Soft-tissue sound-speed-aware ultrasound-CT registration method for computer-assisted orthopedic surgery.

Ultrasound (US) has been introduced to computer-assisted orthopedic surgery for bone registration owing to its advantages of nonionizing radiation, low cost, and noninvasiveness. However, the registration accuracy is limited by US image distortion caused by variations in the acoustic properties of soft tissues. This paper proposes a soft-tissue sound-speed-aware registration method to overcome the above challenge. First, the feature enhancement strategy of multi-channel overlay is proposed for U2-net to improve bone segmentation performance. Secondly, the sound speed of soft tissue is estimated by simulating the bone surface distance map for the update of US-derived points. Finally, an iterative registration strategy is adopted to optimize the registration result. A phantom experiment was conducted using different registration methods for the femur and tibia/fibula. The fiducial registration error (femur, 0.98 ± 0.08 mm (mean ± SD); tibia/fibula, 1.29 ± 0.19 mm) and the target registration error (less than 2.11 mm) showed the high accuracy of the proposed method. The experimental results suggest that the proposed method can be integrated into navigation systems that provide surgeons with accurate 3D navigation information.

Inversion study on elastic-plastic material parameters of red sandstone in uniaxial compression test.

In order to obtain the real material parameters of heterogeneous rock, the material parameters of red sandstone specimens under uniaxial compression tests are inverted based on the Digital Image Correlation (DIC) method and the Finite Element Model Updating (FEMU) method. The DIC method is employed to calculate the displacement field of red sandstone specimens during uniaxial compression loading. Concurrently, a uniaxial compression elastic-plastic finite element numerical model with non-uniform material parameters is developed based on the FEMU method. The model adopts the Mohr-Coulomb yield criterion and adjusts the boundary conditions in real-time to maintain consistency with the test. The vertical displacement field of the numerical model is juxtaposed with that of the test to construct the objective function. Optimization is achieved using the Artificial Fish Swarm algorithm, which enables the acquisition of the non-uniform distribution and evolution process of the material parameters of specimens at different loading moments. The results indicate that this method can spatially obtain the non-uniform distribution field of material parameters and temporally track the evolution of material parameters during the loading process. This research lays a solid foundation for enhancing the accuracy of intelligent coal mining and dynamic disaster monitoring and early warning in coal mines.

Research on microseismic localization algorithm with global search and local optimization.

A microseismic localization algorithm that combines global search and local optimization is proposed. The Fewer Conditions Trigger Difference (FCTD) objective function of global search and local optimization is constructed, the execution process of the algorithm is described by numerical simulation, and the global search and local optimization microseismic localization algorithm is verified and applied by field data analysis. The results show that: (1) the global search and local optimization methods have fast search speed in the global range, high convergence accuracy and stable localization results in the local range, and high localization accuracy and stability without relying on the velocity model and initial values in the process of search. (2) By comparing the localization results of different localization methods, the global search and local optimization algorithms have better localization results.

Accurate and robust registration method for computer-assisted high tibial osteotomy surgery.

PURPOSE: Computer-assisted high tibial osteotomy (HTO) is a frequently used treatment technique for lower extremity orthopedics, and its small incision and low exposure area are major limitations in tibial registration. This work combines skin surface features and gives a suitable registration algorithm based on Iterative Closest Points (ICP) algorithm to improve registration results. Furthermore, the precision, stability and efficiency of the described method is evaluated. METHODS: After the initialization stage, the bone surface and skin surface data are combined to construct registration features. Then, a steepest perturbation search method is performed after the ICP algorithm (SPS-ICP) to obtain the optimal transformation through several iterations. Finally, the registration result is evaluated by establishing ground-truth through manual landmarks. RESULTS: Phantom experiments including simulated human tissue show that the proximal fiducial registration error (FRE) of our method can reach 0.80 ± 0.30 mm (mean ± SD) with an overall rotational error < 1° and translational error < 1.5 mm. Furthermore, it remains stable when the point set is sparse. The average registration time is less than 40 s to ensure the high efficiency of surgical operation. CONCLUSIONS: The approach fully describes a well-defined framework without additional imaging acquisition equipment for Computer-assisted HTO. By the experiment on the basis of a phantom with simulated soft tissue, the proposed method enables the accurate and robust registration of the tibia, and its computation time meets the demands of surgery.

Study of the factors influencing load displacement curve of energy absorbing device by area division simulation.

A pre folded energy absorbing device, which is the key device of energy absorption anti impact for roadway support, is tested by quasi-static compression and simulated. The energy absorbing device is divided into zones, and the influence of the area on the load displacement curve of the energy absorbing device is studied according to the area. It is found that the error of numerical simulation is within 5%, indicating that the finite element modeling procedure is appropriate for the problem analyzed here. The device crushes following the pre folded origami pattern in a stable progressive. The device was divided into four areas: the upper and lower opening region of the concave surface four corner parts; the other areas of opening regions; the middle fold edge; the surrounding four sides edge. Each area has effect on the first drop stage and the second rise stage of the load displacement curve. The middle fold edge area has an effect on the peak load value of load displacement curve. Four indicators of peak load, average load, load efficiency, and specific energy absorption were generated from the results of numerical simulation. The strength enhancement of corner region can ensure the energy absorbing device with low peak load and high mean crushing load. The other areas of opening regions affect the first descending and second ascending of the curve. The first rising stage bears the load from the middle edge.

CD44/Folate Dual Targeting Receptor Reductive Response PLGA-Based Micelles for Cancer Therapy.

In this study, a novel poly (lactic-co-glycolic acid) (PLGA)-based micelle was synthesized, which could improve the therapeutic effect of the antitumor drug doxorubicin hydrochloride (DOX) and reduce its toxic and side effects. The efficient delivery of DOX was achieved by active targeting mediated by double receptors and stimulating the reduction potential in tumor cells. FA-HA-SS-PLGA polymer was synthesized by amidation reaction, and then DOX-loaded micelles were prepared by dialysis method. The corresponding surface method was used to optimize the experimental design. DOX/FA-HA-SS-PLGA micelles with high drug loading rate and encapsulation efficiency were prepared. The results of hydrophilic experiment, critical micelle concentration determination, and hemolysis test all showed that DOX/FA-HA-SS-PLGA micelles had good physicochemical properties and biocompatibility. In addition, both in vitro reduction stimulus response experiment and in vitro release experiment showed that DOX/FA-HA-SS-PLGA micelles had reduction sensitivity. Molecular docking experiments showed that it can bind to the target protein. More importantly, in vitro cytology studies, human breast cancer cells (MCF-7), human non-small cell lung cancer cells (A549), and mouse colon cancer cells (CT26) were used to demonstrate that the dual receptor-mediated endocytosis pathway resulted in stronger cytotoxicity to tumor cells and more significant apoptosis. In and in vivo antitumor experiment, tumor-bearing nude mice were used to further confirm that the micelles with double targeting ligands had better antitumor effect and lower toxicity. These experimental results showed that DOX/FA-HA-SS-PLGA micelles have the potential to be used as chemotherapeutic drugs for precise tumor treatment.

Quantitative initial safety range of early passive rehabilitation after ankle fracture surgery.

BACKGROUND: Early rehabilitation training after ankle fracture surgery is critical to healing and avoiding complications. Inappropriate or excessive motion may impede healing or even lead to secondary injury. Currently, there is a lack of scientific quantitative postoperative rehabilitation methods after ankle fracture. Our purpose was to develop a universal method of quantifying early passive rehabilitation training after surgery by finite element (FE) analysis. METHODS: A three-dimensional (3D) FE model of normal ankle was reconstructed from a computed tomography scan of a healthy male adult. Six types of ankle fractures were considered based on AO classification. We exerted joint motion load to explore the effect of movement on ankle joint mechanics after surgery. The corresponding relationship between the Inter-bone displacement and range of motion was measured to quantifying the ankle range of motion. The 44A3.3 fracture was used as an example to describe the implementation process in detail. RESULTS: During ankle movement, most of the stress was sustained by the internal fixation devices, and the ratio of stress borne by the implants ranged from 67.9 to 94.9%. Flexion/extension exercise did not cause extra stress on the ankle contact surfaces. Ligament traction was the reason for ankle load during flexion/extension motion. The range of early passive postoperative rehabilitation training for six types of ankle fractures (AO classification) were provided. CONCLUSION: A quantitative method of early passive rehabilitation training after ankle fracture surgery was developed using FE analysis. This modeling method has universality for any fracture that can be reconstructed.

Quantitative investigation on the heterogeneity of deformation fields in sandstone pre-existing cracks during damage evolution.

The inherently heterogeneous microstructures of rocks lead to heterogeneity of the deformation distribution within the rock volume. In this study, experiments were conducted on red sandstone specimens with four different pre-existing crack inclinations stressed under uniaxial loading to investigate these features. Acoustic emission and digital image correlation techniques were used to confirm the damage process and obtaining deformation fields, respectively. The results showed that the heterogeneity of the deformation fields in the rock specimens amplifies with increasing stress magnitude, i.e., the displacement field heterogeneity shows two dense bands around the pre-existing crack, and the strain field heterogeneity shows localized regions with a numerical difference (quantified by the normalized standard deviation) and spatial concentration (quantified by the spatial correlation coefficient). The variations in the normalized standard deviation and spatial correlation coefficient were closely related to the damage process. The normalized standard deviation presented four evolution stages: relatively constant low value, steady growth, significant growth, and high rate growth. The spatial correlation coefficient changed from increasing at a relatively constant rate to increasing at a gentle rate and finally increasing rapidly. The evolution rate along with the strain showed two sharp fluctuations. The first could be used as precursor information of the damage. Finally, we confirmed the feasibility of the damage variable obtained from the heterogeneous deformation indicators used to calibrate or form damage evolution laws.

Study on synergistic system of energy-absorbing yielding anti-impact supporting structure and surrounding rock.

Through the improvement of supporting structure and the utilization of the interaction between surrounding rock and supporting structure, the synergistic system of energy-absorbing yielding anti-impact supporting structure and surrounding rock is established. The process of energy absorption device, energy-absorbing yielding anti-impact supporting structure and synergistic system under impact is simulated to analyze the properties of them. The following conclusions could be drawn. The deformation and yielding process under compression of energy absorption device is divided into five stages. Compared with the traditional supporting structure, the energy-absorbing yielding anti-impact supporting structure has the reaction force with lower value and smaller fluctuation range before the deformation of the energy absorption device reaches the third ascending section. The synergy between surrounding rock and supporting structure plays an important role in roadway support. Compared with the supporting structure without surrounding rock, the reaction force of the supporting structure in the synergistic system is lower, and a stationary stage is added in the early stage of the reaction force curve.

Preparation and in vivo/in vitro characterization of Ticagrelor PLGA sustained-release microspheres for injection.

The objective of this paper was to develop a PLGA carrier Ticagrelor sustained-release microspheres preparation, which was expected to continue to release Ticagrelor for 14 days with a high encapsulation rate. Ticagrelor microspheres were prepared successfully with average diameter of 7.31 µm, drug loading of 12.49 ± 0.32% and EE up to 79.09 ± 1.69%. In the release medium of PH7.4 PBS, the microspheres showed good drug release behavior in vitro. In vivo release results also showed that the sustained-release microspheres could effectively control drug release in vivo and maintain a relatively stable blood drug concentration for about 2 weeks. The results indicate that Ticagrelor sustained-release microspheres can be used for long-term treatment of acute coronary syndrome.

Preparation and Properties of Thrombus-Targeted Urokinase/Multi-Walled Carbon Nanotubes (MWCNTs)-Chitosan (CS)-RGD Drug Delivery System.

