Associations of daily sedentary behavior,physical activity,and sleep with irritable bowel syndrome:A prospective analysis of 362,193 participants

Background:Irritable bowel syndrome(IBS)substantially affects quality of life and requires early prevention.This study aimed to elucidate the relationships between IBS and daily behaviors,including sedentary behavior(SB),physical activity(PA),and sleep.In particular,it seeks to identify healthy behaviors to reduce IBS risk,which previous studies have rarely addressed.Methods:Daily behaviors were retrieved from self-reported data of 362,193 eligible UK Biobank participants.Incident cases were determined by self-report or health care data according to RomeⅣcriteria.Results:A total of 345,388 participants were IBS-free at baseline,during a median follow-up of 8.45 years,19,885 incident IBS cases were recorded.When examined individually,SB and shorter(≤7 h/day)or longer(>7 h/day)sleep duration were each positively associated with increased IBS risk,and PA was associated with lower IBS risk.The isotemporal substitution model suggested that replacing SB with other activities could provide further protective effects against IBS risk.Among people sleeping≤7 h/day,replacing 1 h of SB with equivalent light PA,vigorous PA,or sleep was associated with 8.1%(95%confidence interval(95%CI):0.901-0.937),5.8%(95%CI:0.896-0.991),and 9.2%(95%CI:0.885-0.932)reduced IBS risk,respectively.For people sleeping>7 h/day,light and vigorous PA were associated with a 4.8%(95%CI:0.926-0.978)and a 12.0%(95%CI:0.815-0.949)lower IBS risk,respectively.These benefits were mostly independent of genetic risk for IBS.Conclusion:SB and unhealthy sleep duration are risk factors for IBS.A promising way to mitigate IBS risk for individuals sleeping≤7 h/day and for those sleeping>7 h/day appears to be by replacing SB with adequate sleep or vigorous PA,respectively,regardless of the genetic predisposition of IBS.

Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.

Assessing the Validity of a Novel Model of Vertebral Artery Type of Cervical Syndrome Induced by Injecting Sclerosing Agent Next to Transverse Process of Cervical Vertebra

The efficacy of injecting sclerosing agent next to transverse process of cervical vertebra to induce vertebral artery type of cervical syndrome(CSA)was observed.Twenty rabbits were randomly divided into two groups:the model group and the control group.The rabbits in the model group were injected with sclerosing agent next to transverse process of cervical vertebray,on the contrary,the rabbits in the control group were injected with nothing.Transcranial Doppler(TCD)was used to detect the average speed of blo...

Key factors in developing the trinitrobenzene sulfonic acid-induced post-inflammatory irritable bowel syndrome model in rats

AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.

Effects of human mesenchymal stem cell transplantation in the bilateral corpus striatum in a rat model of Tourette's syndrome

Tourette＇s syndrome is treated by behavioral or pharmacological therapy.However,patients with malignant Tourette＇s syndrome also exhibit life-threatening symptoms,which are unresponsive to conservative treatments or neurosurgical procedures,such as deep brain stimulation.In recent years,mesenchymal stem cells（MSCs）have shown therapeutic potential in many neurological diseases.Therefore,the present study proposed to use MSC transplantation as a novel therapy for Tourette＇s syndrome.Stereotypic behaviors in Tourette＇s syndrome rats decreased significantly at21 days after human MSCs transplantation into the striatum.Immunohistochemistry analyses revealed survival of transplanted human MSCs and differentiation into neurons and astrocytes in the rat brain.Results suggest that intrastriatal transplantation of human MSCs could provide therapeutic potential for Tourette＇s syndrome.

Animal model of non-bacterial multiple organ dysfunction syndrome in the elderly

Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in adult and in the elderly rats. Methods Adult and senile rats, injected with different doses of zymosan intraperitoneally were examined for the changes in the function and morphology of the vital organs, including heart, liver, brain, lungs, and kidneys using blood gas and biochemistry analysis and histopathological examination methods. Results Compared with the normal controls of the adult and the elderly rats, the blood gas and blood biochemistry changed in different degrees in the different dosed zymosan groups. Pathological changes were also found in the vital organs including lungs, heart, liver, brain, kidneys, erc in the experimental groups. Under the same concentrations of zymosan, the reductions in respiratory, cardiac and renal functions in the senile groups were much more severe than those in the corresponding adult group. In the similar degree of model duplication, the senile rats had the tendency to die later than the adult rats. Conclusions Zymosan can be used in both elderly and adult rats to induce MODS model, and the best dosage for MODSE was 0.Sg/kg injected peritoneally. The model would hopefully be used in the study of mechanisms and the therapeutics on MODSE.

