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Objective To explore the relationship between gastrointestinal heat retention syndrome and the incidence of pneumonia and recurrent respiratory tract infections (RRTIs) in children. Methods A prospective cohort study was conducted in the pediatric outpatient department of Beijing Dongfang Hospital. Children without respiratory tract infections (RTIs) were consecutively recruited according to the selection criteria. A semi-structured questionnaire was used to record traditional Chinese medicine (TCM) symptoms and demographic and physiological characteristics. Gastrointestinal heat retention syndrome was considered to be a predisposing factor and was diagnosed according to a scale with reliability and validity. The participants were followed up for 12 months. Participants and their parents or guardians were contacted via clinical interviews and telephone every 6 months. Episodes of pneumonia and RTIs were recorded in detail. Results A total of 420 children were included. Of participants, 370 (88.10%) were followed up for 12 months. The mean number of RTI episodes per participant was 5.37 (95% CI: 5.14 to 5.60). In total, 186 participants in the gastrointestinal heat retention syndrome group and 184 participants in the non-gastrointestinal heat retention syndrome group completed the 12-month follow-up period. The baseline of both groups was comparable. The incidence of RRTIs in children with gastrointestinal heat retention syndrome was 1.27 (95% CI: 1.01 to 1.59) times that in children without gastrointestinal heat retention syndrome. Logistic regression analysis revealed that abnormally increased appetite with frequent hunger, foul breath, dry stools, and dark red or purple fingerprints were positively correlated with the incidence of pneumonia. Irascibility and feverish feelings in the palms and soles were positively correlated with the occurrence of RRTI. Conclusions Gastrointestinal heat retention syndrome is a risk factor for RRTIs in children. Studies with larger sample sizes and longer follow-up time are warranted to confirm the degree of causal risk associated with RTIs.

Graphical abstract, The use of herbs to treat various human diseases has been recorded for thousands of years. In Asia's current medical system, numerous herbal formulas have been repeatedly verified to confirm their effectiveness in different periods, which is a great resource for drug innovation and discovery. Through the mining of these clinical effective formulas by network pharmacology and bioinformatics analysis, important biologically active ingredients derived from these natural products might be discovered. As modern medicine requires a combination of multiple drugs for the treatment of complex diseases, previously clinical formulas are also combinations of various herbs according to the main causes and accompanying symptoms. However, the herbs that play a major role in the treatment of diseases are always unclear. Therefore, how to rank each herb's relative importance and determine the core herbs, is the first step to assisting herb selection for active ingredients discovery. To solve this problem, we built the platform FangNet, which ranks all herbs on their relative topological importance using the PageRank algorithm, based on the constructed symptom-herb network from a collection of clinical empirical prescriptions. Three types of herb hidden knowledge, including herb importance rank, herb-herb co-occurrence, and associations to symptoms, were provided in an interactive visualization. Moreover, FangNet has designed role-based permission for teams to store, analyze, and jointly interpret their clinical formulas, in an easy and secure collaboration environment, aiming at creating a central hub for massive symptom-herb connections. FangNet can be accessed at http://fangnet.org or http://fangnet.herb.ac.cn.

Objective: To investigate the association between gastrointestinal heat retention syndrome (GHRS) and adult chronic eczema. Methods: This case–control study compared GHRS/GHRS accompanied by damp-heat syndrome (GHRS-DHS) and other patient characteristics between subjects with (cases) and without chronic eczema (controls) to identify potential factors associated with this condition. Semi-structured questionnaires were used to collect data via face-to-face interviews. Participants were recruited from Dongzhimen Hospital affiliated with Beijing University of Chinese Medicine. A logistic regression analysis was performed on the collected data, and odds ratios (ORs) were calculated. Results: A total of 168 cases and 172 controls were recruited. Among the cases of adult chronic eczema, there were 79 subjects with GHRS and 68 with GHRS-DHS. Sex (P = .02, OR = 0.54, 95% confidence interval [CI]: 0.32–0.91), GHRS (P = .04, OR = 1.90, 95% CI: 1.02–3.51), GHRS-DHS (P

Objective: Bushen Chengyun granule (BCG) is an empirical treatment for female infertility (FI) caused by low endometrial receptivity (LER) involving a poorly understood mechanism. In this study, network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER. Methods: The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature. Disease targets were obtained from the following databases: Comparative Toxicogenomics Database, Human Phenotype Ontology, and Therapeutic Target Database. Treatments for LER using BCG have used target matching (BCG – LER target). Then, the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, triptorelin acetate for injection + menotrophin + chorionic gonadotropin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation. Results: Overall, 156 bioactive chemical components and 1092 targets of BCG were identified. The results indicated that 482 biological processes (FDR

