Objective: To assess the role of NADPH oxidase-related oxidative stress in the intimal hyperplasia induced by adventitial injury. Methods: Animal model of vascular adventitial injury was established by combining collogenase digestion and mechanical dissection. HE staining was used to observe the morphological changes of the vessels after adventitial injury; RT-PCR was used to examine the mRNA expression of NADPH oxidase subunit p22phox and antioxidant heme oxygenase-1; and fluorescence probe was employed to detect the ROS production in the vessels. Results: Adventitial injuries could induce intimal hyperplasia lesions in the vessels; they also led to the elevated expression of p22phox/HO-1 mRNA and increased production of ROS. Conclusion: The vascular adventitia is involved in the pathological process of intimal hyperplasia, and oxidative stress caused by increased NADPH oxidase activity may be one of the mechanisms.

Chlorides ; metabolism ; Diarrhea ; congenital ; Humans

BACKGROUND: Ghildren refractory clubfoot includes idiopathic multiple contracture, untreated idiopathic clubfoot in older children and failure cases of repeated operations. It is very difficult to treat this type of children patients. It has important significance in the exploration of new therapeutic methods.OBJECTIVE: To improve the therapeutic effectiveness of refractory clubfoot in children with Ilizarov method.DESIGN: a self-controlled study.SETTING: Department of Orthopedics, Nanjing Children' s Hospital, Nanjing Medical University.PARTICIPANTS: Totally 3 cases of children idiopathic multiple contracture, 2 cases of idiopathic clubfoot in children aged more than 10 years old without treatment and 6 cases of postoperative recurrent idiopathic clubfoot were admitted by the Department of Orthopedics of Nanjing Children' s Hospital Affiliated to Nanjing Medical University during 1999 to 2000. All cases manifested abnormal ankylosis and shortening deformity in foot.METHODS: Twelve refractory clubfeet in eleven patients were treated with the Ilizarov method. After achilles tendon lengthening and posterior release,kieschner' wires or olive wires with tension were penetrated through multiple planes of the middle lower 1/3 of tibia, calcaneus and the 1st to the 5th metatarsals, which were fixed respectively to external bone fixer of a ring,half-ring or horseshoe shape and connected with each other by multiple screw bars into a three-dimensional external bone fixing set. Plantarflexion, inversion, adduction and shortening deformities were corrected by the adjustment of the distance between each part of the external bone fixing set through extension, compression, and rotation, etc., and navicular and cuboid osteotomy.MAIN OUTCOME MEASURES: All 11 cases were followed up for 2 to 10 years with an average period of 4. 5 years. Indices like foot morphology,talocrural articualr activity range and deformity correction were observed during the follow up.RESULTS: The results were excellent in 5 cases (6 feet), good in 4 cases (4 feet), fair 2 cases(2 feet) according to the Garceau standard scale. The rate of excellent and good clinical results was 83.3%. Mild forefoot adduction was left in 2 feet of 2 cases and quite obvious tarsal articular ankylosis was found in 4 feet of 4 cases; however, there were no significant differences of gait and load bearing between these patients and normal children.CONCLUSION: The Ilizarov technique is a safe and effective method for the treatment of refractory children clubfoot while its indications should be controlled strictly.

Objective To establish the HPLC characteristic chromatogram of Shenshitong Granules. Methods The chromatographie fingerprints were obtained through Thermo Hypersil GOLD-C18 column (4.6 mm×250 mm, 5μm) with the gradient elution solvent system composed of acetonitrile-0.2% phosphoric acid (0-20 min, 5%→10% acetonitrile;20-40 min, 10%→12%acetonitrile;40-60 min, 12%→14%acetonitrile;60-90 min, 14%→20%acetonitrile;90-120 min, 20%→28%acetonitrile). The detective wavelength was set at 280 nm;the flow rate was 1.0 mL/min;the column temperature was maintained at 30 ℃;the analysis time was 120 min. Results The HPLC characteristic chromatogram was built on basis of 10 batches of Shenshitong Granules, including 27 common peaks which contain the characteristic peaks of 6 Chinese herbal medicines, such as Radix Salvia Miltiorrhizae, Herba Lysimachiae, etc. Conclusion The established HPLC fingerprint has high sensitivity and good repeatability, and can be available for quality evaluation of Shenshitong Granules.

