Objective To analyze the differential expressed genes(DEGs)in the lung tissues of rat model of high altitude pulmonary edema(HAPE)by using microarray analysis in order to provide new clues for molecular mechanism of HAPE.Methods Healthy male SD rats(8 weeks old,weighing 200±20 g)were randomized into normoxia control(NC)group,lipopolysaccharide(LPS)group,hypoxia group and hypoxia+low-dose LPS(HL)group.The rats of the LPS group and HL group were injected with 0.1 mL 0.05％LPS per 100 g body weight,and those of the NC group and the hypoxia group were administered with an equivalent volume of normal saline.The rats of the hypoxia group and the HL group were housed in a hypobaric chamber simulating an altitude of 5 000 m,and those of the NC group and the LPS group were raised simultaneously outside of the chamber.The wet/dry mass ratio(WDR)of lung tissue and total protein content in bronchoalveolar lavage fluid(BALF)were measured,and the histopathological changes of lung tissue was observed using HE staining.The total RNA was extracted from the lung tissues,and the mRNA expression profile was obtained with Affymetrix microarray followed by Gene Ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis with Metascape(http://metascape.org).Results The rats of the HL group showed significant congestion,edema,and widened alveolar septa.Compared with the NC group,the HL group had significantly increased lung WDR(P＜0.01)and total protein content in BALF(P＜0.05).Gene expression analysis revealed that there were 79 genes up-regulated and 59 genes down-regulated in the hypoxia group,473 genes up-regulated and 695 genes down-regulated in the LPS group,and especially,669 genes up-regulated and 1 253 genes down-regulated in the HL group.GO and KEGG pathway analyses revealed that the upregulated genes in the HL group were mainly enriched in biological processes,such as cytokine mediated signaling pathways,response to IL-1,regulation of inflammatory response,as well as signaling pathways,including cytokine-cytokine receptor interactions,TNF,NF-κB,IL-17,complement and coagulation cascades,etc.The down-regulated genes were mainly enriched in biological processes,such as extracellular matrix organization,regulation of endothelial cell migration,cell substrate adhesion,as well as signaling pathways,such as focal adhesion,Wnt,cGMP-PKG,PI3K-Akt,Rap1,etc.The mRNA expression of NF-κB,TNF-α,IL-1βand IL-6 was significantly up-regulated in the lung tissue of the HL group(P＜0.01).Conclusion Hypoxia+low-dose LPS is an effective procedure to establish a reliable model for HAPE in rats.Hypoxia can significantly aggravate LPS-induced inflammation and immune response,enhance the expression of inflammatory mediators,and thus promote the pathogenesis of HAPE.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

The theories of pathophysiology come from experimental research,and experimental teaching is an important part of pathophysiology course.Experimental teaching can cultivate the abilities of independent thinking and comprehensive analysis in students,improve their practical skills,and enhance their understanding and application of theoretical knowledge.However,teaching reform should be carried out due to the drawbacks of current pathophysiological experimental teaching.With the teaching idea centered on learning,the quality of pathophysiological experimental teaching can be enhanced by rational arrangement of experimental courses,optimization of teaching contents,and comprehensive application of various teaching models,so as to effectively improve the level of theoretical knowledge and comprehensive practical ability among students.

Pathophysiology is a subject that studies the occurrence,development and mechanism of diseases.It plays important roles in medical education and is an important and difficult point in medical education.Based on our teaching experience and the characteristics of pathophysiology,this paper puts forward the idea of “Focus on learning”,aiming to resolve the problems of insufficient communication,unsound teaching design and single teaching method,etc.existed in teaching process.The active communication with students,a good job of teaching design and the reasonable application of various teaching methods and techniques should be carried out to improve the teaching effect of pathophysiology.

Objective To assess the impact of maximal fat oxidation intensity(FATmax) exercise on arterial stiffness in overweight/obesity young men.Method Thirty two overweight/obesity young men (BMI≥25 kg/m2) without the habit of doing exercises,were divided into an exercise group (n=16) and a control group (n=16) randomly.The exercise group completed a 12-week walk/run(FATmax intensity,3-5 times/week,40-60 min/time) intervention,while the control group maintained normal life style without regular exercise.The body composition,cardiopulmonary function (VO2max),C reactive proteins (CRP) and blood hemodynamic were measured,and the brachial-ankle pulse wave velocity(baPWV) was observed to assess the arterial stiffness before and after the 12-week intervention.Results Significant decrease was observed in the average weight,body mass index,body fat mass,body fat percentage,baPWV,CRP,platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) (P＜0.05),while significant increase was found in the average VO2max and HDL-C(P＜0.05) after the training.After the intervention,the change in baPWV(△) was positively associated with △ CRP(r=0.604),△ NLR(r=0.535) and △ WBC (white blood count) (r=0.406) (P＜0.05,n=32),but negatively correlated with △ VO2max (r=-0.660,P＜0.05,n=32).Conclusion FATmax intensity aerobic exercise is effective to downregulate the inflammation,and improve aerobic fitness and vascular function.However,the potential mechanism of arterial stiffness improvement following exercise needs further study.

OBJECTIVETo determine the effect of obesity on prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH) and develop a PSA-related parameter that can eliminate the effect of obesity.

METHODSWe reviewed the clinical data of 706 patients with BPH. Two PSA-related parameters, namely PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), were calculated for all the patients and the association of BMI with PSA, PSA mass, and PSA mass ratio was assessed.

