Profiles and Source Apportionment of Nonmethane Volatile Organic Compounds in Winter and Summer in Xi’an, China, based on the Hybrid Environmental Receptor Model

Summer and winter campaigns for the chemical compositions and sources of nonmethane hydrocarbons(NMHCs)and oxygenated volatile organic compounds(OVOCs)were conducted in Xi’an.Data from 57 photochemical assessment monitoring stations for NMHCs and 20 OVOC species were analyzed.Significant seasonal differences were noted for total VOC(TVOC,NMHCs and OVOCs)concentrations and compositions.The campaign-average TVOC concentrations in winter(85.3±60.6 ppbv)were almost twice those in summer(47.2±31.6 ppbv).Alkanes and OVOCs were the most abundant category in winter and summer,respectively.NMHCs,but not OVOCs,had significantly higher levels on weekends than on weekdays.Total ozone formation potential was higher in summer than in winter(by 50%)because of the high concentrations of alkenes(particularly isoprene),high temperature,and high solar radiation levels in summer.The Hybrid Environmental Receptor Model(HERM)was used to conduct source apportionment for atmospheric TVOCs in winter and summer,with excellent accuracy.HERM demonstrated its suitability in a situation where only partial source profile data were available.The HERM results indicated significantly different seasonal source contributions to TVOCs in Xi’an.In particular,coal and biomass burning had contributions greater than half in winter(53.4%),whereas traffic sources were prevalent in summer(53.1%).This study’s results highlight the need for targeted and adjustable VOC control measures that account for seasonal differences in Xi’an;such measures should target not only the severe problem with VOC pollution but also the problem of consequent secondary pollution(e.g.,from ozone and secondary organic aerosols).

Source Apportionment of PM2.5 in the Metropolitan Area of Costa Rica Using Receptor Models

In this work, receptor models were used to identify the PM2.5 sources and its contribution to the air quality in residential, comercial and industrial sampling sites in the Metropolitan Area of Costa Rica. Principal component analysis with absolute principal component scores (PCA-APCS), UNIMX and positive matrix factorization (PMF) was applied to analyze the data collected during 1 year of sampling campaign (2010-2011). The PM2.5 samples were characterized through its composition looking for trace elements, inorganic ions and organic and elemental carbon. These three models identified some common sources of PM2.5: marine aerosol, crustal material, traffic, secondary aerosols (secondary sulfate and secondary nitrate resolved by PMF), a mixed source of heavy fuels combustion and biomass burning, and industrial emissions. The three models predicted that the major sources of PM2.5 in the Metropolitan Area of Costa Rica were related to anthropogenic sources (73%, 65% and 69%, respectively, for PCA-APCS, Unmix and PMF) although natural sources also contributed to PM2.5 (21%, 24% and 26%). On average, PCA and PMF methods resolved 94% and 95% of the PM2.5 mass concentrations, respectively. The results were comparable to the estimate using UNMIX.

Source apportionment of polycyclic aromatic hydrocarbons(PAHs) in a sediment core from Lake Dagze Co, Tibetan Plateau, China: Comparison of three receptor models

Receptor models are a useful tool for identifying sources of polycyclic aromatic hydrocarbons(PAHs) in multiple environmental media. In this study, three different receptor models(including the principal component analysis-multiple linear regression(PCA-MLR), positive matrix factorization(PMF), and Unmix models) were used to apportion the sources of 16 priority PAHs in a sediment core of Lake Dagze Co. The ΣPAHs(sum of all 16 measured PAHs) concentrations ranged from 51.89 to 132.82 ng/g with an average of 80.39 ng/g. TheΣ PAHs were dominated by 2-3 ring PAHs, accounting for 80.12% on average, thereby indicating that they mainly originated from biomass and coal combustion and/or from long-range atmospheric transportation. The three models produced consistent source apportionment results. The greatest contributor to ΣPAHs was biomass combustion, followed by coal combustion, vehicle emissions, and petrogenic sources. Moreover, the temporal variation of the common sources was well-correlated among models. The multi-method comparison and evaluation results showed that all three models were useful tools for source apportionment of PAHs, with the PMF model providing better results than the PCA-MLR and Unmix models. The temporal trends of factor contributions were verified by PAHs with different ring numbers. Significant correlations were found between the simulated concentrations of each source factor and the PAHs with different ring numbers(P<0.01), except for the petrogenic source identified by the Unmix model(P>0.05). This study can provide useful information for further investigation of source apportionment of PAHs in the sediment cores.

