Objective: Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs). Methods: (1)Prepare IPCs model: pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups: Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA. Results: After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group (P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated (P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Conclusion GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon.

Objective According to effect of Sorafenib combined Bevacizumab in mice U14 cervical cancer cell lines,observe the changes of cell lines of transplanted tumor U14 cell structure and adjustment effect of Bcl-2 and Bax protein expression.Methods Sixty female 615 mice of healthy inbreeding line,aged from 4 to 6 weeks,average weight is 20.4 g,range from 18 to 25 g.The animals were divided into blank control group (group A)with 10 mice,and U14 cervical cancer cell lines by vaccinating mice a tumor-burdened mice model was established,on the 6th day after subcutaneous inoculation of U14,40 tumor-burdened mice with tumor diameter ≥ 5 mm were selected.The mice were divided into 5 groups according to the completely randomized grouping method:model group (group B),Sorafenib group (group C),low-dose Bevacizumab combined with Sorafenib group (group D),the middle dose Bevacizumab combined with Sorafenib group (group E),and the high dose Bevacizumab combined with Sorafenib group (group F),8 mice in each group.The treatment regimen consisted of 1 ml of 0.9％ sodium chloride solution in group A and group B,Sorafenib 12 mg/kg in group C,and Bevacizumab 2.5 mg/kg + Sorafenib 12 mg/kg in group D,Bevacizumab 5 mg/kg + Sorafenib 12 mg/kg in group E,and Bevacizumab 10 mg/ kg + Sorafenib 12 mg/kg in group F.All mice were injected intraperitoneally and sacrificed by dislocation 24 days later.The tumor weight (g) was measured every 6 days,and the body weight of each group was observed,and calculated the tumor inhibition rate of each group of mice.The histopathological changes of the transplanted mice were observed by hematoxylin-eosin staining.The transplantation of each group of mice was observed by electron microscope.Morphological changes of tumor tissue;the expression of Bcl-2 and Bax protein in each group were observed by immunohistochemistry.The measurement data were expressed as mean standard deviation (Mean ± SD),univariate analysis of variance was used for inter-group comparison,and LSD method was used for pairwise comparison.Results At the beginning of the intraperitoneal injection of the drug,the body weight of the mice began to increase slowly and continuously,and the trend of the mice in each group was basically the same.The tumor inhibition rate of group C was 8.02％,4.92％ in group D,11.10％ in group E,and 5.42％ in group F.Group E had the highest tumor inhibition rate and the best effect.The difference in tumor weight between group A and the other groups was statistically significant (P ＜ 0.05).The results of electron microscopy showed that the cell structure changes in C,D,E and F groups were similar,and the apoptosis of tumor cells appeared after treatment.The apoptosis of group E was the best.The apoptosis-related proteins in group C,D,E and F were observed.The expression of Bax was up-regulated,and the positive number in group E was the highest.The expression of proto-oncogene Bcl-2 was down-regulated in group C,D,E and F,and the number of positive in group E was the least,and the difference was statistically significant (P ＜ 0.05).Conclusions Sorafenib combined with Bevacizumab can promote tumor cell apoptosis by up-regulating Bax and down-regulating Bcl-2 protein expression.Among them,Sorafenib combined with Bevacizumab at medium dose promotes tumor cell apoptosis better than other methods,providing a basis for clinical treatment.

Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the tumor penetration and the anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.

Objective:To explore clinical application value of color Doppler ultrasound (CDU) assigned to diagnose triple-negative breast cancer (TNBC) and axillary lymph node metastasis (ALNM).Methods:A retrospectively analyzed of proved of clinical data on the 863 patients breast cancer in women by CDU inspection,operation and pathology.According results will be divided into TNBC group and non negative breast cancer (NTNBC) group via clinical pathological and immunohistochemical detection.Using multi-factor unconditioned Logistic regression analysis the CDU supposed the diagnosis and the correlation of TNBC.Results:The coincidence rate of CDU and pathological diagnosis was 90.96％ (785/863),78 cases (9.04％) remove breast masses,105 patients TNBC group and NTNBC group 680 patients.The mass circular or elliptic (48.57％ vsl0.70 ％),the tumor maximum diameter 5.0 cm (21.90％ vs 15.30 ％),micro calcifications (87.62％ vs 74.12 ％),state clearly (56.19％ vs 41.47 ％),no burr edge character (74.29％ vs 41.62 ％),peripheral hyperechoic halo ring (74.29％ vs46.76 ％),rear echo attenuation (72.38％ vs 46.76 ％),no ALNM (61.90％ vs 37.35％) comparing the two groups exists significant difference (P＜ 0.05),while the mass number,and vertical and horizontal diameter ratio,degree of echo,echo distribution and blood flow classification comparing the two groups were no significant difference (P＞ 0.05).The CDU fu points ＞ 10 divided into NTNBC and pathological coincidence rate 93.93％ (680/724),8 ～ 10 points TNBC suspected diagnosis coincidence rate 11.51％ (16/139),＜ 8 points TNBC tendency diagnosis coincidence rate 64.03％ (89/139),TNBC total diagnostic coincidence rate was 75.54％ (105/139).In CDU diagnosed 785 cases of breast cancer,the ALN enlargement in 319 cases (40.64％),with TNBC group was 61.90％ (65/105),NTNBC group was 37.35％ (254/680).Logistic regression analysis results:tumor assumes the circular or elliptic,edge without burr,peripheral hyperechoic halo ring,rear echo attenuation and ALNM with TNBC has certain correlation (P＜0.05).Conclusion:The seemingly benign breast diseases and axillary lymph node enlargement,the CDU,supposed less than 8 points,age 50 or less or not at the same time,menopause or having a history of breast cancer susceptibility to family,important reference index,clinical value has high of CDU diagnostic of TNBC and ALNM.