Background Communication between colorectal cancer and stromal cells alters the tumor microenvironment to regulate locoregional disease and cancer progression. However, colon cancer–stromal cell interactions are difficult to study in vivo. Limitations of existing animal models include the use of immunocompromised mice, the inability to genetically modify a cell population in a single organ system, or a lack of anatomic context. Our goal was to develop a novel mouse model of colorectal cancer that is capable of studying tumor-stromal cell interactions in the native colon of immune-competent mice. Methods Primary mouse myofibroblasts were isolated from the colon of C57BL/6 mice and were grown in cell culture. Genetically defined (ApcΔ/Δ; Kras G12D/+; Trp53Δ/Δ) primary mouse colon cancer cells were suspended in serum-free media (20 μL) at varying concentrations (5 × 103 to 4 × 104 cells) either alone or in combination with syngeneic myofibroblasts (2 × 105 cells). After isoflurane anesthesia, a colonoscopy was performed on immune-competent 8- to 10-week-old C57BL/6 mice with endoscopic microinjection of the cell suspension into the submucosal space of the colon wall utilizing a small animal colonoscope. Surveillance endoscopy was used to assess for tumor growth, along with histologic analysis. Tumor size is presented on a grading system based on tumor diameter relative to colon circumference. Results A total of 33 mice were injected with a survival rate of 88% (29/33). Endoscopic microinjection of colorectal cancer cells resulted in dose-dependent tumor growth in the distal mouse colon that could be assessed endoscopically without animal sacrifice. Growth curves varied depending on the concentration of injected colorectal cancer cells, with no growth at the lowest concentration of injected cells (5 × 103 cells), progressive growth over 4 wk using 1-2 × 104 cells, while the highest colorectal cancer cell concentration (4 × 104 cells) led to larger tumors at week 1 followed by a steady decline in tumor growth over the 4-wk time period. Combined microinjection of 2 × 104 colorectal cancer cells with 2 × 105 myofibroblasts resulted in much larger tumors that persisted over the 4-wk time period and which were composed primarily of colorectal cancer cells. Immunofluorescence microscopy after coinjection of colorectal cancer cells with green fluorescent protein positive myofibroblasts confirmed that the injected myofibroblasts are present and remain viable over the 4-wk time period. Conclusions Endoscopic submucosal microinjection of primary mouse colorectal cancer cells is feasible and leads to reliable and reproducible short-term growth of colon tumors in immune-competent mice. Coinjection of primary mouse colorectal cancer cells with syngeneic myofibroblasts leads to enhanced tumor growth. Coimplantation of colorectal cancer cells with syngeneic myofibroblasts provides a novel platform to study tumor-stromal interactions in the native colon of immune-competent mice.

In this paper, a third-order reconstructed DG( p 1 p 2 ) method based on the variational reconstruction (VR) (Wang et al., 2017 [24] ) is developed for simulating the two dimensional steady-state compressible flows on unstructured and hybrid grids. The proposed method combines the advantages of the DG discretization with the flexibility of the variational reconstruction, which exhibits its superior potential in enhancing the level of accuracy compared to the underlying DG method. In this variational rDG( p 1 p 2 ) method, the low order degrees of freedom are evolved through the underlying DG( p 1 ) method, while the high order degrees of freedom are reconstructed through the variational reconstruction, in which the constitutive relations are built by minimizing the so-called ‘cost function’. The cost function is defined by the total interfacial jump integration in the computational domain using the variational method. The large sparse linear system resulted by the variational reconstruction is solved in an efficient way coupled with the temporal discretization for the steady-state simulations. A number of test cases are presented to assess the performance of the new high order variational rDG( p 1 p 2 ) method.

In this work, an adjoint-based airfoil shape optimization algorithm is developed based on the adaptive isogeometric discontinuous Galerkin method for compressible Euler equations to investigate the significance of each design variable of airfoil B-spline parameterization. We first parameterize the airfoil by B-spline curve approximation with some control points viewed as design variables, and build the B-spline representation of the flow field with the curve to apply the goal-oriented h -adaptive isogeometric DG method for flow solution. Then we compute and employ the discrete adjoint solutions for both multi-target error estimation in adaptive mesh refinement. With the isogeometric nature, not only all the geometrical cells but also the numerical basis functions can be analytically expressed by the design variables, indicating that the numerical solutions and objective could be differentiable with respect to those variables. Consequently, the gradient is totally computed in an accurate approach, and the sensitivity analysis is thus improved, by reducing the spatial discretization error and introducing the analytical expression of derivative, to reveal the key parameters for optimization in an intuitive and efficient manner. Although the SQP optimization algorithm is adopted in the paper, the given accurate gradient can be applied to any gradient-based optimization algorithm. The proposed algorithm is demonstrated on RAE2822 airfoil with inviscid transonic flow, where the shape is optimized to minimize the drag coefficient at a constrained lift and airfoil area. The numerical results show that the drag is much more sensitive to the design variables near the tailing edge at the beginning but sensitivity is reduced when optimal.