PM_(2.5) source apportionment in a French urban coastal site under steelworks emission influences using constrained non-negative matrix factorization receptor model

The constrained weighted-non-negative matrix factorization（CW-NMF） hybrid receptor model was applied to study the influence of steelmaking activities on PM_（2.5）（particulate matter with equivalent aerodynamic diameter less than 2.5 μm） composition in Dunkerque,Northern France. Semi-diurnal PM_（2.5）samples were collected using a high volume sampler in winter 2010 and spring 2011 and were analyzed for trace metals, water-soluble ions, and total carbon using inductively coupled plasma – atomic emission spectrometry（ICP-AES）,ICP- mass spectrometry（ICP-MS）, ionic chromatography and micro elemental carbon analyzer. The elemental composition shows that NO_3^-, SO_4^（2-）, NH_4~＋and total carbon are the main PM_（2.5）constituents. Trace metals data were interpreted using concentration roses and both influences of integrated steelworks and electric steel plant were evidenced. The distinction between the two sources is made possible by the use Zn/Fe and Zn/Mn diagnostic ratios. Moreover Rb/Cr, Pb/Cr and Cu/Cd combination ratio are proposed to distinguish the ISW-sintering stack from the ISW-fugitive emissions. The a priori knowledge on the influencing source was introduced in the CW-NMF to guide the calculation. Eleven source profiles with various contributions were identified： 8 are characteristics of coastal urban background site profiles and 3 are related to the steelmaking activities. Between them,secondary nitrates, secondary sulfates and combustion profiles give the highest contributions and account for 93% of the PM_（2.5）concentration. The steelwork facilities contribute in about 2%of the total PM_（2.5）concentration and appear to be the main source of Cr, Cu, Fe, Mn, Zn.

Human androgen deficiency： insights gained from androgen receptor knockout mouse models

The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.

Impact of Probiotics on Toll-like Receptor 4 Expression in an Experimental Model of Ulcerative Colitis

Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacterium） on the expression of TLR4 and tumor necrosis factor-alpha （TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid （TNBS）/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group （P〈0.01 for both）. No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group （P〉0.05）, whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group （P〈0.01）. There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

Homology Model and Ligand Binding Interactions of the Extracellular Domain of the Human α4β2 Nicotinic Acetylcholine Receptor

Addiction to nicotine, and possibly other tobacco constituents, is a major factor that contributes to the difficulties smokers face when attempting to quit smoking. Amongst the various subtypes of nicotinic acetylcholine receptors (nAChRs), the α4β2 subtype plays an important role in mediating the addiction process. The characterization of human α4β2-ligand binding interactions provides a molecular framework for understanding ligand-receptor interactions, rendering insights into mechanisms of nicotine addiction and may furnish a tool for efficiently identifying ligands that can bind the nicotine receptor. Therefore, we constructed a homology model of human α4β2 nAChR and performed molecular docking and molecular dynamics (MD) simulations to elucidate the potential human α4β2-ligand binding modes for eleven compounds known to bind to this receptor. Residues V96, L97 and F151 of the α4 subunit and L111, F119 and F121 of the β2 subunit were found to be involved in hydrophobic interactions while residues S153 and W154 of the α4 subunit were involved in the formation of hydrogen bonds between the receptor and respective ligands. The homology model and its eleven ligand-bound structures will be used to develop a virtual screening program for identifying tobacco constituents that are potentially addictive.

The remedial effect of soluble interleukin-1 receptor type Ⅱ on endometriosis in the nude mouse model

Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.

Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

Molecular Characterization, 3D Modeling of Grass Carp Interleukin-10 Receptor 1 (IL10R1)

Interleukin-10 (IL-10) is an important cytokine that plays a pivotal role in natural and adaptive immune systems. However, in lower vertebrates, especially in teleost the receptor of this cytokine is still largely unknown. This paper described the cloning and characterization of grass carp interleukin-10 receptor 1 (gcIL10R1) and the 3D structure of its extracellular domain was predicted. The gcIL10R1 cDNA included 180 bp5’ untranslated region (UTR), 870 bp3’ UTR and an open reading frame (ORF) of 1632 bp. The ORF was found to encode a 543 amino acid protein with a putative JAK1 binding site, one STAT3 binding site. The phylogenetic analysis clusters gcIL10R1 with other teleost IL10R1s but independently of the amphibian, avian and mammalian IL10R1s. The 3D structure of its extracellular domain was the first homology model of a fish IL10R1 that revealed a high similarity with its mammalian and avian counterparts.

