.8-MHz circular array transducer is developed using a Pb(Mg $_{\text {1/3}}$ Nb $_{\text {2/3}}$) $\text{O}_{{3}}$ -PbTiO3 (PMN-PT) 1–3 composite with a coefficient of high electromechanical coupling (${k}_{{\text {t}}} \sim 0.78$) and good mechanical flexibility. The characterization results exhibit a large average bandwidth of 58%, a high average sensitivity of 100 mVpp, and a crosstalk of less than −37 dB near the center frequency. Imaging performance of the PMN-PT composite-based array transducer is evaluated by a wire phantom, an anechoic cyst phantom, and an ex-vivo swine intestine. This work demonstrates the superior performance of the crucial ultrasonic device based on an advanced PMN-PT composite material and may lead to the development of next-generation biomedical ultrasonic devices for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

This paper reports a stretchable silicone phase-reversal (PR) Fresnel zone plate (FZP) that can focus ultrasonic energy at different focal lengths with a high transmission coefficient in water. Unlike a traditional FZP that creates focused by constructive interference of waves diffracted through open annular zones in an opaque screen, the silicone PR-FZP takes advantage of all the zones of the FZP contribute to the focal area by adding phase compensation regions instead of opaque regions. More interestingly, the silicone PR-FZP can be stretched, and the focal length increases gradually with the unchanged full width at half maximum as the PR-FZP is stretched. The aforementioned performance aspects are verified in both experiments and simulations. The proposed stretchable PR-FZP with a tunable focal length has potential applications in the broad field of ultrasonics, such as ultrasonic imaging and ultrasound neuromodulation. [ABSTRACT FROM AUTHOR]

Ultrasound, a non-invasive stimulation method, has proved effective in neurostimulation. Previous studies have demonstrated that low-frequency ultrasound (less than 1 MHz) is preferable owing to better penetrability through tissue and skull. However, the large size of low-frequency transducers, which are used in ultrasound neurostimulation studies, makes it difficult to perform multiple-target neurostimulation, especially in small animals such as mice. In this paper, a proposed low-frequency ultrasound needle transducer based on the multi-layer lateral-mode coupling method with a miniature aperture of 0.6 mm × 0.6 mm and a thickness of 1.65 mm was designed and fabricated. The measured electrical impedance of the fabricated 8-layer lateral-mode PZT-5H ceramic was 50.76 Ω at a resonant frequency of 866 kHz. The −6 dB bandwidth of 8-layer lateral-mode transducer was 29% at a center frequency of 876 kHz. The maximum ultrasound peak pressure amplitude at 820 kHz reached approximately 300 kPa, 4–5 times higher than that of the single-layer thickness-mode transducer with 200 V input voltage. The ultrasound beam showed no attenuation and low shift through mouse skull. To verify the feasibility of using the needle transducer to perform multiple-target nerve stimulation in mice brains, we constructed an ultrasound stimulus system to simultaneously stimulate two areas (M2 and V1) of the mouse brain in vivo and detected the c-Fos expression by immunofluorescence to evaluate the effect of stimulation. The results showed that a high ultrasound peak pressure amplitude with this transducer configuration is useful for ultrasound neurostimulation and multiple-target stimulation in mice. [ABSTRACT FROM AUTHOR]

Rapid development of ultrafast ultrasound imaging has led to novel medical ultrasound applications, including shear wave elastography and super-resolution vascular imaging. However, these have yet to incorporate endoscopic ultrasonography (EUS) with a circular array, which provides a wider view in the alimentary canal than traditional linear and convex arrays. A coherent diverging wave compounding (CDWC) imaging method was proposed for ultrafast EUS imaging and implemented on a custom circular array. In CDWC, virtual acoustic point sources are allocated and virtually insonified diverging waves from each source are achieved by adjusting all circular array elements’ emission time delays. Diverging waves emitted from different virtual sources are coherently compounded, generating synthetic transmit focusing at every location in the image plane. As the field of view of the circular array is centrally symmetric, all virtual sources are equidistantly distributed on a concentric circle of radius ${r}$. To achieve the highest frame rate possible with image quality comparable to that obtained with the traditional multi-focus imaging method, the effects of various radii ${r}$ and virtual source quantities on the compounded image quality were theoretically analyzed and experimentally verified. Simulation, phantom, and ex-vivo experiments were conducted with an 8 MHz, 124-element circular array, with a 5.35 mm radius. When 16 virtual sources were used with ${r}=1.605$ mm, image quality comparable to that obtained with the multi-focus approach was achieved at a frame rate of 1000 frames/s. This demonstrates the feasibility of the proposed ultrafast EUS imaging method and promotes further development of multi-functional EUS devices. [ABSTRACT FROM AUTHOR]

