Objective The influencing parameters of solid and fluid computing fields for the scaffolds models with regular square holes were discussed by nonlinear fluid-solid-coupling approaches.The numerical computational resuits of which the models were regarded as both rigid body and non-linear elasticity were compared as well.Method One direct fluid-solid-coupling approach and two indirect fluid-solid-coupling approaches were adopted,and the calculating reliability of three kinds of fluid-solid coupling methods was verified.Rasults The solid-fluidcoupling computational results are obtained in light of 12 kinds of scaffolds models which are constructed by 3 groups of square side length(50,100 and 150 μm)and 4 groups of porosity(61%,65%,77%and 84%).The field parameters of those solid models including stress,strain and displacement and those fluid models including static pressure,velocity,wall shear stress and strain rate are achieved and compared.Conclusion There appear some difference between the results of porous scaffold models as a rigid body and as non-linear elasticity.The different porosity with the same pore radius or the different pore radius with the same porosity would affect the field parameters of solid models and fluid models in varying degrees.

Objective To investigate the effect of the prescription of Yiqiyangyin Huoxuehuayu on the mice model with viral dilated cardiomyopathy by examining the levels of serum ?-IFN.Methods Replicated the animal models of early viral dilated cardiomyopathy by injecting the CVB3m virus to the peritoneal cavity of the Balb/c mice.Two hundred and ten Balb/c mice were divided into 4 groups at random:blank group,model group,high and low dose traditional Chinese medicine group.The blank group has 30 mice.The other three group has 60 mice each.The mice of high dose traditional Chinese medicine group and low dose traditional Chinese medicine group were treated with the prescription of Yiqiyangyin Huoxuehuayu.The change of pathomorphology in the cardiac muscle tissue,the rate of death,the weight change and the cardiac weight index were observed after 4 weeks of the treatment.At the same time,ELISA method was used to exam the levels of serum ?-IFN.Results The prescription of Yiqiyangyin Huoxuehuayu can induce the expression of serum ?-IFN in the mice with viral dilated cardiomyopathy.The mean level of serum ?-IFN of the high dose traditional Chinese medicine group and low dose traditional Chinese medicine group were significantly higher than that of the model group.Conclusions The prescription of Yiqiyangyin Huoxuehuayu can inhibit the viral replication and regulate the immunologic function.

BACKGROUND:Polyvinyl alcohol (PVA) hydrogel with similar porous structure and mechanical properties to the natural cartilage is very suitable for the repair of articular cartilage. However, the pure PVA hydrogel after lyophilization wil be accompanied by the shrinkage of the polymer network and the col apse of the pores, leading to the inhomogeneous performance of the material even in the state of re-swel ing. Addition of the active polymer wil increase the cel adhesion ability of PVA hydrogel. OBJECTIVE:To construct PVA/lota-carrageenan (l-CA) composite materials with different mass fractions of l-CA and evaluate the biocompatibility with vascular endothelial cel s. METHODS:PVA/l-CA composite films with different contents of l-CA were fabricated and then co-cultured with vascular endothelial cel s. Attachment, proliferation and morphological changes of vascular endothelial cel s on the composite were observed by scanning electron microscope and MTT assay to evaluate its biocompatibility. PVA/l-CA three-dimensional scaffold with different contents of l-CA were constructed, and hemolysis experiment was conducted according to the biological evaluation standards of medical devices, and the porosity and pore size were observed using scanning electron microscope. RESULTS AND CONCLUSION:In vitro experimental results showed that the addition of l-CA could significantly increase the biological activity of PVA hydrogel, and promote the cel attachment and proliferation on the scaffold. The hemolysis rate of each experimental group was less than 5%(the accepted safety standard), suggesting that the composite materials were in accordance with the standard of medical devices for hemolysis experiment. These findings indicate that the composite scaffolds with 20%-30%l-CA possess the pore size suitable for cel growth and proliferation and the porosity beneficial for transportation of nutrients and metabolites, which can serve as an excel ent scaffold for tissue engineering.

