Comparative Study on the Costs of Treating Diabetic Foot, Necrotizing Fasciitis, and Stage IV Pressure Ulcers

Objective: To compare the total treatment costs for patients with diabetic foot with osteomyelitis, necrotizing fasciitis, and stage IV pressure ulcers in Dalian city, to explore the economic burden of diferent types of chronic wounds. Methods: Aretrospective analysis design was used, collecting data from 18 patients (6 of each wound type) from the electronic medical record system of a large hospital in Dalian. One-way ANOVAand Tukey’s HSD post-hoc tests were applied to compare the treatment costs of diferent wound types. Results: The treat-ment costs for the necrotizing fasciitis group were signifcantly higher than those for the stage IV pressure ulcer group, while the costs for the diabetic foot group did not show signifcant diferences from the other two groups. This fnding highlights the impact of chronic wound types on treatment costs and the importance of early intervention. Conclusion: The results provide data support for the optimized allocation of med-ical resources, especially in a context of limited resources. They emphasize the necessity of early identifcation and management of chronic wounds and provide a basis for establishing cost-efective treatment strategies

Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor

Background: Aberrant activation of RAS-RAF-MEK-ERK signaling pathway has been implicated in more than one-third of all malignancies. MEK inhibitors are promising therapeutic approaches to target this signaling pathway. Though four MEK inhibitors have been approved by FDA, these compounds possess either limited efficacy or unfavorable PK profiles with toxicity issues, hindering their broadly application in clinic. Our efforts were focused on the design and development of a novel MEK inhibitor, which subsequently led to the discovery of tunlametinib.Methods: This study verified the superiority of tunlametinib over the current MEK inhibitors in preclinical studies. The protein kinase selectivity activity of tunlametinib was evaluated against 77 kinases. Anti-proliferation activity was analyzed using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) or (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay. ERK and phospho-ERK levels were evaluated by Western blot analysis. Flow cytometry analysis was employed to investigate cell cycle and arrest. Cell-derived xenograft (CDX) and Patient-derived xenograft (PDX) models were used to evaluate the tumor growth inhibition. The efficacy of tunlametinib as monotherapy treatment was evaluated in KRAS/BRAF mutant or wild type xenograft model. Furthermore, the combination studies of tunlametinib with BRAF/KRASG12C/SHP2 inhibitors or chemotherapeutic agent were conducted by using the cell proliferation assay in vitro and xenograft models in vivo.Results:In vitro, tunlametinib demonstrated high selectivity with approximately 19-fold greater potency against MEK kinase than MEK162, and nearly 10–100-fold greater potency against RAS/RAF mutant cell lines than AZD6244. In vivo, tunlametinib resulted in dramatic tumor suppression and profound inhibition of ERK phosphorylation in tumor tissue. Mechanistic study revealed that tunlametinib induced cell cycle arrest at G0/G1 phase and apoptosis of cells in a dose-proportional manner. In addition, tunlametinib demonstrated a favorable pharmacokinetic profile with dose-proportionality and good oral bioavailability, with minimal drug exposure accumulation. Furthermore, tunlametinib combined with BRAF/KRASG12C/SHP2 inhibitors or docetaxel showed synergistically enhanced response and marked tumor inhibition.Conclusion: Tunlametinib exhibited a promising approach for treating RAS/RAF mutant cancers alone or as combination therapies, supporting the evaluation in clinical trials. Currently, the first-in-human phase 1 study and pivotal clinical trial of tunlametinib as monotherapy have been completed and pivotal trials as combination therapy are ongoing

Identification of ferroptosis-related molecular clusters and genes for diabetic osteoporosis based on the machine learning