Hydrogen sulphide (H2S), a gasotransmitter, plays an important role in the regulation of bone homeostasis. However, the precise effect of H2S on osteoclasts was still elusive. The goal of this study was to determine the potential role of H2S in regulation of osteoclasts and the underlying mechanisms by which H2S affected osteoclastogenesis. The present study applied western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase staining, pit formation assay, immunofluorescence confocal microscopy, transmission electron microscopy and annexin V-fluorescein isothiocyanate/propidium iodide double-staining assay. The results showed that the expressions of cystathionine b-synthase (CBS) and cystathionine c-lyase (CSE) were obviously increased in osteoclast differentiation induced by the receptor activator of nuclear factor kappa-β ligand (RANKL). In addition, H2S promoted RANKL-induced osteoclastogenesis and inhibited apoptosis of mature osteoclasts. Mechanistically, H2S inhibited autophagy in Raw 264.7 cells. Autophagy activator (rapamycin) alleviated the induction of osteoclast differentiation by H2S. Further studies showed that H2S inhibited autophagy by activating the PI3K/AKT/mTOR signalling pathway. Taken together, our results implicated that exogenous H2S could promote osteoclastogenesis by activating the PI3K/AKT/mTOR pathway to downregulate autophagy. [ABSTRACT FROM AUTHOR]

Ultrasonic neuromodulation on large animals, like non-human primates, requires the array transducer to have a good steering ability to arbitrarily stimulate various brain locations. Moreover, due to the different sizes of the animal heads, the array is preferred to be conveniently adjustable to different aperture sizes. To meet these requirements, a scalable 2D plane array, which can consist of up to tens of 256-element square modules, has been designed and fabricated in this study. Arrays with large apertures, consisting of 12 and 48 modules (including 3072 and 12288 elements, respectively), have been assembled and tested. The square modules were driven at a center frequency of 1.04 MHz. The transcranial and steering abilities of the modules were verified in a water tank on an ex vivo macaque skull. A focused beam transmitted by single module could pass through the skull with its peak acoustic pressure reduced to 18.1% of that in the free-field, with an acceptable transverse steering range up to 10 mm. Moreover, a much smaller focal spot was obtained by simultaneous transmission using two vertical-placed modules. Compared to the single module, the focal zone axial size was reduced from 29.7 mm to 3.3 mm, and the “stripes” pattern in the focal zone caused by standing waves was eliminated using a difference-frequency transmitting strategy. Such scalable 2D plane array, which can provide a small-size focal spot and has a large steering range and an acceptable transcranial ability, can be useful in research on ultrasonic neuromodulation on non-human primates. [ABSTRACT FROM AUTHOR]

Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded in situ and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations. [ABSTRACT FROM AUTHOR]

Neuromodulation is an important method for investigating neural circuits and treating neurological and psychiatric disorders. Multiple-target neuromodulation is considered an advanced technology for the flexible optimization of modulation effects. However, traditional methods such as electrical and magnetic stimulations are not convenient for multiple-target applications due to their disadvantages of invasiveness or poor spatial resolution. Ultrasonic neuromodulation is a new noninvasive method that has gained wide attention in the field of neuroscience, and it is potentially able to support multiple-target stimulation by allocating multiple focal points in the brain using an array transducer. However, there are no reports in the literature of the efficacy of this technical concept, and an imaging tool for localizing the stimulation area for evaluating the neural effects in vivo has been lacking. In this study, we designed and fabricated a new system specifically for imaging-guided dual-target neuromodulation. The design of the array transducer and overall system is described in detail. The stimulation points were selectable on a B-mode image. In vivo experiments were carried out in mice, in which forelimbs shaking responses and electromyography outcomes were induced by changing the stimulation targets. The system could be a valuable tool for imaging-guided multiple-target stimulation in various neuroscience applications. [ABSTRACT FROM AUTHOR]