Construction of Rat Model of Hepatic Fibrosis with Blood Stasis Syndrome Integrated with Traditional Chinese Medicine(TCM)Syndrome and Western Medicine Disease

[ Objective ] According to the theory of blood stasis in traditional Chinese medicine （ TCM）, the animal modeling method of hepatic fibrosis integrated with pathology and symptoms was explored and improved, to construct a new type of rat model of hepatic fibrosis with blood stasis syndrome integrated with tradition- al Chinese and westem medicine. [ Method] The hepatic fibrosis model of blood stasis with blood stasis syndrome was constructed by jointing multi factors, inclu- ding intragastric administration of ethanol, high fat and low protein feeding, joint injection of dimethylnitrosamine （DMN）, bovine serum albumin （BSA） and nor- epinephrine （NE）. The modeling method was further compared with traditional CC14 single-factor modeling method from the aspects of mortality, blood stasis syn- drome of TCM, syndrome grading, general morphology of liver pathology, liver function changes, as well as expression levels of three kinds of collagen （type I and type III collagen, a-SMA） determined by immunohistochemical staining method, and four items of rat hepatic fibrosis （HA, P3NP, LN, CIV content） determined by radio enzyme immunoassay. [ Result ] In blood stasis group, （ 1 ） the mortality of rats was 20% ; （2） model rats appeared typical blood stasis syndromes of TCM such as ecchymosis, dark purple tongue, loose stool, and blood stasis syndrome grading was high; （3） fibrosis changes of liver such as dark white surface, dense gray nodules and brittle texture were observed in general morphological examination; （4） serological liver function tests found that ALT and AST of model rats, as well as TBIL, DBIL and IBIL contents increased significantly; （5） immunohistochemical staining demonstrated that the expression levels of three kinds of collagen （type I and type III collagen, ot-SMA） increased significantly; （6） four items of rat serum hepatic fibrosis, HA, P3NP, LN, CIV content, increased significantly; （7） the above results in blood stasis syndrome model group （except morality and liver function） were higher than those in CC14 modeling group, and the difference was statistically significant （P 〈 0.05 ）. [ Conclusion ] The new improved modeling method effectively reduces high mortality in traditional CC 14 modeling method. In addition to low mortality, the model animal has dual characteristics of disease in western medicine and syndrome in TCM. It is consistent with the pathological characteristics of hepatic fibrosis in western medicine when according with the basic characteristics of blood stasis syndrome in TCM.

Expression of Resistin mRNA in Adipose Tissue of Rat Model with Polycystic Ovarian Syndrome and Its Implication

Summary: To investigate the relationship between the insulin resistance (IR) of polycystic ovarian syndrome (PCOS) rat model induced by dehydroeplandrosterone (DHEA) and hormonal changes in the ovarium and the resistin mRNA levels in adipose tissue, 21-day-old female SD rats were divided into two groups in pairs. The rats in group 1 were injected daily (s.c) with DHEA for up to 20 days and the rats in group 2 injected with oil at the same time. Ovarian weight, serum insulin levels and sex hormone levels in rat blood of both groups were determined. Oral glucose tolerance tests, light microscopic and electronic microscopic examination were performed. The levels of resistin mRNA in adipose tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR). Our results showed that the ovarian weight in group 1 was greater than that in group 2 (P<0.05). The ovaria in group 1 showed multiple follicular cysts, The serum testeosterone and etrasdiol concentration were significantly higher in group 1 than those in group 2 (P<0.001 and P<0.05 respectively), so as the fasting serum glucose (P<0.001) and fasting serum insulin (P<0.05). The value of 1/FINS×FGC was significantly higher in group 1 than that in group 2 (P<0.001). Moreover, the resistin mRNA level of white adipose tissue in the DHEA-induced group was significantly higher than that in the control rats (P<0.05). It is concluded that the DHEA-induced PCOS rat models were similar to those of the patients with PCOS, and the IR was observed. Resistin secreted by adipose tissue may mediate IR in PCOS, and it is likely involved in the pathogenesis and development of PCOS.