There are some shortcomings of animal experiments applied in chemical toxicity testing, such as long period, large cost, species differences and dose differences, which limit the use of animal experiments' results in predicting human toxicity.Accordingly, we established a toxicity testing alternative screening system in line with the toxicity endpoints which required in chemical safety evaluation and risk assessment (genotoxicity, carcinogenicity, reproductive toxicity, acute toxicity and general toxicity) based on 3R principles (replacement, reduction, refinement) for animal experiments.This system covers most of the endpoints of toxicity assessment, and molecular biology technology was also applied to integrate the toxicity test, as well as some operation was optimized in order to shorten the experimental period, reduce experimental costs, improve animal welfare.Furthermore, the results from the screening system have higher clinical relevance because it is based on the toxicity mechanisms.

Epilepsy is a complications of brain injury or stroke,and is a common diseases in reha-bilitation or neurology department.Transcranial magnetic stimulation as a classical treatment means for stroke or brain injury,but also can promote the recovery of epilepsy.However,there is no clear clinical re-port for safety of epilepsy patients use both donepezil and transcranial magnetic stimulation .The article re-views the literature.Clinicians maybe provided some help.

Objective To investigate correlative relations between the ultrasonic classification diagnosis and the clinicopathological features of thyroid calcification lesions.Methods The clinical data of 198 cases diagnosed as thyroid calcification lesions by ultrasonic,surgery and pathology were retrospectively analyzed.Spearman method was used to analyze the relationship of TCL ultrasonic diagnosis,clinical pathological traits and the classification of differentiated thyroid carcinoma(DTC).Results Among the 198 TCL cases,ultrasonic diagnosis and pathologic diagnosis were accordant in 178 (90.40％) cases.Among 119(60.10％) cases of thyroid carcinoma (TC),101 cases(84.87％)were papillary carcinoma,11 cases(9.24％)were follicular carcinoma,5 cases(4.20％) were medullary carcinoma and 2 cases(1.68％)were anaplastic carcinoma.Among 79 cases (39.90％) of benign lesions,34 cases(43.04％)were adenoma,27 cases(34.18％)were nodular goiter,and 18 cases(22.78％)were hashimoto's thyroiditis (HT).Calcified classification were as following 74 cases (37.37％)were type Ⅰ a and 4 cases (2.02％) were type Ⅰ b(both were TC);20 cases(10.10％)were type Ⅰ c,among which 19 cases were nodular goiter,and 1 case was TC.Among the 37 cases (23.74％) of type Ⅱ,28 cases were TC,and 19 cases were benign lesions.Among the 20 cases(10.10％) of type Ⅲ,8 cases were TC,and 12 cases were benign lesions.Among 22 cases(11.11％) of type Ⅳ,2 cases were TC,and 20 cases were benign lesions.Among 11 cases(5.56％) of type V patients,2 cases were TC,and 9 cases were benign lesions.The rate of TC with cervical metastasis was 41.18％(49/119).68.91％(82/119) of carcinoma nodules were grade Ⅱ-Ⅲ in color Doppler flow imaging (CDFI),grade 0-Ⅰ were mainly benign nodules,and grade Ⅲ with mussy blood flow in CDFI were HT.Conclusions Type Ⅰ a and Ⅰ b micro calcification is the pathological basis of ultrasonic diagnosis of papillary thyroid carcinoma and follicular carcinoma,which is closely related to DTC.Calcified isolation nodule of type Ⅱ and Ⅲ with level Ⅱ-Ⅲ bleeding is a risk factor for TC.Type Ⅰ c,Ⅲ,Ⅳ and Ⅴcalcification is closely related to benign TCL.CDFI has important value for identifying benign and malignant CLT.