As an effective method of transgenesis, the plasmid of PiggyBac transposon containing GFP (PiggyBac) transposon system has been widely used in various organisms but not yet in mollusks. In this work, piggyBac containing green fluorescent protein (GFP) was transferred into the Pacific oyster (Crassostrea gigas) by sperm-mediated gene transfer with or without electroporation. Fluorescent larvae were then observed and isolated under an inverted fluorescence microscope, and insertion of piggyBac was tested by polymerase chain reaction (PCR) using genomic DNA as template. Oyster larvae with green fluorescence were observed after transgenesis with or without electroporation, but electroporation increased the efficiency of sperm-mediated transgenesis. Subsequently, the recombinant piggyBac plasmid containing gGH (piggyBac-gGH) containing GFP and a growth hormone gene from orange-spotted grouper (gGH) was transferred into oysters using sperm mediation with electroporation, and fluorescent larvae were observed and isolated. The insertion of piggyBac-gGH was tested by PCR and genome walking analysis. PCR analysis indicated that piggyBac-gGH was transferred into oyster larvae; genome walking analysis further showed the detailed location where piggyBac-gGH was inserted in the oyster genome. This is the first time that piggyBac transposon-mediated transgenesis has been applied in mollusks. [ABSTRACT FROM AUTHOR]

Light-sensitivity is an important aspect of mollusk survival as it plays a vital role in reproduction and predator avoidance. In the Pacific oyster Crassostrea gigas light sensitivity has been demonstrated in the larval stage but has not yet been conclusively demonstrated in adult oysters. In this paper we describe an experiment which was undertaken to determine if adult Pacific oysters were sensitive to light. One LED flashlight was used to shine light onto adult oysters while they were filtering seawater through their shell openings. We found that the degree of opening increased gradually during the light period but rapidly decreased when the flashlight was turned off in the treated group but not in the control group. These results suggest that adult Pacific oyster may be sensitive to light. [ABSTRACT FROM AUTHOR]

Objectives: To conduct a meta-analysis of randomized controlled trials assessing the effect on clinical outcomes of intramedullary nailing for femoral fractures via a retrograde or antegrade approach.Data Sources: Randomized controlled trials using PubMed, Embase, and the Cochrane Library databases.Study Selection: We used the following search terms with no language or study type restrictions: femoral shaft fractures, internal fixation, treatment outcome, intramedullary nailing, and retrograde or antegrade approach.Data Extraction: Two independent authors extracted the data and we assessed the quality of the included studies based on Jadad score; allocation concealment; similarity of baseline characteristics; eligibility criteria; blinding; completeness of follow-up; and intention-to-treat analysis. Our primary outcome measure was the union rate and the secondary outcome measures were nonunion, knee pain, and heterotopic ossification. A total of 240 patients from three randomized controlled trials were included.Data Synthesis: Risk ratios (RRs) and 95% confidence intervals (CIs) were computed for dichotomous variables, and weighted mean differences and 95% CIs for continuous variables. Heterogeneity among studies was assessed using the I (2) statistic, with I (2 )> 50% considered significant. If heterogeneity was not significant, a fixed effects model was chosen to assess the overall estimate. Otherwise, a random effects model was used. We used Egger's regression asymmetry test and Begg's adjusted-rank correlation to assess publication bias.Conclusions: Both retrograde and antegrade intramedullary nailing produced high union rates. We found no significant difference in union rate between the retrograde nailing group and the antegrade nailing group for femoral fractures (RR 1.02, 95% CI: 0.94-1.11, p = 0.59, I (2 )= 0%). [ABSTRACT FROM AUTHOR]

Abstract: Introduction: This study describes a new surgical strategy for lumbosacral plexus avulsion by transfer of the unaffected contralateral S1 nerve root. Methods: A surgical reconstruction of the sacral nerve was performed on a 10-year-old boy with left lumbosacral plexus avulsion. The unaffected S1 nerve root (right side) is severed extradurally for transfer. A 25-cm long nerve graft from the common peroneal nerve of the affected side was used as donor nerve. One end of the nerve graft was anastomosed to the proximal stump of the right-sided extradural S1 nerve. The distal end of the nerve graft was divided into two fascicles and anastomosed to the left-sided inferior gluteal nerve and the branch of the sciatic nerve innervating the left-sided hamstrings. Results: According to motor score of the British Medical Research Council (MRC) system, the strength of glutei and hamstrings improved to the level of M3 1.5 years after surgery. Conclusions: The extradural S1 nerve root in the unaffected side can be considered as a suitable donor nerve for transfer in patients with root avulsion of the lumbar or sacral nerve plexus. [Copyright &y& Elsevier]

