OBJECTIVE To investigate possible electrophysiological mechanisms of psychogenic disorders caused by the classical hallucinogen 2,5-dimethoxy-4-methylamphetamine(DOM).METHODS Microelectrode array implantation in the orbitofrontal cortex(OFC)was performed in adult male SD rats.After one week of recovery from surgery,the drugs were administered intraperitoneally to rats in the following order:DOM(0.5,1.5,and 3.0 mg·kg-1),DOM 3.0 mg·kg-1+ketanserin 1.0 mg·kg-1,DOM 3.0 mg·kg-1+SB242084 3.0 mg·kg-1,ketanserin 1.0 mg·kg-1,SB242084 3.0 mg·kg-1.Saline was given as a control group before each drug treatment.The changes of field potential(LFP)in OFC were recorded by the Plexon in vivo multichannel recording system.There was one week of washout of drugs between medications.RESULTS DOM(0.5,1.5 and 3.0 mg·kg-1)increased the power of high frequency oscillations(HFO,P<0.05)but decreased the power of low γ oscillations(P<0.05,P<0.01)in OFC compared to saline.Ketanserin(1.0 mg·kg-1)antagonized DOM induced changes in low γ oscilla-tions(P<0.01)and HFO(P<0.05)power,but SB242084(3.0 mg·kg-1)did not.CONCLUSION DOM can cause such psychoneurological disorders as hallucinations,which may be related to the power decrease of low γ oscillations and increase of HFO in OFC by acting at 5-HT2A receptors.

OBJECTIVE To investigate the types of neurons that influence the head twitch response(HTR)induced by 5-hydroxytryptaminergic(5-HTergic)psychedelic mescaline in mice.METHODS①Adult male C57BL/6J mice were randomly divided into the normal control group and mescaline(1.56,3.125,6.25,12.5,25 and 50 mg·kg-1)groups,with 15 mice in each group.The drugs of the corresponding groups were ip given,and the HTR frequency of mice was recorded for 30 min.② 5-HT 2A receptor(5-HT2AR)gene bilateral LoxP homozygous mice(5-HT2A flox/flox)were hybridized with calmodulin depen-dent protein kinaseⅡα cyclization recombination enzyme positive(CaMKⅡαcre/+),parvalbumin(PV)cre/+,somatostatin(SOM)cre/+or vasoactive intestinal peptide(VIP)cre/+mice to obtain 5-HT2A R conditional knockout(cKO)mice(5-HT2AΔCaMKⅡα,5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP).Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 15 mice in each group.The drugs of the corresponding groups were ip given before the HTR frequency of mice within 30 min was recorded.③ Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 12 mice in each group.After receiving the corresponding drug via ip,they were placed in a spontaneous activity test box for 30 minutes and their activity levels were recorded.RESULTS ① Compared with the normal control group,mescaline 3.125,6.25,12.5 and 25 mg·kg-1 significantly increased the HTRs of mice(P<0.05,P<0.01).② Among the different neuronal types of 5-HT2AR cKO mice,only 5-HT2A ΔCaMKⅡα mice had no difference in HTR frequency between the normal control group and the mescaline 12.5 mg·kg-1 group.In 5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP mice,the HTRs of mice in the mescaline 12.5 mg·kg-1 group were significantly increased(P<0.01)compared with the normal control group.③ There was no difference in spontaneous activity between the normal control group and the mescaline 12.5 mg·kg-1 group of all cKO mice.CONCLU-SION Pyramidal neurons are involved in mediating the induction of mescaline on HTRs in mice.

OBJECTIVE To investigate the effect of psychedelics on innate fear behavior of mice in Looming model(LM)and its neurobiological mechanism.METH-ODS ① Adult male C57BL/6J mice were randomly divid-ed into saline group,DOM group,psilocybin group and mescaline group.The drugs of the corresponding groups were given ip injecction 5 min in advance and LM were used to test the effect of them on freezing time in shelter of mice.② The mice were performing ip given DOM or psilocybin following 5-HT2A receptor antagonist M100907 ip 30 min later involved looming experiments.③Quan-tified the expression of EGR1 protein in mouse brains by immunofluorescence staining,then use ibotenic acid(IBO)damaged the mouse brain regions based on the result above and performed looming experiments.④ Specifically activate or inhibit CaMK Ⅱ,PV,VIP and SOM neurons of mice in saline or psilocybin groups respec-tively by chemical genetic methods and followed looming experiments.RESULTS ① In LM,the freezing time in shelter of mice in DOM,psilocybin and mescaline groups was significantly shorter compared to the saline group(P<0.05),and the dose-effect curves of above psyche-delics were U-shaped.② Compared with the vehicle + psilocybin/DOM groups,the freezing time in shelter of mice in M100907 + psilocybin/DOM groups was signifi-cantly prolonged(P<0.05),and there was no significant difference between the vehicle + saline group and the M100907 + psilocybin/DOM groups.③ Psilocybin signifi-cantly increased the expression of EGR1 protein in prelim-bic cortex(PrL)compared with saline,and the damage of PrL could effectively antagonized the effect of psilocybin shortening the freezing time in LM.④ Chemicalgenetic specific inhibition of CaMK Ⅱ,PV or VIP neurons in PrL could effectively antagonize the effect of psilocybin in LM,while chemicalgenetic specific activation of CaMK Ⅱneurons could significantly shorten the freezing time of saline-treated mice.CONCLUSION Psychedelics have capability to waken the innate fear behavior like freez-ing of mice in LM,and this effect is mediated by 5-HT2A receptor and CaMK Ⅱneuron in PrL.