Development and external validation of models to predict acute respiratory distress syndrome related to severe acute pancreatitis

BACKGROUND Acute respiratory distress syndrome(ARDS)is a major cause of death in patients with severe acute pancreatitis(SAP).Although a series of prediction models have been developed for early identification of such patients,the majority are complicated or lack validation.A simpler and more credible model is required for clinical practice.AIM To develop and validate a predictive model for SAP related ARDS.METHODS Patients diagnosed with AP from four hospitals located at different regions of China were retrospectively grouped into derivation and validation cohorts.Statistically significant variables were identified using the least absolute shrinkage and selection operator regression method.Predictive models with nomograms were further built using multiple logistic regression analysis with these picked predictors.The discriminatory power of new models was compared with some common models.The performance of calibration ability and clinical utility of the predictive models were evaluated.RESULTS Out of 597 patients with AP,139 were diagnosed with SAP(80 in derivation cohort and 59 in validation cohort)and 99 with ARDS(62 in derivation cohort and 37 in validation cohort).Four identical variables were identified as independent risk factors for both SAP and ARDS:heart rate[odds ratio(OR)=1.05;95%CI:1.04-1.07;P<0.001;OR=1.05,95%CI:1.03-1.07,P<0.001],respiratory rate(OR=1.08,95%CI:1.0-1.17,P=0.047;OR=1.10,95%CI:1.02-1.19,P=0.014),serum calcium concentration(OR=0.26,95%CI:0.09-0.73,P=0.011;OR=0.17,95%CI:0.06-0.48,P=0.001)and blood urea nitrogen(OR=1.15,95%CI:1.09-1.23,P<0.001;OR=1.12,95%CI:1.05-1.19,P<0.001).The area under receiver operating characteristic curve was 0.879(95%CI:0.830-0.928)and 0.898(95%CI:0.848-0.949)for SAP prediction in derivation and validation cohorts,respectively.This value was 0.892(95%CI:0.843-0.941)and 0.833(95%CI:0.754-0.912)for ARDS prediction,respectively.The discriminatory power of our models was improved compared with that of other widely used models and the calibration ability and clinical utility of the prediction models performed adequately.CONCLUSION The present study constructed and validated a simple and accurate predictive model for SAPrelated ARDS in patients with AP.

Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome

AIM:To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome. METHODS:Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide(LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration,and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker.RESULTS:Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed,especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase,3389.5 ± 499.5 IU/L; blood urea nitrogen,13.9 ± 1.3 mmol/L; Cr,78.1 ± 2.9 μmol/L; K+,6.1 ± 0.5 mmol/L; Na+,130.9 ± 1.9 mmol/L; Cl-,90.2 ± 1.9 mmol/L; tumor necrosis factor-α,1699.6 ± 599.1 pg/m L; endothelin-1,95.9 ± 25.9 pg/m L; P < 0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually,which was most significant at 12 h after treatment with D-galactosamine/LPS,and was characterized by massive hepatocyte necrosis,while the structures of glomeruli,proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate(GFR)1,0.79 ± 0.11 m L/min; GFR2,3.58 ± 0.49 m L/min·kg BW-1; GFR3,0.39 ± 0.99 m L/min·g KW-1]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction.CONCLUSION:The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.

A risk prediction score model for predicting occurrence of post-PCI vasovagal reflex syndrome： a single center study in Chinese population

Background The vasovagal reflex syndrome （VVRS） is common in the patiems undergoing percutaneous coronary intervemion （PCI） However, prediction and prevention of the risk for the VVRS have not been completely fulfilled. This study was conducted to develop a Risk Prediction Score Model to identify the determinants of VVRS in a large Chinese population cohort receiving PCI. Methods From the hos- pital electronic medical database, we idemified 3550 patients who received PCI （78.0% males, mean age 60 years） in Chinese PLA General Hospital from January 1, 2000 to August 30, 2016. The multivariate analysis and receiver operating characteristic 01OC） analysis were performed. Results The adverse events of VVRS in the patients were significantly increased after PCI procedure than before the operation （all P 〈 0.001）. The rate of VVRS [95% confidence interval （CI）] in patients receiving PCI was 4.5% （4.1%-5.6%）. Compared to the patients suffering no VVRS, incidence of VVRS involved the following factors, namely female gender, primary PCI, hypertension, over two stems im- plantation in the left anterior descending （LAD）, and the femoral puncture site. The multivariate analysis suggested that they were independ- ent risk factors for predicting the incidence of VVRS （all P 〈 0.001）. We developed a risk prediction score model for VVRS. ROC analysis showed that the risk prediction score model was effectively predictive of the incidence of VVRS in patients receiving PCI （c-statistic 0.76, 95% CI： 0.72-0.79, P 〈 0.001）. There were decreased evems of VVRS in the patients receiving PCI whose diastolic blood pressure dropped by more than 30 mmHg and heart rate reduced by 10 times per minute （AUC： 0.84, 95% CI： 0.81-0.87, P 〈 0.001）. Conclusion The risk prediction score is quite efficient in predicting the incidence of VVRS in patients receiving PCI. In which, the following factors may be in- volved, the femoral puncture site, female gender, hypertension, primary PCI, and over 2 stents implanted in LAD.

