Escitalopram, a selective serotonin re-uptake inhibitor (SSRI) antidepressant which is the (S)-enantiomer of citalopram, is worldwide used for the treatment of depressive and anxious disorders in clinical practice, however, recent data have indicated that high therapeutic escitalopram doses may cause the potential of QTc prolongation effect, which is a predisposing factor for arrhythmia. Nevertheless, in March 2012, the Food and Drug Administration (FDA) issued a safety bulletin advising the daily dosage of escitalopram should be restricted to a maximum of 20 mg daily in healthy adults and 10 mg maximum in high risk patients (eg>60 years of age). In this review, we aimed to investigate what factors can affect and how escitalopram gives rise to QTc prolongation.

Adult ; Female ; Humans ; Ovarian Diseases ; diagnosis ; Ovarian Neoplasms ; diagnosis ; Pregnancy

OBJECTIVETo quantify the interleukin (IL)-1beta mRNA and IL-6 mRNA expression induced by lipopolysaccharides ([PS) extracted from Porphyromonoas endodontalis (P. endodontalis) in osteoblasts, and to relate P. endodontalis LPS to the bone resorptive pathogenesis in the lesions of chronic apical periodontitis.

METHODSMG63 cells was pretreated with PD98059 or SB203580 for 1 h and then treated with P. endodontolis LPS for 6 h. The expression of IL-1beta mRNA and IL-6 mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) technique.

RESULTSThe production of IL-1beta mRNA induced by P. endodontalis LPS decreased in osteoblasts pretreated with PD98059. Both of the production of IL-1beta mRNA and JL-6 mRNA induced by P. endodontalis LPS decreased in osteoblasts pretreated with SB203580.

CONCLUSIONThe synthesis of IL-1beta mRNA stimulated by Pendodontalis LPS in MG63 probably occur via extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen activated protein kinase (MAPK) signal transduction system. The synthesis of IL-6 mRNA stimulated by P.endodontalis LPS in MG63 probahly occur via p38MAPK signal transduction system.

Humans ; Imidazoles ; Interleukin-6 ; Lipopolysaccharides ; MAP Kinase Signaling System ; Osteoblasts ; Porphyromonas endodontalis ; Pyridines ; RNA, Messenger ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases

OBJECTIVE To investigate the regulation of{O2 (2,4-dinitrophenyl)1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1, 2-diolate} (JS-K), a nitric oxide donor, on tumor energy metabolism in H22 tumor-bearing mice. METHODS The hepatoma animal model in BALB/c mice was established with H22 cell line. The inoculated mice were randomly divided into four groups. The JS-K group and model group received JS-K (0.75 and 1.50 mg?kg-1) and saline via tail the vein intravenously once every 3 d for 14 d, and 5 injections, respectively. The fluorouracil (5-FU) group received 5-FU 20 mg·kg-1 by intra-peritoneal injection once a day for 14 d. On the 15th day after the first administration, mice were sacri-ficed and the tumor, thymus and spleen were isolated and weighed immediately. The tumor growth inhibitory rate and organ index were calculated. The activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), succinate dehydrogenase (SDH), adenosinetriphosphatase (ATPase), and the levels of lactic acid (LD) and adenosine triphosphate (ATP) in tumor tissues were determined by colorimetric method. The expression of hypoxia-inducible factor 1 alpha (HIF-1α) and hexokinaseⅡ(HKⅡ) in the tumor tissue was analyzed by Western blotting. RESULTS Compared with model group, the tumor mass of JS-K 0.75 and 1.50 mg · kg-1 groups was significantly reduced (P<0.01), and the tumor growth inhibitory rate was 23.9%and 50.3%, respectively. There was no diffrence in thymic and splenic indexes between JS-K group and model group. The activity of HK, PFK, SDH, PK and ATPase of tumor tissue in model group was 22.6±3.7, 14.4±2.6, (10.5±2.6) U·g-1protein, (12.9±3.2) kU·g-1 protein and (0.70 ± 0.10) mmolPi · g-1protein · h-1, respectively, which dropped by 42.0%, 26.6%, 22.7%, 23.3%and 21.7%respectively (P<0.01, P<0.05) in JS-K 1.50 mg?kg-1 group. Compared with the model group, the level of ATP of tumor tissue in JS-K 1.50 mg?kg-1 groups dropped by 16.6%(P<0.01) and the level of LD in JS-K 0.75 and 1.50 mg?kg-1 groups dropped by 38.7%and 59.4%(P<0.01), respectively. In addi-tion, the expression of HIF-1αof tumor tissue in JS-K 1.50 mg?kg-1 group was decreased (P<0.01), and the expression of HKⅡ of tumor tissue in JS-K 0.75 and 1.50 mg?kg-1 groups was decreased signifi-cantly (P<0.05, P<0.01). CONCLUSION JS-K can inhibit the growth of tumor in H22 tumor-bearing mice and its mechanism may be related to regulating the tumor energy metabolism by inhibiting glycolysis and aerobic oxidation.