Usually, the temperature dependence of specific heats is neglected or the specific heats are frozen in interface computations for compressible two-material flows. In this paper, we present a practical interface treatment to faithfully capture the effect of high temperature on interface evolutions. A general technique for solving the Riemann problem equipped with a wide variety of equations of state (EOS) is established. In a unified framework for computing the interfacial states, it provides a convenient way to deal with the thermally perfect gas (PG) that considers the effect of temperature on specific heats. The algorithm of the complete and exact solution to Riemann problem with thermally PG is also designed in detail. Based on this technique, the modified ghost fluid method with an approximate Riemann solver is further extended to handle the interface of two-material flows involving thermally PG with chemical reactions. Several typical problems are selected to validate and test the present algorithm for the interaction between the thermally PG and other gases or liquids. The results indicate that the present algorithm enables an effective implementation for simulating various two-material multi-species flows with different types of EOS. As temperature increases, the behavior of the interfacial flows under the assumption of thermally PG EOS gradually differs from that under the assumption of calorically PG EOS.

In this work, an integral exact solution is proposed for one-dimensional elastic-perfectly plastic solid Riemann problem. Owing to the possible existence of elastic to plastic “phase” transition within the solid, the exact solution of its Riemann problem is much more complicated than that for the medium equipped with a uniform equation of state (EOS) or constitutive model. By constructing a five-equation hyperbolic governing system fully describing the nonlinear behavior of the solid in the Eulerian reference frame and scrutinizing every possible wave pattern of its Riemann problem, we acquire a complete list of exact solutions that contains as many as sixty-four different solution types neglecting the generation of vacuum. Each type of exact solutions is presented, and numerical simulations agree well with the obtained theoretical results.

In this paper, a class of new high order reconstructed DG (rDG) methods based on the compact least-squares (CLS) reconstruction [23] , [24] is developed for simulating the two dimensional steady-state compressible flows on hybrid grids. The proposed method combines the advantages of the DG discretization with the flexibility of the compact least-squares reconstruction, which exhibits its superior potential in enhancing the level of accuracy and reducing the computational cost compared to the underlying DG methods with respect to the same number of degrees of freedom. To be specific, a third-order compact least-squares rDG( p 1 p 2 ) method and a fourth-order compact least-squares rDG( p 2 p 3 ) method are developed and investigated in this work. In this compact least-squares rDG method, the low order degrees of freedom are evolved through the underlying DG( p 1 ) method and DG( p 2 ) method, respectively, while the high order degrees of freedom are reconstructed through the compact least-squares reconstruction, in which the constitutive relations are built by requiring the reconstructed polynomial and its spatial derivatives on the target cell to conserve the cell averages and the corresponding spatial derivatives on the face-neighboring cells. The large sparse linear system resulted by the compact least-squares reconstruction can be solved relatively efficient when it is coupled with the temporal discretization in the steady-state simulations. A number of test cases are presented to assess the performance of the high order compact least-squares rDG methods, which demonstrates their potential to be an alternative approach for the high order numerical simulations of steady-state compressible flows.

In this paper, an adjoint-based high-order h-adaptive direct discontinuous Galerkin method is developed and analyzed for the two dimensional steady state compressible Navier–Stokes equations. Particular emphasis is devoted to the analysis of the adjoint consistency for three different direct discontinuous Galerkin discretizations: including the original direct discontinuous Galerkin method (DDG), the direct discontinuous Galerkin method with interface correction (DDG(IC)) and the symmetric direct discontinuous Galerkin method (SDDG). Theoretical analysis shows the extra interface correction term adopted in the DDG(IC) method and the SDDG method plays a key role in preserving the adjoint consistency. To be specific, for the model problem considered in this work, we prove that the original DDG method is not adjoint consistent, while the DDG(IC) method and the SDDG method can be adjoint consistent with appropriate treatment of boundary conditions and correct modifications towards the underlying output functionals. The performance of those three DDG methods is carefully investigated and evaluated through typical test cases. Based on the theoretical analysis, an adjoint-based h-adaptive DDG(IC) method is further developed and evaluated, numerical experiment shows its potential in the applications of adjoint-based adaptation for simulating compressible flows.