ObjectiveThe functional model of six major components of Astragali Radix-Angelicae Sinensis Radix combination against the proliferation of vascular smooth muscle cells （VSMCs） was constructed by uniform design， the relationship between the compatibility of these six main components and the inhibition of VSMCs proliferation was analyzed， and the effect of the compatibility of these main components of Astragali Radix-Angelicae Sinensis Radix on the proliferation of VSMCs as well as the feasibility of uniform design test in the study of multi-component compatibility of Chinese medicines were discussed. MethodCell proliferation and toxicity assay kit （CCK-8） method was used to determine the inhibitory effect of the six components of Astragali Radix-Angelicae Sinensis Radix on platelet derived growth factor-BB （PDGF-BB）-induced VSMCs proliferation in rats and the half inhibitory concentration （IC₅₀） of each component were obtained. Six chemical components of Astragali Radix-Angelicae Sinensis Radix （formononetin， astragaloside Ⅰ， astragaloside Ⅳ， calycosin， ferulic acid and calycosin-7-O-β-D-glucoside） were taken as the independent variables X₁， X₂， X₃， X₄， X₅， X₆， respectively， and the cell proliferation inhibition rate as the dependent variable Y. U24*（24⁹） uniform design table and mathematical models （including linear and quadratic polynomial） were selected， the stepwise regression method was used to screen the variables， and the better equations were obtained in theory. The actually better relationship equations were screened by setting the different dose compatibility of these six components for verification tests. According to the purpose of the experiment， the selected regression equation was processed by data centralization， so as to compare the regression coefficients of the data centralization equation and analyze the correlation between components and efficacy. ResultThe six components of Astragali Radix-Angelicae Sinensis Radix could inhibit abnormal proliferation of VSMCs in a dose-dependent manner. IC₅₀ values of formononetin， astragaloside Ⅰ， astragaloside Ⅳ， calycosin， ferulic acid and calycosin-7-O-β-D-glucoside were 123.453， 113.184， 81.655， 141.159， 101.187， 151.016 mg·L^-1， respectively. Two superior models were selected by experimental verification， including equation 1 of Y₁=73.137 897-0.207 888X₁+0.000 508X₂²+0.000 347X₁X₆ and equation 2 of Y₂=70.038 433-0.236 665X₁+0.000 577X₂²+0.000 260X₁X₄+0.000 415X₁X₆+0.000 370X₃X₅. After data centralization， equation 2 was adjusted to Y=-1.480 260-0.146 281X₁+0.000 673X₂²+0.000 314X₁X₄+0.000 456X₁X₆+0.000 737X₃X₅， the regression coefficients showed that the astragaloside Ⅰ had a positive effect on the inhibition rate of cell proliferation， formononetin-calycosin， formononetin-calycosin-7-O-β-D-glucoside and astragaloside Ⅳ-ferulic acid had an interaction effect on the inhibition rate of cell proliferation， and the synergistic effect of astragaloside Ⅳ and ferulic acid was higher than other interaction items. ConclusionThe combination of six main components of Astragali Radix-Angelicae Sinensis Radix can inhibit the abnormal proliferation of VSMCs， and it is demonstrated that the uniform test design can be used to predict the correlation between the chemical composition of Chinese medicines with their pharmacological effects， which can provide an experimental basis for the rational use of uniform design and regression analysis to construct mathematical models to study the compatibility relationship of Chinese medicines.

Objective:To investigate the relationship between gallbladder carcinoma and gallbladder stones, and provide theoretical basis for the prevention and treatment of gallbladder carcinoma.Methods:A case-control study was used to retrospectively analyze the clinical data of 134 patients(study group) with gallbladder stones and gallbladder carcinoma treated in the Xinjiang Uygur Autonomous Region Corps Hospital of Chinese People′s Armed Police Forces from January 2010 to December 2012.Another 134 patients with gallbladder stones were selected as control group, and the clinical characteristics of the two groups were compared.Results:The average age of patients in the study group was (60.5±11.7)years, which was significantly older than that in the control group [(49.6±10.3)years], the difference was statistically significant ( t=7.916, P<0.05). The history of gallbladder stones in the study group and control group were (9.3±4.1)years and (4.6±2.5)years, respectively, and the difference between the two groups was statistically significant( t=11.682, P<0.01). The multiple stones, maximum stone diameter and maximum gallbladder wall thickness in the study group were 75 cases, (2.4±0.6)cm and (0.59±0.16)cm, respectively, which in the control group were 46 cases, (1.3±0.5)cm and (0.87±0.23)cm, respectively, the differences between the two groups were statistically significant(χ 2=3.978, t=6.217, 5.110, all P<0.05). The incidences of cholecystitis and jaundice in the study group were higher than those in the control group, and the differences were statistically significant(all P<0.05). Conclusion:Gallbladder stones are one of the causative factors of gallbladder carcinoma.Early diagnosis of gallbladder carcinoma is difficult.Patients with high-risk gallbladder stones who are old, have a long history of gallbladder stones, multiple stones, large stone diameters, and thick gallbladder walls should actively undergo surgical intervention.

