Objective: To explore the mechanism of damaging effect of advanced glycation end products (AGEs) on human umbilical vein endothelial cell (HUVEC) in vitro. Methods: The HUVEC was incubated with exogenous AGEs for 12 h, and ergamine (Hi) and catalase (CAT) were used as control. The activity, monolayer permeability, apoptosis rate, biochemical indexes and morphous changes were detected in HUVEC. Results: The activities of HUVEC were dose-dependently reduced by exogenous AGEs(40 mg/L, 120 mg/L and 160 mg/L), meanwhile the monolayer permeability, the malondialdehyde (MDA) content and apoptosis rate were increased，the activity of superoxide dismutase（SOD）was decreased（P < 0.05, respectively). There was no significant difference in damaging effect between exogenous AGEs and Hi(P ＞ 0.05). The damaging effect of exogenous AGEs was obviously inhibited by CAT in HUVEC. Conclusion: Exogenous AGEs induced the damaging effect on vascular endothelial cells, which may be related to the oxidative stress.

OBJECTIVE:To evaluate the rationality and validity of chemical medicine tablet production equipment cleaning pro-cedure. METHODS:Among several chemical medicines prepared by similar production technology as Metoprolol succinate sus-tained-release tablets,Captopril tablets,Isosorbide mononitrate tablet and Metformin hydrochloride tablet,Metoprolol succinate sus-tained-release tablets had strongest toxicity and were included in validation test. The production equipment was cleaned and disinfect-ed according to cleaning procedure. The point which was most difficult to clean could be wiped and sampled by using the cotton swab method. The detection limit and the limit of quantitation of the residue limits were verified as well as the recovery rate of wip-ing,in order to evaluate whether the results meet the requirements. RESULTS:The cotton swab method is adopted to wipe sample and detect the point which is most difficult to clean. The visible foreign body has not been found in each sampling point. The amount of residual drug is <29.75 μg/cotton bud,and microbial limits are <50 CFU/cotton bud,indicating test items are in line with the standard. CONCLUSIONS:The cleaning method can effectively clean the production equipment,and can effectively pre-vent product contamination and cross contamination to ensure the quality,efficacy and safety of the next batch of products.

Objective To investigate the effect of sertraline on the viability and the expression of tyrosine hydroxylase (TH) and phosphorylated ERK1/2 in NGF-induced rat pheochromocytoma (PC12) cells.Methods NGF-induced PC12 cells were pretreated or directly treated with different concentrations of sertraline for 24 or 48 hours and the pretreated groups were then subjected to serum withdrawal condition. Then cell viability was determined by the cell counting Kit-8 (CCK-8). The expression of Tyrosine hydroxylase (TH) and pERK1/2in NGF-induced PC12 cells was determined by immunohistochemistry and western blot respectively. Results The viability of NGF-induced PC12 was improved after administration with sertra]ine. After 24h sertraline administration, the cells activity of PC 12 cells at 20μM ( 1.32 ± 0. 11 ) , 10μM ( 1. 17 ± 0.05 ) of direct effect, and 20μM ( 1.15 ±0.11 ) of protect effect increased dramatically as compared with control group. But high dose ( 50μM )sertraline express high toxic effect to PC12 cells. The expression of TH was increased by sertraline 20 μM at both 24h(ratio of TH/β-actin = 1.27 ±0.05) and 48h(ratio of TH/β-actin = 1. 23 ±0.08) compare with control group,and the expression of pERK1/2 also increased dramatically by sertraline 20 μM at both 24h (ratio of (pERK1/2)/β-actin = 1.41±0.05) and 48h( ratio of (pERK1/2)/β-actin = 1.40 ±0.06) compare with control group(P＜0. 01, P ＜ 0. 05). Immunohistochemistry showed similar results. Conclusion These data suggest that the neuroprotective effect of sertraline may play an important role in depression therapy, and this effect might be mediated by TH and pERK1/2 up-regulation.

Objective To compare the dosimetric difference on organ at risk (OAR) in intensitymodulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) in treatment with cervical carcinoma. Methods 36 cases of cervical cancer patients accepted radiotherapy both on IMRT and 3D-CRT in the same time,clinical target volume (CTV) focused on primary tumor and its lymphatic drainage area.Lymphatic drainage area was determined as follows:1.0 cm extension were added to the margin of pelvic vessels,the obturator lymph nodes region was extended by 1.8 cm from the pelvis inner margin.CTV does not include pelvic tissue. Data of dose distribution and irradiation volume of OAR on the basis of distributing on 45 Gy and 50 Gy were analyzed individually. The margins of planning target volume (PTV) was obtained based on CTV margins by which added 1.0 cm extension in inferior and superior directions,0.7 cm were added in all other directions. Results With the comparison of variety on irradiation volume of organs at risk (OAR) by DVH in both groups,underlying the treatment dose 45 Gy,the individual volume of D30,D40 and D45 were all lesser in IMRT plan than that of 3D-CRT plan. Even on the dose 50 Gy at pelvic wall lymph nodes regions,the volume of OAR was lesser than that in 3D-CRT plan.Conclusion In the radiotherapy of cervical cancer,IMRT should have improved protections for tumor surrounding OAR which has domestic superiority in clinical application.