RESULTSA higher BMI was significantly associated with a greater plasma volume and prostate volume (P<0.05). Linear regression analysis revealed a greater adjusted R2 of BMI versus plasma volume than of BMI PSA (0.569 vs 0.027). PSA was positively associated with the prostate volume and negatively with BMI and plasma volume (P<0.05). PSA mass was positively associated with prostate volume (P<0.05) but was not associated with BMI or plasma volume (P>0.05). PSA mass ratio was not associated with prostate volume (P>0.05) but negatively associated with BMI and plasma volume. Plasma volume and prostate volume, PSA, and PSA mass ratio (P<0.05), but not PSA mass (P>0.05), differed significantly among normal-weight, overweight, and obese patients.

CONCLUSIONA higher BMI is associated with a greater plasma volume in BPH patients. In obese patients with BPH, a lower PSA concentration may result from hemodilution caused by a greater plasma volume, and PSA mass can eliminate the effect of obesity on PSA.

Body Mass Index ; Hemodilution ; Humans ; Male ; Obesity ; pathology ; Organ Size ; Overweight ; pathology ; Prostate ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; diagnosis ; Prostatic Neoplasms ; diagnosis

BACKGROUND:Studies have shown that chitosan and other natural polysaccharides have heparin-like anticoagulant function after sulfonated modification. Sulfonated chitosan has good anticoagulant property because the sulfonate group formed by sulfonated chitosan is similar with the active group of heparin. OBJECTIVE: To prepare the anticoagulant chitosan nanoparticles and to detect its morphology, physical and chemical properties and biological security. METHODS: Chitosan nanoparticles were synthesized by emulsion-chemical cross link. Sulfonated chitosan nanoparticles were synthesized by sulfonation reaction. Its morphology was described by transmission electron microscope. The peak-value change of its specific groups was observed by infrared spectroscopy. (1) Coagulation experiment: Heparin, chitosan nanoparticles and 10, 30 and 50 mg of sulfonated chitosan nanoparticles were added into the blood of Spraque-Dawley rats. The coagulation indicators were detected. (2) Hemolysis experiment: deionized water, physiological saline and 10, 30, 50 g/L sulfonated chitosan nanoparticles extracts were added into 2% red blood cel suspension of rabbits. The hemolysis rate was detected. (3) Cytotoxicity experiments: DMEM medium containing fetal bovine serum and 10, 30, 50 g/L sulfonated chitosan nanoparticle extracts were used to culture human umbilical vein endothelial cels. Cel relative growth rate and toxicity grading were detected after 72 hours. RESULTS AND CONCLUSION: Scanning electron microscopy showed that sulfonated chitosan nanoparticles had good morphology, with a diameter of 50 nm. Infrared spectroscopy showed that the sulfonated replacement occurred.In vitro coagulation experiments showed that sulfonated chitosan nanoparticles had significant anticoagulant effects in a dose-dependent manner. Sulfonated chitosan nanoparticles meet the national safety standard for hemolysis rate of less than 5%, non-induced hemolysis property. Cytotoxicity assays showed that sulfonated chitosan nanoparticles extracts had no significant cytotoxicity, and its biological safety was in line with the national standards.

Objective To determine the effect of obesity on prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH) and develop a PSA-related parameter that can eliminate the effect of obesity. Methods We reviewed the clinical data of 706 patients with BPH. Two PSA-related parameters, namely PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), were calculated for all the patients and the association of BMI with PSA, PSA mass, and PSA mass ratio was assessed. Results A higher BMI was significantly associated with a greater plasma volume and prostate volume (P<0.05). Linear regression analysis revealed a greater adjusted R2 of BMI versus plasma volume than of BMI PSA (0.569 vs 0.027). PSA was positively associated with the prostate volume and negatively with BMI and plasma volume (P<0.05). PSA mass was positively associated with prostate volume (P<0.05) but was not associated with BMI or plasma volume (P>0.05). PSA mass ratio was not associated with prostate volume (P>0.05) but negatively associated with BMI and plasma volume. Plasma volume and prostate volume, PSA, and PSA mass ratio (P<0.05), but not PSA mass (P>0.05), differed significantly among normal-weight, overweight, and obese patients. Conclusion A higher BMI is associated with a greater plasma volume in BPH patients. In obese patients with BPH, a lower PSA concentration may result from hemodilution caused by a greater plasma volume, and PSA mass can eliminate the effect of obesity on PSA.

Objective To determine the effect of obesity on prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH) and develop a PSA-related parameter that can eliminate the effect of obesity. Methods We reviewed the clinical data of 706 patients with BPH. Two PSA-related parameters, namely PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), were calculated for all the patients and the association of BMI with PSA, PSA mass, and PSA mass ratio was assessed. Results A higher BMI was significantly associated with a greater plasma volume and prostate volume (P<0.05). Linear regression analysis revealed a greater adjusted R2 of BMI versus plasma volume than of BMI PSA (0.569 vs 0.027). PSA was positively associated with the prostate volume and negatively with BMI and plasma volume (P<0.05). PSA mass was positively associated with prostate volume (P<0.05) but was not associated with BMI or plasma volume (P>0.05). PSA mass ratio was not associated with prostate volume (P>0.05) but negatively associated with BMI and plasma volume. Plasma volume and prostate volume, PSA, and PSA mass ratio (P<0.05), but not PSA mass (P>0.05), differed significantly among normal-weight, overweight, and obese patients. Conclusion A higher BMI is associated with a greater plasma volume in BPH patients. In obese patients with BPH, a lower PSA concentration may result from hemodilution caused by a greater plasma volume, and PSA mass can eliminate the effect of obesity on PSA.