Drug eluting stents (DESs) have revolutionized the interventional cardiology over the past decade since the first DES became commercially available in Europe in 2002. Compared to bare metal stents that are deployed to keep the vessel open by mechanical force, DESs have an additional function of reducing restenosis by the action of the drug on the target site. Coatings on the stent surface which ensure the maximum delivery of therapeutic agents to the target site with minimal systematic toxicity, also play an important role in adjusting the drug release profile. Coating material and technology not only affect the surface biocompatibility and the integrity maintenance during the implanting process, but also decide the way of drug delivering and transmitting from the coating. This paper reviews the basic principles of DES coating design, the categories of DES coatings, the commonly used clinical DES coatings and their efficiency in reducing restenosis, and finally provides the future perspectives for DES coatings.
Biocompatible Materials ; Drug Carriers ; Drug Delivery Systems ; Drug-Eluting Stents ; Lactic Acid ; Phosphorylcholine ; Polyethylenes ; Polyglycolic Acid ; Prosthesis Design ; Titanium

Objective To develop the humanized animal model for RA cartilage erosion,and study the mechanisms of its pathogenesis.Methods RA synovium and normal human cartilage under the kidney cap- sule of the SCID mice were engrafted,and were maintained for 4～16 weeks.In addition,mice underwent simi- lar surgery except the engraftment served as controls.After 4,8,12 or 16 weeks,the mice were killed and the grafts were harvested and the cartilage destruction was assessed histologically by haematoxylin/eosin-stained paraffin sections.Results Histological examination revealed the presence of infiltration of RA synovium cells into the cartilage after 4 weeks and the cartilage was destructed evidently.These studies demonstrated that the RA-SCID model maintained many of the phenotypic and functional features of RA.Conclusion This RA-SCID mouse is a useful animal model for study of the pathogenesis and the development of new drugs for RA patients.

OBJECTIVETo investigate the apoptosis effect induced by D-limonene on BGC-823 gastric cancer cells.

METHODSThe expression of p53, bc1-2 in BGC-823 cells and qualitative, quantitative index of cell apoptosis were detected with MTT, electron microscopy, flow cytometry and immunohistochemical method.

RESULTSD-limonene could induce the formation of apoptotic bodies in a dose- and time-dependent manner. The expression of bcl-2 protein decreased and p53 protein increased in BGC-823 cells treated with D-limonene, compared with the control cells.

CONCLUSIOND-limonene exerts its cytotoxic effect on BGC-823 gastric cancer cells by inducing apoptosis.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cyclohexenes ; Dose-Response Relationship, Drug ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Terpenes ; administration & dosage ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Objective To explore the clinical effects of two doses of atorvastatin in patients with acute ischemic stroke .Methods A total of 128 patients with acute ischemic stroke were randomly divided into two groups ,64 cases in each group .The patients in atorvastatin 20 mg group were given atorvastatin 20 mg daily , and the patients of the atorvastatin 10 mg group were given atorvastatin 10 mg daily.The treatment lasted for six months.Blood lipid , nerve function defect grading , atherosclerotic plaque area and adverse drug reactions were observed before and after six months.Results The total effective rate in the atorvastatin 20 mg group (98.4%) was significantly higher than that in the atorvastatin 10 mg group (84.4%) (P<0.05).Blood lipid, nerve function defect grading and atherosclerotic plaque area were obviously improved in two groups (P<0.05), and the atorvastatin 20 mg group had a better improvement against the atorvastatin 10 mg group ( P <0.05 ) . The incidence of adverse drug reactions in two groups were 4.7%, no statistical signifi-cance (P>0.05).Conclusion Aatorvastatin 20 mg can better improve the clinical symptoms , blood lipid level as well as atherosclerotic plaque area in patients with acute ischemic stroke , accordingly improve the quality of life in those patients .

OBJECTIVETo review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations.

METHODSThe 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing.

RESULTSAll patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered.

CONCLUSIONMacrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; metabolism ; Amino Acid Sequence ; Base Sequence ; Brain Diseases, Metabolic ; diagnosis ; genetics ; metabolism ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; metabolism ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mutation ; Sequence Alignment

OBJECTIVETo investigate the prognostic influence on long-term overall survival (OS) from treatment with Chinese medicine (CM) and chemotherapy or targeted therapy in advanced non-small-cell lung cancer (NSCLC) patients.

METHODSThe clinical data of 206 advanced NSCLC patients who were treated with CM and Western medicine in Beijing Cancer Hospital from April 1999 to July 2013 were retrospectively analyzed. Long-term survivors were defined as OS ≥ 3 years after treatment with CM and chemotherapy. Twenty-eight patients had OS ≥ 3 years, 178 had OS < 3 years, and all clinical data were statistically analyzed with the Cox model. Variables were gender, age, smoking status, performance status (PS) score, pathological type, clinical stage, first-line chemotherapy, targeted therapy, and use of CM. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank sequential inspection. Multivariate survival analysis was used to analyze the meaningful factors of univariate survival analysis with the Cox model.

RESULTSThe survival rate of patients with OS ≥ 3 years was 13.6% (28/206). Cox multivariate regression analysis showed that PS score, clinical stage, disease control rate to first-line chemotherapy, and use of CM were independent factors of longterm OS (all <0.05). However, gender, age, smoking, and use of epidermal growth factor receptor tyrosine-kinase inhibitor were not significant (P>0.05).