With the increasing aging population globally, issues that come with aging are becoming more severe. This prompted the governments and society to focus on the social security of the elderly. To guarantee the safety of the elderly, satisfy their emotional requirements, and assist them in adapting to a fast-changing socio-technical environment, researchers have proposed many design methods. Various researchers have studied the relevant literature and design techniques for the elderly. However, it was discovered that China is second, followed by the United States, in terms of research impact in this area. We used the literature from China National Knowledge Infrastructure (CNKI) for China. We selected 1221 papers on geriatric design techniques from the Web of Science and Scopus (W&S) and CNKI. Bibliometrics analysis was used to evaluate the current state, development process, and future trend of research on the design methods for the elderly. The findings indicated that (1) the number of studies on geriatric design approaches in W&S and CNKI is rising every year, and (2) the accentuation and complementarity of W&S and CNKI are distinct. It will be a crucial area of study in the future to develop more pleasant and convenient goods and services for the elderly, as well as to address their emotional needs and experiences. [ABSTRACT FROM AUTHOR]

Background: A few studies focused on open reduction and internal fixation (ORIF) or nonoperative treatment of displaced 3-part or 4-part proximal humeral fractures in elderly patients have been published, all of whom had a low number of patients. In this meta-analysis of randomized controlled trials (RCTs), we aimed to assess the effect of ORIF or nonoperative treatment of displaced 3-part or 4-part proximal humeral fractures in elderly patients on the clinical outcomes and re-evaluate of the potential benefits of conservative treatment. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing ORIF and nonoperative treatment of displaced 3-part or 4-part proximal humeral fractures in elderly patients. Our outcome measures were the Constant scores. Results: Three randomized controlled trials with a total of 130 patients were identified and analyzed. The overall results based on fixed-effect model did not support the treatment of open reduction and internal fixation to improve the functional outcome when compared with nonoperative treatment for treating elderly patients with displaced 3-part or 4-part proximal humeral fractures (WMD −0.51, 95% CI: −7.25 to 6.22, P = 0.88, I2 = 0%). Conclusions: Although our meta-analysis did not support the treatment of open reduction and internal fixation to improve the functional outcome when compared with nonoperative treatment for treating elderly patients with displaced 3-part or 4-part proximal humeral fractures, this result must be considered in the context of variable patient demographics. Only a limited recommendation can be made based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of shoulder function is required to more adequately assess the role for ORIF or nonoperative treatment. [ABSTRACT FROM AUTHOR]

Establishing the spatial relationship between 2D images captured by real cameras and 3D models of the environment (2D and 3D space) is one way to achieve the virtual–real registration for Augmented Reality (AR) in outdoor environments. In this paper, we propose to match the 2D images captured by real cameras and the rendered images from the 3D image-based point cloud to indirectly establish the spatial relationship between 2D and 3D space. We call these two kinds of images as cross-domain images, because their imaging mechanisms and nature are quite different. However, unlike real camera images, the rendered images from the 3D image-based point cloud are inevitably contaminated with image distortion, blurred resolution, and obstructions, which makes image matching with the handcrafted descriptors or existing feature learning neural networks very challenging. Thus, we first propose a novel end-to-end network, AE-GAN-Net, consisting of two AutoEncoders (AEs) with Generative Adversarial Network (GAN) embedding, to learn invariant feature descriptors for cross-domain image matching. Second, a domain-consistent loss function, which balances image content and consistency of feature descriptors for cross-domain image pairs, is introduced to optimize AE-GAN-Net. AE-GAN-Net effectively captures domain-specific information, which is embedded into the learned feature descriptors, thus making the learned feature descriptors robust against image distortion, variations in viewpoints, spatial resolutions, rotation, and scaling. Experimental results show that AE-GAN-Net achieves state-of-the-art performance for image patch retrieval with the cross-domain image patch dataset, which is built from real camera images and the rendered images from 3D image-based point cloud. Finally, by evaluating virtual–real registration for AR on a campus by using the cross-domain image matching results, we demonstrate the feasibility of applying the proposed virtual–real registration to AR in outdoor environments. [ABSTRACT FROM AUTHOR]