Objective To discuss the relationship between repetitive variable deceleration with a short interval (RDSI) in labor and neonatal acidosis.Methods One hundred and seventy-seven electronic fetal heart monitoring (EFM) patterns within one hour preceding delivery in term singleton pregnancies were collected in Peking University Third Hospital between February 2011 to October 2013.Continued EFM were recorded before delivery.Analysis was conducted on general information of both mothers and babies,including pregnant complications,duration of labor,cord and placental factors,nature of amniotic fluid,Apgar score and neonatal cord blood gas.RDSI was defined as that over 50％ intervals between two decelerations (the end of the last deceleration to the beginning of the next one) ≤ 60 s which appeared repetitevly in a period of 20 minutes.Independent sample t test,rank sum test,Chi-square test and Fisher's exact test were applied for statistics and receiver operating characteristic curve was obtained from the information of those with RDSI.Results Twenty-four of the 177 women with RDSI were assigned to the study group (24 cases,13.6％) and the rest 153 cases without RDSI to the control group.Background information of women in the two groups was comparable according to the maternal age,gestational weeks at delivery and duration of labor (all P ＞ 0.05).The occurrence of meconium stained amniotic fluid in the study group was higher than that of the control group [16.7％ (4/24) vs 5.2％ (7/153),x2=5.204,P=0.045],while the pH and base excess value of the neonatal blood gas in the study group were lower [7.20 (7.13-7.28) vs 7.29 (7.25-7.33),Z=-4.490;-6.10 (-4.67 to-9.62) mmol/L vs-3.20 (-4.90 to-1.55) mmol/L,Z=-5.044;P ≤ 0.01] resulting a higher rate of neonatal acidosis [50.0％(12/24) vs 7.8％ (12/153),x2=31.456,P ＜ 0.01].No significant difference was found in the incidence of neonatal asphyxia between the two groups.The area under the curve was 0.774 (95％CI:0.579-0.969).Conclusion RDSI in labor might indicate a high risk of neonatal acidosis.

Objective To evaluate the bioequivalence of domestic and imported terazosin hydrochloride tablets after single oral dose .Methods It was a single center ,randomized ,open ,cross-over trail design ,21 subjects were fasting oral adminis-tered of 2 mg domestic and imported terazosin hydrochloride tablets in different periods ,venous blood 4 ml were collected in different time points before and 60 h after administration ,plasma concentration of terazosin was determined by LC-MS/MS . Results The main pharmacokinetic parameters of domestic and imported terazosin hydrochloride tablets were as follows :t1/2 :(13.2± 2.39)hvs(12.5±1.93)h,tmax :(1.01±0.83)hvs(1.08±0.69)h,Cmax :(40.1±10.6)ng/mlvs(37.3± 9 .57) ng/ml;AUC0- ∞ :(428 ± 82 .1) ng · h/ml vs (426 ± 85 .2) ng · h/ml .The relative bioavailability of domestic terazosin hydrochloride tablets was (101 .2 ± 14 .7)% .90% CI of domestic and imported terazosin hydrochloride tablets AUC0-t and Cmax geometric mean ratio fell between 80% -125% .Conclusion The domestic tablets are bioequivalent to the imported tablets .

BACKGROUND:Studies have shown that bone marrow mesenchymal stem cells have the ability to persistently generate hepatocytes and biliary cells, and thus in the repair process of liver injury, replenish the reduced number of hepatocytes due to damage and participate in damaged liver structure.
OBJECTIVE:To investigate the effect of bone marrow mesenchymal stem cells transplantation on acute liver failure and the expression of CD163 and interleukin-10 in rat serum and liver tissue.
METHODS:D-galactose and lipopolysaccharidewere used to make acute liver failure models in 60 Sprague-Dawley rats. Then, the rats were divided into control group and transplantation group. Bone marrow mesenchymal stem cells at passage 3 were injected through tail vein in the transplantation group, and normal saline was injected in the control group. After transplantation 24, 120, 168 hours, serum samples and liver tissues were col ected.
RESULTS AND CONCLUSION:After transplantation 120 and 168 hours, the serum alanine transaminase and aspartate aminotransferase activities of the transplantation were significantly lower than those of the control group (P<0.05). In the transplantation group the apoptotic index was stil lower compared with the control group, and the difference was significant (P<0.05). The levels of CD163 and interleukin-10 in the serum and liver tissue in the transplantation group were decreased significantly compared with the control group (P<0.05). The results suggested that there were highly significant correlations between CD163 and interleukin-10 (P<0.01). Bone marrow mesenchymal stem celltransplantation has a therapeutic effect on acute liver failure rats. CDl63 and interleukin-10 play a very important role in the pathogenesis of acute liver failure, which can be used as sensitive serum marker proteins for diagnosis and prognosis of acute liver failure.