FXR： a metabolic regulator and cell protector

Farnesoid X receptor （FXR） is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid, cholesterol, lipid, and glucose metabolism. Therefore, FXR is a potential drug target for a number of metabolic disorders, especially those related to the metabolic syndrome. More recently, our group and others have extended the functions of FXR to more than metabolic regulation, which include anti-bacterial growth in intestine, liver regeneration, and hepatocarcinogenesis. These new findings suggest that FXR has much broader roles than previously thought, and also higi.light FXR as a drug target for multiple diseases. This review summarizes the basic information of FXR but focuses on its new functions.

Properties of oxide coating on the surface of ZrH_(1.8) prepared by microarc oxidation with different positive voltages

Zirconia coatings as hydrogen permeation barriers were formed on disktype ZrHj.s substrate speci mens in phosphate solution system by microarc oxidation technique. Influence of positive voltage on hydrogen per meation barriers on the surface of zirconium hydride was investigated as the main factor. The thickness of total oxide layer increased from 42.5 to 55.0 ~tm the increase of positive voltage increasing from 325 up to 425 V. The permeation reduction factor （PRF） was observed under different voltages, which increased with the increasing positive voltages. The phase structure of oxide layer was monoclinic Zr02 and tetragonal ZrO1.88. No reduction reaction occured in the process of hydrogen escaping, and it indicates that hydrogen permeation through oxide layer is restricted.

Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study

BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodeficiency virus(HIV)-negative patients with Talaromyces marneffei(T. marneffei) infection.METHODS: We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis.RESULTS: Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat(ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suff ered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen(BUN), alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactic dehydrogenase(LDH), myoglobin(Mb), procalcitonin(PCT), and galactomannan were related to poor prognosis(hazard ratio [HR]>1, P<0.05).CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

HOX transcript antisense intergenic RNA represses E-cadherin expression by binding to EZH2 in gastric cancer

AIM To clarify the mechanisms of HOX transcript antisense intergenic RNA(HOTAIR) in gastric cancer(GC) migration and invasion.METHODS Quantitative real-time polymerase chain reaction(qp CR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve(AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qp CR,western blot and immunohistochemistry were used to evaluate the m RNA and protein expression of E-cadherin. RNAbinding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin.RESULTS The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues(p < 0.001). Its over-expression was correlated with tumor-node-metastasis(TNM) stage(p = 0.024),tumor invasion(p = 0.018),lymph node metastasis(p = 0.023),and poor prognosis(p < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival(p = 0.033),together with TNM stage(p = 0.002) and lymph node metastasis(p = 0.002). The AUCROC was up to 0.709(95%CI: 0.623-0.785,p < 0.001). Knockdown of HOTAIR by si RNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines,and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC.

Photodynamic therapy for middle-advanced stage upper gastrointestinal carcinomas: A systematic review and meta-analysis

AIM To determine the therapeutic effect of photodynamic therapy(PDT) for middle-advanced stage upper gastrointestinal carcinomas. METHODS We searched PubM ed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database from inception to April 2018 for randomized controlled studies. These studies compared PDT with other palliative therapies(radiotherapy, chemotherapy, or Nd:YAG laser) and compared PDT, radiotherapy, or chemotherapy alone with PDT combined with chemotherapy/radiotherapy. In our meta-analysis, both fixed and random effects models were used to estimate the risk ratio(RR) for dichotomous outcomes(the response rate and one-year survival rate).RESULTS Ten random controlled clinical studies with 953 patients were included in the analysis. The effective rate for PDT was better than that of radiotherapy or Nd:YAG laser for the treatment of middle-advanced upper gastrointestinal carcinomas [RR = 1.36; 95% confidence interval(CI): 1.13-1.65; P = 0.001]. In addition, PDT combined with chemotherapy had significantly better efficacy and a higher one-year survival rate than PDT or chemotherapy alone(significant remission rate, RR = 1.62; 95%CI: 1.34-1.97; P < 0.00001; one-year survival rate, RR = 1.81; 95%CI: 1.13-2.89; P = 0.01).CONCLUSION PDT is a useful method for the treatment of middleadvanced stage upper gastrointestinal carcinomas. PDT combined with chemotherapy or radiotherapy can enhance its efficacy and prolong survival time.

Dynamic parameters of multi-cabin protective structure subjected to low-impact load e Numerical and experimental investigations

The dynamic response of a multi-cabin protective structure subjected to impact load directly affects the protective performance of materials;thus,studying the dynamic response and communication law of wave effect of the load plays an important role in the prediction of protective performance.In this study,the protection experiments of box-structure under air-and/or water-medium are conducted,the dynamic response of the structure subjected to low-impact load is analyzed,and the corresponding numerical simulations are analyzed using the theory of finite element method(FEM).Combined with experimental and FEM simulations,the shock strain distribution,acceleration attenuation,and signal energy in defensive materials are determined.Based on the results,the metal structure exhibits good absorption characteristics for shock vibration.Using the experimental data,we also show that the attenuation of shock wave in water medium should be significantly better than that in air medium,and the protective structure should be designed for a combination of water and air mediums.Meanwhile,the numerical simulation can provide a quantitative analysis process for dynamic analysis of defensive materials.