In a recent work Feng, Liu and Wang (2020) [10] , we imbedded characteristic compressing into an artificial neuron (AN) to propose a shock wave indicator on uniform mesh. In this work, the indicator is developed to unstructured grid. To achieve that, we retrain an AN on 1D randomly perturbed mesh, two prior information, (a) eigenvalue variable and (b) side-weighted average, is used in data pre-processing for reducing the influence of mesh size and keeping AN structure simple. The output of AN is then modified into a generalized and explicable form, which is used as the present shock wave indicator. We show that the troubled-cells detected by the present indicator include discontinuities caused by compressing of characteristic curves. The present indicator is then extended to multi-dimensional unstructured grid through constructing side-weighted average of eigenvalue on each spatial dimension. Numerical results are presented to demonstrate the performance of the present indicator combined with slope limiter and artificial viscosity, respectively, on various unstructured grids, the results show that the present indicator can detect shock and contact waves with low noise, and improves the indicating efficiency as well, the present indicator provides an attractive alternative in detecting shock waves on arbitrary grids and can be combined with various discontinuity-processing techniques.

In this paper, a residual-based h-adaptive high-order reconstructed DG (rDG) method based on the hybrid reconstruction strategy is developed for solving the compressible Euler equations on unstructured grids. The proposed method combines the advantages of high-order rDG discretization with appropriate residual-based error estimation techniques and h-adaptive refinement strategies, which exhibits its superior potential compared to the underlying DG methods. To be specific, a third-order hybrid rDG(p1p2) method has been carefully designed and evaluated on incompatible quadrilateral grids with hanging nodes in order to preserve 2-exactness property during the implementation of mesh refinement and coarsening. A residual-based error estimator is used as local error indicator during the h-adaptive procedures. A number of test cases are presented to assess the performance of the high-order h-adaptive rDG method. The hybrid reconstruction strategy combined with h-adaptive techniques presented in this work demonstrates promise for improving the level of accuracy and reducing the computational cost for numerical simulations of compressible inviscid flows.

Riemann-problem-solver-based ghost fluid method (GFM) provides us an effective manner to simulate compressible gas-liquid flows. Interfacial parameters are indispensable to define interface conditions and usually solved by an implicit approximate Riemann problem solver (ARPS). In this work, we design explicit pressure-based/velocity-based ARPS with a stiffened equation of state. Moreover, the ranges of application of these implicit and explicit ARPSs are discussed in detail. Equipped with these explicit ARPSs, it is more convenient to utilize the idea of modified GFM (MGFM) or practical GFM (PGFM) to define ghost fluid states in numerical applications. Results from the proposed explicit method compare well with that from the implicit method. Especially the PGFM with the present explicit velocity-based ARPS is more widely used and more efficient for large scale scientific computation.

Objective To examine the effects of accumulated heat in GI tract (AHGIT) on lung tissue protein expression in pneumonic mice. Methods Nebulized lipopolysaccharides (LPS) were administered to induce a pneumonic mouse model (M1), and a high-calorie/protein diet combined with nebulized LPS was used to induce AHGIT pneumonia (M2). Isobaric tag for relative and absolute quantitation (iTRAQ) proteomics was applied to study lung protein expression, followed by bioinformatics analysis. Results M1 mice developed alveolar damage with prominent septum thickening, vascular dilation, hyperaemia and infiltration of large amounts of inflammatory cells. M2 mice developed more severe pathological responses. A total of 2626 proteins were reliably identified in the lung tissue. Compared with normal mice, the M1 mice had 344 differentially expressed proteins in their lungs, which are involved in the following biological processes: response to organic substance, response to cytokine, response to external stimulus, defense response and immune system process. They are also involved in the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: ECM-receptor interaction, leukocyte transendothelial migration, Fc gamma R-mediated phagocytosis, complement and coagulation cascades, and antigen processing and presentation. Compared with the M1 group, the M2 mice had 164 differentially expressed proteins in their lungs, including 14 upregulated and 150 downregulated proteins. These proteins are involved in the following biological processes: small molecule metabolism, ribose phosphate metabolic process, cell adhesion and biological adhesion. The relevant KEGG pathways included oxidative phosphorylation, Citrate cycle (TCA cycle), complement and coagulation cascades, and vascular smooth muscle contraction. Conclusions AHGIT aggravated the lung inflammatory damage in the mice with LPS-induced pneumonia. It may affect the mouse substance/energy metabolism, and therefore the immune function, to aggravate the LPS-induced inflammatory damage.