CONCLUSIONPS score, clinical stage, disease control rate to first-line chemotherapy, and use of CM are probably independent prognostic factors for long-term OS in patients with advanced NSCLC.

Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Molecular Targeted Therapy ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Smoking ; adverse effects ; Survival Analysis ; Time Factors

OBJECTIVETo explore the impact factors and treatment of post pancreatoduodenectomy complications.

METHODSThe clinical data of 412 cases between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed retrospectively. There were 232 male, 180 female. Univariate and multivariate logistic regression model were used to identify the risk factors related to occurrence of postoperative complications.

RESULTSThe overall postoperative morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter and pancreatic texture had effects on postoperative pancreatic fistula statistically. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. Delayed gastric empting occurrence in the patients with pylorus-preserving pancreaticoduodenectomy was higher than those with standard pancreaticoduodenectomy significantly. The multivariate Logistic regression analysis revealed that duct diameter and pancreatic texture were the independent risk factors of pancreatic fistula. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were independent risk factors of bleeding. There were no statistically significant differences between the radical group and the standard group when postoperative complication rates were analyzed (P < 0.05).

CONCLUSIONSPancreaticojejunal anastomoses by means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and end-to-end invaginated pancreaticojejunostomy is fit for the patients with undilated pancreatic duct. The prevention of postoperative bleeding depends on total uncinate process resection and meticulous hemostatic technique during operation. The pancreatic fistula is one of the most important factors which can result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV resection and extended lymphadenectomy do not significantly increase the morbidity rates.

Aged ; Anastomosis, Surgical ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Middle Aged ; Pancreaticoduodenectomy ; adverse effects ; methods ; Postoperative Complications ; diagnosis ; etiology ; therapy ; Retrospective Studies ; Risk Factors

OBJECTIVETo analyze the clinical features and SLC25A13 gene mutations of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia.

METHODSThe patient was subjected to physical examination and routine laboratory tests. Blood amino acids and acylcarnitines, and urine organic acids and galactose were analyzed respectively with tandem mass spectrometry and gas chromatographic mass spectrometry. SLC25A13 gene mutation screening was conducted by high resolution melt (HRM) analysis.

RESULTSThe petechiae on the patient's face and platelet count (27×10(9)/L, reference range 100×10(9)/L-300×10(9)/L) supported the diagnosis of immunologic thrombocytopenic purpura (ITP). Laboratory tests found that the patient have abnormal coagulation, cardiac enzyme, liver function and liver enzymes dysfunction. Tandem mass spectrometry also found methionine to be increased (286 μmol/L, reference ranges 8-35 μmol/L). The patient did not manifest any galactosemia, citrullinemia and tyrosinemia. Analysis of SLC25A13 gene mutation found that the patient has carried IVS16ins3kb, in addition with abnormal HRM result for exon 6. Direct sequencing of exon 6 revealed a novel mutation c.495delA. The same mutation was not detected in 100 unrelated healthy controls. Further analysis of her family has confirmed that the c.495delA mutation has derived from her farther, and that the IVS16ins3kb was derived from her mother.

CONCLUSIONThe clinical features and metabolic spectrum of citrin deficiency can be variable. The poor prognosis and severity of clinical symptoms of the patient may be attributed to the novel c.495delA mutation.

Amino Acid Metabolism, Inborn Errors ; genetics ; pathology ; Calcium-Binding Proteins ; deficiency ; genetics ; DNA Mutational Analysis ; methods ; Female ; Glycine N-Methyltransferase ; deficiency ; genetics ; Humans ; Infant ; Mitochondrial Membrane Transport Proteins ; genetics ; Organic Anion Transporters ; deficiency ; genetics ; Pedigree ; Purpura ; genetics ; pathology ; Seizures ; genetics ; pathology

OBJECTIVETo assess the feasibility of high-resolution melting (HRM) analysis for screening patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

METHODSBased on previous studies on SLC25A13 gene in Chinese patients with NICCD, four hotspot mutations (851del4, 1638ins23, IVS6+5G>A and IVS16ins3kb) were selected. Results of the HRM analysis was validated using 50 negative controls and 20 patients with NICCD whose genotypes were confirmed previously by direct sequencing. With the established protocol, 171 suspected patients were enrolled. Samples with abnormal melting curves were further validated by DNA sequencing.

RESULTSHRM analysis can accurately determine the genotypes of all negative controls and patients. The sensitivity and specificity of the technique reached 100% (70/70). The melting curves of samples with the same genotype were highly reproducible. In 171 suspected patients, seven NICCD patients were detected by HRM. Identified mutations have included one case of 851del4 homozygote, one case of IVS6+5G>A heterozygote, 3 cases of 851del4 heterozygotes, one case of [IVS6+5G>A]+[ 851del4] and one case of [1638ins23+IVS16ins3kb]+[1638ins23]. All mutations were subsequently confirmed by DNA sequencing.

CONCLUSIONHRM analysis is a convenient, high-throughput and rapid technique for the screening of NICCD patients.

Anion Transport Proteins ; genetics ; Base Sequence ; Calcium-Binding Proteins ; deficiency ; China ; Citrullinemia ; diagnosis ; genetics ; metabolism ; DNA ; chemistry ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Mitochondrial Proteins ; genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Denaturation ; Organic Anion Transporters ; deficiency ; Sensitivity and Specificity