Effect prediction of stiffened-ring cylindrical shells subjected to drop mass impact

This study focuses on the effect of lateral mass impact on ring-stiffened thin-walled cylindrical shell.Cylindrical shells were fabricated to validate the numerical modeling and analytical techniques,and drop tests were performed using a rigid spherical indenter.Next,stiffened-ring cylindrical shells with various structural size parameters were simulated using ABAQUS software.The relationships between the impact force,deformation displacement,and rebound velocity were established,on the basis of impact mechanics theory and simulation results.It derived fitting functions to analyse the relationship between the maximum load and maximum displacement of ring-stiffened cylindrical shell under dynamic mass impact.Based on the validation of the simulation model,the fitting function data were compared with the simulation results,and the functions showed a good accuracy.Besides,the parameters,mass ratio and stiffened-ring mass ratio were used to reflect the effect of the mass change in the ring-stiffened cylindrical shell.Furthermore,parametric studies on ring-stiffened cylindrical shell models were conducted to analyse the progressive impact responses.

Epidemiological features and dynamic changes in blood biochemical indices for COVID-19 patients in Hebi

BACKGROUND Millions of people have died of coronavirus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)infection,and retrospective studies of the disease in local regions are necessary.AIM To characterize the epidemiological features and dynamic changes in blood biochemical indices for SARS-Co V-2-infected patients in Hebi,a representative city with a large floating population in North China.METHODS From January 25 to February 10,2020,the clinical data of patients who tested positive for SARS-Co V-2 by quantitative real-time polymerase chain reaction in Hebi city(China)were evaluated at admission,and laboratory data for hematologic parameters,inflammatory indices,coagulation function indices,liver function indices,blood lipid indices,renal function indices,myocardial enzyme activities and five blood biochemical markers of immunity were evaluated at admission,upon hospitalization and before discharge.RESULTS Sixteen confirmed COVID-19 patients developed pneumonia but were cured after adequate treatment.Fever and fatigue were the common symptoms.The most common laboratory abnormalities of patients at admission were leukopenia,eosinopenia,decreased percentage of eosinophils,elevated high sensitivity C-reactive protein and fibrinogen levels,hypoalbuminemia,mildly increased aspartate transferase activity and levels of bilirubin,and increased levels ofβ2-microglobulin.Importantly,aggravated liver dysfunction was detected in most patients,which may be partially attributed to virus infection as well as medicinal treatment.CONCLUSION This study provides several potential diagnostic markers and dynamic biochemical indices of disease progression to better prevent,diagnose and treat COVID-19 infection.

Effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer

Objective:To study the effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer.Methods:78 patients with advanced ovarian cancer who were treated in our hospital between July 2011 and December 2015 were selected and divided into observation group and control group (n=39) according to the single-blind randomized control method. Before treatment and after 4 cycles of treatment, electrochemical luminescence immunity analyzer was used to detect serum tumor marker levels;RIA method was used to determine serum apoptosis molecule levels;enzyme-linked immunosorbent assay (ELISA) was used to detect the serum angiogenesis molecule levels.Results:Before treatment, differences in serum levels of tumor markers, apoptosis molecules and angiogenesis molecules were not statistically significant between two groups of patients (P>0.05). After 4 cycles of treatment, serum carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), human epididymis protein 4 (HE4), carcinoembryonic antigen (CEA), human chorionic gonadotropin (β-HCG), Bcl-2, Survivin, Bag-1, angiogenin-2 (Ang-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels of observation group were significantly lower than those of control group (P<0.05) while Bax level was significantly higher than that of control group (P<0.05).Conclusions:Continuous recombinant human endostatin pumping combined with TP chemotherapy can decrease the malignant degree of advanced ovarian cancer and inhibit angiogenesis.

Characterization of ZrO_(2) ceramic coatings on ZrH1.8 prepared in different electrolytes by micro-arc oxidation

ZrO_(2)ceramic coatings were directly prepared on the surface of ZrH_(1.8) in silicate and phosphate elec-trolytes by micro-arc oxidation(MAO)technique,respec-tively.The microstructure,chemical composition and phase composition of ZrO_(2)ceramic coatings were inves-tigated by X-ray diffraction(XRD),energy-dispersive spectrometry(EDS)and scanning electron microscopy(SEM).The anti-permeation effect was measured by means of vacuum dehydrogenation experiment.It is found that the coating fabricated in phosphate electrolyte is more compact than that in silicate electrolyte.The coatings fabricated on the surface of ZrH_(1.8) are composed of M-ZrO_(2),T-ZrO_(2) and C-ZrO_(2).EDS analysis indicates that the coatings are mainly composed of O and Zr.Vacuum dehydrogenation experiment shows that the permeation reduction factor(PRF)of coating prepared in phosphate electrolyte is su-perior to that in the silicate electrolyte,and the PRF value reaches up to 11.2,which can enhance the resistance effect of hydrogen significantly.

Optimization of electrical parameters for micro-arc oxidation of zirconium hydride alloy

The present work aims to present the micro-arc oxidation(MAO)zirconia coating with superior compact-ness and moderate thickness on zirconium hydride.The experiments were designed according to L16(44)orthog-onal array to optimize electrical parameters(frequency,negative voltage,positive voltage and MAO time),with four levels of each factor.The optimized value was pre-dicted and verified by the confirmation experiment.The anti-permeation effect was tested by means of vacuum dehydrogenation experiment.The optimized coating parameters are listed as follows:treating time of 25 min,frequency of 200 Hz,negative voltage of 150 V and pos-itive voltage of 380 V.Experimental results show that the optimized coating exhibits the highest compactness of 0.3705 mg·μm^(-1).This dense coating significantly enhan-ces the hydrogen anti-permeation effects,and the PRF value is improved by nearly 13 times in contrast with that of uncoated ZrH_(1.8).