Neuroactive alkaloids that modulate the neuronal nicotinic receptor and provide neuroprotection in an Alzheimer's disease model:the case of Teline monspessulana

Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i.e., bioactive com- pounds obtained from Ecteinascidia turbinate to treat some types of cancer or rapamycin from Streptomyces hygroscop- icus to prevent organ rejection after transplant. This trend will continue simply due to the fact that Mother Nature has been synthesizing molecules for millions of years. In our lab- oratory, we have characterized several compounds obtained from natural sources and that possess important neuronal effects,

Design of N-11-Azaartemisinins Potentially Active against Plasmodium falciparum by Combined Molecular Electrostatic Potential, Ligand-Receptor Interaction and Models Built with Supervised Machine Learning Methods

N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties εLUMO+1 (one level above lowest unoccupied molecular orbital energy), d(C6-C5) (distance between C6 and C5 atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.

Expression of metabotropic glutamate receptor 1a in a rat cortical neuronal model of in vitro mechanical injury and the effects of its competitive antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid

The present study established a rat cortical neuronal model of in vitro mechanical injury. At 30 minutes after injury, the survival rate of the injured cortical neurons was decreased compared with normal neurons, and was gradually decreased with aggravated degree of injury. Reverse transcription-polymerase chain reaction results showed that at 1 hour after injury, there was increased expression of metabotropic glutamate receptor la in cortical neurons. Immunohistochemical staining results showed that at 30 minutes after injury, the number of metabotropic glutamate receptor 1a-positive cells increased compared with normal neurons. At 12 hours after injury, lactate dehydrogenase activity in the （RS）-l-aminoindan-1, 5-dicarboxylic acid （AIDA）-treated injury neurons was si[jnificantly decreased than that in the pure injury group. At 1 hour after injury, intracellular free Ca＂＋ concentration was markedly decreased in the AIDA-treated injury neurons than that in the pure injury neurons. These findings suggest that after mechanical injury to cortical neurons, metabotropic glutamate receptor la expression increased. The resulting increase in intracellular free Ca2＋ concentration was blocked by AIDA, indicating that AIDA exhibits neuroprotective effects after mechanical injury.

成纤维细胞生长因子受体1 抑制剂对胶原诱导关节炎模型大鼠骨破坏的影响

背景:课题组前期的研究表明靶向成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)可能是治疗类风湿性关节炎的有效靶点。目的:探讨FGFR1抑制剂(PD173074)对胶原诱导关节炎模型大鼠骨破坏的影响。方法:将25只雌性SD大鼠随机分为5组,正常对照组、模型组、甲氨蝶呤组、PD173074低剂量组、PD173074高剂量组。除正常对照组外,其余各组大鼠建立Ⅱ型胶原诱导关节炎模型。造模成功后正常组及模型组大鼠腹腔注射无菌PBS,甲氨蝶呤组药物注射剂量为1.04 mg/kg,PD173074低剂量组和高剂量组药物注射剂量分别为5,20 mg/kg,1次/周。给药4周后取材,观察大鼠临床症状以及关节肿胀情况,踝关节Micro-CT三维重建及分析,观察踝关节病理变化,检测关节周围血管生成情况及核因子κB受体活化因子配体的表达,检测关节滑膜中p-FGFR1、血管内皮生长因子A、抗酒石酸酸性磷酸酶的表达,观察肝、脾、肾病理变化并计算肝、脾、肾指数。结果与结论:①PD173074能够减轻模型大鼠踝关节临床症状及关节肿胀,延缓骨质丢失,改善骨结构,减轻关节滑膜侵袭以及软骨骨侵蚀,降低关节周围破骨细胞数量,抑制关节滑膜组织中的血管生成,降低核因子κB受体活化因子配体的表达,抑制FGFR1磷酸化蛋白、抗酒石酸酸性磷酸酶和血管内皮生长因子A的蛋白表达。②大鼠肝、脾、肾病理观察表明经过PD173074治疗后无明显的毒副作用。③研究证明了FGFR1抑制剂能够延缓Ⅱ型胶原诱导关节炎模型大鼠关节炎症及骨破坏的进展,并抑制血管的生成。初步验证了PD173074在Ⅱ型胶原诱导关节炎模型中的治疗作用,其可能是通过抑制FGFR1磷酸化发挥作用,为寻找类风湿性关节炎新的治疗靶点提供了方向。

Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.