BackgroundDiabetic osteoporosis exhibits heterogeneity at the molecular level. Ferroptosis, a controlled form of cell death brought on by a buildup of lipid peroxidation, contributes to the onset and development of several illnesses. The aim was to explore the molecular subtypes associated with ferroptosis in diabetic osteoporosis at the molecular level and to further elucidate the potential molecular mechanisms.MethodsIntegrating the CTD, GeneCards, FerrDb databases, and the microarray data of GSE35958, we identified ferroptosis-related genes (FRGs) associated with diabetic osteoporosis. We applied unsupervised cluster analysis to divide the 42 osteoporosis samples from the GSE56814 microarray data into different subclusters based on FRGs. Subsequently, FRGs associated with two ferroptosis subclusters were obtained by combining database genes, module-related genes of WGCNA, and differentially expressed genes (DEGs). Eventually, the key genes from FRGs associated with diabetic osteoporosis were identified using the least absolute shrinkage and selection operator (LASSO), Boruta, support vector machine recursive feature elimination (SVM ­ RFE), and extreme gradient boosting (XGBoost) machine learning algorithms. Based on ROC curves of external datasets (GSE56815), the model’s efficiency was examined.ResultsWe identified 15 differentially expressed FRGs associated with diabetic osteoporosis. In osteoporosis, two distinct molecular clusters related to ferroptosis were found. The expression results and GSVA analysis indicated that 15 FRGs exhibited significantly different biological functions and pathway activities in the two ferroptosis subclusters. Therefore, we further identified 17 FRGs associated with diabetic osteoporosis between the two subclusters. The results of the comprehensive analysis of 17 FRGs demonstrated that these genes were heterogeneous and had a specific interaction between the two subclusters. Ultimately, the prediction model had a strong foundation and excellent AUC values (0.84 for LASSO, 0.84 for SVM ­ RFE, 0.82 for Boruta, and 0.81 for XGBoost). IDH1 is a common gene to all four algorithms thus being identified as a key gene with a high AUC value (AUC = 0.698).ConclusionsAs a ferroptosis regulator, IDH1 is able to distinguish between distinct molecular subtypes of diabetic osteoporosis, which may offer fresh perspectives on the pathogenesis of the disease’s clinical symptoms and prognostic heterogeneity

Study on the emissivity of solid and liquid materials from cryogenic temperature to very high temperature

L’échange d’énergie par rayonnement est proportionnel à l’émissivité. Ce facteur dépend de la température et de la longueur d’onde mais aussi de l’état de surface, de la composition et de la phase. Sa mesure précise est donc toujours un défi à cause des influences connues ou inconnues. Par rapport à d’autres travaux, le but de ce travail est de l’étudier dans des conditions extrêmes, des températures cryogéniques aux hautes températures : Nous avons ainsi étudié à 80K l’absorption d’un diélectrique pour la protection thermique d’un satellite et celles de surfaces en or de différentes rugosités. A la température ambiante nous avons déterminé par une méthode en réflexion, l’émission de vitrages dans le but de la recherche d‘économie d’énergie. Nous avons aussi étudié la variation de l’émissivité pendant le changement de phase solidus-liquidus et α-β de second ordre. Autour de 100°C le soufre devient plus émissif lorsqu’il passe du solide au liquide mais par contre il n’y a pas de différence sur l’émissivité pour ses deux variétés allotropiques principales. A une beaucoup plus haute température, le silicium liquide se comporte comme un métal avec une émissivité très faible et un saut net a été constaté à son passage au point de fusion. Une variation marquée de l’émissivité pour les deux phases solides du SiC a été observée entre 8-11μm dans notre étude. Contrairement aux résultats de la littérature, les sommets d’émissivité diminuent progressivement avec l’augmentation de la température. Enfin trois points X, longueur d’onde où l’émissivité ne dépend pas de la température, ont été observés pour chaque phase.Heat transferred by radiation is proportional to the emissivity. This coefficient depends not only on the wavelength and the temperature, but also on the surfaceroughness, the chemical composition and the phase. A precise measurement is always a challenge because of the known and unknown factors. Compared with others, this thesis aims at the studies in extreme conditions, from cryogenic temperature to very high temperature: The absorptivity of a dielectric applied to the thermal protector for the satellite and the emissivity of gold surfaces with different roughness have been measured at 80K. The emissivity of different windows has been determined by the reflection method at room temperature for the research of energy saving. We have also studied the variation of the emissivity during the solid to liquid and α-β phase transition. The sulfur becomes more emissive when it changes from solid to liquid around 100°C, but there is no difference on the emissivity between its two major allotropies. The liquid silicon behaves like a metal with a very low emissivity and an obvious bound has been measured when it crosses its melting point. A marked variation of the emissivity of SiC for its two solid-state phases has been observed between 8-11μm. Contrary to other results, the peak values of the emissivity attenuate with the increase of temperature. Finally, three X points at which the emissivity doesn’t depend on the temperature have been measured for each phase

