ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Objective To investigate the effect of vitamin B6(VB6)on vascular endothelial injury of atherosclerosis(AS)mice and its mechanism.Methods Thirty-six ApoE-/-mice were randomly divided into control group,AS group,VB6 group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group,with 6 mice in each group.The mice in the AS group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group were fed with high-fat diet for 12 weeks to establish the AS model;the mice in the control group and VB6 group were given regular diet and normal drinking water for 12 weeks.After 12 weeks,the mice in the control group were given conventional diet and the same volume of physiological saline as the VB6 group daily by gavage;the mice in the VB6 group were given routine diet and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+LiCl group were given high-fat diet continuously and LiCl(1 mg·kg-1)by gavage daily;the mice in the AS+VB6 group were given high-fat diet continuously and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+VB6+LiCl group were given high-fat diet continuously and VB6(50 mg·kg-1),LiCl(1 mg·kg-1)by gavage daily;all mice were intervened for 4 weeks.After intervention,the serum nitric oxide(NO),malondialdehyde(MD A)levels and superoxide dismutase(SOD)activity of mice in each group were measured by enzyme linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the morphology of thoracic aortic tissue of mice in each group and the percentage of AS plaque area to total vascular area was calculated.The vasodilatation rate of thoracic aorta was detected by isolated vascular ring experiment.The expression of sodium/hydrogen exchanger 1(NHE1)protein in thoracic aorta was detected by immunohistochemistry.Results Compared with the control group,the NO level and SOD activity in the serum of mice in the AS group decreased,while the MDA level increased(P＜0.05);there was no significant difference in the NO,MDA levels and SOD activity in the serum of mice between the VB6 group and the control group(P＞0.05).Compared with the AS group,the serum NO level and SOD activity of mice in the AS+VB6 group increased,while the MDA level decreased(P＜0.05);there was no significant difference in serum NO,MDA levels and SOD activity of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).Compared with the AS+VB6 group,the serum NO level and SOD activity of mice in the AS+VB6+LiCl group decreased,while the MDA level increased(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice among the VB6 group and the control group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).In the control group,the vascular endothelium of mice was smooth with orderly arrangement of cells;in the AS group,AS+LiCl group and AS+VB6+LiCl group,the tissue structure of vascular of mice was disordered and the vascular endothelium was rough;in the VB6 group and AS+VB6 group,the vascular wall structure of mice was normal,the vascular endothelium was smooth,and the cells were arranged orderly.The vasodilatation rate of thoracic aorta of mice induced by acetylcholine(Ach)in the AS group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between the VB6 group and the control group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).There was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by sodium nitroprusside among the six groups(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice between the VB6 group and the control group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice among the AS+LiCl group,AS+VB6+LiCl group and the AS group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).Conclusion VB6 can improve vascular endothelial injury in AS mice via inhibiting the expression of NHE1 protein.

Objective To assess the feasibility of establishing a nude mouse model of endometriosis fibrosis of human origin and to determine whether endometrial mesenchymal stem cells are involved in inducing endometriosis fibrosis.Methods Four endometrial tissue specimens were collected and transplanted 1∶3 into 12 BABL/c nude mice by subcutaneous injection.The morphology and volume of the lesions were recorded.The nude mice were sacrificed on the 15th day after transplantation to observe the morphology of the lesions and their adhesion to the periphery of the abdominal wall.HE staining was used to judge the result of modelling,Masson staining was used to assess the extent of fibrosis,and immunofluorescence was used to track the role of endometrial mesenchymal stem cells in the fibrotic process of endometriosis.Results The volume of ectopic lesions in nude mice increased over time and showed restricted,vesicular-like changes.The tight adhesion of the lesions to the abdominal wall,endometrioid glands,and collagen fiber deposition were seen microscopically.The success rate of the modelling was 83.4%,and the collagen fiber volume fraction of the lesions was significantly higher after modelling(P＜0.01).Confocal imaging suggested that endometrial mesenchymal stem cells(SUSD2+)differentiated into myofibroblasts(α-SMA+)in vivo.Conclusions The nude mouse model established by human allogeneic transplantation via subcutaneous injection was consistent with the lesion characteristics of endometriosis fibrosis.The modelling method is simple and feasible and provides a better reference model for further investigating the pathogenesis of endometriosis fibrosis.In addition,in vivo observations using the model indicated that endometrial mesenchymal stem cells are involved in inducing the formation of endometriosis fibrosis.

[Objective]To explore the effect of Wenshen Xiaozheng Decoction on pain in mice with endometriosis(EMS)and its mechanism based on cyclooxyfenase-2/prostaglandin E2(COX-2/PGE2)signaling pathway.[Methods]Forty EMS mouse models were established by intraperitoneal injection as modeling group,which was randomly divided into EMS model group(0.2 mL sterile distilled water),Wenshen Xiaozheng Decoction group(0.2 mL Wenshen Xiaozheng Decoction),positive control group(0.2 mL aspirin suspension),and another 10 mice were set as sham operation group.During the 21 days of modeling,the Von Frey fiber test and hot plate test were used to detect mechanical and thermal pain in mice in modeling group and sham operation group.During the 21 days of administration,Von Frey fiber test and hot plate test were used to detect mechanical and thermal pain in EMS model group,Wenshen Xiaozheng Decoction group and positive control group.After 21 days of drug administration,vaginal smears were taken daily to determine the estrous cycle of the mice.During the same estrous cycle,mice were euthanized and serum,peritoneal fluid(PF),endometrial tissue(in situ endometrium,ectopic lesions),thalamus,spinal cord and dorsal root ganglion(DRG)were collected.Enzyme-linked immunosorbent assay(ELISA)was used to determine the contents of COX-2,PGE2,transient receptor potential vanilloid 1(TRPV1),sodium channel protein type 11 subunit alpha(SCN11A).[Results]Compared with sham operation group,after modeling the pain thresholds of the feet and abdomen of the mice decreased(P<0.05).Compared with EMS model group,the mice in Wenshen Xiaozheng Decoction group showed an increase in foot and abdominal pain thresholds after administration(P<0.05).Compared with EMS model group,the mice in Wenshen Xiaozheng Decoction group showed the expression levels of COX-2,PGE2 in serum,in situ endometrium,PF,nervous system(thalamus,spinal cord,DRG),TRPV1 in central nervous system(thalamus,spinal cord),and SCN11A in peripheral nervous system(DRG)decreased(P<0.05).Compared with positive control group,the expression of PGE2 levels in serum,ectopic lesions and spinal cord of the mice in Wenshen Xiaozheng Decoction group decreased after administration(P<0.05).[Conclusion]Wenshen Xiaozheng Decoction can alleviate pain in EMS model mice,and its mechanism may be related to inhibiting the overexpression of COX-2/PGE2 signaling pathway.

Although drugs such as barbiturates and benzodiazepines are often used for the treatment of insomnia, they are associated with various side effects such as habituations, tolerance and addiction. Alternatively, natural products with minimal unwanted effects have been preferred for the treatment of acute and/or mild insomnia, with additional benefits of overall health-promotion. Basic and clinical researches on the mechanisms of action of natural products have been carried out so far in insomnia treatments. Recent studies have been focusing on diverse chemical components available in natural products, with an interest of developing drugs that can improve sleep duration and quality. In the last 15 years, our co-workers have been actively looking for candidate substances from natural products that can relieve insomnia. This review is, therefore, intended to bring pharmacological data regarding to the effects of natural products on sleep duration and quality, mainly through the activation of GABAA receptors. It is imperative that phytochemicals will provide useful information during electroencephalography (EEG) analysis and serve as an alternative medications for insomnia patients who are reluctant to use conventional drugs.
Barbiturates ; Benzodiazepines ; Biological Products* ; Electroencephalography ; Humans ; Phytochemicals ; Sleep Initiation and Maintenance Disorders

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter expressed in the central nervous systems. Previously, several reports demonstrated that nucleus accumbal-injected CART peptide positively modulated behavioral sensitization induced by psychostimulants and regulated the mesocorticolimbic dopaminergic pathway. It is confirmed that CART peptide exerted inhibitory effect on psychostimulant-enhanced dopamine receptors signaling, Ca2+/calmodulin-dependent kinase signaling and crucial transcription factors expression. Besides modulation of dopamine receptors-related pathways, CART peptide also exhibited elaborated interactions with other neurotransmitter receptors, such as glutamate receptors and γ-aminobutyric acid receptors, which further account for attribution of CART peptide to inhibition of psychostimulant-potentiated locomotor activity. Recently, CART peptide has been shown to have anxiolytic functions on the aversive mood and uncontrolled drug-seeking behaviors following drug withdrawal. Moreover, microinjection of CART peptide has been shown to have an anti-depressant effect, which suggests its potential utility in the mood regulation and avoidance of depression-like behaviors. In this review, we discuss CART pathways in neural circuits and their interactions with neurotransmitters associated with psychostimulant-induced depression.
Central Nervous System ; Depression* ; Dopamine ; Drug-Seeking Behavior ; Microinjections ; Motor Activity ; Neurotransmitter Agents ; Phosphotransferases ; Receptors, Dopamine ; Receptors, Glutamate ; Receptors, Neurotransmitter ; Transcription Factors