A Direct Discontinuous Galerkin (DDG) method is developed for solving the compressible NavierStokes equations on arbitrary grids in the framework of DG methods. The DDG method, originally introduced for scalar diffusion problems on structured grids, is extended to discretize viscous and heat fluxes in the NavierStokes equations. Two approaches of implementing the DDG method to compute numerical diffusive fluxes for the NavierStokes equations are presented: one is based on the conservative variables, and the other is based on the primitive variables. The importance of the characteristic cell size used in the DDG formulation on unstructured grids is examined. The numerical fluxes on the boundary by the DDG method are discussed. A number of test cases are presented to assess the performance of the DDG method for solving the compressible NavierStokes equations. Based on our numerical results, we observe that DDG method can achieve the designed order of accuracy and is able to deliver the same accuracy as the widely used BR2 method at a significantly reduced cost, clearly demonstrating that the DDG method provides an attractive alternative for solving the compressible NavierStokes equations on arbitrary grids owning to its simplicity in implementation and its efficiency in computational cost.

A class of reconstructed discontinuous Galerkin methods is described for solving compressible flow problems on arbitrary grids. Both Green-Gauss and least-squares reconstruction methods and a least-squares recovery method are presented to obtain a quadratic polynomial representation of the underlying linear discontinuous Galerkin solution on each cell via a so-called in-cell reconstruction process. The devised in-cell reconstruction is aimed to augment the accuracy of the discontinuous Galerkin method by increasing the order of the underlying polynomial solution. These three reconstructed discontinuous Galerkin methods are used to compute a variety of compressible flow problems on arbitrary meshes to assess their accuracy. The numerical experiments demonstrate that all three reconstructed discontinuous Galerkin methods can significantly improve the accuracy of the underlying second-order DG method, although the least-squares reconstruction method provides the best performance in terms of both accuracy, efficiency, and robustness I. Abstract The discontinuous Galerkin methods 1-25 (DGM) have recently become popular for the solution of systems of conservation laws. Nowadays, they are widely used in computational fluid dynamics, computational acoustics, and computational electromagnetics. The discontinuous Galerkin methods combine two advantageous features commonly associated to finite element and finite volume methods. As in classical finite element methods, accuracy is obtained by means of high-order polynomial approximation within an element rather than by wide stencils as in the case of finite volume methods. The physics of wave propagation is, however, accounted for by solving the Riemann problems that arise from the discontinuous representation of the solution at element interfaces. In this respect, the methods are therefore similar to finite volume methods. The discontinuous Galerkin methods have many attractive features:1) They have several useful mathematical properties with respect to conservation, stability, and convergence; 2) The method can be easily extended to higher-order (>2 nd

The discontinuous Galerkin (DG) methods have attained increasing popularity for solving the incompressible Navier-Stokes (INS) equations in recent years. However, the DG methods have their own weakness due to the high computational costs and storage requirements. In this work, we develop a high-order hybrid reconstructed DG (rDG) method for solving the INS equations on arbitrary grids. To be specific, the inviscid term of the INS equations is discretized by applying the third-order hybrid rDG( P 1 P 2 ) method with a simplified artificial compressibility flux, while the viscous term of the INS equations is discretized by using the simple direct DG (DDG) method. A number of incompressible flow problems, in both steady and unsteady forms, for a variety flow conditions are computed to numerically assess the performance of the hybrid rDG( P 1 P 2 ) method, which confirm its ability to achieve the optimal third order of accuracy at a significantly reduced computational costs. Furthermore, a detailed comparison of a variety of different reconstructed strategies is performed and presented. Numerical results demonstrate that the hybrid rDG( P 1 P 2 ) method outperforms the rDG( P 1 P 2 ) method based on either the original least-squares reconstruction or the Green-Gauss reconstruction for solving the INS equations.

Ethnopharmacological relevance “Xiaoerhuashi Pill, XP”, with a history of 30 years in China, was included in the first part of the 2015 edition of the Chinese Pharmacopoeia and is widely used in the treatment for pediatric diseases in clinical application. Its main indications include the accumulation of heat caused by food stagnation in children, which has the effect of digestive stagnation and purge heat to relax the bowels. Aim of the study High-calorie diet, closely related to the occurrence and development of multiple diseases, is an unhealthy status of life. However, there is no effective intervention in clinic. Thus, based on animal experiments and bioinformatics, this study aims to explore the potential mechanisms of action of Chinese patent medicine- “Xiaoerhuashi Pill, XP” in the intervention of high-calorie diet. Materials and methods A high-calorie diet model was prepared by 3-week-old rats. The defecation and intestinal mucosal morphology were observed after intragastric administration of “Xiaoerhuashi Pill, XP”. The components of “Xiaoerhuashi Pill, XP” were obtained by chromatography-mass spectrometry, with the corresponding targets obtained by database and target fishing. The key effects substances were obtained by molecular docking, with the obtaining of the ore pathway of “Xiaoerhuashi Pill, XP” in intervention of high-calorie diet based on the enrichment analysis. Results “Xiaoerhuashi Pill, XP” can actively interfere with defecation and intestinal mucosal structures in high-calorie diet animals. A total of 37 substances were identified in the pediatric digestion solution, and 356 target proteins were mapped, 25 of which were associated with a high-calorie diet. Overall, the analysis shows that the highest degree of integration was quercetin and PON1 protein, with the highest enrichment of insulin resistance pathway. Conclusion “Xiaoerhuashi Pill, XP” can intervene in the health status of high-calorie diet animals. Integration of quercetin and PON1 protein can regulate lipid levels, which may be the key mechanisms of action in “Xiaoerhuashi Pill, XP”. The mechanisms, more specifically, may be related to the regulation of pancreas islet function, thus providing a reference for the clinical application of “Xiaoerhuashi Pill, XP”, clinical intervention of high-calorie diet and new drug development.