Analysis of Operation Rules of Provincial Peak Shaving Auxiliary Service Market

In order to implement the requirements of the power system reform, to ensure the safety, stability and economic operation of the power system, and to promote the consumption of new energy, all provinces in China have built the peak-control auxiliary service market, and explore the establishment of a new mechanism for sharing and sharing of peak-control auxiliary services. Based on the operating rules of the peaking auxiliary service market in Xinjiang, Shanxi, Gansu, Fujian, Jiangsu, Jiangxi, Northeast, Anhui, Ningxia, Shanghai, Shandong and other places, the author compares and evaluates the key content of the market operating rules from four aspects: market members and their responsibilities, deep peaking transaction details, emergency start-stop peaking transaction details, and measurement and settlement, and also finds a direction for the provinces to revise or adjust the rules of peaking auxiliary services in the future for the reference of power grid dispatching, power plant operations and other departments, in order to improve the understanding of relevant personnel of the peaking auxiliary service market

Experimental Development of Coal-Like Material with Solid-Gas Coupling for Quantitative Simulation Tests of Coal and Gas Outburst Occurred in Soft Coal Seams

Solid-gas coupling coal-like materials are essential for simulating coal and gas outbursts and the long-term safety study of CO2 sequestration in coal. However, reported materials still differ substantially from natural coal in mechanical, deformation and gaseous properties; the latter two aspects are common not considered. There is a lack of a definite and quantitative preparation method of coal-like materials with high similarity for future reference. Here, 25 groups of raw material ratios were designed in the orthogonal experiment using uniaxial compression, shearing and adsorption/desorption tests. Experiment results indicated that the coal-like materials were highly similar to soft coals in properties mentioned above. And range analysis revealed the key influencing factors of each mechanical index. The gypsum/petrolatum ratio controls the density, compressive strength, elastic modulus, cohesion and deformation characteristic. The coarse/fine coal powder (1–2 and 0–0.5 mm) controls the internal friction angle and is the secondary controlling factor for compressive strength and elastic modulus. The effect of coal particle size on the sample strength was studied using scanning electron microscope (SEM). When the gypsum/petrolatum ratio increased, the deformation characteristics changed from ductile to brittle. The different failure modes in the samples were revealed. The coal powder content is a key in the gas adsorption/desorption properties and an empirical formula for estimating the adsorption capacity was established. Based on the range analysis of experimental results, a multiple linear regression model of the mechanical parameters and their key influencing factors was obtained. Finally, a composition closely resembling the natural coal was determined, which differs by only 0.47–7.41% in all parameters except porosity (11.76%). Possible improvements and extension to similar materials are discussed. The findings of this study can help for better understanding of coal and gas outburst mechanism and stability of CO2 sequestration in soft coal seams

Research on Particle Filter Based on Neural Network for Receiver Autonomous Integrity Monitoring

This paper is under in-depth investigation due to suspicion of possible plagiarism on a high similarity index.According to the measurement noise feature of GPS receiver and the degeneracy phenomenon of particle filter (PF), in order to alleviate the sample impoverishment problem for PF, GPS receiver autonomous integrity monitoring (RAIM) algorithm based on PF algorithm combining neural network was proposed, which was used to improve the importance state adjustment of particle filter algorithm. The PF algorithm based on neural network is analized. And the test statistic of satellite fault detection is set up. The satellite fault detection is undertaken by checking the cumulative log-likelihood ratio (LLR) of system state of GPS receiver.The proposed algorithm was Validated by the measured real raw data from GPS receiver, which are deliberately contaminated with the bias fault and ramp fault, the simulation results demonstrate that the proposed algorithm can accurately estimate the state of GPS receiver in the case of non-Gaussian measurement noise, effectively detect and isolate fault satellite by establishing log-likelihood ratio statistic for consistency test and improve the accuracy of detection performance