Objective:To examine differences in metabolic characteristics and metabolites between elderly overweight patients with metabolic syndrome and healthy elderly people, and to identify related factors.Methods:A group of 36 MS patients(the MS group)admitted to The Fourth Central Hospital of Tianjin from April to August 2018 and 43 elderly people(the control group)who underwent physical examination during the same period were included in this prospective study.Serum samples of the patients with metabolic syndrome and elderly healthy controls were collected, and ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)based non-targeted metabolomics was used to search for differences in metabolites between the serum samples of the two groups.The Pearson correlation statistical method was used to find related clinical factors.Results:Comparison of baseline data of the enrolled participants showed that there were statistically significant differences between the two groups in body mass index[(26.9±2.0)kg/m 2vs.(21.7±1.4)kg/m 2], waist circumference, systolic blood pressure, fasting blood glucose, triglycerides and high-density lipoprotein cholesterol( P<0.01). Metabolomics results showed that there were differences in 65 serum metabolites between elderly overweight patients with metabolic syndrome and elderly normal controls, and these differences were enriched in 21 pathways.Correlation analysis showed that waist circumference had the largest number of differential metabolites, followed by body mass index.The major differential metabolites were monosaccharides such as mannose, lyxose and glucose, linolenic acid and its derivatives, and pyroglutamate. Conclusions:Compared with normal elderly people, elderly patients with overweight metabolic syndrome have a variety of differential metabolites, and these metabolites are highly correlated with clinical indicators related to overweight, such as body mass index and waist circumference, and they include monosaccharides, linolenic acid derivatives and amino acids.

The basic pathogenesis of diabetes is yin deficiency as the root and dry heat as the symptoms, both of which are reciprocal causation. The occurrence and development of this disease is closely related to pathogenic heat, and pathogenic heat has different degrees of deficiency and excess, and is often cemented with tangible pathogenic factors, such as dampness, phlegm and blood stasis. Clinical application of Traditional Chinese Medicine treatment of the eight methods of "clearing therapy" in the treatment of diabetes and its complications has often achieved significant efficacy, which is specifically divided into Qingxie method (clearing heat and purging fire method), for the syndrome of excessive heat in the viscera, and the representative prescriptions are Dahuang Huanglian Xiexin Decoction and Longdan Xiegan Decoction; Qingli method (clearing heat and draining dampness method), for the accumulation of damp heat in the spleen and stomach, gastrointestinal, block triple energizer, and the representative prescription is Gegen Qinlian Decoction; Qinghua method (clearing heat and resolving phlegm, removing blood stasis method) for the disease caused by phlegm, the course of the disease is lingering, complex and changeable, or caused by blood stasis. The disease is various, more serious, with more experience in clinical use of self-made prescriptions; Qingbu method (clearing heat and nourishing method) is for the patients with diabetes for a long time. The pathogenic heat hurts yin and consumes qi, and the representative prescriptions are Baihu Jia Renshen Decoction, Huanglian Ejiao Decoction, and Yu'nyu Decoction.

To explore how to create and optimize a promotion index system of medical quality evaluation, this article focuses on the hospital visiting process from patients, using analyzing collected those index system from couples of Grade Ⅲ hospitals in Beijing, and combining the results of literal study, field study and specialist consult, according to the different situation of general hospitals and specially hospitals, with the spirit of "maintaining the patients benefits, safeguarding the patients safety,and enhancing the medical quality", introduces the framework of the promotion index system, the rules to select the indicator, and so on, and discusses several problerns related to creating the index system.

Background: Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL).Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma. Methods: We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis. Results: Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (＜0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P ＜ 0.05). A survival analysis showed that progression-free survival (PFS) (P =0.003) and overall survival (OS) (P ＜0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P ＜0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P ＜0.05). Conclusion A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.

OBJECTIVETo investigate the effects of bufalin in reversing hepatocyte growth factor (HGF)-induced resistance to afatinib in H1975 lung cancer cells, and explore its possible mechanism.

METHODSThe afatinib-resistant H1975 lung cancer cells (H1975AR) were induced by exogenous HGF and transfected with recombinant adenoviral vector Ad-HGF-GFP. The cytostatic effects of bufalin, afatinib and bufalin plus afatinib on H1975AR cells were evaluated by MTT assay. The impact of combined therapy with bufalin and afatinib on invasion of H1975AR cells was determined by transwell migration assay. The concentrations of HGF in the culture supernatants of H1975/Vec and H1975/HGF cells were determined by ELISA. The expression of EGFR, cMET and EMT signal pathway-related proteins in H1975AR cells treated with bufalin, afatinib and bufalin plus afatinib were detected by Western blot.

