Objective:To study the mechanism of the effectiveness loss of methotrexate(MTX)in the treatment of rheumatoid arthri-tis.Methods:The culture system of rat whole bone marrow cells(WBMCs)and tartrateresistant acid phosphatase(TRAP)staining were utilized to evaluate osteoclastogenesis.The mRNA expression of osteoclastogenesis factors in the WBMCs culture system was examined by semi-quantitative RT-PCR.Results:Deoxyadenosine(dAdo)decreased MTX-induced suppression of osteoclastogenesis.The recov-ery effect of dAdo on MTX was partially prevented by caffeine.MTX significantly reduced mRNA expression of receptor activator of nu-clear factor kappa-B ligand(RANKL),dAdo partially recovered RANKL mRNA expression and inhibited osteoprotegerin(OPG)expres-sion.Conclusion:The accumulation of dAdo may induce the effectiveness loss of methotrexate in rheumatoid arthritis treatment.Com-bination of MTX and caffeine can be a potential therapeutic strategy.

Objective To explore the role of GRK5 in sustained β adrenergic receptor (βAR)-stimulated increased levels of oxidative stress.Methods Male SD rats (180-200 g) were separated into 4 groups according to the random principal: control group (CTRL), control with NAC supplement group (CTRL+NAC), ISO treated group (ISO), and ISO treated with NAC supplement group (ISO+NAC), with 6 rats in each group.ISO group was treated by method of intraperitoneal injection for 3 mg/(kg· d).CTRL rats received same volume of physiological saline by same method, while NAC was treated by supplement in drinking water for 15 g/L per day.After 2 weeks of treatment, BP, heart mass index (HMI), histology changes, expression of NOX4 and GRK5 of myocardium was examined.Results HMI of ISO rats was significantly higher than that of the CTRL group [(3.99±0.10 vs 3.31±0.13) mg/g, P＜0.05], and the cardio-myocyte cross-sectional area of ISO group was also significantly increased compared with CTRL group [(11 117.00±387.57 vs 4572.23±176.39) μm, P＜O.05].ISO+NAC significantly reduced the ISO-induced increases of heart weight index (3.56±0.12 mg/g, vs ISO, P＜0.05) and myocyte cross-sectional area (6160.33±141.44 μm2, vs ISO,P＜0.05).The immunohistochemistry results showed that the expression of myocardial NOX4 of ISO group was significantly higher than that of CTRL group [(10.59±1.61 vs 4.35±1.65), P＜0.05], and NAC reduced the ISO induced NOX4 expression increase [(4.67±1.25 vs 10.59±1.61), P＜0.05].Western Blot and immunohistochemistry were used to detect the protein expression of myocardial GRK5.Both results showed that there were no significant differences between ISO and CTRL, ISO+NAC and ISO group (P＞0.05).RT-qPCR detected no significant differences of myocardial GRK5 mRNA expression between ISO and CTRL, ISO+NAC and ISO groups (P＞0.05).Arterial blood pressure showed no significant difference among the 4 groups of rats (P＞0.05).No significant differences were found between rats from CTRL+NAC and CTRL group.Conclusions In the mechanism of sustained βAR-stimulated cardiac hypertrophy, GRK5 may not participate the regulation of hypertrophy-induced factor, and this process needs to be proved in further study.

A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of betamethasone in human plasma. The analyte was isocratically eluted on a Venusil XBP C8 column (200 mm ×3.9 mm ID, 5 μm) with methanol-water with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 393.3→355.2 for betamethasone and m/z 361.3→343.2 for prednisolone (IS). Betamethasone was extracted from 0.5 mL human plasma with ethyl acetate. The validation study demonstrated excellent precision and accuracy across the calibration range of 0.5 - 80.0 injection in healthy Chinese volunteers.