Objective: To explore the relationship between smoking and hyperuricemia in Chinese residents. Methods: Based on data from the China Health and Nutrition Survey (CHNS), residents with blood samples provided in the 2009 round (including information of socio-demographic factors, lifestyle behaviors, medical history, and laboratory examinations etc.) were selected as the participants in the current analysis. Unconditional logistic regression models were utilized to compute the ORs and corresponding 95%CIs for assessing the relationship between smoking and hyperuricemia. Results: Among the 8 785 subjects, 1 435 had hyperuricemia with a prevalence rate of 16.3%, consisting of 886 men and 549 women with prevalence rates of 21.6% (886/4 110) and 11.7% (549/4 675) , respectively. Compared with never smokers, the adjusted OR (95%CI) for hyperuricemia was 0.83 (0.70-0.98) among current smokers, 0.77 (0.63-0.94) among current smokers with 20-39 years of smoking, and 0.79 (0.65-0.97) among current smokers with 11-20 cigarettes per day. When stratified by gender and compared with non-smoker, the adjusted OR (95%CI) for hyperuricemia among current smokers compared with never smokers was 0.83 (0.70-0.98) among men, while no significant association was found in female current smokers (OR=0.73, 95%CI: 0.42-1.26, P=0.260). Conclusion In Chinese residents, there is an inverse association between smoking and hyperuricemia prevalence, and this association may be related to duration and intensity of smoking among current smokers. The findings need to be validated in large prospective cohort studies.

Objective To investigate the relationship between fibrosis and M2 macrophages in endometriosis. Methods BALB/c mice model of endometriosis was established by intraperitoneal injection. The growth of ectopic lesions in mice was observed on the 7th,14th and 21th day after modeling. Masson staining was used to observe the degree of fibrosis and immunohistochemical method to detect the expression of CD206 and CD68 of mice. Image-Pro-Plus 6.0 was used for semi quantitative analysis of staining and the correlation between the degree of fibrosis and the expression of M2 macrophages was explored. Results The success rate of the establishment of endometriosis model by intraperitoneal injection was 100%. There was a positive correlation between fibrosis and the expression of M2 macrophages in endometriosis mice model. Conclusions The mice model of endometriosis can be established successfully by intraperitoneal injection and M2macrophages may promote fibrosis in endometriosis.

Objective To confirm the interference effect of heparin lithium on turbidimetry method for detecting total protein , and to conduct performance evaluation of it .Methods Eight different concentrations of total protein urine specimen with and with ‐out heparin lithium were detected respectively ,to confirm the interference of heparin lithium on the experiment .Adding different concentration of heparin lithium solution to the prepared total protein samples with concentration of 0 .172 ,0 .427 g/L(a series of interference experiment samples ,with heparin lithium concentrations of 0 .000 ,0 .025 ,0 .030 ,0 .035 ,0 .040 ,0 .045 ,0 .050 mg/L ) , repeat four times detection ,and then conduct the dose‐effect experiment of interference .Results The biggest bias of the testing re‐sults in the two paired samples was 159 .37% ,the mini‐bias was 11 .37% ,the difference of the results in two groups was statistical significant(t= 17 .24 ,P< 0 .05) .95% confidence interval of the interference effect in the total protein samples with concentration of 0 .172 g/L was 0 .034 ~ 0 .062 ,while in the total protein samples with concentration of 0 .427 g/L was 0 .043 - 0 .053 .When the heparin lithium were 0 .025 mg/mL and 0 .050 mg/mL respectively ,the results of bias of the total protein samples with concentra‐tion of 0 .172 g/L were 27 .33% ,58 .14% respectively .But in the 0 .427 g/L total protein samples ,the results of bias were 11 .24% 、18 .74% respectively .Dose effect of interference both showed a linear relationship in the series concentration of the hepa ‐rin lithium and interference of sample of 0 .172 g/L and 0 .427 g/L ,and the linear equations were Y = 1 .974X - 0 .001 03 ,Y = 1 .599 X - 0 .000 5 respectively .Conclusion Heparin lithium is the exogenous interfering substance to the detection of total protein in tur ‐bidimetry method ,it is the positive interference to the determination results of total proteins ,especially for the low level of total pro‐tein detection ,and as heparin lithium concentration increases ,the stronger the interference effect .

The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the 3rd day. CART peptides were over-expressed on the 5th day in the striata of behaviorally sensitized mice. A higher proportion of CART+ cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both D1R and D2R antagonists, SCH 23390 (D1R selective) and raclopride (D2R selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D1R and D2R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the D1R-KO mice, but not in the D2R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D1R.
Adenosine ; Animals ; Cocaine* ; Mice ; Motor Activity ; Nucleus Accumbens ; Peptides* ; Phosphotransferases ; Putamen ; Raclopride ; Receptors, Dopamine ; RNA, Messenger ; Signal Transduction