While the effects of potassium ion (K + ) on the settlement and metamorphosis of mollusc larvae have been studied in some species, little of this research has focused on the Pacific oyster ( Crassostrea gigas ). It is still unclear which of the potassium channels, the voltage-gated channel or the inward rectifier channel, plays the more important role in the settlement and metamorphosis of mollusc larvae. In this study, the effects of K + and K + channel inhibitors on the settlement and metamorphosis of Pacific oyster larvae were examined. After 24, 48, or 72 h, the highest oyster larval settlement rate was observed at 19 mM K + . The relative metamorphosis rate (number of larvae at metamorphosis ∕ number of larvae at settlement) decreased with increasing K + concentration, however, the highest total metamorphosis rate (number of larvae at metamorphosis ∕ total number of larvae) was observed at 19 mM K + as a result of the very high settlement rate at this concentration. Treatment with tetraethyl-ammonium, the voltage-gated potassium channel inhibitor, resulted in a more obvious suppression of K + -induced oyster larval settlement than Glyburide (Glib), an inhibitor of the inward rectifier potassium channel. These results suggest that the voltage-gated potassium channel may play a more important role than the inward rectifier potassium channel in the settlement of oyster larvae. [ABSTRACT FROM AUTHOR]

Ultrasound imaging offers a noninvasive, radiation-free method for visualizing internal tissues and organs, with deep penetration capabilities. This has established it as a crucial tool for physicians in diagnosing internal tissue pathologies and monitoring human conditions. Nonetheless, conventional ultrasound probes are often characterized by their rigidity and bulkiness. Designing a transducer that can seamlessly adapt to the contours and dynamics of soft, curved human skin presents significant technical hurdles. We present a novel flexible and stretchable ultrasound transducer (FSUT) designed for adaptability to large-curvature surfaces while preserving superior imaging quality. Central to this breakthrough is the innovative use of screen-printed silver nanowires (AgNWs) coupled with a composite elastic substrate, together ensuring robust and stable electrical and mechanical connections. Standard tensile and fatigue tests verify its durability. The mechanical, electrical, and acoustic properties of FSUTs are characterized using standard methods, with large tensile strains (≥110%), high flexibility ( R ≥ 1.4 mm), and lightweight ( ≤ 1.58 g) to meet the needs of wearable devices. Center frequency and -6-dB bandwidth are approximately 5.3 MHz and 66.47%, respectively. Images of the commercial anechoic cyst phantom yielded an axial and lateral resolution (depths of 10-70 mm) of approximately 0.31 and 0.46, and 0.34 and 0.84 mm, respectively. The complex curved surface imaging capabilities of FSUT were tested on agar-gelatin-based breast cyst phantoms under different curvatures. Finally, ultrasound images of the thyroid, brachial, and carotid arteries were also obtained from volunteer wearing FSUT.

Background: Microtubules are attractive targets for anticancer drugs. However, the microtubule-targeting agents (MTAs) currently in clinical use exhibit inevitable drug resistance. Therefore, there is an urgent need to discover novel MTAs for the clinical treatment of cancer., Methods: Bioactive compounds extracted from Lithospermum erythrorhizon were assessed for in vitro anti-proliferative activities against a panel of human cancer cell lines using cell counting kit-8 (CCK-8) assay. Tubulin polymerization inhibition assay, colchicine competitive binding site assay, and immunofluorescence were used to validate the tubulin inhibition effect of acetylshikonin. Flow cytometry, Hoechst staining, and caspase-3 activity evaluation were performed to assess cell cycle arrest and cell apoptosis. 5,5',6,6'-tetrachloro-1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide (JC-1) staining and dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining were used to evaluate mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), respectively., Results: Acetylshikonin exhibited potent anti-proliferative activities against a panel of human cancer cell lines (IC 50 values: 1.09-7.26 µM) and displayed comparable cytotoxicity against several drug-resistant cell lines. Further mechanism studies revealed that acetylshikonin induced cell cycle arrest of MHCC-97H cells at G 2 /M phase, and significantly promoted apoptosis marked by a collapse of MMP and abnormal ROS accumulation., Conclusions: In this study, acetylshikonin was identified as MTA against hepatocellular carcinoma and can serve as a promising lead compound for further development of anti-cancer drug, underscoring its potential clinical significance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-842/coif). The authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Flexible ultrasound transducers (FUTs), capable of conforming to irregular surfaces, have become a research hotspot in the field of medical imaging. With these transducers, high-quality ultrasound images can be obtained only if strict design criteria are fulfilled. Moreover, the relative positions of array elements must be determined, which are important for ultrasound beamforming and image reconstruction. These two major characteristics present great challenges to the design and fabrication of FUTs compared to that for traditional rigid probes. In this study, an optical shape-sensing fiber was embedded into a 128-element flexible linear array transducer to acquire the real-time relative positions of array elements to produce high-quality ultrasound images. Minimum concave and convex bend diameters of approximately 20 and 25 mm, respectively, were achieved. The transducer was flexed 2000 times, and yet no obvious damage was observed. Stable electrical and acoustic responses confirmed its mechanical integrity. The developed FUT exhibited an average center frequency of 6.35 MHz, and average -6-dB bandwidth of 69.2%. The array profile and element positions measured by the optic shape-sensing system were instantly transferred to the imaging system. Phantom experiments for both spatial resolution and contrast-to-noise ratio proved that FUTs can maintain satisfactory imaging capability despite bending to sophisticated geometries. Finally, color Doppler images and Doppler spectra of the peripheral arteries of healthy volunteers were obtained in real time.

