OBJECTIVE:To improve the synthesis technology of sorafenib tosylate (Ⅰ). METHODS:The intermediate N-methyl-(4-chlorpyridin-2-yl)carboxamide(Ⅳ)was obtained by chlorination and amidation with 2-picolinic acid as the starting com-pound. Meanwhile,N-[4-chloro-3-(triflouromethyl)phenyl]-N′-(4-hydroxyphenyl)urea (Ⅶ) was prepared from aminophenol and 4-chloro-3-trifluoromethyl phenyl isocyanate,which was obtained from 4-chloro-3-(trifluoromethyl)aniline(Ⅴ)by reaction with initiator triethylamine. Sorafenib tosylate was synthesized from Ⅳ and Ⅶ with potassium tert-butoxide by condensation and salt for-mation. The target compound was characterized by 1H-NMR. RESULTS:The target compound was confirmed as Ⅰ,with the over-all yield of 74% [based on 4-chloro-3-(trifluoromethylanilin)]. The purification of chromatogram was 94%. Optimized technology improves yield and simplifies multi-step intermediate decompression,distillation and purification process;the application of initia-tor shortens the duration of reaction. CONCLUSIONS:Ⅰ is prepared successfully,and raw material can be obtained easily and is easy to operate with high yield.

Objective To investigate the relationships between seven single nucleotide pdymorphisms(SNPs), including 6788895(SIAH2 gene), rs10941679(5p12), rs889312(MAP3K1), rs13387042(2q35), rs6504950(17q23), rs17530068(6q14) and rs2284378(20q11), and female breast cancer of Hui and Han nationalities.Methods A hospital-based case-control using age and nationallity as frequency matching conditions was conducted in Affiliated General Hospital of Ningxia Medical University.Results ①A total of 225 breast cancer patients and 225 controls were enrolled in this study.There was no significant differentce between case group and control group in age(48.27±9.27 vs 48.48±9.36, t=0.238,P=0.812) or nationallity (181 Han people and 44 Hui people vs 184 Han people and 41 Hui people, x2=0.131, P=0.718).②The subjects of study conformed to Hardy-Weinberg equilibrium principles.③The genotype and allele distribution of the above seven SNPs were not significantly different between cases group and control group of Hui and Han nationalities.Conclusion The seven SNPs mentioned above may not be related to breast cancer among people Hui and Han nationalities.

Objective To evaluate the efficacy of Qingfei-Jiedu decoction in the treatment of Acne. Methods A total of 93 female patients with acne were randomly divided into 3 groups according to random number table, 31 in each group. The observation group took the oral Qingfei-Jiedu decoction, and the Chinese medicine control group took the oral tanshinone capsule, and the western medicine control group took the oral acetic acid ring propyl alcohol progesterone. All 3 groups were treated for 4 weeks. The levels of serum dihydro (DHT), IL-6 and IL-8 were measured by ELISA. The changes of the lesions before and after treatment were observed and the adverse events were recorded during the treatment. The clinical effect was evaluated. Results After treatment, the serum DHT (56.94 ± 15.74 pg/ml vs. 74.48 ± 18.53 pg/ml, t=2.089), IL-6 (22.84 ± 11.77 pg/ml vs. 30.37 ± 14.50 pg/ml, t=2.135), IL-8 (22.64 ± 7.38 pg/ml vs. 29.54 ± 9.65 pg/ml, t=2.057) in the observation group were significantly lower than those in the Chinese medicine control group (P<0.05). After treatment, the disappearance rate of skin lesions (65.4% ± 15.0% vs. 44.7% ± 12.9%, 42.7% ± 13.6%, F=6.862) and comprehensive syndrome effective rate (57.2% ± 12.6% vs. 46.3% ± 12.8%, 44.8% ± 11.7%, F=5.322) in the observation group were significantly higher than those in the other two control groups (P<0.05). The observation group and the traditional Chinese medicine control group did not have adverse events, but the western medicine control group showed one case nausea. Conclusions The Qingfei-Jiedu decoction can reduce the level of serum DHT, IL-6 and IL-8 in female patients with acne vulgaris, and improve the skin lesion disappearance rates and comprehensive syndrome rates.

The antitumor activities of NL-101,aHDACi/DNA damage dual-targeting drug,on human multiple myeloma in vitro and in vivo were studied.Furthermore,the primary mechanisms were revealed.We detected the anti-proliferative activity of NL-101 on 10 human multiple myeloma cell lines,and the combinational effect of NL-101 and bortezomib on RPMI 8226 cell line.The inducing effects of NL-101 on cell cycle arrest and apoptosis were detected by FACS.The effects of NL-101 on acetyled-Histone H3,total Histone H3,acetyled α-Tubulin,total α-Tubulin,phospho-Histone H2A.X and total Histone H2A.X were evaluated by Western blott.We also demonstrated the antitumor activity of NL-101 and the combinational effect of NL-101 and bortezomib on RPMI 8226 xenograft tumor model in vivo.Results showed that NL-101 possessed strong antitumor activities on human multiple myeloma cells in vitro and in vivo.NL-101exhibited significant HDAC inhibitory activity and DNA alkylating activity.NL-101not only inhibited histone deacetylation level,but also increased the DNA damage in multiple myeloma cells.Meanwhile,NL-101 induced cell cycle arrest and apoptosis.Also,the synergistic effect of NL-101 was discovered when combined with bortezomib in vitro and in vivo.These data demonstrated that NL-101 may be a potent agent for the treatment of human multiple myeloma in future.

