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.

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.

Design and synthesis of novel 2-(6-thioxo-1,3,5-thiadiazinan-3-yl)-N'-phenylacethydrazide derivatives as potential fungicides.

A series of novel 2-(6-thioxo-1,3,5-thiadiazinan-3-yl)-N'-phenylacethydrazide derivatives were designed, synthesized and evaluated for their antifungal activities against Fusarium graminearum (Fg), Rhizoctonia solani (Rs), Botrytis cinerea (Bc) and Colletotrichum capsici (Cc). The bioassay results in vitro showed that most of the title compounds exhibited impressive antifungal activities against the above plant fungi. Particularly, the compounds 5c, 5f, 5g, 5i, 5m and 5p displayed desirable anti-Rs activities, with the corresponding EC50 values of 0.37, 0.32, 0.49, 0.50, 0.46 and 0.45 µg/mL, respectively, which are superior to the positive control carbendazim (0.55 µg/mL). Further in vivo bioassay results showed that the anti-Rs activity of title compound 5f at 200 µg/mL reached 95.84% on detached rice leaves and 93.96% on rice plants. Featuring convenient synthesis, novel structures and desirable antifungal activity, these 2-(6-thioxo-1,3,5-thiadiazinan-3-yl)-N'-phenylacethydrazide derivatives could be further studied as the potential candidates of novel agricultural fungicides.

The mTOR Kinase Inhibitor CZ415 Inhibits Human Papillary Thyroid Carcinoma Cell Growth.

BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) plays an important role in papillary thyroid carcinoma (PTC) cell progression. CZ415 is a novel, highly-efficient and specific mTOR kinase inhibitor. The current study tested the potential anti-tumor activity of CZ415 in human PTC cells. METHODS: The established (TPC-1 cell line) and primary human PTC cells were treated with CZ415. Cell survival and growth were tested by Cell Counting Kit-8 assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by caspase-3/-9 activity assay, Hoechst-33342 staining assay and single-stranded DNA ELISA assay. Cell cycle progression was tested by propidium iodide-FACS assay. The mTOR signaling was tested by Western blotting assay and co-immunoprecipitation assay. The mouse xenograft tumor model was applied to study the effect of CZ415 in vivo. RESULTS: In cultured human PTC cells, treatment with CZ415 at nM concentrations significantly inhibited cell survival and growth. CZ415 induced apoptosis activation and cell cycle arrest in human PTC cells. CZ415 disrupted assembling of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-GßL association) in TPC-1 cells, which led to de-phosphorylation of the mTORC1 substrates (S6K1 and 4E-BP1) and the mTORC2 substrate AKT (Ser-473). Further studies show that the autophagy inhibitor 3-methyladenine (3-MA) or Beclin-1 shRNA aggravated CZ415-induced cytotoxicity against PTC cells. In vivo, CZ415 oral administration inhibited TPC-1 xenograft tumor growth in mice. CONCLUSION: Our results show that mTOR blockage by CZ415 inhibits PTC cell growth in vitro and in vivo.

Historical Trends of Polycyclic Aromatic Hydrocarbons in the Reservoir Sediment of the Dianchi Watershed, Southwest China.

Using gas-chromatography/mass spectrometry (GC-MS) method dating data (210Pb and 137Cs) and OCPs signatures, the temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was investigated in dated sediment core from Baoxianghe reservoir in Dianchi watershed, Southwest China. The concentrations of total PAHs were in the range of 162.3-762.2 ng g-1 from 1945 to 2013. There showed an obvious increase from 1960s to 2000s. The distributions of PAHs were influenced by local population and Gross Domestic Product (GDP) during the period between1962 and 2004. PAHs sources changed from biomass or domestic coal combustion (before 1980) to liquid fossil fuel combustion (after 1980). Total toxic toxicity equivalents (TEQs) of the carcinogenic PAHs were very low (3.03-28.08 ng g-1).

The metabolism and biotechnological application of betaine in microorganism.

Glycine betaine (betaine) is widely distributed in nature and can be found in many microorganisms, including bacteria, archaea, and fungi. Due to its particular functions, many microorganisms utilize betaine as a functional chemical and have evolved different metabolic pathways for the biosynthesis and catabolism of betaine. As in animals and plants, the principle role of betaine is to protect microbial cells against drought, osmotic stress, and temperature stress. In addition, the role of betaine in methyl group metabolism has been observed in a variety of microorganisms. Recent studies have shown that betaine supplementation can improve the performance of microbial strains used for the fermentation of lactate, ethanol, lysine, pyruvate, and vitamin B12, during which betaine can act as stress protectant or methyl donor for the biosynthesis of structurally complex compounds. In this review, we summarize the transport, synthesis, catabolism, and functions of betaine in microorganisms and discuss potential engineering strategies that employ betaine as a methyl donor for the biosynthesis of complex secondary metabolites such as a variety of vitamins, coenzymes, and antibiotics. In conclusion, the biocompatibility, C/N ratio, abundance, and comprehensive metabolic information of betaine collectively indicate that this molecule has great potential for broad applications in microbial biotechnology.

Role of thioredoxin nitration in bleomycin-induced pulmonary fibrosis in rats.

Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate-buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF.

High frequency ultrasound features and pathological characteristics of medullary thyroid carcinoma.

To study high-frequency ultrasound features and pathological characteristics of medullary thyroid carcinoma (medullary thyroid carcinoma, MTC) with the purpose to improve the diagnostic accuracy of this disease. The clinical data of 20 cases of patients with MTC confirmed by the clinical surgery were retrospectively analyzed. And the high-frequency ultrasound features were analyzed and compared with the pathological characteristics. There were 16 cases with tumor invasion into one side of the thyroid gland; 17 cases with tumor in the middle-upper pole of the thyroid gland. And 8 cases were detected with uneven echo of high frequency ultrasound appearance and pathological manifestations of cystic degeneration to necrosis seen under the light microscope or normal thyroid tissue within part of the lump. 16 cases were tested with even echo of high frequency ultrasound appearance, and tumor cells were formed in the solid and block-like shape under the light microscope. And 18 cases were manifested with low echo, with proliferation of fibrous tissue within the intercellular substance under the light microscope. 18 cases could be seen the calcification points and often amyloid-like content deposited in the intercellular substance seen under the light microscope. In addition, the pathological manifestations of the 8 cases combined with lymph node metastasis were the "lash tumor" of the metastatic lymph nodes and primary tumor. MTC was commonly located in the middle-upper region of the thyroid gland and in one leaf of the thyroid gland, combined with lymph node metastasis. The high frequency ultrasound appearance was the even low-echo tumor in round or quasi-circular shape, with obscure boundary and often combined with rough calcification. High frequency ultrasound could be used as the prior physical diagnostic method for medullary thyroid carcinoma.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.