Lepista sordida is an edible mushroom possessing high nutritional value and high medicinal value. The artificial cultivation technology of L. sordida made a breakthrough and has been popularized in Yunnan, Guizhou, Sichuan province with good economic benefits. The secondary metabolites were investigated from ethyl EtOAc (acetate extract) of solid cultures of L. sordida. Silica gel column chromatography, semi-preparation HPLC, recrystallization, and medium pressure column chromatography were applied to obtain 15 compounds. Nine compounds were first isolated from genus Lepista and 11 compounds were first isolated from species L. sordida. Moreover, compounds 13 and 14 exhibited strong scavenging activity of ABTS.

Objective: The morphological and hemodynamic characterization of the microvascular network around the gastrointestinal (GI) tract can be of significant clinical value for the early diagnosis and treatment of GI tract cancer. Ultrasound localization microscopy (ULM) imaging has been demonstrated to be capable of resolving the microvascular network. However, the endoscopic application of ULM imaging techniques is still unknown. In this study, an endoscopic ultrasound localization microscopy (e-ULM) imaging technique was developed to evaluate the changes of microvasculature during GI tract tumor growth., Methods: A customized circular array transducer (center frequency: 6.8 MHz) and the coherent diverging wave compounding method were used to generate B-mode images. Spatiotemporal singular value decomposition processing was used to eliminate the background signals before signal localizations. The centroids of spatially isolated signals were localized and summed to generate the final super-resolution image., Results: The final microvasculature map of a rabbit GI tract tumor reveals that e-ULM can be used to surpass the diffraction limit in traditional endoscopic ultrasound (EUS) imaging. Furthermore, it is observed that data from different stages of tumor growth exhibit significant differences in microvascular pattern and density., Conclusion: Our study demonstrated the implementation and application of an in vivo e-ULM imaging technique for the evaluation of the microvasculature of GI tumors., Significance: The efficient e-ULM imaging technique shows potential for use in the detection of GI tract tumor microcirculation changes and subsequent diagnosis of GI tract cancer.

Acoustic tweezers have great application prospects because they allow noncontact and noninvasive manipulation of microparticles in a wide range of media. However, the nontransparency and heterogeneity of media in practical applications complicate particle trapping and manipulation. In this study, we designed a 1.04 MHz 256-element 2D matrix array for 3D acoustic tweezers to guide and monitor the entire process using real-time 3D ultrasonic images, thereby enabling acoustic manipulation in nontransparent media. Furthermore, we successfully performed dynamic 3D manipulations on multiple microparticles using multifoci and vortex traps. We achieved 3D particle manipulation in heterogeneous media (through resin baffle and ex vivo macaque and human skulls) by introducing a method based on the time reversal principle to correct the phase and amplitude distortions of the acoustic waves. Our results suggest cutting-edge applications of acoustic tweezers such as acoustical drug delivery, controlled micromachine transfer, and precise treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ye Yang et al.)

Brain ultrasound has attracted great attention recently due to its noninvasive treatment function for brain diseases. However, ultrasound is still difficult to pass through an intact skull. Phase correction is recognized as an effective method for skull compensation. Half-wavelength pitch transducer is important for the phase correction and, hence, thousands of elements array is required to cover large area human tissue. The clock synchronization between elements is crucial for the phase correction; however, the traditional clock scheme which is designed for 128- or 256-element system is not suitable for thousands of elements. In addition, the clock scheme needs to be magnetic resonance imaging (MRI) compatible since MRI-guided intervention is becoming a routine operation for the brain ultrasound. This study is the first to propose an optical fiber-based clock synchronization method for MRI-guided ultrasound array system. The optical fiber not only distributes the clock but also sets up a link to transmit the data for ultrasound beamformer. The link is full-duplex so both the clock and the data can be transmitted and received simultaneously. The precision of clock synchronization is less than 557 ps when using 50 MHz clock, and the period jitter of the clock is less than 10 ps (rms). Multiple 128- or 256-channel ultrasonic systems can be synchronized, and the error between the channels can be less than 10 ns when using 1-MHz ultrasound transducer. The system can work in an MRI scanning room and communicate with a console via only one fiber. In vivo primate animal study has been achieved, and it has been proven that the proposed clock scheme is suitable for MRI-guided large-scale ultrasound array system.