Aim To study the anti-tumor effect of 20(S)-Protopanaxadiol(PPD)at different concentration on human liver cell line SMMC-7721 in vivo and in vitro.Methods The subcutaneous transplantable tumor model of human liver cancer in nude mice was established and the anti-tumor effect was calculated.Cell growth rate was determined with MTT assay.The apoptosis was analyzed by FITC-AnnexinⅤ/PI and Hoechst33342 staining method,and the activity of Caspase-3 was detected.Results In vivo,PPD could obviously inhibit the growth of transplanted tumor.In vitro,PPD induced inhibition of human liver cancer SMMC-7721 cells was time-dependent and dose-dependent.The apoptotic body was observed by Hoechst33342 staining.PPD could induce cell apoptosis of SMMC-7721,and the increase of Caspase-3 activity was observed in each PPD group.Conclusion PPD could inhibit the growth of human liver cancer SMMC-7721 cells in vivo and in vitro by up-regulating the activity of Caspase-3 and inducing the cell apoptosis.

Objective:To investigate the effect of body mass index (BMI) on clinical pregnancy and neonatal outcomes in patients with polycystic ovary syndrome (PCOS) during frozen-thawed embryo transfer.Methods:A total of 650 patients with PCOS who received routine in vitro fertilization or intracytoplasmic sperm injection treatment for frozen-thawed embryo transfer from June 2014 to June 2019 in Tianjin Central Hospital of Gynecology Obstetrics were retrospectively analyzed. According to BMI, PCOS patients were divided into group A (18.5≤BMI<23 kg/m 2, n=253), group B (23≤BMI<25 kg/m 2, n=167), and group C (BMI≥25 kg/m 2, n=230). The general information, clinical pregnancy outcomes, pregnancy complications, the incidence of macrosomia and low-birth-weight infants were compared in the three groups, and the influencing factors of neonatal birth weight were analyzed. Results:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate all showed downward trend with the increase of BMI, but the differences were not statistically significant (all P>0.05). The live birth rate in group C [47.0% (108/230)] was significantly lower than those in groups A and B, with statistical significance ( χ2 =7.43, P=0.024). The late miscarriage rate was higher in group C [9.4% (13/139)] than in groups A and B ( χ2 =7.66, P=0.022). The birth rates of macrosomia in groups B [22.2% (16/72)] and group C [21.1% (16/76)] were significantly higher than that in group A, and the difference was statistically significant ( χ2 =14.15, P=0.001). There was no statistically significant difference in the incidence of gestational diabetes between the three groups ( χ2 =3.81, P=0.149). The incidence of hypertension disorders complicating pregnancy increased with the increase of BMI, and the difference was not statistically significant ( P>0.05). Regression analysis showed that macrosomia was significantly associated with maternal pre-pregnancy BMI and gestational weeks, and the risk of macrosomia increased by 15% (95% CI: 3%-28%) for every increase in maternal BMI. Conclusions:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of PCOS patients in frozen-thawed embryo transfer cycles show downward trend with the increase of BMI. Obese patients with PCOS have a significant increase in late miscarriage rate and a significant decrease in live birth rate. The incidence of hypertension disorders complicating pregnancy in PCOS patients in the obese group has an increasing trend, and the birth rate of macrosomia has increased significantly. Therefore, it is recommended that obese women with PCOS lose weight scientifically before pregnancy to improve pregnancy and neonatal outcomes.

Animals ; Biofilms ; Caenorhabditis elegans ; metabolism ; Genes, Bacterial ; Yersinia pestis ; genetics ; metabolism

Objective To investigate the clinicopathological features, postoperative survival and prognostic influencing factors of male patients with hepatocellular carcinoma (HCC). Methods The clinicopathological features and the follow-up data of 155 male HCC patients who received hepatectomy from Jan. 1995 to Dec. 2002 were retrospectively analyzed and the prognostic influencing factors were defined by uni-and multi-variate analysis. Results Compared with 24 female patients at the same period, males were about six-year older and both of their hepatitis B surface antigen (HBsAg) and liver cirrhosis positive rates were higher (P

