OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

BackgroundTrabeculectomy is the most efficient surgical treatment. Prevention failure of bleb cicatrix would lead to unsatisfactory postoperative intraocular pressure (IOP) controlling and unsatisfactory success rate. The aim of this study was to evaluate the 5-year outcomes of trabeculectomy with a cross-linked sodium hyaluronate gel implantation for Chinese glaucoma patients.

MethodsThis is a prospective, case-controlled study. Patients who were to be applied first-time trabeculectomy in the Department of Ophthalmology of Peking University Third Hospital between 2010 and 2012 were included in the study. Totally, 60 eyes were randomly assigned to the trabeculectomy group (TA group) or the trabeculectomy with cross-linked sodium hyaluronate gel implantation group (TH group). Follow-up was finished at 1 week, 1 month, 3 months, 1 year, 3 years, and 5 years after the operation. The statistical index of demographic data, IOP, bleb shape, and any complications or medications or surgical procedures were recorded and assessed by SPSS 19.0 software through independent t-test, one-way analysis of variance (ANOVA) and Pearson's Chi-square test, respectively.

ResultsThe baseline IOP was comparable between the two groups (t= -1.00, P= 0.32) while the postoperative IOP was significantly lower in the TH group at 1, 3 and 5 years' time points (P = 0.00, P= 0.01 and P = 0.01, respectively). According to the Indiana Bleb Appearance Grading Scale, the height and extent of bleb were better in the TH group at all follow-up time points (P < 0.05), however, the comparison of bleb vascularity showed no statistical difference (P > 0.05). TA group had a higher percentage of complications (13% vs. 3%) compared to TH group; however, there was no statistical difference in the comparison of each statistical item (P > 0.05, respectively). The complete success at 5 years was higher in the TH group than that in the TA group (78% vs. 54%, P = 0.03).

ConclusionOur results suggested that implantation of cross-linked sodium hyaluronate gel with trabeculectomy was more efficient and would improve the prognosis of glaucoma patients.

Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Glaucoma ; therapy ; Humans ; Hyaluronic Acid ; therapeutic use ; Intraocular Pressure ; Male ; Middle Aged ; Prospective Studies ; Trabeculectomy ; Treatment Outcome

OBJECTIVETo investigate the effect of infiltrating mast cells on neuroendocrine differentiation (NED) and docetaxel sensitivity of prostate cancer (PCa) cells in vitro.

METHODSHuman PCa cell lines (LNCaP and C4-2) were co-cultured with human mast cell line (HMC-1) in Transwell chambers. Androgen receptor (AR) was silenced in C4-2 cells using sh-AR lentivirus, and p21 was knocked down and overexpressed by transfecting C4-2 cells with pLKO.1-sh-p21 and pCMV-p21, respectively. The morphological changes of LNCaP and C4-2 cells were observed. MTT assay and colony formation assay were used to assess the proliferation of LNCaP and C4-2 cells. CCK8 assay was used to detect the cell viability of C4-2 cells following docetaxel trreatment. RT-qPCR and Western blotting were performed to determine the mRNA and protein expressions of neuroendocrine markers, AR and p21 in the cells.

RESULTSCo-culture with HMC-1 cells enhanced the neuroendocrine phenotypes, inhibited the proliferation and up-regulated the expression of p21 in LNCaP and C4-2 cells. P21 positively regulated NED through a non-AR-dependent signaling pathway, while p21 knockdown partially reversed NED promoted by the mast cells. PCa cells co-cultured with HMC-1 cells showed increased resistance to docetaxel, and silencing p21 partially reversed docetaxel resistance in PCa cells.

CONCLUSIONInfiltrating mast cells up-regulates p21 to promote NED and increase docetaxel resistance in PCa cells in vitro.

Objective To investigate the effect of laser artificial shrinkage(LAS)on pregnancy outcome in vitrification of human expanded blastocysts.Methods We selected 3859 frozen-thawed blastocyst-stage embryo transfers from January 2014 to December 2015.The transfers were divided into LAS group(n=3 176)and non-LAS group(n=683),which were then subdivided into ＜36 y subgroup and ≥36 y subgroup according to their age.Main outcomes measures were thawing rate,implantation rate and clinical pregnancy rate.Results Thawing rate, clinical pregnancy rate and implantation rate were 97.32%(5 453/5 603),66.81%(2 118/3 170),and 53.55%(2 912/5 438)in LAS group.In non-shrink group,they were 95.13%(1 173/1 233),62.70%(427/681),and 49.74%(582/1 170),which did not significantly differ from those in the former group(P＜0.05).Further analysis of the subgroups showed that thawing rate was significantly higher in LAS group than in non-shrink group of patients＜36 y(97.27% vs.95.33%;P＜0.05).Thawing rate and biochemical pregnancy rate were significantly higher in LAS group than in non-shrink group in patients ≥36 y(97.75% vs.93.66%;65.45% vs.50.65%,P＜0.05). Cancellation rate was not significantly different between the two groups(0.19% vs.0.29%, P ＞ 0.05). Conclusion LAS technique can increase thawing rate,clinical pregnancy rate and implantation rate before cryopreservation of blastocysts.