Objective To study the inhibition effect of non custodial terpenes-3β-alcohol to experimentally in-duced autoimmune encephalomyelitis in guinea pigs. Methods Different doses (25 mg/kg, 50 mg/kg and 100 mg/kg) of non custodial terpenes-3β-alcohol were given to the experimentally induced autoimmune encephalomyelitis model of guinea pigs by gavage for 8 weeks. Plasma levels of CD4+/CD8+, IL-1, IL-2, IL-6, IL-10, neuropeptide Y (NPY), beta endorphin (β-EP) , transforming growth factor-β(TGF-β), matrix metalloproteinase (MMP-2), nitric oxide synthase (NOS) and leuko-cyte differentiation antigen CD3 were assessed. The brain neuron morphology changes was observed under light microscopy while its ultrastructure changes was observed under electron microscope. NOS expression in neurons was observed through immunofluoresce technology. Results Non custodialterpenes-3β-alcohol inhibited the increase of plasma CD4+/CD8+, IL-1, IL-2, IL-6, IL-10, MMP-2, CD3 and NPY while decrease of plasmaβ-EP, brain TGF-β. It also increase NOS expres-sion in neuronal cytoplasm and maintained neuron morphology. Conclusion Non custodial terpenes-3β-alcohol inhibit-ed the experimental autoimmune encephalomyelitis in guinea pig.

OBJECTIVETo prepare the gastric retenting and chronopharmacologic drug delivery tablets containing sinomenine hydrochloride as a model drug, evaluate the effects of the coating layers formulation and technics on drug release behavior, and to elucidate the mechanism of drug release based on obtained results.

METHODThe gastric retenting and chronopharmacologic drug delivery tablets were prepared by press-coated technics. The types of disintegrants were chosen according to the expanding rate and the lag-time. The effects of formulation and technics of coating layer on the release characteristic of the drug were investigated by dissolution testing. The mechanism of drug release was proved by erosion test.

RESULTThe tablets had typical chronopharmacologic drug delivery properties with a lag time followed by a rapid release phase. CMS-Na was selected as the disintegrant. The lag-time was prolonged with the increase of the ratio of HPMC/carrrageenan and the amount of matrix material in coating layer. The compressing pressure and preparation method of coat material had minor influence on the lag-time of the tablets. Coating layer erosion and tablet core swelling were involved in the mechanism of drug release.

CONCLUSIONThe tablets had typical chronopharmacologic drug delivery properties. A suitable lag-time can be achieved by adjusting formulation of coating layer to meet the requirement of chronotherapy.

Chemistry, Pharmaceutical ; Drug Chronotherapy ; Drug Delivery Systems ; methods ; Humans ; Morphinans ; chemistry ; pharmacokinetics ; Stomach ; drug effects ; Tablets, Enteric-Coated ; chemistry ; pharmacokinetics

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

Objective: To explore the value of SYNTAX revascularization index (SRI) on evaluating the long-term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug-eluting stents (BP-DES) and define the best threshold of SRI for predicting all-cause mortality in these patients. Methods: Data used in this study derived from the I-LOVE-IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, non-inferiority study. A total of 1 829 patients implanted with BP-DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, myocardial infarction(MI), stroke, and/or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut-off point of SRI for 48-month all-cause mortality. The Cox regression analysis was used to identify independent predictors of the all-cause death and PoCE at 48 months. Results: Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all-cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut-off point to predict the all-cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48-month all-cause mortality (HR=2.06, 95%CI 1.25-3.38) and PoCE (HR=1.34, 95%CI 1.09-1.66). Conclusions SRI serves as a good index for predicting long-term prognosis and SRI<65% is an independent predictor of 48-month PoCE and all-cause mortality for CAD patients with BP-DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

Objective To explore the value of SYNTAX revascularization index (SRI) on evaluating the long?term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug?eluting stents (BP?DES) and define the best threshold of SRI for predicting all?cause mortality in these patients. Methods Data used in this study derived from the I?LOVE?IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I?LOVE?IT 2 trial was a prospective, multicenter, randomized, assessor?blinded, non?inferiority study. A total of 1 829 patients implanted with BP?DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48?month patient?oriented composite endpoint (PoCE), a composite of all?cause mortality, myocardial infarction(MI), stroke, and / or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut?off point of SRI for 48?month all?cause mortality. The Cox regression analysis was used to identify independent predictors of the all?cause death and PoCE at 48 months. Results Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all?cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut?off point to predict the all?cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48?month all?cause mortality ( HR=2.06, 95%CI 1.25-3.38) and PoCE ( HR=1.34, 95%CI 1.09-1.66). Conclusions SRI serves as a good index for predicting long?term prognosis and SRI<65% is an independent predictor of 48?month PoCE and all?cause mortality for CAD patients with BP?DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

Objective:To analyze the research hotspots and frontiers of English literature on breastfeeding quality management and provide reference for further research and practice of breastfeeding quality management in China.Methods:Relevant literature on breastfeeding quality management research included in the Web of Science core collection from 2000 to 2021 was retrieved and screened, and the included literature was analyzed with CiteSpace 5.8.R3.Results:A total of 641 papers were included, and the number of papers published increased rapidly since 2006. The top three countries with the most publications were the United States, Italy, and Australia. Research hotspots included breastfeeding promotion, breastmilk infection, and breastmilk quality control. Research frontiers comprised breastfeeding nutrition mechanism, breastfeeding for hospitalized neonatals, breastmilk bank, and quality management for breastmilk use process.Conclusions:The quality management of breastfeeding has drawn more and more attention. Most developed countries have established a joint management model of breastmilk bank and neonatology department, and made national policies for breastmilk bank management. China should increase research efforts and deepen research cooperation, explore the breastfeeding quality management plan that is truly suitable, and promote the standardization of breastmilk management process.