In order to improve the therapeutic effect, prolong the action time and reduce the side effects of the first generation thrombolytic drug urokinase (UK), a novel UK/multi-walled carbon nanotubes (MWCNTs)-chitosan (CS)-arginine-glycine-aspartic acid (Arg-Gly-Asp) (RGD) drug delivery system was synthesized by chemical bonding/non covalent bond modification/ultrasonic dispersion. The results showed that the diameter of the UK/MWCNTs-CS-RGD drug delivery system was about 30-40 nm, there was a layer of UK was attached to the surface of the tube wall, and the distribution was relatively uniform. The average encapsulation efficiency was 83.10%, and the average drug loading was 12.81%. Interestingly, it also had a certain sustained-release effect, and its release law was best fitted by first-order kinetic equation. Moreover, the accelerated and long-term stability test results show that it had good stability. Compared with free UK, UK/MWCNTs-CS-RGD had thrombolytic effect in vitro. In addition, MTT experiment showed that the prepared MWCNTs-CS-RGD nanomaterials had good biocompatibility. A rabbit model of carotid artery thrombosis was used to conduct targeted thrombolysis experiments in vivo. Compared with free UK, UK/MWCNTs-CS-RGD could be enriched in the thrombosis site to achieve thrombus targeting. UK/MWCNTs-CS-RGD drug delivery system was expected to become an effective thrombolytic drug for targeted therapy of thrombosis.

Study on improvement of prefolded energy absorption device to constant resistance and its mechanical properties.

When the rock burst occurs, energy absorption support is an important method to solve the impact failure. To achieve constant resistance performance of energy absorption device, as an important component of the support, the mechanical properties of one kind of prefolded tube is analyzed by quasi-static compression test. The deformation process of compression test is simulated by ABAQUS and plastic strain nephogram of the numerical model are studied. It is found that the main factors affecting the fluctuation of force-displacement curve is the stiffness of concave side wall. The original tube is improved to constant resistance by changing the side wall. The friction coefficient affects the folding order and form of the energy absorbing device. Lifting the concave side wall stiffness can improve the overall stiffness of energy absorption device and slow down the falling section of force-displacement curve. It is always squeezed by adjacent convex side wall in the process of folding, with large plastic deformation. Compared with the original one, the improved prefolded tube designed in this paper can keep the maximum bearing capacity (Pmax), increase the total energy absorption (E), improve the specific energy absorption (SEA), and decrease the variance (S2) of force-displacement curve.

Preparation and properties of Pue-loaded HA-ADH-PS nanomicelles.

Puerarin (Pue) is the most abundant isoflavonoid in kudzu root. It has been widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, poor-bioavailability of puerarin is the main obstacle to its widespread clinical applications. In this paper, HA-ADH-PS nanomicelles were prepared by chemical modification, noncovalent modification and etc, and characterized by means of FT-IR, ultraviolet (UV) and thermogravimetric analysis (TG). The encapsulation efficiency and drug loading of Pue-loaded HA-ADH-PS nanomicelles were 45.1% and 19.89% by UV, respectively. It could be observed from the transmission electron microscopy (TEM) images that HA-ADH-PS micelles appeared obvious spherical structure in the water. The particle size of HA-ADH-PS nanomicelles and Pue-loaded HA-ADH-PS nanomicelles were about 136.8 nm and 119.5 nm with a PDI of 0.237 and 0.272, respectively. The fluorescence probe method was used to characterize the critical micelle concentration, the critical micelle concentration (CMC) value of the nanomicells was 0.002 g/L and the results met the requirements and ensured the stability of micelles after dilution. DPPH assay suggested that Pue-loaded HA-ADH-PS nanomicelles had an obvious radical scavenging effect in vitro. MTT test showed that Pue-loaded HA-ADH-PS nanomicelles was non-toxic and had good biocompatibility. Thus, Pue-loaded HA-ADH-PS nanomicelles could be used as a potential drug carrier for puerarin.

