Aim To study the cardiotoxicity of celastrol to zebrafish embryo.Method 48 h post-fertilization zebrafish embryos were used as model for analysis of heart toxicity and were treated with various concentrations of celastrol.6,12,24 h after treatment morphological and functional changes of embryos hearts were observed.Results Cardiotoxicity was not found in embryos during 24 h treatment with 1 ?mol?L-1 concentration of celastrol.Toxic symptoms of embryos were caused by 2,3,4 ?mol?L-1 concentrations of celastrol with appearance of heart linearization,heart membrane hemorrhage and hemocytes accumulation in cardiac region.Moreover,heart rate decreased significantly with increase of concentration and prolongation of treatment.The EC50(24 h)of decrease of heart rate was about 1.78 ?mol?L-1.Conclusion Celastrol is cardiotoxic to zebrafish embryo.

Aim To investigate the modeling of breast cancer in zebrafish embryos and its related protein expression. Methods 48hpf wild type AB/ TG(Transgenic) zebrafishs were micro-in-jected with breast cancer cell line: MCF-7,T-47D, MDA-MB-231 respectively, the relationship between the number of tumor and model application was investigated, and the number of sub-intestinal veins(SIVs) was detected under confocal microscope, as well as the metastasis of tumor cells in embryos; then the ze-brafish xenografts of MB-231 were co-cultured with tofacitinib/ptk787 for 48 h, optical density(OD) of the cell survival and subintestinal veins(SIVs) were evaluated under confocal micro-scope, and Western blot(WB) analysis was used to test micro-circumstances related protein. Results When the number of in-oculated cells was more than 200 per embryo, xenograft model rate woule be more than 0. 90;MB-231 xenografts showed metas-tasis feature in zebrafish, which could be inhibited by tofacitinib (P < 0. 01), while the number of xenograft MB-231 cells was reduced significantly(P < 0. 01); in another zebrafish xenografts SIVs assay, the tumor could promote the proliferation of SIVs, and 4 mg·L - 1 PTK787 showed inhibiton effect( P < 0. 01). Western blot showed 4d T-47D xenograft zebrafish got more HER2 expression than AB embryos; VEGFa expression in ze-brafish MB-231 model group was higher, and model zebrafish P53 expressi was higher after treated by tofacitinib. Conclusion A zebrafish xenograft model of human brest cancer can be es-tablished, which demonstrates applicability for screening com-pounds in drug discovery studies.

As a model organism, zebrafish have many advantages over other animal models and is suitable for studies on establishment of human disease model and mechanism.In zebrafish, there are two phases of endocrine formation during early development, which are directed by concomitant activity of many signaling pathways.Zebrafish pancreas possess similar cell structure with that of other animals, which can express various endocrine hormones including insulin.The main organs required for metabolic control, such as the pancreas, islet, and insulin sensitive tissue (muscle, liver) are conserved in zebrafish, and the mechanisms of glucose regulation in zebrafish is similar to that seen in mammalian models.These render it an excellent model to study glucose metabolism.Hyperglycemia in zebrafish model can be induced by administration of the diabetogenic drug, streptozotocin (STZ), alternatively immersion of the fish in glucose solution and water, or disturbing of signaling pathways associated with glucose metabolism.Glucose levels in adult zebrafish blood or embryo tissue and phenotype of retinal cell layers or retinal vasculature are the commonly used measurement organs in zebrafish diabetic models.

Objective To evaluate family economic burden of children with autism, or with physical disability or with intellectual disability.Methods227 parents of children with autism, children with physical disability, children with intellectual disability and normal children were interviewed for their family economic burden.ResultsThe medical cost and caring cost of children with disability were significantly more than those of normal children, and the education cost, clothes cost and amusement cost of children with disability were significantly less than those of normal children. Family income was only affected by education level of parents. Families of children with disability received more economic assistance than families of normal children except families of autistic children. More children the family had, less economic assistance the family acquired. Compared with normal children, the family economic burden of children with disability were as following, children with autism (19582.4 RMB per year), children with physical disability (16410.1 RMB per year), children with intellectual disability (6391.0 RMB per year). ConclusionFamilies of children with autism, children with physical disability and children with intellectual disability had heavier economic burden than families of normal children.