The Relationship of the Expression of Estrogen Receptor in Cartilage Cell and Osteoarthritis Induced by Bilateral Ovariectomy in Guinea Pig

To investigate the estrogen receptor（ER） expression in cartilage cell in the development of oste0arthritis induced by bilateral ovariectomy in guinea pig and to find their relationship. 30 two-month-old female guinea pigs were randomly divided into two groups （n=15 each） ： sham operation （control）group and ovariectomized group （OVX）; Scanning electorne microscope （SEM） and transmission electron microscope （TEM） were obtained to analysis the cartilage degeneration of the hind limb knee joint after 6 and 12 weeks of ovariectomy. Dextran-Coated-Charcoal （DCC） was taken to quantitively detect the expression of ER. The serum levels of estrogen and gestone were detected by immune contest assay. The results showed that ER do exist in the cartilages of the guinea pigs, with higher expression in the control group than in OVX group at the same time point （P〈0. 05）. It was increased also at 12 th week after operation than that of preoperation. The blood serum levels of estrogen and gestone showed a similar tendency to the expression of ER. Joint cartilage degeneration detected by SEM and TEM could be found at 6 th week, but severe degenerative lesions at 12 th week in the OVX group compared with the control group （P〈0.01）. The data suggested that bilateral ovariectomy in guinea pig lead to severe os.teoarthritis which mighgt be related to the lower serum level of estrogen and the downregulation of the expression of ER in the cartilage also.

Pharmacokinetic-Pharmacodynamic modeling of the analgesic effect of bupredermTM, in mice

Purpose: BupredermTM-Buprenorphine transdermal delivery system (BTDS) was developed for the treatment of post-operative and chronic pains. This study examined the relationship between the plasma concentration of buprenorphine and its analgesic effect (tail flick test) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modeling in describing this relationship. Methods: After patch application, plasma concentrations of bu- prenorphine in mice were measured for 72 hours with a validated LC/MS/MS system, and the analgesic effects were assessed by tail flick test for the period of 24 hours. A modified two- compartment open model was used to explain the PK properties of BTDS, and the PD model was characterized by slow receptor binding. Results: The peak buprenorphine level in plasma was achieved at 1-24 h and the effective therapeutic drug concentration was maintained for 72 hours. BupredermTM induced prolongation of tail-flick latency in a dose and time dependent manner. Maximum analgesic effect was attained at 3-6 h and was maintained for 24 h after patch application. Counter-clockwise hysteresis between the plasma concentration and the analgesic efficacy of BTDS was observed after BupredermTM application, indicating there was a delay between plasma concentrations and the effect observed. From the developed PK-PD model, Kd values (0.69-0.82 nM) that were derived from the pharmacodynamic parameters (Kon and Koff) are similar to the reported values (Kd = 0.76 ± 0.14 nM). Good agreement between the predicted and observed values was noted for the rate of change in analgesic effect data (R2 = 0.822, 0.852 and 0.774 for 0.24, 0.8 and 2.4 mg/patch, respectively). Conclusions: The established PK- PD model successfully described the relationship between plasma concentration of buprenorphine and its analgesic efficacy measured by the tail flick test. Our model might be useful in estimation and prediction of onset, magnitude and time course of concentration and pharmacological effects of BTDS and will be useful to simulate PK-PD profiles with clinical regimens.

Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model

AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.