Age-related cataract (ARC) is a main cause of blindness for elderly people. MicroRNA hsa_miR-29c-3p (miR-29c-3p) was implicated in many biological processes in complicated diseases. However, the biological mechanism of miR-29c-3p in ARC is still undefined. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that miR-29c-3p was lowly expressed, while FBJ murine osteosarcoma viral oncogene homolog (FOS) and KCNQ1 overlapping transcript 1 (KCNQ1OT1) were highly expressed in cataract tissues and in TGF-β2-treated SRA01/04 cells. Western blot assay indicated that TGF-β2 could promote epithelial-mesenchymal transition (EMT). Moreover, our data suggested that miR-29c-3p overexpression suppressed EMT, cell proliferation and promoted apoptosis in TGF-β2-treated SRA01/04 cells. The dual-luciferase reporter assay verified that FOS was a target of miR-29c-3p and miR-29c-3p was directly targeted by KCNQ1OT1. Furthermore, KCNQ1OT1 could regulate FOS expression by sponging miR-29c-3p. Functional assays revealed that miR-29c-3p regulated FOS to repress EMT, cell proliferation and facilitate apoptosis in TGF-β2-treated SRA01/04 cells mediated by KCNQ1OT1. In conclusion, KCNQ1OT1/miR-29c-3p/FOS axis played a vital role in the progression of ARC.

Graphical abstract, Highlights • A total of 129 compounds of QFPD were dissected by UPLC-MS and molecular networking of MS data. • COVID-19 disease network was constructed to generate the QFPD therapeutic network based on chemical constituents and target prediction. • Toll-like signaling pathway was found to be important pathway regulated by QFPD. • Transcriptomic analysis revealed MXSG Decoction regulated multiple complement, coagulation cascades and thrombin system to interfere infection., The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.

Objective To explore the association between dietary habits and recurrent respiratory infection (RRI) in children aged 0–14 years. Methods This case–control study compared dietary data of children with (cases) and without RRI (controls) collected via structured questionnaire. Participants were recruited from Chinese medicine clinics, hospitals, and children's learning institutions in Beijing. A logistic regression analysis and odds ratio (OR) calculations were conducted using SPSS 17.0 software. Results A total of 241 questionnaires were collected (case:control ratio: approximately 2:1). Frequent consumption of processed foods (OR = 2.988, 95% confidence intervals 1.375–6.491) and high-sugar foods (OR = 2.268, 95% confidence intervals 1.163–4.424), frequent picky eating (OR = 2.614, 95% confidence intervals 1.363–5.014), and a meat-heavy diet with fewer vegetables (OR = 1.830, 95% confidence intervals 1.358–2.467) correlated positively correlated with RRI. Additionally, 57.80% of the children with RRI were addicted to high-sugar foods, compared with 41.57% of the children without RRI ( P = .015). Furthermore, 63.16% of the children with RRI were picky eaters, compared with 48.31% of the children without RRI ( P = .024). Finally, 30.92% of the children with RRI frequently consumed processed foods, compared with only 17.98% of the children without RRI ( P = .027). Conclusion Although RRI correlates positively with several dietary habits, in the future, prospective cohort studies with larger samples are needed to generalize these findings.

In this paper, we develop the Runge–Kutta discontinuous Galerkin (RKDG) methods with the finite volume weighted essentially non-oscillatory (WENO) reconstruction as limiters to solve for the unsteady cavitating flow under the employment of the isentropic one-fluid model. To treat the cavitating flow and suppress the possible spurious oscillations in the vicinity of the cavitation boundary, the TVB limiter is used as an indicator to detect the “troubled cells” and hence take the advantage of utilizing the WENO reconstruction for the freedoms of the RKDG methods. Numerical results are provided to illustrate the viability of these procedures.