Construction of poly(ethylene glycol)-poly(L-lactic acid)-stearic acid reverse aspirin-loaded micelles and optimization of preparation process.

This work aims to study the construction of reverse aspirin-loaded micelles prepared from amphiphilic PEG-PLA-SA triblock copolymers and the optimization of the preparation process. Using polyethylene glycol (PEG) as the initiator, ring-opening polymerization of L-lactide (L-LA) was used to prepare PEG-PLA diblock copolymers. Final product PEG-PLA-SA triblock copolymers were prepared by the reaction of stearic acid (SA) and PEG-PLA catalyzed by 4-dimethylaminopyridine (DMAP) and N,N'-Dicyclohexylcarbodiimide (DCC). Fourier transform infrared spectrometer (FT-IR) was used to characterize the product structure. PEG-PLA-SA triblock copolymers self-assembled in toluene/ethanol/water system to form reverse micelles, which could encapsulate aspirin into a hydrophilic core. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to determine the size and morphology of reverse micelles. The results showed that the reverse micelles are spherical, with a particle size of less than 70 nm. Response surface analysis method was applied to optimize the preparation process of PEG-PLA-SA. In vitro drug release was achieved by embedding reverse aspirin-loaded micelles in the biocompatible membrane in phosphate buffer saline (PBS) at 37°C. In the first 8 h, the drug release rate of the triblock copolymers was slower than that of the diblock copolymers. After 8 h, the drug release rate of both tended to be flat. The stability of aspirin-loaded reverse micelles was studied through accelerated test. These results indicate that reverse micelle PEG-PLA-SA may be a promising carrier for hydrophilic drugs like aspirin.

MicroRNA-7 regulates the proliferation and metastasis of human papillary carcinoma cells by targeting Bcl-2.

Papillary carcinoma is the most common type of thyroid cancer responsible for significant number of mortalities across the globe. This study was conducted to investigate the role and therapeutic implications of microRNA-7 in human papillary carcinoma. Gene expression analysis was carried out through quantitative real time PCR method. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to determine the cell proliferation. Clonogenic assay was used to assess the colony forming ability of cancer cells. Cell apoptosis was analyzed by 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB) and annexin V/PI staining assays. Migration of cancer cells was estimated through scratch heal assay and cell invasion was determined by transwell assay method. Western blotting was done to examine the protein expression. Xenografted mice models were employed to examine the effects of miR-7 overexpression in vivo. Results showed miR-7 to be significantly (P < 0.05) repressed in papillary carcinoma. Cancer cell proliferation was inhibited by miR-7 through induction of apoptotic cell death as revealed by DAPI, AO/EB and annexin V/PI staining assays. The colony forming potential of cancer cells also decreased under miR-7 overexpression. miR-7 overexpression also inhibited the migration and invasion of cancer cells. Bcl-2 was identified as the intracellular target of miR-7 and regulatory effects of miR-7 were seen to be exerted through translation repression of Bcl-2. The results of xenograft study revealed miR-7 overexpression significantly (P < 0.05) suppressed the growth of the tumor in vivo. The results point towards the therapeutic implications of miR-7 in the management of papillary carcinoma.

Utilization of public health care by people with private health insurance: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review was to explore the association between private health insurance and health care utilization. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases for relevant articles since 2010. Studies were eligible if they described original empirical research on the utilization of public health care by individuals with private health insurance, compared with individuals without private insurance. A pooled measure of association between insurance status with health care utilization was assessed through meta-analysis. RESULTS: Twenty-six articles were included in the final analysis. We found that patients with private insurance did not use more public health care than people without private insurance (P < 0.05). According to the subgroup analysis, people with private insurance were more likely to be hospitalized than people with no insurance (OR 1.67; 95% CI, 1.18 to 2.36). CONCLUSIONS: People with private insurance did not increase their use of health care (outpatient services), compared to those without private insurance. Private health insurance coverage may ease the financial burden on patients and on the public health insurance system.

Existence and functions of a kisspeptin neuropeptide signaling system in a non-chordate deuterostome species.