BACKGROUND:Three-dimensional finite element has been widely used in the oral cavity field, but little is reported on the three-dimensional finite element reconstruction of the mandibular body using titanium plate. OBJECTIVE:To study the biomechanical characteristics of reconstructing the mandibular body using titanium plate. METHODS:We established a three-dimensional finite element model of mandibular body defect undergoing reconstruction using bicortical titanium screws and titanium plate. Under the simulated normal occlusion state, a 200 N vertical load was added to the central fossa of the occlusal surface of the right mandible first molar. Then, stress distribution and maximum displacement of the mandible, titanium screw, and titanium plate were analyzed. RESULTS AND CONCLUSION:Under the simulated normal occlusion state, mandible stress was concentrated in the mandibular body and mandibular branch, especial y in the anterior and posterior edges of the mandibular branch and the lower edge of the mandible. The stress in the posterior edge of the mandible was lower than that in the anterior edge of the mandible, and moreover, the contact site between the titanium plate and the mandible also presented a concentration of stress. The maximum stress of the bicortical titanium screws appeared near the screw cap, and the stress was also concentrated at the contact site between the titanium screw and the titanium plate. The maximum stress of the titanium screw at the ascending branch of the mandible was higher than that of the titanium screw at the anterior end of the defect. For the titanium plate, the stress was mainly concentrated at the fixed site of the titanium screws;the peak stress of the anterior and posterior edges of the titanium plate was found at the contact site between the anterior end of mandibular defect and the titanium stress as wel as between the ascending branch of the mandible and the titanium screw. After mandibular body reconstruction using the titanium plate, a displacement was likely to occur at the contact site between the anterior end of mandibular defect and the titanium plate. In conclusion, these findings indicate that mandibular body reconstruction using bicortical titanium screws and titanium plate is relatively stable, but the titanium plate fixed at the anterior part of the mandibular angle is prone to breakage.

A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of betamethasone in human plasma. The analyte was isocratically eluted on a Venusil XBP C8 column (200 mm x 3.9 mm ID, 5 microm) with methanol-water mol x L(-1) ammonium formate) (80:20) at a flow rate of 0.4 mL x min(-1), and detected (containing 5 mmol x L(-1) ammonium formate) (80:20) at a flow rate of 0.4 mL x min(-1), and detected with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 393.3-->355.2 for betamethasone and m/z 361.3-->343.2 for prednisolone (IS). Betamethasone was extracted from 0.5 mL human plasma with ethyl acetate. The average recovery is 88.24% and the low limit of quantitation (LLOQ) was 0.5 ng x mL(-1). The 3-day validation study demonstrated excellent precision and accuracy across the calibration range of 0.5-80.0 ng x mL(-1). The method was successfully applied to the pharmacokinetic study of compound betamethason injection in healthy Chinese volunteers.
Anti-Inflammatory Agents ; blood ; pharmacokinetics ; Area Under Curve ; Betamethasone ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Humans ; Injections, Intramuscular ; Male ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods ; Young Adult

AIM:To provide rational evidence for the administration of warfarin in clinic by investigating the utilization of warfarin in our hospital.METHODS:By retrospective analysis,the prescription of warfarin in our hospital was obtained from November 2016 to February 2017 from the system for clinical pharmacist.The general situation of the inpatient,the diagnosis of disease,the use of warfarin,and the combination of drugs and the number of International Normalized Ratio (INR) were statistically and descriptively analyzed.RESULTS:In this investigation,200 patients were included,of whom 53％ were males and 47％ were females with an average age of (55.28 ± 13.56) years.Only 21％ of the average INR values reached the predicted range (2 ＜ INR ＜ 3) during hospitalization and the average dose of warfarin was (2.62 ± 0.60)mg.In patients with INR ＜ 2,there were 66.92％ of patients combined with more than one kind of drugs,which decreased the effect of warfarin.In patients with INR ＞ 3,there were 80％ of patients combined with more than one kind of drugs,which increased the effect of warfarin.CONCLUSION:The rate of warfarin compliance is low and the warfarin-drug interactions exert a great influence on the patients whose INR value did not reach the predicted range.Thus,to keep the drug safety of patients,more attention should be paid on drug interactions and direct personalized medicine using professional knowledge of pharmacy.