Since the (original) ghost fluid method (OGFM) was proposed by Fedkiw et al. in 1999 [5], a series of other GFM-based methods such as the gas-water version GFM (GWGFM), the modified GFM (MGFM) and the real GFM (RGFM) have been developed subsequently. Systematic analysis, however, has yet to be carried out for the various GFMs on their accuracies and conservation errors. In this paper, we develop a technique to rigorously analyze the accuracies and conservation errors of these different GFMs when applied to the multi-medium Riemann problem with a general equation of state (EOS). By analyzing and comparing the interfacial state provided by each GFM to the exact one of the original multi-medium Riemann problem, we show that the accuracy of interfacial treatment can achieve ''third-order accuracy'' in the sense of comparing to the exact solution of the original mutli-medium Riemann problem for the MGFM and the RGFM, while it is of at most ''first-order accuracy'' for the OGFM and the GWGFM when the interface approach is actually near in balance. Similar conclusions are also obtained in association with the local conservation errors. A special test method is exploited to validate these theoretical conclusions from the numerical viewpoint.

The study of radially symmetric compressible fluid flows is interesting both from the theoretical and numerical points of view. Spherical explosion and implosion in air, water and other media are well-known problems in application. Typical difficulties lie in the treatment of singularity in the geometrical source and the imposition of boundary conditions at the symmetric center, in addition to the resolution of classical discontinuities (shocks and contact discontinuities). In the present paper we present the implementation of direct generalized Riemann problem (GRP) scheme to resolve this issue. The scheme is obtained directly by the time integration of the fluid flows. Our new contribution is to show rigorously that the singularity is removable and derive the updating formulae for mass and energy at the center. Together with the vanishing of the momentum, we obtain new numerical boundary conditions at the center, which are then incorporated into the GRP scheme. The main ingredient is the passage from the Cartesian coordinates to the radially symmetric coordinates.

An adaptive ghost fluid finite volume method is developed for one- and two-dimensional compressible multi-medium flows in this work. It couples the real ghost fluid method (GFM) [C.W. Wang, T.G. Liu, B.C. Khoo, A real-ghost fluid method for the simulation of multi-medium compressible flow, SIAM J. Sci. Comput. 28 (2006) 278-302] and the adaptive moving mesh method [H.Z. Tang, T. Tang. Moving mesh methods for one- and two-dimensional hyperbolic conservation laws, SIAM J. Numer. Anal. 41 (2003) 487-515; H.Z. Tang, T. Tang, P.W. Zhang, An adaptive mesh redistribution method for non-linear Hamilton-Jacobi equations in two- and three-dimensions, J. Comput. Phys. 188 (2003) 543-572], and thus combines their advantages. This work shows that the local mesh clustering in the vicinity of the material interface can effectively reduce both numerical and conservative errors caused by the GFM around the material interface and other discontinuities. Besides the improvement of flow field resolution, the adaptive GFM also largely increases the computational efficiency. Several numerical experiments are conducted to demonstrate robustness and efficiency of the current method. They include several 1D and 2D gas-water flow problems, involving a large density gradient at the material interface and strong shock-interface interactions. The results show that our algorithm can capture the shock waves and the material interface accurately, and is stable and robust even for solutions with large density and pressure gradients.

The Runge-Kutta discontinuous Galerkin (RKDG) method for solving hyperbolic conservation laws is a high order finite element method, which utilizes the useful features from high resolution finite volume schemes, such as the exact or approximate Riemann solvers, TVD Runge-Kutta time discretizations, and limiters. In this paper, we investigate using the RKDG finite element method for compressible two-medium flow simulation with conservative treatment of the moving material interfaces. Numerical results for both gas-gas and gas-water flows in one-dimension are provided to demonstrate the characteristic behavior of this approach.

It is found that the one-fluid cavitation model developed by Schmidt et al. [Schmidt DP, Rutland CJ, Corradini ML. A fully compressible, two-dimensional model of small, high speed, cavitating nozzles. Atomiz Sprays 1999;9:255–76] (Schmidt Model) does not work consistently when applied to simulate the unsteady transient cavitating flows with a large vapor to liquid density ratio or under the condition of a low surrounding pressure. In this work, the apparent difficulties of the Schmidt model are analyzed and a modified Schmidt model is proposed for greater robustness and consistency. The modified Schmidt model is then applied to study the creation, evolution and collapse of transient cavitation commonly observed in underwater explosions and industrial pipe flow. The model is firstly verified by simulating several cavitating flows where analytical, experimental or numerical results are available for comparison, and then applied to multi-dimensional transient cavitating flows generated by underwater explosions. The numerical results show that the modified Schmidt model can overcome the difficulties associated with the (original) Schmidt model and be applied to both small and large scale transient cavitating flows to predict the pressure surge caused by cavitation collapse regardless of the surrounding pressure.