Objective To investigate the safety of cleaning and disinfection of duodenoscope used in endoscopic retrograde cholangiopancreatography (ERCP).Methods The duodenoscopes,which were used in Endoscopy Center of Digestive Disease Hospital,Heilongjiang Provincial Hospital from May 4 to May 31 2016,were cleaned manually and disinfected with sterilization powder.The samples from elevator and elevator channel were collected for bacterial culture to evaluate the safety of clinical application of duodenoscope.Results Among 60 high level disinfections,one was excluded because disinfectant concentration wasn't effective.Among 59 elevator samples no positive cultures were detected,while among 59 channel samples,4(6.8％) cultures were positive and all from the same duodenoscope,including 3 cases of Klebsiella pneumonia and 1 case of Pseudomonas aeruginosa.Conclusion Sterilization powder is effective for disinfection of duodenoscope used for ERCP.Residual organic material can't be excluded from elevator sample even if it is negative for culture.Duodenoscope with high level disinfection still has the risk of transmitted infection,and should be monitored regularly by culture and reprocessed in time.

Objective To evaluate the efficacy and safety of clip traction in endoscopic submucosal dissection (ESD) for heterotopic pancreas in stomach.Methods Data of 62 patients with pathologically confirmed heterotopic pancreas treated by ESD between May 2013 and February 2016 were retrospectively studied in Department of Gastroenterology of Xinqiao Hospital,whose lesions were single and origins were submucosal.Thirty-six cases underwent ESD with clip traction (clip group,n=36),and 26 cases underwent ESD without clip traction (non-clip group,n =26).The procedure time,visualization of the submucosal during dissection,complications and the result of follow-up were evaluated between the two groups.Results ESD was successful in all cases.The procedure time was significantly shorter in the clip group than in the non-clip group (19.35±10.34 min VS 27.02± 14.27 min,t'=2.333,P=0.023),and good visualization was obtained by applying clip traction.The rate of bleeding in the clip group was 55.6％ (20/36),and that in the non-clip group was 61.5％ (16/26).There was no significant difference between the two groups(x2 =0.222,P =0.638).Moreover,perforation did not occur in the clip group,but occurred in one patient in the non-clip group (3.8％,1/26).There was no significant difference between the two groups (P =0.419).All patients were followed up,there was no recurrence.Conclusion ESD is effective and safe for heterotopic pancreas in stomach.Clip traction can shorten the operation time and reduce complications of ESD.

Objective To study the bioequivahnce of a single dose galanthamine hydrobromide orally disintegrating tablets in Chinese healthy volunteers.Methods Twenty healthy volunteers were divided into 2 groups.Twenty mg single oral dose of galanthamine hydrobromide orally disintegrating tablets was given to 20 heahy volunteers.The concentrations of plasma samples collected from the volunteers respectively were determined by LC-MS/MS.The pharmaeokinetie parameters were calaulated by DAS ver 2.1 software.Results The main pharmacokinetic parameters of galanthamine hydrobromide orally disintegrating test and reference tablets were as follows:t_(max) were(1.06±0.81)and(0.85±0.26)h;t_(1/2) were(8.39±1.60)and(8.22±1.58)h;C_(max) were (39.69±8.17)and(43.41±11.58)μg·L~(-1);AUC_(0-t) were (384.88±101.75)and(407.53±101.12)μg·h·L~(-1);AUC_(0-∞)were(396.92±105.85)and(420.10±103.73)μg·h·L~(-1),respectively.The relative bioavailability of drug was(95.5±1 6.2)%.Conclusion The two kinds of galanthamine hydrobromide tablets are bioequivalent.