Objective: To explore the predictors in patients of paroxysmal atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). Methods: A total of 142 PAF patients received RFCA in our hospital from 2013-03 to 2016-03 were studied. The patients were divided into 2 groups: Recurrence group, n=46 and Non-recurrence group, n=96. Clinical data was compared between 2 groups and AF recurrent predictors were studied by single and multivariate Logistic regression analysis. Based on quartiles of uric acid (UA) level, the patients were categorized in another set of 4 groups: Q1 group, UA<259 &mu;mol/L, n=33, Q2 group, UA 259-320 &mu;mol/L, n=37, Q3 group, UA 321-380 &mu;mol/L, n=37 and Q4 group, UA>380 &mu;mol/L, n=35. The influence of UA on AF recurrence was measured by Kaplan-Meier test, the predictive value of UA combining metabolic syndrome (UA+MS) on AF recurrence was studied by ROC curve analysis. Results: The BMI, diabetes, MS, AF duration, CHADS2 score, creatinine, UA and BNP were different between Recurrence group and Non-recurrence group, all P<0.05. Logistic regression analysis indicated that AF duration (OR=1.02,95% CI 1.01-1.03, P=0.002), UA level (OR=1.01, 95% CI 1.00-1.01, P=0.046) and MS (OR=4.73, 95% CI 1.36-16.45, P=0.014) were the independent predictors for AF recurrence. UA quartile analysis indicated that gender, BMI, MS, creatinine, LVEF and the incidence of AF recurrence had signifcant discrepancy by different UA levels, all P<0.05. ROC curve showed that the predictive values for UA+MS in AF recurrence had the sensitivity at 80.4%, specificity at 74.1% (AUC 0.79±0.04, 95% CI 0.71-0.89, P=0.0001), for UA in AF recurrence had the sensitivity at 73.9%, specificity at 57.2% (AUC 0.66, 95% CI 0.56-0.76, P=0.02); UA+MS had the higher predictive value than UA alone, P<0.05. Conclusion: Both UA and MS were related to AF recurrence, high UA level combining MS had certain predictive value for AF recurrence in PAF patients after RFCA.

The aim of this study was to investigate the proliferation-inhibitory and inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5 µmol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5 µmol/L DAC for 48 h was detected by flow cytometry with PI staining and AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The results indicated that DAC (0.01 - 0.5 µmol/L) inhibited the proliferation of NB4-R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and 0.064 µmol/L respectively. DAC (0.05 - 5 µmol/L) induced NB4-R2 cell apoptosis in dose-dependent manner with down-regulation of MDR 1 gene expression. It is concluded that a low concentration of DAC (< 0.5 µmol/L) inhibits cell proliferation, while higher concentration of DAC (1 or 5 µmol/L) induces apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.
Apoptosis ; drug effects ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Resistance, Neoplasm ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; pathology ; Tretinoin ; pharmacology

Objective To explore the thoughts and medication rules of the contemporary inheritors of Lingnan LUO's Gynecology in differentiating and treating menopausal syndromes based on data mining technology.Methods The medical records of menopausal syndrome differentiated and treated by the contemporary inheritors of Lingnan LUO's Gynecology in clinic were collected.The Ancient and Modern Medical Records Cloud Platform(V2.3.5)was used to perform frequency statistics,association rule analysis,cluster analysis and complex network analysis of the data of medical records.Results A total of 191 medical records and 191 prescriptions were finally included,involving 160 kinds of Chinese medicinals.The statistics of four-examination information and syndrome types showed that the pathogenesis of menopausal syndrome was characterized by deficiency of the origin,which resulted in the dysfunction of healthy qi and the disturbance of the pivot,and then multiple viscera were involved;among the syndrome types,liver and kidney yin deficiency syndrome was the most common type.There were 26 high-frequency Chinese medicinals with the frequency being or over 40 times,and the top 5 Chinese medicinals were Lilii Bulbus,Codonopsis Radix,Corni Fructus,Paeoniae Radix Alba,and Rehmanniae Radix Praeparata.Most of the medicines were sweet in flavor and mild in nature,and had the meridian tropism of the liver,heart,kidney and spleen meridians.A total of 15 pairs of high-confidence drug combinations were obtained after association rule analysis.Cluster analysis of high-frequency Chinese medicinals yielded 5 core drug combinations.The complex network analysis revealed the core prescription which was composed of Rehmanniae Radix Praeparata,Corni Fructus,Cuscutae Semen,Lilii Bulbus,Ziziphi Spinosae Semen,Salviae Miltiorrhizae Radix et Rhizoma,and Margaritifera Concha.The association rule analysis showed that the drug pairs with high frequency of use were Ligustri Lucidi Fructus-Corni Fructus,Ligustri Lucidi Fructus-Salviae Miltiorrhizae Radix et Rhizoma.Conclusion For the treatment of menopausal syndrome,the contemporary inheritors of Lingnan LUO's Gynecology take the therapy of nourishing liver and kidney as the key,and also adopt the therapies of nourishing the heart and calming the mind,benefiting qi and invigorating the spleen,and harmonizing the pivot.The medicines prescribed by the inheritors mostly are sweet-light and mild tonics,and their prescription and medication rules are consistent with Professor LUO Yuan-Kai's academic thoughts.

Objective To investigate the perinatal complications, birth defects and growth of children conceived through intracytoplasmic sperm injection (ICSI). Methods A total of 575 children conceived by ICSI in our reproductive medical center, were studied. The follow-up study would include items as pregnant complications, neonatal complications, birth defects in perinatal period, subsequently detected birth defects, body weight and body length/height growth. Results Prematurity and low birth weight of ICSI children were higher in the multiple births than in the singleton births. The rates of materal gestational hypertension, neonatal asphyxia, respiratory distress syndrome, infection diseases were higher in the multiple pregnancies than in the singleton pregnancies(P＜0.05). Eleven ICSI children had died. Ten of them died in the neonatal period and they were preterm infants. One fullterm singleton ICSI child died of hepatoblastoma at the age of 2. The rate of birth defects in perinatal period was higher in ICSI children of multiple pregnancies than in the general population (P＜0.05). The body weight and body length/height of most ICSI children had obtained the standard range between 1 to 3 year-olds. Conclusion The higher rates of perinatal complications in ICSI children were closely related to multiple pregnancies.

Laser induced breakdown spectroscopy ( LIBS ) was proposed to rapidly discriminate microbe species. Ten species of microbes were prepared in lab. Filter papers were selected as substrate for enriching bacteria and enhancing the quality of LIBS. The images of plasma were collected by ICCD camera and LIBS spectra were obtained by spectrometers. The results displayed that the images and spectra were different from 10 bacteria. It was demonstrated that this method was feasible to discriminate bacteria species by analyzing image and/or spectroscopy. Furthermore, nine smooth and multiple scattering correction ( MSC) were utilized to preprocess the LIBS full-spectrum data in the wavelength range of 200-420 nm and 560-680 nm. And principal component analysis ( PCA) and PCA-RF ( Random forest) were compared to validate the accuracy of discrimination. The investigation showed that the PCA-RF model coupled with suitable methods in preprocessing data could identify bacteria. The accuracy was 99. 6% for ten species of microbes by evaluating LIBS spectra in training set, and 96. 7% in predicting set. This report indicated that it is feasible to differentiate bacteria species by analyzing LIBS spectra.

Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.