Animals ; Carotid Arteries ; surgery ; Carotid Artery Injuries ; etiology ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred C57BL ; Microsurgery ; Random Allocation

ObjectiveTo study the effect and mechanism of vagus nerve stimulation(VNS) on seizure in animal with epilepsy.MethodsSeizures of 34 rats and 8 rabbits were induced by Penicillin, Kainic acid(KA) and Strychnice respectively. Electrocorticographic(ECoG), electrical activition of hippocampal neurons and behaviour were observed to evidence the effects of left intermittent VNS .ResultsVNS could suppress seizures in animal models with epilepsy. There were significant changes in epileptiform ECoG, discharges of hippcampal neuron and behaviour. ConclusionSomatic seizure can be effectively inhibited by visceral afferent inputs through integration in cortical and hippocampal parts.

OBJECTIVETo study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM).

METHODSThe UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR).

RESULTSEA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P <0.05). 1HNMR analysis showed that in the model group, contents of glutamic acid, cholesterol, very low density lipoproein (VLDL) in the pallium obviously decreased, while alanine and low density lipoprotein (LDL) significantly increased. After EA, levels of lactic acid, glutamic acid, total cholesterol (TC), and VLDL all increased, and levels of alanine and LDL decreased. All indices were approximate to those of the blank control group.

CONCLUSIONEA at Foot Yangming channel was found to have some effect on metabolites in the brain tissue of UC model rats, which had specific metabonomic material basis and mechanism based on the Pi/Wei-brain related theory.

Objective:Living organ transplantation prolongs the life of many dying patients, but there are many disputes, especially the definition ofliving organ transplantation between non relatives. The definition of this ter-minology is closely related to medical students′cognitive ofliving organ transplantation between non relatives. The medical students are the main reserve army of medical staff and the executor of living donor organ transplantation in the future, who directly determine the organ transplantation and affect the doctor-patient relationship. This paper is to investigate and analyze the status of the medical students′recognition of cross transplantation between non rela-tives. Methods:A total of 450 medical students of Qingdao university were selected with cluster method and were investigated using self-designed questionnaire. Data were analyzed by SPSS 22. 0. Results:The overall recogni-tion rate toliving organ cross transplantation between non relatives was relatively low. The difference was statisti-cally significant (P<0. 05), namely that students in higher grade had lower recognition. The difference was statis-tically significant (P < 0. 05) between different specialties, and the recognition degree of students majoring in clinical medicine and ecsomatics was higher. Conclusion:The medical students of Qingdao University understand the concept of living organ cross transplantation between non relativesfuzzily, and the recognition degree is low.

Objective To explore the effects of the stromal cell-derived factor on chemotaxis of cord blood ACl33+ cells.Methods The optimal SDF-1 concentration is detected in Transwell system.Migration was calculated from the number of cells found to have passed through an 8-um pore size polycarbonate membrane.Results The chemotactic rate of fresh cord blood AC133+ cells increases along with the concentration of SDF-1,however,it tends to be stable when the concentration of SDF-1 reaches 150 ng/ml.There is no difference in the chemotactic rate of cord blood AC133+ cells between the group with CXCR4-blocking antibody and the group without SDF-1.Conclusion Transwell Plate can simulate the phenomenon of cell crossing endothelium.The chemotactic rate of cord blood AC133+ cells increases progressively along with the concentration of SDF-1,however,the chemotactic rate tends to equability when SDF-1 reaches a certain concentration.The chemotactic rate does not have a marked change while continuing to increase the concentration of SDF-1.There is no difference in the chemotactic rate of cord blood AC133+ cells between the group using CXCR4-blocking antibody and the group without SDF-1.

Objective To detect the expressions of apoptosis-related factors and inflammatory cytokines in superficial and deep layers of as well as anagen hair follicles in lesions of early alopecia areata (AA).Methods Scalp biopsy samples were collected from 25 patients with early AA and 15 healthy human controls.Fluorescence-based quantitative PCR was performed to detect mRNA expressions of apoptosis-related genes p53,caspase 3,Fas,survivin and bcl-2,as well as those of inflammatory cytokines interleukin (IL)-4,IL-10,IL-12 and interferon (IFN)-γ.An immunohistochemical assay was conducted to measure the expression of p53 protein in anagen hair follicles.Results Compared with control skin samples,anagen hair follicles in AA lesions showed significantly increased mRNA expression levels (expressed as 2-△△Ct) of pro-apoptotic factors caspase 3,p53 and Fas (6.78,8.01,9.74,respectively,all P ＜ 0.05),but decreased mRNA expression levels of antiapoptotic factors bcl-2 and survivin (0.08 and 0.03 respectively,both P ＜ 0.01),and similar mRNA expression levels of inflammatory cytokines.There was a significant increase in mRNA expression levels of Th1 cytokines IFN-γ and IL-12 (2.75 vs.1.00,P ＜ 0.05; 85.67 vs.1.00,P ＜ 0.01),but a significant decrease in the expression level of the Th2 cytokine IL-10 (0.002 vs.1.000,P ＜ 0.01) in superficial layers of AA lesions compared with those of normal control skin.The degree of changes in mRNA expression levels of IL-10 and IL-12 was significantly higher in superficial layers than in deep layers of AA lesions (P＜0.01 and 0.05 respectively).The immunohistochemical assay showed that the number of p53-positive cells per 100 cells in anagen hair follicles of AA lesions was higher than that in those of control skin (t =23.79,P ＜ 0.01).Conclusions Anagen hair follicles in AA lesions exhibit high expressions of pro-apoptosis factors,but low expressions of antiapoptotic factors,suggesting that apoptotic factors play a role in the occurrence of AA.