RESULTSThe results of MTT assay showed that afatinib did not inhibit the growth of H1975 cells, but after 72 h of the combined treatment with bufalin and afatinib and in the presence of HGF, the growth rate of H1975 cells was (38.67 ± 8.76)%, significantly lower than the growth rate of (63.45 ± 12.65)% in the H1975 cells treated with HGF alone (P < 0.05). The results of transwell migration assay showed that in the presence of HGF, afatinib plus bufalin combination therapy markedly decreased the number of invaded H1975 cells through the Matrigel chamber (48.98 ± 11.43), significantly lower than the 118.92 ± 37.29 of afatinib-treated or the 88.84 ± 19.53 of bufalin-treated cells (P < 0.05 for all). The result of ELISA showed that H1975/HGF cells secreted high levels of HGF, and afatinib and bufalin had no effect on the HGF secretion in H1975/HGF cells. The results of Western blot analysis showed that the expression of p-EGFR, p-cMet, p-AKT, p-ERK, vimentin and snail in H1975AR cells treated with bufalin puls afatinb was down-regulated markedly, and the expression of E-cadherin was up-regulated markedly.

CONCLUSIONSCombination of bufalin and afatinib strongly inhibits the growth of H1975AR lung cancer cells and decreases their invasion ability. The possible mechanism of combined treatment with bufalin and afatinib may be related to the blocking of cMet/PI3K/AKT and cMet/MAPK/ERK pathways and inhibiting of epithelial-mesenchymal transition.

Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Bufanolides ; pharmacology ; Cadherins ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Coloring Agents ; Drug Resistance, Neoplasm ; drug effects ; Epithelial-Mesenchymal Transition ; drug effects ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; MAP Kinase Signaling System ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; Quinazolines ; pharmacology ; Receptor, Epidermal Growth Factor ; Signal Transduction ; Tetrazolium Salts ; Thiazoles

Objective: To investigate the effect of cartilage tissue engineering scaffold PVA/ι-CA on the biological behavior of the ATDC-5 cells,and to evaluate its feasibility on constructing tissue engineering cartilage. Methods:The polyvinyl alcohol (PVA)and carrageenan were used to make the composite scaffold material PVA/ι-CA according to a certain proportion by physical blending technology and repeated freezing thawing method,and the porosity and pore size of PVA/ι-CA were detected.The ATDC-5 cells were seeded into the composite scaffold and its growth was observed; the expressions of collagen type Ⅱ in the ATDC-5 cells were tested by immunohistochemical staining and immunofluorescence staining; the morphology of the ATDC-5 cells was confirmed by Toluidine blue staining.The growth and secretion of extracellular matrix of the ATDC-5 cells were observed under scanning electron microscope (SEM);the proliferative rates of ATDC-5 cells in composite scaffold materials in negative control group (added with DMEM culture media)and experimental group (added with DMEM contain scaffold)were determined by MTT assay.The composite scaffolds were implanted subcutaneously in the SD rats.The histocompatibility and vascularization in vivo of the composite scaffolds were evaluated.Results:The average porosity of cartilage tissue engineering scaffold PVA/ι-CA was (86.88±3.88)%,and the average pore size was 20-40 μm.The HE staining results showed that the ATDC-5 cells grew well with the polygon and plumpness morphology. All the samples were stained positive for collagen type Ⅱ by immunohistochemistry and immunofluorescence staining,which verified the normal phenotype of chondrocytes on the scaffolds. All the sample were stained positive for toluidine blue staining,which verified ECM deposition of the ATDC-5 cells on the scaffolds.The number of the positive cells was significantly increased with the prolongation of time.After cultured for 7 d,few of the ATDC-5 cells presented polygonal;after cultured for 14 d,the ATDC-5 cells distributed more densely,and contacted with each other on the scaffold;after cultured for 21 - 28 d,the ATDC-5 cells filled the interconnected pores of the scaffolds,synthesizing a significant amount of neo-formed ECM.The proliferation of ATDC-5 cells in PVA/ι-CA grew fast during 7-14 d,and it became slow during 21-28 d;the difference was not statistically significant compared with control group (P >0.05).The subcutaneous implantation results showed the inflammatory reactions were slight at the early stage and eviated gradually,there was an increasing angiogenesis at the late stage,and the degradation and absorption of the meterial were slight.Conclusion:PVA/ι-CA composite material will be an ideal material for the cartilage tissue engineering.

Objective: To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods: We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot. Results: The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC₅₀) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC₅₀ of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells. Conclusions MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.