OBJECTIVETo prepare effervescent osmotic pump tablet (EOPTs) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen and to study the mechanism of drug released of that tablets.

METHODSince compound Danshen consist of compounds with polyphenolic groups or carboxyl groups, such as phenolic acids, flavonoids, and triterpenoids that they were acidic. EOPTs were prepared from tablet cores which containing NaHCO3 as effervescent, NaCL and manitol as osmotic agents, HPMC as retarding agents coating with CA membrane. And study the mechanism of drug released according to the change of tablet osmotic pressure.

RESULTThe results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release EOPTs. The drug was completely released from the device with a zero-order release rate over 12 h.

CONCLUSIONEOPTs are Successfully obtained EOPT which the drug is released from the device over 12 h and the release mechanism of EOPTs is explained.

Coronary Disease ; physiopathology ; Drug Compounding ; Drugs, Chinese Herbal ; administration & dosage ; metabolism ; Infusion Pumps ; Osmosis ; Salvia miltiorrhiza ; metabolism ; Tablets ; Time Factors

OBJECTIVETo prepare pulsed-release tablet (PTS) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen.

METHODPTS were achieved by coating the core which contains drugs, CMS-Na, lactose, succinic acid and MCC with separation layer (Eudragit RL), swelling layer (HPMC E5), and controlled-release membrane (Eudragit RS-RL-EC).

RESULTThe results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release from the two-step release system. And it indicated that swelling was the basis and prerequisite for drug release from PTS, and the diffusion, organic acid-induced, and osmotic pumping mechanism were involved in drug release, but the latter they were the dominant factors.

CONCLUSIONSuccessfully obtained the PTS of a certain lag-time behind the rapid release which indicate that after bed time administration of such device, the drug plasma concentration-time curve CAN meet the requirements of chronotherapy of cardiovascular disease.

Benzaldehydes ; metabolism ; Catechols ; metabolism ; Chromatography, High Pressure Liquid ; Coronary Disease ; drug therapy ; Diffusion ; Drug Compounding ; methods ; Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; metabolism ; therapeutic use ; Ginsenosides ; metabolism ; Osmosis ; Salvia miltiorrhiza ; chemistry ; Tablets ; Time Factors

Aim To investigate the anti-angiogenesis and anti-xenograftes of UA in zebrafish larvaes. Meth-ods 24 hour post-fertilization ( hpf ) TG zebrafish was treated with different concentration of UA for 24h, and the number of intersegmental vessels( IVS) were detec-ted under fluorescent microscope respectively;then the models of AB/TG zebrafish xenografts were established by be micro-injected with SMMC-7721 or HT-29 cell at 48hpf respectively, and after cocultured with UA for 48h, optical density (OD) of the SMMC-7721 cell and subintestinal veins ( SIVs) induced by HT-29 were e-valuated under confocal microscope. Results ISV as-say showed that UA could cause IVS missing or disap-perance, inhibition ratio reaching 20. 25% and 26. 65%. UA blocked the spread of SMMC-7721 cells in zebrafish and OD value,and inhibition ratios at three concentrations were 38. 01%, 54. 69%, 61. 88%, re-spectively; in another SIVs assay induced by xeno-grafts, UA at concentration 10 and 15mg·L-1 showed that SIVs were inhibited (P<0. 01) obviously. Con-clusion UA could inhibit the angiogenesis and the growth of SMMC-7721/HT-29 xenografts,and the anti-tumor mechanism may be related with VEGFR2 expres-sion.