The kisspeptin system is a central modulator of the hypothalamic-pituitary-gonadal axis in vertebrates. Its existence outside the vertebrate lineage remains largely unknown. Here, we report the identification and characterization of the kisspeptin system in the sea cucumber Apostichopus japonicus. The gene encoding the kisspeptin precursor generates two mature neuropeptides, AjKiss1a and AjKiss1b. The receptors for these neuropeptides, AjKissR1 and AjKissR2, are strongly activated by synthetic A. japonicus and vertebrate kisspeptins, triggering a rapid intracellular mobilization of Ca2+, followed by receptor internalization. AjKissR1 and AjKissR2 share similar intracellular signaling pathways via Gαq/PLC/PKC/MAPK cascade, when activated by C-terminal decapeptide. The A. japonicus kisspeptin system functions in multiple tissues that are closely related to seasonal reproduction and metabolism. Overall, our findings uncover for the first time the existence and function of the kisspeptin system in a non-chordate species and provide new evidence to support the ancient origin of intracellular signaling and physiological functions that are mediated by this molecular system.

Incidence and risk factors of gastrointestinal neuroendocrine neoplasm metastasis in liver, lung, bone, and brain: A population-based study.

BACKGROUND: Neuroendocrine neoplasm is a rare solid tumor. Metastatic pattern of the gastrointestinal neuroendocrine neoplasm (GI-NEN) has not been fully explored. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (SEER-9 registry) from 1973 to 2015. Incidence was estimated by Joinpoint regression analyses. Data with additional treatment fields of GI-NEN were extracted from the SEER-18 registry from 1 January 2010 to 31 December 2015. A total of 14 685 GI-NEN patients were included in this study. Statistical analyses were performed with SPSS 25.0, the Intercooled Stata SE 15.0, and GraphPad Prism 7. RESULTS: Incidence of GI-NENs increased from 0.51 per 100 000 patients in 1973 to 6.20 per 100 000 patients in 2015. Of them, 2003 patients were stage IV GI-NEN at the time of diagnosis, including 1459 (72.84%) patients with liver metastasis, 144 (7.19%) lung metastasis, 115 (5.74%) bone metastasis, and 27 (1.35%) brain metastasis. Esophageal NEN had the highest risk of metastasis (52.68%). The median survival for patients with liver, lung, bone, and brain metastasis was 38, 6, 9, and 2 months, respectively. The presence of lung or liver metastasis indicated higher risk of concurrent existence of bone and brain metastasis than those without. CONCLUSION: Bone and brain metastasis should be screened in the GI-NEN patients if they had lung or liver metastasis. Findings of the current study could help clinicians to identify distant metastasis of GI-NENs as early as possible, and by which, to improve survival rate of GI-NENs.

Suppression of Tafazzin promotes thyroid cancer apoptosis via activating the JNK signaling pathway and enhancing INF2-mediated mitochondrial fission.

Tafazzin has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of Tafazzin and mitochondrial homeostasis in thyroid cancer have not been explored. The aim of our study is to investigate the influences of Tafazzin on thyroid cancer apoptosis with a focus on mitochondrial fission. Our results indicated that Tafazzin deletion induced death in thyroid cancer via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, was activated by Tafazzin deletion. Furthermore, we found that Tafazzin affected mitochondrial stress by triggering inverted formin 2 (INF2)-related mitochondrial fission. The loss of INF2 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that Tafazzin regulated INF2 expression via the JNK signaling pathway; moreover, the blockade of JNK prevented Tafazzin-mediated INF2 expression and improved cancer cell survival. Taken together, our results highlight the key role of Tafazzin as a master regulator of thyroid cancer viability via the modulation of INF2-related mitochondrial fission and the JNK signaling pathway. These findings defined Tafazzin deletion and INF2-related mitochondrial fission as tumor suppressors that act by promoting cancer apoptosis via the JNK signaling pathway, with potential implications for new approaches to thyroid cancer therapy.