Guipi decoction effects on brain somatostatin levels and receptor mRNA expression in rats with spleen deficiency

BACKGROUND： Somatostatin is abundant in the hypothalamus, cerebral cortex, limbic system, and mesencephalon. Somatostatin mRNA expression in the brain of rats with spleen deficiency is noticeably reduced, as well as attenuation of cognitive function. OBJECTIVE： To observe the interventional effect of Guipi decoction on somatostatin level and somatostatin receptor 1 （SSTRl） mRNA expression in different encephalic regions of rats with spleen deficiency, and to compare the interventional effects of Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet. DESIGN： A randomized controlled observation. SETTING： Basic Medical College, Beijing University of Traditional Chinese Medicine. MATERIALS： Fifty adult Wistar male rats, of clean grade, weighing （160 ± 10） g, were provided by Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd. The protocol was performed in accordance with ethical guidelines for the use and care of animals. Somatostatin 1 polyclonal anti-rabbit antibody and SSTRl in situ hybridization kit were provided by Department of Neuroanatomy, Shanghai Second Military Medical University of Chinese PLA. The drug for developing rat models of spleen deficiency was composed of Dahuang, Houpu and Zhishi, and prepared at 2：1：1. Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet recipes were made according to previous studies. METHODS： This study was performed at the Basic Medical College, Beijing University of Traditional Chinese Medicine from March 2002 to March 2005. The rats were randomly divided into 5 groups, with 10 rats in each group： normal, model, Guipi decoction, Chaihu Shugan powd.er, and Tianwang Buxin pellet groups. Rat models of the latter 4 groups were developed by methods of purgation with bitter and cold nature drugs, improper diet, and overstrain. The rats received 7.5 g/kg of the drugs each morning and were fasted every other day, but were allowed free access to water at all times. The rats were forced to swim in 25 ℃ water until fatigued. Rats in the normal group were intragastrically administered the same amount of normal saline. Rats in the Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet groups were intragastrically administered 7.5 g/kg Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet, respectively, every afternoon. All rats were treated for 6 weeks. MAIN OUTCOME MEASURES： Somatostatin protein and SSTRI mRNA expression in the ventral nucleus of hypothalamus, hippocampal CAl region, and cortex of prefrontal lobe were determined by immunohistochemistry and in situ hybridization, respectively. RESULTS： Fifty rats were included in the final analysis. In the model group, expression of somatostatin protein and SSTRl mRNA in the ventral nucleus of hypothalamus, hippocampal CAl region, and cortex of prefrontal lobe were significantly less than in the normal group （P 〈 0.01）. Above-mentioned indices were identical in the Chaihu Shugan powder and model groups. However, expression of somatostatin protein and SSTRl mRNA were significantly higher in the Guipi decoction group compared to model group （P 〈 0.01）. In the Tianwang Buxin pellet group, SSTRl mRNA expression in rat ventral nucleus of hypothalamus and somatostatin level in rat hippocampal CAl region and cortex of prefrontal lobe, as well as ventral nucleus of hypothalamus, were significantly higher compared to model group （P 〈 0.01 ）. CONCLUSION： Somatostatin level and SSTRl mRNA expression in rats with spleen deficiency were lower than in normal rats. Guipi decoction and Tianwang Buxin pellet up-regulated somatostatin level and SSTRl mRNA expression.

Effect of green flickering light on myopia development and expression of M1 muscarinic acetylcholine receptor in guinea pigs

AIM： To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor（mAChR） M1 in the eyes of guinea pigs.METHODS： Thirty guinea pigs（15-20 days old） were randomly divided into three groups（n=10/group）. Animals in group I were raised in a completely closed carton with green flickering light illumination. Those in group II were kept in the open top closed carton under normal natural light. Guinea pigs were raised in a sight-widen cage under normal natural light in group III. The refractive status and axial length were measured before and after 8 weeks＇ illumination. Moreover, total RNA extracted from retinal, choroidal, and scleral tissues were determined by real-time reverse transcription polymerase chain reaction（RT-PCR）. The expressions of the receptor M1 were also explored in the retina, choroid, and sclera using immunohistochemistry.RESULTS： There was a remarkable reduction in refractive error and increase in axial length after 8-weeks＇ green flickering light stimulation（P〈0.001）. The expression of M1 receptor mRNA in sclera and retina in myopia group were remarkably lower than that in group II and III（P〈0.01）. Significant reduced expression of M1 receptor stimulated by green flickering light in retina and sclera tissues were also observed（P〈0.05）. However, there was no M1 receptor expression in choroid in 3 groups.CONCLUSION： Myopia can be induced by 8 weeks＇ green flickering light exposure in the animal model. M1 receptor may be involved causally or protectively in myopia development.