Background: This retrospective study was conducted to evaluate the efficacy of dual locking plate osteosynthesis for treating 3- or 4-part proximal humeral fractures combined with multiple fractures of the greater tuberosity., Methods: From January 2012 to December 2018, 19 skeletally mature patients, who suffered 3- or 4-part proximal humeral fractures combined with multiple fractures of the greater tuberosity, were treated with open reduction and internal fixation using a dual locking plate technique through a delto-pectoral approach. Indexes for evaluation included fracture healing, quality of reduction, and incidence of complications (infections, screw perforation into the glenohumeral joint, subacromial impingement, hardware failure, avascular necrosis, and loss of reduction). Shoulder function was evaluated using Constant-Murley scoring., Results: The patients were assessed at a mean time of 25.3 months after surgery. Union of fractures was radiographically confirmed for all 19 patients. The mean Constant-Murley patient score was 85.2 points, and complications were identified in two patients during follow-up evaluations., Conclusions: The method of using dual locking plate osteosynthesis through a delto-pectoral approach resulted in a satisfactory union rate, excellent fracture reduction, low complication rate and good shoulder function for patients with complex proximal humeral fractures. The method is effective for treating 3- or 4-part proximal humeral fractures combined with multiple fractures of the greater tuberosity., Competing Interests: Conflict of interestThere are no conflicts of interests., (© Indian Orthopaedics Association 2020.)

As an effective method of transgenesis, the plasmid of PiggyBac transposon containing GFP ( PiggyBac ) transposon system has been widely used in various organisms but not yet in mollusks. In this work, piggyBac containing green fluorescent protein (GFP) was transferred into the Pacific oyster ( Crassostrea gigas ) by sperm-mediated gene transfer with or without electroporation. Fluorescent larvae were then observed and isolated under an inverted fluorescence microscope, and insertion of piggyBac was tested by polymerase chain reaction (PCR) using genomic DNA as template. Oyster larvae with green fluorescence were observed after transgenesis with or without electroporation, but electroporation increased the efficiency of sperm-mediated transgenesis. Subsequently, the recombinant piggyBac plasmid containing gGH ( piggyBac-gGH ) containing GFP and a growth hormone gene from orange-spotted grouper ( gGH ) was transferred into oysters using sperm mediation with electroporation, and fluorescent larvae were observed and isolated. The insertion of piggyBac-gGH was tested by PCR and genome walking analysis. PCR analysis indicated that piggyBac-gGH was transferred into oyster larvae; genome walking analysis further showed the detailed location where piggyBac-gGH was inserted in the oyster genome. This is the first time that piggyBac transposon-mediated transgenesis has been applied in mollusks.

Bombyx batryticatus ( B. batryticatus ), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of B. batryticatus . The aim of the paper is to provide more comprehensive references for modern B. batryticatus study and application. In Traditional Chinese Medicine (TCM) culture, drugs containing B. batryticatus have been used to treat convulsions, headaches, skin prurigo, scrofula, tonsillitis and fever. Many studies indicate B. batryticatus contains various compounds, including protein and peptides, fatty acids, flavonoids, nucleosides, steroids, coumarin, polysaccharide and others. Numerous investigations also have shown that extracts and compounds from B. batryticatus exert a wide spectrum of pharmacological effects both in vivo and in vitro, including effects on the nervous system, anticoagulant effects, antitumor effects, antibacterial and antifungal effects, antioxidant effects, hypoglycemic effects, as well as other effects. However, further studies should be undertaken to investigate bioactive compounds (especially proteins and peptides), toxic constituents, using forms and the quality evaluation and control of B. batryticatus . Furthermore, it will be interesting to study the mechanism of biological activities and structure-function relationships of bioactive constituents in B. batryticatus .