Research Survey of Animal Model of Hepatic Fibro-sis Integrated with Western Medicine Diseases and Traditional Chinese Medicine^TCM~)Syndrome

Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, deficiency of qi, liver depression, phlegm-dampness and blood stasis because of single-factor model- ing. Animal models of hepatic fibrosis and animal models integrated disease and syndrome were reviewed, and several new types of integrated disease and syndrome animal models constructed by multiple-factor modeling method were evaluated, under the guidance of etiological theory of TCM. This kind of hepatic fibrosis model animals has dual characteristics of disease and syndrome. It is consistent with pathological characteristics of hepatic fibrosis in western medicine when replicating the basic characteristics accorded with TCM syndrome. Thus, the pathogenesis and pathogenic process of clinical disease and syndrome formation is simulated more ac- curately, providing a new platform and pathway for studying hepatic fibrosis disease with integrated traditional Chinese and western medicine.

Advances in the pathogenesis of Rett syndrome using cell models

Rett syndrome(RTT)is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum disorders.MeCP2 protein loss-of-function in neural lineage cells is the main cause of RTT pathogenicity.As it is still hard to understand the mechanism of RTT on the basis of only clinical patients or animal models,cell models cultured in vitro play indispensable roles.Here we reviewed the research progress in the pathogenesis of RTT at the cellular level,summarized the preclinical-research-related applications,and prospected potential future development.

Novel rat model of multiple mitochondrial dysfunction syndromes(MMDS)complicated with cardiomyopathy

Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.

Novel spontaneous myelodysplastic syndrome mouse model

Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Research on the Mathematical Model of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome

[Objective] The aim of this study was to analyze and forecast the transmission trend of highly pathogenic porcine reproductive and respiratory syndrome（HP-PRRS）by mathematical model.[Method]The pigs were divided into the susceptible population S,the incidence population I and the removed population R.Dynamics models of transmission rate β（t）,recovery rate γ（t）and incidence rate δ（t）were analyzed,and the mathematical models of diseased pigs each day I（t）and healthy pigs each day H（t）of HP-PRRS were established in transmission process.[Result]Transmission rate β（t）,recover rate γ（t）and incidence rate δ（t）were conformed to the results of the actual figures,and the mathematical models of diseased pigs each day I（t）and healthy pigs each day H（t）of HP-PRRS were accorded with the objective law of transmission.[Conclusion]This mathematical model could be better used to analyze the transmission trend of HP-PRRS.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

A New Model of Erythrocyte Injury in Rats with Xueyu Syndrome and Its Application

A new model of rats with Xueyu Syndrome which was characterized by erythrocyte injury was presented. Observation of morphology and functions of erythrocytes showed that this model could not only be used as a model in Xueyu Syndrome and Huoxuequyu treatment study, but also be used for screening of drugs with the effect of preventing and treating damage of red blood cells.

Integrated systemic inflammatory response syndrome epidemic model in scale-free networks

Based on the scale-free network, an integrated systemic inflammatory response syndrome model with artificial immunity, a feedback mechanism, crowd density and the moving activities of an individual can be built. The effects of these factors on the spreading process are investigated through the model. The research results show that the artificial immunity can reduce the stable infection ratio and enhance the spreading threshold of the system. The feedback mechanism can only reduce the stable infection ratio of system, but cannot affect the spreading threshold of the system. The bigger the crowd density is, the higher the infection ratio of the system is and the smaller the spreading threshold is. In addition, the simulations show that the individual movement can enhance the stable infection ratio of the system only under the condition that the spreading rate is high, however, individual movement will reduce the stable infection ratio of the system.

Causes of failure in acute respiratory distress syndrome modeling and treatment in animal research and new approaches

Acute respiratory distress syndrome(ARDS) is a major cause of morbidity, death and cost in intensive careunits. Despite intensive research, pharmacotherapy has not passed the experimental stage and mortality rates are still high. Animal models provide a bridge between patients and the laboratory bench. Different animal models have been developed in order to mimic human ARDS, but they have limitations. The purpose of this review was to summarize the properties of the most commonly used experimental animal models mimicking the causes and pathology of human ARDS, the limitations of ARDS models, treatment failure and new therapeutic approaches.