Human Nestin (hNestin) has been found to express in melanoma,and its expression is positively correlated with the advanced stage of melanoma.However,the precise role of hNestin in the development of melanoma has not been fully understood.The present study aimed to explore the role of hNestin in the proliferation and invasion of melanoma cells.The lentivirus vector carrying a short hairpin RNAs (shRNAs) targeting hNestin (hNestin-shRNA-LV) was stably infected into human melanoma cells UACC903,which expressed high levels of hNestin.The effects of hNestin knockdown on the proliferation,apoptosis,migration of melanoma cells and the related signaling pathways were investigated by immunofluorence,Western blotting and reverse transcription polymerase chain reaction (RT-PCR),respectively.The results showed that hNestin was expressed in most melanoma specimens and the melanoma cells studied.Knockdown of hNestin expression significantly inhibited the proliferation of melanoma cells,blocked the formation of cell colony,arrested cell cycle at G1/S stage and suppressed the activation of Akt and GSK3β.hNestin-silent cells also showed a sheet-like appearance with tight cell-cell adhesion,decreased membrane expression of N-cadherin and β-catenin,and attenuated migration.Furthermore,hNestin silence resulted in the inhibition of tumor growth in vivo.Our study indicates that hNestin knockdown suppresses the proliferation of melanoma cells,which might be through affecting Akt-GSK3β-Rb pathway-mediated G1/S arrest,and hNestin silence inhibits the migration by selectively modulating the expression of cell adhesion molecules in the process of epithelial-mesenchymal transition.

OBJECTIVETo study the inhibition of the expression of bcl-xL gene induced by RNA interference in CNE-2Z cell line in addition to the inhibition of its proliferation and apoptotic induction.

METHODSSmall interfering RNAs targeting bcl-xL gene were synthesized by using web design software provided by Amnion and the silencer short interfering RNA (siRNA) construction kit; fluorescein-labeled siRNAs were done by FAM-silencer siRNA labeling kit; siRNAs were transfected into CNE-2Z cells by using lipofectamine 2000 reagent; siRNA transfection efficiencies were analyzed by fluorescent microscopy; down-regulation of bcl-xL was detected by RT-PCR; thiazolyl blue (MTT) assay was used to assess the cell growth; apoptosis of CNE-2Z cells was analyzed by flow cytometry.

RESULTSGreen fluorescence in the cells was seen clearly in FAM-labeled siRNA transfected group under the fluorescent microscope while none in the untransfected group. Different down-regulations of bcl-xL mRNA expression were found in the transfected groups. The expression of bcl-xL mRNA decreased by 10% - 70% in the siRNAs transfected CNE-2Z by RT-PCR scan analysis. The inhibitory rate of cell proliferation depended on time and concentrations to some extent. Different cell apoptosis could be induced by different concentrations of siRNA4.

CONCLUSIONSThe synthesized siRNAs in vitro were able to down-regulate the expression of bcl-xL There were different capabilities of the specific siRNAs down-regulation. The transient transfected bcl-xL siRNA4 could effectively inhibit the growth of the cancer cells and induce theirs apoptosis. It was suggested that the siRNA technique provide not only an extremely powerful tool for the functional analysis of genome but also a new method for anti-nasopharyngeal carcinoma gene therapy.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Nasopharyngeal Neoplasms ; genetics ; pathology ; RNA Interference ; RNA, Messenger ; genetics ; Transfection ; bcl-X Protein ; genetics

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.
Animals ; Anticholesteremic Agents ; chemical synthesis ; chemistry ; pharmacology ; Azepines ; chemical synthesis ; chemistry ; pharmacology ; Benzene Derivatives ; chemical synthesis ; chemistry ; pharmacology ; Chenodeoxycholic Acid ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Crystallization ; Humans ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Isoxazoles ; chemical synthesis ; chemistry ; pharmacology ; Ligands ; Molecular Structure ; Multienzyme Complexes ; chemical synthesis ; chemistry ; pharmacology ; Pregnenediones ; chemical synthesis ; chemistry ; pharmacology ; Receptors, Cytoplasmic and Nuclear ; agonists ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship