According to the results of activity-structure relationship (SAR) studies of alpha1-adrenoceptor antagonists hydantoin-phenylpiperazine and benzimidazo-arypiperazine derivatves, to design and synthesize a series of novel phenylpiperazine alpha1-adrenoceptor antagonists with more potent vasorelaxant activity, active metabolites of naftopidil were used as lead compounds. Ten novel R,S-1-substituted phenyl-4-[3-(naphthal-yl-oxy)-2-hydroxy propyl]-piperazine were designed and synthesized, their vasorelaxant activity was evaluated by calculating inhibition rate of phenylephrine-induced vasocontration of rabbit artery trips. Five compounds exhibited vasorelaxant activity, and compound 16 showed significant vasorelaxant activity in vitro. At 0.01 and 1 micromol x L(-1), its inhibition rates were 7.03% and 22.72%, respectively. This compound possessed ideal vasorelaxant activity in vitro, and would be selected for further anti-hypertension evaluation in vivo. Moreover, by analyzing the primary activity and structure relationship of these compounds, it could be concluded that the SAR results of the reported phenylpiperazine alpha1-adrenoceptor antagonists could be used for reference in designing novel derivatives of naftopidil with optimal pharmacological properties.
Adrenergic alpha-1 Receptor Antagonists ; Animals ; Antihypertensive Agents ; chemical synthesis ; chemistry ; pharmacology ; In Vitro Techniques ; Molecular Structure ; Piperazines ; chemical synthesis ; chemistry ; pharmacology ; Rabbits ; Structure-Activity Relationship ; Vasoconstriction ; drug effects

Objective To explore whether puerarin induced apoptosis of SKOV3 ovarian cancer cells by microRNA-125b.Methods Using the qRT-PCR technique to detect the change of microRNA-125b after puerarin pretreated SKOV3.Using RNA interference technology to inhibit microRNA-125b expression in SKOV3 cells.Using Western blot technique to detect apoptosis related proteins after microRNA-125b lower expression.Results Puerarin could significantly inhibit ovarian cancer cell SKOV3 proliferation activity and promote its apoptosis related proteins expression.And puerarin can promote the expression of microRNA-125b.Inhibition of microRNA-125b expression in ovarian cancer cell SKOV3 could reduce apoptosis protein expression in SKOV3 cell.Conclusion MicroRNA-125b was involved in puerarin induced SKOV3 cell apoptosis,and prompt microRNA-125b is key molecular of the drug resistance in SKOV3.

OBJECTIVETo investigate the expression of heparanase mRNA and its relation with the clinicopathological features and angiogenesis in primary hepatocellular carcinoma (HCC).

METHODSExpression of heparanase mRNA was detected by RT-PCR in 51 HCC lesions, and microvessel density (MVD) was detected by immunohistochemical stain with a factor VIII-related monoclonal antibody.

RESULTSExpression of heparanase mRNA was shown in 49.0% (25/51) HCC lesions. The positive rate of heparanase expression in tumors larger than 3 cm (63.6%, 21/33) was significantly higher than those in smaller tumors (22.2%, 4/18; P < 0.01). Heparanase expression was more frequent in highly invasive tumors (70.0%, 14/20) compared with moderately invasive tumors (46.7%, 7/15) and low invasive ones (25.0%, 4/16; P < 0.05). Moreover, heparanase expression in tumors with high MVD (62.5%, 20/32) was significantly higher than those in tumors with low MVD (26.3%, 5/19; P < 0.05).

CONCLUSIONHeparanase mRNA expression may be important for the growth, invasion and angiogenesis of hepatocellular carcinoma.

Adult ; Carcinoma, Hepatocellular ; blood supply ; enzymology ; pathology ; Female ; Glucuronidase ; biosynthesis ; genetics ; Humans ; Liver ; enzymology ; Liver Neoplasms ; blood supply ; enzymology ; pathology ; Male ; Microcirculation ; pathology ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; enzymology ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Burden

OBJECTIVETo study the optimum technology of extracting bioactive component named geniposidic acid in Eucommia Ulmiodes by orthogonal test.

METHODAn orthogonal test table L16(4(5)) was used with the factors of extracting time, temperature, times, ethanol consistency and the ratio of solid to liquid. The content of geniposideic acid was determined by RP-HPLC.

RESULTThe optimum technology was: temperature 50 degrees C, time 1 h, once, consistency 80%, and the ratio of solid and liquid 1:12. Under the condition, the best material of Eucommia Ulmiodes for extracting geniposidic acid was chosen.

CONCLUSIONThe technology can provide some theoretic advice for industry.

Chromatography, High Pressure Liquid ; Ethanol ; Eucommiaceae ; chemistry ; Glucosides ; analysis ; isolation & purification ; Iridoid Glucosides ; Iridoids ; analysis ; isolation & purification ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; Technology, Pharmaceutical ; methods ; Temperature ; Time

Four-stage selected random samples were used to analyze the prevalence and distributing feature of hyperuricemia and gout in 13 559 Han,Uighur,and Hazakh adults in Xinjiang. The prevalence of hyperuricemia was 11.00%,3.27%,and 3.94% respectively in Han,Uighur,and Hazakh populations,and 1.32%, 0.65%,and 0.70% for gout,with statistically significant difference among three groups(all P＜0.05). No-conditional logistic regression analysis showed that nationality,body mass index,renal function,and serum lipid were risk factors of hyperuricemia,while female and physical activity were protective factors. Eating seafood and animal visceral organs were independent risk factors of hyperuricemia in Han population. Eating animal visceral organs and drinking alcohol were independent risk factors of hyperuricemia in Hazakh population.

Objective To investigate the multi-detector computed tomography (MDCT) evaluating the clinical staging of adenocarcinoma of the esophagogastric junction (AEG) after neoadjuvant chemotherapy.Methods The retrospective cross-sectional study conducted.The clinicopathological data of 46 AEG patients who were admitted to the Peking University Cancer Hospital between January 2016 and April 2018 were collected.All patients underwent MDCT before and after neoadjuvant chemotherapy and at preoperative 2 weeks,the distance between tumor center and boundary of esophagogastric junction (EGJ) was judged through coronal measured values and axial formula method.Patients underwent radical resection of gastric cancer + D2 lymph node dissection after neoadjuvant chemotherapy,pathologists reviewed the distance between center of AEG and boundary of EGJ,T staging (ycT) and N staging (ycN) of clinical staging,T staging (ypT) and N staging (ypN) of pathological staging after neoadjuvant chemotherapy were determined according to TNM staging of American Joint Committee on Cancer (AJCC) (8th edition),and tumor regression grading (TRG) was determined according to the criterion established by National Comprehensive Cancer Network.Observation indicators:(1) CT examination after neoadjuvant chemotherapy;(2) clinical staging after neoadjuvant chemotherapy;(3) postoperative pathological examination;(4) postoperative pathological staging;(5) accuracy of clinical staging after neoadjuvant chemotherapy;(6)relationship between imaging changes of CT examination and pathological reactions.Count data were described as absolute number or percentage,and comparisons among groups were analyzed by the chi-square test.Comparisons of ordinal data were analyzed by the non-parametric test.Results (1) CT examination after neoadjuvant chemotherapy:5 of 46 AEG patients,coronal images of CT showed whole tumor and boundary of EGJ,axial images of CT showed EGJ wall thickening,heterogeneous enhancement in all layers of lesions,and unsmooth serosal surface;the distance between tumor center and boundary of EGJ is less than 2 cm by direct measurement,5 patients were confirmed as esophageal cancer staging.For 41 patients,the same coronal image of CT cannot showed whole tumor and boundary of EGJ,axial images of CT showed EGJ wall thickening,heterogeneous enhancement in all layers of lesions,and irregular-shaped serosal surface;27 patients whose calculated values were negative based on formula method used esophageal cancer staging,and 14 patients whose calculated values were positive used gastric staging.(2) Clinical staging after neoadjuvant chemotherapy:among 46 AEG patients,ycT staging:staging ycT1,ycT2,ycT3,ycT4a and ycT4b were respectively detected in 1,6,31,6 and 2 patients;ycN staging:staging ycN0,ycN1,ycN2 and ycN3a were respectively detected in 5,14,23 and 4 patients.(3) Postoperative pathological examination:of 46 patients,38,3,3 and 2 were respectively confirmed as adenocarcinoma,adenocarcinoma with signet-ring cell carcinoma,adenocarcinoma with neuroendocrine carcinoma and adenocarcinoma with squamous carcinoma.Of 46 patients,the distance between tumor center and boundary of EGJ can be observed in 14 patients by gastric cancer staging and 32 patients by esophageal cancer staging.(4) Postoperative pathological staging:ypT staging:1,3,5,29,7 and 1 patients were respectively detected in staging ypT0,ypT1,ypT2,ypT3,ypT4a and ypT4b;ypN staging:17,4,15,9 and 1 patients were respectively detected in staging ypN0,ypN1,ypN2,ypN3a and ypN3b.One,3,16 and 26 patients were confirmed as staging TRG 0,TRG 1,TRG 2 and TRG 3,including 20 patients tumor regression and 26 patients without tumor regression.(5) Accuracy of clinical staging after neoadjuvant chemotherapy:the accuracies of ycT staging and ycN staging were 78.3％ (36/46) and 54.3％ (25/46).(6) Relationship between imaging changes of CT examination and pathological reactions:of 46 patients,33 and 13 had respectively reduced and stable gastric wall thickness of primary lesion.Among 20 patients with tumor regression,17 and 3 had respectively reduced and stable gastric wall thickness of primary lesion;of 26 patients without tumor regression,reduced and stable gastric wall thickness of primary lesion were respectively in 16 and 10 patients,with no statistically significant difference (x2 =3.069,P＞0.05).Of 46 patients,31,14 and 1 had respectively reduced,stable and increased sum of minor diameters of suspicious celiac lymph nodes.The reduced,stable and increased sum of minor diameters of suspicious celiac lymph nodes were detected in 16,4,0 of 20 patients with tumor regression and 15,10,1 of 26 patients without tumor regression,respectively,with no statistically significant difference (Z =-1.629,P＞ 0.05).The changes of gastric wall thickness of primary lesion and sum of minor diameters of celiac lymph nodes before operation were not consistent to that after operation in 3 patients.CT examination showed gastric wall thickness of primary lesion reduced after chemotherapy,and sum of minor diameters of celiac lymph nodes didn't change;pathological staging and clinical staging were respectively in staging ypN0 and ycN1.Conclusion According to the TNM staging of AJCC (Sth edition),the distance between tumor center and boundary of EGJ is judged through coronal measured values and axial formula method and therefore determining to select staging system of esophageal cancer or gastric cancer,meanwhile,rectifying over T3 staging of Siewert Ⅱ gastric cancer and increasing overall accuracy of clinical staging.

Objective: To study the safety and effectiveness of infra-hepatic inferior vena cava clamping combined with Pringle’s maneuver during hepatectomy. Methods: The databases of PubMed, Cochrane Center, CNKI, VIP, Wan Fang were searched to extract the relevant data for the meta-analysis using the Revmanage 5.3 software. Results: A total of 14 studies with 1595 patients were included in this meta-analysis. The results showed that total bleeding during the combined clamping was significantly lower than that of the Pringle’s maneuver alone (MD=-314.59, 95%CI: -362.37~-266.81, P<0.05). Bleeding during hepatectomy was significantly lower (MD=-217.79, 95% CI: -284.57~-151.00, P<0.05); so was the intraoperative blood transfusion rate (OR=0.48, 95% CI: 0.36~0.62, P<0.05). The incidence of complications was significantly lower (OR=0.74, 95% CI: 0.57~0.95, P<0.05). However, there were no significant differences in operation time, length of hospital stay, intraoperative monitoring index and postoperative liver and kidney function recovery (P>0.05). Conclusions Infra-hepatic inferior vena cava clamping combined with Pringle’s maneuver in hepatectomy was safe and reliable. Compared with the Pringle’s maneuver alone, the combined technique reduce bleeding and the incidence of complications. This technique is worth promoting in clinical practice.

OBJECTIVETo explore the toxic effect of fluoride on the human thyroid cells (Nthy-ori 3-1) and its mechanism.

METHODSNthy-ori 3-1 cells were exposed to 0.0, 0.1, 1.0, 3.0 mmol/L of sodium fluoride (NaF) in vitro. After 24 hours incubation, 3 (4,5-Dimethylthiazol-z-yl)-3, 5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to measure cell viability and the LDH leakage rate. Reactive oxygen species (ROS) level, constituent ratio of the cell cycle, and apoptosis rate were measured by flow cytometry.

RESULTSComparing to viability of control group (set as 100.00%), the cell viability of the 1.0, 3.0 mmol/L fluoride-treated groups (76.64 +/- 9.13)%, (64.04 +/- 6.32)% were significantly decreased (all P values <0.01). LDH leakage rate and ROS level of the 3.0 mmol/L fluoride-treated group ((48.66 +/-7.15)%, (29993.50 +/- 1786. 86) FI) were significantly increased (all P values <0.01) compared to control group ((35.24 +/- 3.02)%, (13021.33 +/- 1067.55) FI). The G0/G1 phase cells of the 1.0 mmol/L fluoride-treated group ((40.76 +/- 5.65)%) were lower than control group (60.09 +/- 1.76)% (P < 0.01), yet the percentage of cells in S phase ((54.05 +/- 4.59)%) were higher than the control group (32.59 +/- 2.43) % (P < 0.01). Comparing to control group ((9.64 +/- 3.44)%), the percentage of apoptosis cells increased in the 3.0 mmol/L fluoride-treated group ((20.09 +/- 3.22)%) (P < 0.01).

CONCLUSIONTo Nthy-ori 3-1 cells, fluoride under experimental concentrations decreases cell viability, improve the LDH leakage rate, and ROS level. It blocks the cells in S phase and induce cell apoptosis.

Apoptosis ; drug effects ; Cell Cycle ; Cell Division ; Cell Line ; Fluorides ; toxicity ; Humans ; Reactive Oxygen Species ; analysis ; Thyroid Gland ; cytology ; drug effects