This note gives a numerical investigation for the popular high resolution conservative schemes when applied to inviscid, compressible, perfect gas flows with an initial high density ratio as well as a high pressure ratio. The results show that they work very inefficiently and may give inaccurate numerical results even over a very fine mesh when applied to such a problem. Numerical tests show that increasing the order of accuracy of the numerical schemes does not help much in improving the numerical results. How to cure this difficulty is still open.

An analysis is carried out for the ghost fluid method (GFM) based algorithm as applied to the gas-water Riemann problems, which can be construed as two single-medium GFM Riemann problems. It is found that the inability to provide correct and consistent Riemann waves in the respective real fluids by these two GFM Riemann problems may lead to inaccurate numerical results. Based on this finding, two conditions are suggested and imposed for the ghost fluid status in order to ensure that correct and consistent Riemann waves are provided in the respective real fluids during the numerical decomposition of the singularity. Using these two conditions to analyse some of the existing GFM-based algorithms such as the original GFM [J. Comput. Phys. 152 (1999) 457], the new version GFM [J. Comput. Phys. 166 (2001) 1; J. Comput. Phys. 175 (2002) 200] and the modified GFM (MGFM) [J. Comput. Phys. 190 (2003) 651], it is found that there are ranges of conditions for each type of solution where either the original GFM or the new version GFM or both are unable to provide correct or consistent Riemann waves in one of the real fluids. Within these ranges, examples can be found such that either the original GFM or the new version GFM or both are unable to provide accurate results. The MGFM is also found to encounter difficulties when applied to nearly cavitating flow. Various examples are presented to demonstrate the conclusions obtained. The MGFM with proposed modification when applied to nearly cavitating flow is then found to be quite robust and can provide relatively reasonable results.

Unlike attached cavitation, where the cavitation boundary is steady or changes relatively slowly and periodically, the cavitation such as that observed in an underwater explosion consists of a dynamically developing boundary and can evolve to a certain dimension before collapsing very violently. The development and collapse of such cavitation is sustained mainly by the pressure jump across the cavitation boundary. In this work, the focus is on developing a one-fluid model for such cavitating flows. Alter the analysis and discussion are carried out for some existing one-fluid cavitation models, such as Vacuum model, Cut-off model and Schmidt's model, a mathematically more consistent one-fluid model is then developed to study the creation, evolution and collapse of such unsteady cavitation by assuming that the cavitating flow is a homogeneous mixture of isentropic gas and liquid components. In the model, both the ambient water and the mixture of cavitating flow are taken as compressible. Besides the theoretical analysis, the present model is also tested against various problems with either exact solution, or experimental data or comparison to other existing models, and then applied to a 3D underwater problem in a cylinder.

Purpose: Unexplained chronic fatigue (CF) is common symptom in worldwide. According to the theory of Korean Medicine (KM), CF is considered to be the imbalance of interorgan functions or the four essential components of the human body, including qi, blood, yin and yang. Thus CF appears to have individual differences, it can be subdivided into different pattern identification (PI) for a personalized diagnosis in KM. However, there are no diagnostic tools, such as questionnaires or medical devices. The purpose of this studywas to develop PI questionnaires and to complete a clinical trial to determine the correlation between CF and Qi Blood Yin Yang Deficiency Questionnaires (QBYYDQs). Methods: A total of 151 participants, including 121 CF patients and 30 healthy subjects, were asked to complete the QBYYQs. Two Korean medical doctors independently assessed participants’ qi, blood, yin and yang deficiency patterns (DPs) by the PI guidelines. We selected reliable questionnaire items for symptoms corresponding to each DP based on the results of a preliminary study. These itemswere used to estimate internal consistency and construct validity. A multinomial logistic regression analysis (MLRA) was performed by each DP score. Results: The qi (9 items), blood (8 items), yin (9 items) and yang (6 items) DQs showed sufficient internal consistency (0.816, 0.826, 0.807 and 0.717, respectively). Two subscales from each DQ were extracted by an explanatory factor analysis. The variances for each qi, blood, yin, and yang DQ were 52.8%, 58.0%, 52.2%, and 63.5%, respectively. Odds ratios from the MLRA demonstrated that each deficiency score was positively associated with each corresponding DP (adjusted odds ratio: qi score=0.041, blood score=5.877, yin score=12.57, yang score=13.56, reference category: qi deficiency). Conclusion:These results suggest that the QBYY-Q is a reliable and valid instrument for estimating the influence of qi, blood, yin and yang deficiencies on CF. Contact: Jihye Kim, wisdom00311@kiom.re.kr