Nonlinear Elasto-Visco-Plastic Creep Behavior and New Creep Damage Model of Dolomitic Limestone Subjected to Cyclic Incremental Loading and Unloading

For many rock engineering projects, the stress of surrounding rocks is constantly increasing and decreasing during excavating progress and the long-term operation stage. Herein, the triaxial creep behavior of dolomitic limestone subjected to cyclic incremental loading and unloading was probed using an advanced rock mechanics testing system (i.e., MTS815.04). Then, the instantaneous elastic strain, instantaneous plastic strain, visco-elastic strain, and visco-plastic strain components were separated from the total strain curve, and evolutions of these different types of strain with deviatoric stress increment were analyzed. Furthermore, a damage variable considering the proportion of irrecoverable plastic strain to the total strain was introduced, and a new nonlinear multi-element creep model was established by connecting the newly proposed damage viscous body in series with the Hookean substance, St. Venant body, and Kelvin element. The parameters of this new model were analyzed. The findings are listed as follows: (1) When the deviatoric stress is not more than 75% of the compressive strength, only instantaneous deformation, transient creep, and steady-state creep deformation occur, rock deformation is mainly characterized by the instantaneous strain, whereas the irrecoverable instantaneous plastic strain accounts for 38.02–60.27% of the total instantaneous strain; (2) Greater deviatoric stress corresponds to more obvious creep deformation. The visco-elastic strain increases linearly with the increase of deviatoric stress, especially the irrecoverable visco-plastic strain increases exponentially with deviatoric stress increment, and finally leads to accelerated creep and delayed failure of the sample; (3) Based on the experimental data, the proposed nonlinear creep model is verified to describe the full creep stage perfectly, particularly the tertiary creep stage. These results could deepen our understanding of the elasto-visco-plastic deformation behavior of dolomitic limestone and have theoretical and practical significance for the safe excavation and long-term stability of underground rock engineering

Nonlinear Elasto-Visco-Plastic Creep Behavior and New Creep Damage Model of Dolomitic Limestone Subjected to Cyclic Incremental Loading and Unloading

For many rock engineering projects, the stress of surrounding rocks is constantly increasing and decreasing during excavating progress and the long-term operation stage. Herein, the triaxial creep behavior of dolomitic limestone subjected to cyclic incremental loading and unloading was probed using an advanced rock mechanics testing system (i.e., MTS815.04). Then, the instantaneous elastic strain, instantaneous plastic strain, visco-elastic strain, and visco-plastic strain components were separated from the total strain curve, and evolutions of these different types of strain with deviatoric stress increment were analyzed. Furthermore, a damage variable considering the proportion of irrecoverable plastic strain to the total strain was introduced, and a new nonlinear multi-element creep model was established by connecting the newly proposed damage viscous body in series with the Hookean substance, St. Venant body, and Kelvin element. The parameters of this new model were analyzed. The findings are listed as follows: (1) When the deviatoric stress is not more than 75% of the compressive strength, only instantaneous deformation, transient creep, and steady-state creep deformation occur, rock deformation is mainly characterized by the instantaneous strain, whereas the irrecoverable instantaneous plastic strain accounts for 38.02–60.27% of the total instantaneous strain; (2) Greater deviatoric stress corresponds to more obvious creep deformation. The visco-elastic strain increases linearly with the increase of deviatoric stress, especially the irrecoverable visco-plastic strain increases exponentially with deviatoric stress increment, and finally leads to accelerated creep and delayed failure of the sample; (3) Based on the experimental data, the proposed nonlinear creep model is verified to describe the full creep stage perfectly, particularly the tertiary creep stage. These results could deepen our understanding of the elasto-visco-plastic deformation behavior of dolomitic limestone and have theoretical and practical significance for the safe excavation and long-term stability of underground rock engineering