Objective To investigate the effect of matrine on the cardiac function and left ventricular remodeling in rats with isoproterenol (ISO) -induced cardiac hypertrophy.Methods Seventy-two adult male SD rats were randomly divided into six groups as follows:normal group,model group,control group (matrine 200 mg · kg-1 · d-1),large-,medium-and small-dose experimental groups(matrine 200,100,50 rng · kg-1 · d-1),and there were 12 rats in each group.The 5 mg · kg-1 · d-1 isoproterenol (ISO) was subcutaneously injected to establish the model of chronic pathological left ventricular hypertrophy in model group and experimental groups.The 0.9％ NaCl was administrated to rats in normal group and control group.The aforementioned medications were offered once daily to 12 rats of each group for 7 successive days.On day 8,cardiac function was evaluated by the biological function experiment system.The hematoxylin-eosin staining was used to observe pathological morphology changes of the left ventricular tissues.Insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1(TGF-β1)levels in serum were determined by ELISA.Expression levels of IGF-1and TGF-β1 genes in myocardial tissues were detected by real time fluorescence quantitative PCR method.Results After drug-concerned treatment,serum IGF-1 levels in normal group,model group,control group,large-,medium-and small-dose experimental groups were separately (2.04 ± 0.52),(3.66 ± 0.97),(2.08±0.95),(1.98 ± 0.98),(1.93 ±0.78) and (1.59 ± 0.48)ng · mL-1;moreover,serum TGF-β1 levels in those groups were (94.11 ±10.63),(139.98 ± 37.64),(90.36 ± 30.02),(84.55 ± 45.70),(74.74 ± 42.18) and (72.84 ± 21.43) pg · mL-1.In contrast with model group,the serum IGF-1 or TGF-β1 levels were lowered in other groups (P ＜ 0.05).Similarly,expression levels of cardiac IGF-1 genes in normal group,model group,control group,large-,medium-and small-dose experimental groups were sequentially 3.34 ± 3.27,10.91 ± 7.44,3.09 ± 1.86,0.62 ± 0.44,0.64 ± 0.26,1.00 ± 0.35;furthermore,expression levels of cardiac TGF-β1 genes were successively 0.70 ± 0.67,10.97 ± 9.86,0.63 ± 0.32,1.25 ± 0.98,1.76 ± 2.40,0.86 ± 0.46;and hence the TGF-β1 gene levels in model group were much higher than those of other groups (P ＜ 0.01).Conclusion Matrine significantly improved the cardiac function in rats with ISO-induced left ventricular hypertrophy and simultaneously regulated the cardiac hypertrophy-causing cytokines.

The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacokinetics ; Camptothecin ; analogs & derivatives ; pharmacokinetics ; Chromatography, Liquid ; Colon ; metabolism ; Half-Life ; Injections, Intravenous ; Lung ; metabolism ; Mice ; Nanoparticles ; administration & dosage ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

OBJECTIVE: To develop an LC-MS/MS method for determination of irinotecanin nanoparticles and its metabolite SN-38 in rats whole blood. METHODS: The drugs were using liquid-liquid extraction method in rats of whole blood, with diazepam as an internal standard. The Shim-pack XR-ODS (2.0 mm×100 mm, 2.2 μm) column was used. The gradient mobile phase consisted of 5 mmol·mL-1 ammonium formates solution (A) and Acetonitrile (B) at the flow rate of 0.3 mL·mL-1, the injection volume was 10 μL and the column temperature was 35°C. The total time of the analysis was 4.2 min. Electrospray ionization sourceand selective ion monitoringwere employed. RESULTS: The linear ranges of irinotecan and SN-38 were 1-2000 and 0.5-100 ng·mL-1, respectively; lower limit of quantification (LLOQ) was 1 and 0.5 ng·mL-1, respectively; the intra-batch RSD were less than 9.43% and 11.39%, respectively, the inter-batch RSD were less than 9.73% and 11.79%, respectively. The extraction recoveries were 73.7%-117.4% and 61.7%-75.5%, respectively. CONCLUSION: The method had less interference and is sensitive, accurate for the determination of irinotecan and its metabolite SN-38 in the whole blood of rats.

To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Camptothecin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Female ; Injections, Intravenous ; Male ; Mice ; Nanoparticles ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Tissue Distribution

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.
Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Atorvastatin Calcium ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Cross-Over Studies ; Dogs ; Drug Interactions ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; blood ; pharmacokinetics ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Random Allocation ; Thiazolidinediones ; administration & dosage ; blood ; pharmacokinetics

OBJECTIVE: To study the effects of betaine, taurine, lycium barbarum polysaccharides (LBP) in Lycium barbarum L. on the pharmacokinetics of β-carotenes(β-C) in beagle dogs. METHODS: Six Beagle dogs divided into two groups randomly, were given β-carotenes or β-carotenes combined with betaine, taurine or LBP, respectively. The concentrations of β-caro-tenes, retinol and retinol palmitate in dog plasma at different time points were determined by HPLC method. The main pharmacokinetic parameters were processed by the software DAS2.0.1. RESULTS: Compared with β-carotenes group, the t1/2 of β-carotenes was prolonged (P < 0.05) after coadministration of betaine, and the AUC0-t, and MRT of β-carotenes were increased, whereas the clearance was decreased (P < 0.05) after coadministration of taurine. No significant difference was found between β-carotenes pharmacokinetic parameters of the β-carotenes and β-carotenes + LBP groups (P > 0.05). CONCLUSION: Other ingredients in Lycium barbarum L. could influence the pharmacokinetic process of in Beagle dogs. The functions of nourishing liver and improving eyesight by Lycium barbarum L. did not result from a single component, but from its multi-ingredients.