Objective:To compare and analyze the calcification characteristics and diagnostic efficiency of different breast lesion types using digtal breast tomosynthesis (DBT) and full-field digital mammography (FFDM).Methods:Totally 1 263 patients who underwent both DBT and FFDM at the same time from January 2015 to December 2018 in Dahua Hospital, Xuhui district, Shanghai were analyzed retrospectively. Benign and malignant calcification should be confirmed by pathology or a follow-up of 24 months or more using mammography, and the results of DBT and FFDM were taken as a gold standard. The detection rate and diagnostic efficiency of different types of benign and malignant breast calcification with the two methods were compared and analyzed. The detection rate of morphology and distribution of malignant calcification were compared among groups.Results:There were 240 cases with non-dense breast including 56 cases with benign calcification and 13 cases with malignant calcification. Meanwhile, there were 1 023 cases with dense breast, including 356 cases with benign calcification and 63 cases with malignant calcification. In the cases of non-dense breast, the detection rates of benign calcification by DBT and FFDM were 22.9% (55/240) and 21.7% (52/240), whereas the rates of malignant calcification were 5.0% (12/240) and 4.6% (11/240), all without statistically significances（χ2=0.108, 0.046, P>0.05). No significant differences were observed in the morphology and distribution of malignant calcification detection rates ( P>0.05). In the cases of dense breast, the benign calcification detection rates by DBT and FFDM were 34.2% (350/1 023) and 31.9% (326/1 023), whereas the detection rates of malignant calcification were 6.0% (61/1 023) and 4.9% (50/1 023), all without statistically significances (χ2=1.273 and 1.153, P>0.05). DBT detected more cases of amorphous and cluster distribution of malignant calcification than FFDM, with statistically significant differences (χ2=12.921 and 11.667, P<0.05). The area under ROC curve of DBT and FFDM in diagnosis of non-dense breast were 0.993 and 0.992, and 0.987 and 0.964 in dense breast, respectively, with no significant differences ( Z= 0.136 and 1.391, P>0.05). Conclusions:Compared with FFDM, DBT shows no statistical difference in the diagnostic efficiency of breast calcification. However, it has certain advantages in detecting malignant, amorphous, and clustered calcification in dense breast. DBT has a potential to improve the accuracy of BI-RADS classification of breast calcification.

OBJECTIVETo explore the impact of plasma homocysteinemia(Hcy) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients.

METHODSConsecutive 684 ACS patients undergoing first PCI in our department between January 2013 and December 2014 were prospectively enrolled.Patients were divided into 2 groups according to the pre-procedural plasma Hcy level: high-Hcy group (Hcy≥10 μmol/L, n=404) and control group (Hcy<10 μmol/L, n=280). The CIN was defined as serum creatinine ≥ 44.2 μmol/L or 25% increase compared to baseline within 48-72 h after PCI.The baseline clinical data and the ratio of CIN were compared between the 2 groups.Multivariate logistic regression analysis was used to define the independent risk factors for CIN.

RESULTSCIN occurred in 133(19.4%) out of 684 enrolled patients, and the incidence of CIN was significantly higher in high Hcy group than in the control group (22.0%(89/404)vs. 15.7%(44/280), P=0.040). After adjusting the confounding factors, including age, acute myocardial infarction, co-morbidities(hypertension, diabetes mellitus, and old myocardial infarction), laboratory examination (level of cystatin C and uric acid), glomerular filtration rate, left ventricular ejection fraction, angiographic and procedural characteristics (3 diseased vessels, multiple stent implantation), treatment at admission (spironolactone, digoxin), multivariate logistic regression analysis showed that high Hcy was independently associated with the development of CIN (OR=1.70, 95%CI 1.60-2.64, P=0.021).

CONCLUSIONElevated Hcy prior PCI is an independent risk factor of CIN in ACS patients undergoing first PCI.

Acute Coronary Syndrome ; Diabetes Mellitus ; Glomerular Filtration Rate ; Humans ; Hyperhomocysteinemia ; Incidence ; Kidney Diseases ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Risk Factors ; Ventricular Function, Left

Objective To explore the spatial description of Keshan disease(KD)and to provide a basis for reasonable allocation of health resources and for making precision prevention and control strategies. Methods In 2013 and 2014, the KD's condition, prevention and control measures and their effects were investigated in the diseased affected counties in the provinces through combination of case search and key survey. Results A total of 16(100.0%,16/16)diseased provinces,315(96.0%,315/328)diseased counties were surveyed,and 1 562 people with KD were detected in 281 000 residents, the detection rate was 55.6/10 000. Chronic and latent KD detection rates were 8.9/10 000(250)and 46.7/10 000(1 312),respectively.There were 261(82.9%)diseased counties that had reached the control standards of KD,and 54(17.1%)did not meet the control standards,which mainly distributed in the provinces of Henan, Inner Mongolia, Gansu and Shanxi. Conclusions The detection rate of KD has been at a low level, but in Henan, Inner Mongolia, Gansu, and Shanxi, there are prevalent KD areas that have not yet reached the control level.This part of the areas should be treated as key prevention and control areas of KD.