Cas9 is a RNA-guided double stranded DNA nuclease that participates in the CRISPR/Cas9 system. Wide-type Cas9 directly silences the expression of target gene by gene splicing. The engineered dCas9 protein with the mutation at D10A and H840A lacks the Cas9' s endonuclease function but keeps its DNA binding activity. dCas9 can activate special genes by fusing with transcription activator. Meanwhile,it can inhibit the gene transcription by directly binding to the target gene and stop gene transcrip?tion. Combination of light sensitive structures and CRISPR can produce light-inducible CRISPR/Cas9 system for control of gene expres?sion. This system is able to activate or inhibit gene expression via the use of controlling blue light(470 nm). In this review,we mainly discuss the development of the light inducible CRISPR/Cas9 system as well as its application in the control of gene expression.

Objective To explore the effects of self-efficacy theory on coping style and quality of life of patients with bladder cancer underwent the targeted therapy.Methods A total of 84 advanced bladder cancer patients in our hospital from May 2011 to May 2016 were selected in the study using convenience sampling method. All patients were randomly divided into control group and observation group,each 42 cases. Patients in both groups were given the combination of conventional chemotherapy and targeted therapy with trastuzumab intravenous injection. The therapy was observed for 4 cycles. Patients in the control group were given routine nursing during the treatment, while patients in the observation group received additional nursing intervention based on self-efficacy. The prognosis and curative effect, coping style and quality of life scores of patients were recorded in the two groups.Results The total curative effective rate of patients in the observation group was 52.38%, which was higher than that in the control group (28.57%). The difference was statistically significant between two groups (P<0.05). After the intervention, the positive coping scores of two groups significantly increased (P<0.05), while the negative coping scores significantly decreased (P<0.05). The changes in the observation group was significantly better than that in the control group (P<0.05). The average quality of life score of the observation group after the intervention was significantly higher than that of the control group (P<0.05).Conclusions The application of self-efficacy theory in the bladder cancer patients underwent the targeted therapy can promote the transformation of positive coping style and improve the quality of life of patients, which is beneficial to the improvement of the overall total effectiveness.

Hypoxia refers to the reduction in tissue oxygen supply or utilization. It occurs in various pathological symptoms like embolism,anthracemia,and chronic obstructive sleep. At high altitude, lower partial pressure of oxygen compromises the supply of adequate oxygen to the tissues and leads to many clinical syndromes,such as acute mountain sickness,high-altitude cerebral edema,and high-altitude pulmonary edema. Histamine H3 receptor, primarily as a presynaptic receptor, is widely expressed in the central and peripheral systems. Histamine,dopamine,acetylcholine and many other neurotransmitters are regulated by histamine H3 receptor. Studies have shown that histamine H3 receptor is involved in the hypoxic response of the respiratory network. In addition,histamine,espe?cially histamine H3 receptor,participates in the regulation of cerebral ischemia in the central nervous system. In this paper,we reviewed the structure and functions of histamine H3 receptor and explained its role in the regulation of hypoxia so as to evaluate the possibility of histamine H3 receptor as a drug target for the therapy of hypoxia-induced injuries.

OBJECTIVE To investigate the protective effect of sGC003,a novel agonist of soluble guanylate cyclase,on endothelin-1(ET-1)-induced cardiomyocyte hypertrophy. METHODS Cardiomy?ocytes were isolated from neonatal Sprague-Dawley rats using serial enzymatic digestion and then incubated with ET-1 10 nmol·L-1 in the absence or presence of sGC003 0.01,0.1 and 1.0μmol·L-1. Hyper?trophic responses including the cardiomyocyte area(Image-Pro Plus 6.0),the expression of atrial natri?uretic peptide gene(ANP)mRNA(RT-PCR method)and total protein content(BCA method)were detect?ed. RESULTS After 48 h stimulation with ET-1 10 nmol·L-1,the cardiomyocyte area increased by 80%(P<0.01),the total protein content increased by 120%(P<0.01) and the expression of ANP mRNA up-regulated by 140%(P<0.01). sGC003 0.01,0.1 and 1.0μmol · L-1 elicited antihypertrophic actions, including inhibition of ET-1-mediated increase in the cardiomyocyte area(P<0.01),raised total protein content(P<0.05)and upregulation of ANP mRNA(P<0.05). CONCLUSION sGC003 has protective,car?diomyocyte-selective antihypertrophic effects in vitro.