Mutant KRAS proto‑oncogene GTPase (KRAS) serves an important role in predicting the development, diagnosis, treatment and efficacy of targeted drug therapies for colorectal cancer. To improve the detection efficacy of trace amount of mutant KRAS, the locked nucleic acid‑based method was modified in the present study. Internal competitive amplification fragments were used to improve the inhibition of wild‑type KRAS with a wild‑type blocking (WTB) probe and specifically amplify the trace amounts of mutant KRAS. The modified method, quantitative clamp‑based polymerase chain reaction technology using WTB coupled with internal competitive reference to enhance the amplification specificity, named WIRE‑PCR, completely blocked the amplification of wild‑type KRAS in 50‑150 ng DNA templates. The added internal competitive amplified fragments were amplified together with the target gene, which were used to reduce base mismatch due to the high number of cycles in PCR and quantify the total amount of DNA. The results demonstrated that WIRE‑PCR facilitated the detection of mutated alleles at a single molecular level. In the colorectal biopsies from 50 patients with suspected colorectal cancer, 18 cases (36%) contained mutant KRAS, and the amount of mutant DNA accounted for 18.6‑64.2% of the total DNA. WIRE‑PCR is a simple, rapid and low‑cost quantitative analysis method for the detection of trace amounts of the mutant KRAS.

Introduction: This study was conducted to evaluate the clinical outcome of the treatment of type C pilon fractures by using an external fixator combined with limited open reduction and absorbable internal fixation., Patients and Methods: Twenty-five type C pilon fractures, including 4 open fractures, were included in this retrospective study. The procedure of first-stage manipulation and external fixation spanning the ankle joint was conducted as early as possible. For the second stage, the tibial and fibular fractures were reduced and fixed with absorbable screws or rods through a limited incision. Clinical and radiographic evaluations were performed. The American Orthopaedic Foot & Ankle Society score (AOFAS) was obtained for evaluation of function. Twenty-one patients were followed postoperatively for a minimum of 18 months., Results: The mean time of union was 4.8 months. Delayed union of the distal tibia occurred in 1 patient. Minor infection occurred in 8 patients and deep infection in 1 patient. No skin necrosis, malunion, loss of reduction, nonunion, or fixation failure was observed during the follow-up period. No hardware removal was needed, nor was adverse tissue reaction to the implants observed. An excellent or good AOFAS outcome was obtained in 81% (17/21) of the patients., Conclusions: External fixator combined with limited open reduction and absorbable internal fixation was a reliable treatment for closed and open AO/OTA type C pilon fractures of the distal tibia.

Background: Whether treatment with adenosine receptor antagonists such as theophylline can prevent contrast-induced acute kidney injury (AKI) remains controversial., Study Design: We conducted a meta-analysis of randomized controlled trials using MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), Web of Science (1986 to July 2011), and the Cochrane Central Register of Controlled Trials (1996 to July 2011), without language restriction., Setting & Population: Patients undergoing contrast procedures., Selection Criteria for Studies: Randomized controlled trials assessing adenosine antagonists versus control for prevention of contrast-induced AKI., Intervention: Adenosine antagonists with or without N-acetylcysteine versus control with or without N-acetylcysteine., Outcomes: Contrast-induced AKI, change in serum creatinine level, requirement of dialysis, and in-hospital mortality., Results: 16 trials (1,412 participants) were included. Theophylline significantly decreased the risk of contrast-induced AKI (13 trials, 1,222 patients; risk ratio, 0.48; 95% CI, 0.26-0.89; P = 0.02; I(2) = 45%) and had a protective effect on the absolute change in serum creatinine concentration (13 trials, 1,170 patients; standardized mean difference, -0.31 mg/dL; 95% CI, -0.50 to -0.11; P = 0.002; I(2) = 60%). Meta-regression showed a significant relation between the relative risk of contrast nephropathy and baseline serum creatinine level or Jadad score. No clear effects of treatment on risk of dialysis and in-hospital mortality were identified., Limitations: Power to assess clinical end points was limited., Conclusions: Theophylline treatment significantly reduced the incidence of contrast-induced AKI and had a modest improvement on kidney function after contrast exposure in the general population. However, beneficial effects of theophylline were not observed in patients with high baseline creatinine values (serum creatinine ≥1.5 mg/dL). In addition, the long-term effect of this agent on more clinically important outcomes was not established. Future large-scale high-quality multicenter trials in participants with different underlying risks of contrast-induced AKI and that incorporate the evaluation of clinically relevant outcomes are required., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of short-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy., Methods: We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2-5 days after contrast administration and need for dialysis., Results: Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR =0.51, 95% CI 0.34-0.76, p =0.001; I(2) = 0%). The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05-2.10, p = 0.24; I(2) = 0%). The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD -0.64, 95% CI: -1.57 to 0.29, P = 0.18, I(2) = 97%)., Conclusions: Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention.