Objective To summarize the characteristics and clinical value of multi-slice spiral computed tomography (MSCT) examination in the biliary gallbladder-duodenal fistula.Methods The imaging data of 28 patients with gallbladder-duodenal fistula who were admitted to the Wuxi No.2 Hospital of Nanjing Medical University between June 2012 and March 2015 were retrospectively analyzed.All the 28 patients received MSCT examinations,and the imaging changes were observed and analyzed,including the location of lesions,figures of fistulous tract,shrinking or enlarging gallbladder,pneumotosis and stones of gallbladder or bile duct.Results Of the 28 patients,fistula located at the duodenal bulb were detected in 14 patients,junction of the bulb and the descending part of the duodenum in 2 patients,ascending duodenum in 7 patients,horizontal part in 5 patients.Indirect signs of biliary gallbladder-duodenal fistula included that gallbladder volume in 28 patients was significantly reduced,cross sectional area of gallbladder was 2 cm × 1 cm-6 cm × 2 cm,and gallbladder wall was thickened with an average thickness of 5 mm (range,4-9 mm).Adhesion of gallbladder and duodenum,unclear boundary,structure disorder and visible effusion surrounding gallbladder were detected.Among 21 patients with biliary gas,19 patients had pneumotosis of gallbladder and 17 had biliary pneumatosis.Biliary stones were detected in 23 patients including cholecystolithiasis in 19 patients,gallbladder neck stones in 6 patients,common bile duct stones in 13 patients and intra-and extra-hepatic cholangiolithiasis in 1 patient.The diverticulum signs appeared in the duodenum of 11 patients.The direct signs of MSCT in the biliary gallbladder-duodenal fistula included that fistulous tract of 13 patients clearly showed and some were dumbbell-shaped.Two and 2 patients were complicated with gallstone ileus and multiple liver abscesses,respectively.The diagnostic results of MSCT in 28 patients were compared with the results of operative exploration,with an diagnostic concordance rate of 78.6％ (22/28),and the diagnostic concordance rate of gallbladder stones was 82.1％ (23/28).Conclusions The indirect signs of MSCT in patients with biliary gallbladder-duodenal fistula include pneumotosis of gallbladder or/ and biliary gas,gallbladder neck stones or common bile duct stones,gallbladder shrank,adhesion of gallbladder and duodenum,unclear boundary,diverticulum signs in the adhesions of duodenum and gallbladder,and clear orificium fistulae of gallbladder-duodenum is a direct sign of MSCT.

OBJECTIVE:To virtually screen lignanoid compounds with inhibitory effect of histone deacetylase(HDAC)by vir-tual screening method. METHODS:Using“lignanoid”as keyword,requiring CNKI,VIP,PubMed and other database,lignanoid compounds were collected as ligand to establish ligand base, histone deacetylase receptor HDAC2 (PDB code:4LXZ) and HDAC8 (PDB code:1T69) were selected from PDB database,and then ligands and 3D active site of receptors were docked by SYBYL-X 2.0 software. The affinity of receptors to ligand was reflected by total score. RESULTS:345 lignanoid compounds, 4LXZ and 1T69 primary ligand were used to establish ligand base which included 347 ligands. Ligands No.275,271,110,200, 056,258,181,129,037,270,187 were demonstrated good affinity with receptors HDAC2 and HDAC8. Ligands and receptors residue were docked via hydrogen bond. CONCLUSIONS:Lignanoid compounds have inhibitory effect on HDAC;virtual screen-ing method is effective in natural product activity prediction,which can provide quick access to and theoretical guidance for new pharmacological studies of lignanoid compounds.

Objective To translate and revise the Individualized Care Scale-Patient Version(ICS-P) into Chinese,then to assess the reliability and validity of the Chinese version of the Individualized Care Scale-Patient Version (C-ICS-P).Methods Standard forward-back translation techniques were used in the translation of the ICS-P according to the Brislin translation model.Cross-cultural revision of the translated ICS-P was carried out through group discussion and pretesting.Totally 223 patients were recruited through convenience sampling method from a tertiary hospital in Changsha and investigated using general information questionnaire and the C-ICS-P,and its reliability and validity were assessed.Results The C-ICS-P contained two subscales,and both C-ICS-P-A and C-ICS-P-B contained 3 factors explaining 61.330％ and 65.263％ of the total variance.The dimensions of C-ICS-P-A were clinical characteristics (6 items),personal life characteristics (4 items) and participation willingness (5 items);the dimensions of C-ICS-P-B were clinical care (6 items),personal life care (4 items) and decisional control over care (5 items).The Cronbach's α coefficients of C-ICS-P-A and its dimensions were 0.897,and 0.730～0.774;the Cronbach's α coefficients of C-ICS-P-B and its dimensions were 0.909,and 0.688～0.754.Split-half reliability was 0.856 for C-ICS-P-A and 0.688～0.754 for its dimensions;split-half reliability was 0.889 for C-ICS-P-B and 0.750～0.758 for its dimensions.Analysis of content validity of the C-ICS-P indicated that I-CVI was at least 0.83,S-CVI was 0.943.Conclusion The reliability and validity of C-ICS-P are satisfactory and well meet the requirements of psychological measurement,indicating C-ICS-P is a reliable and valid instrument in the context of Chinese culture.

Objective To investigate the role of cerebrospinal fluie( CSF)cytology on eiagnosis of meningeal cancer. Methods Retrospectively analyzee the clinical eata of 23 cases with meningeal cancer. Results (1)Of 23 patients,CSF eetection of 17 cases were showee with cancer cells at the first lumbar puncture,3 cases at the 2ne lumbar puncture,2 cases at the 3re eetection,ane 1 case at 4th eetection.(2)Of 23 cases with cerebrospinal fluie cytology positive patients,17 cases were carriee cranial MRI scan. The MRI showee that 9 were normal ane 8 cases were brain parenchyma ane meningeal image enhance. Ten cases were performee the enhancee MRI scan,5 cases were with extensive meningeal thickening,3 cases were showee meningeal extensive enhancement of brain surfer ane intracranial cerebral sulci,1 case was the circular shaeow strengthen at eifferent size at next to the eouble lateral parietal,occipital ane left cerebella hemisphere,ans 1 case was with tough brain surface ane abnormally long T1,long T2 signal at lateral ventricles,thire ventricle, fourth ventricle epeneymal.(3)The relationship between the primary tumor ane cancer eetection in cerebrospinal fluie:19 patients were foune with primary tumor lesions,inclueing 5 cases leukemia(3 cases with acute lymphoblastic leukemia,2 cases with acute non-lymphocytic leukemia),4 cases with lung cancer,3 cases with breast cancer,2 cases with brain lymphoma,1 case with melanoma,1 case with Hoegkin′s lymphoma,l case with nasopharyngeal carcinoma, 1 case with vaginal squamous cell carcinoma, 1 case with gastric carcinoma. Conclusion Multiple cerebrospinal fluie cytology eetection may improve meningeal cancer eetection rate. CSF cytology eetection can improve eiagnosis rate of meningeal cancer. No relationship between the eetection of cancer cells in cerebrospinal fluie ane brain MRI meningeal lesions,ane the further research neee to be eone with expaneing the sample size.

OBJECTIVETo investigate the feasibility of in vivo tumor detection using magnetic resonance (MR) molecular imaging with targeted magnetic nanoparticles as imaging probe.

METHODSTargeted probe was synthesized by covalently linking the recombinant human gonadotropin releasing hormone analog (the targeting portion) with the ultrasmall superparamagnetic iron oxide nanoparticles (the imaging portion). The imaging portion served as the control material. The in vitro tumor cell experiment and the in vivo experiment using nude mice bearing tumors were carried out to test the targeting ability of the probe. In the in vitro experiment, the targeting probe and control materials were incubated separately with A549 cells which had high affinity to gonadotropin releasing hormone. Then the cells were taken out and lysed. The resultant solution was then subjected to MR imaging. The T2 value of the solutions was measured and compared. In the in vivo experiment, the targeting probe was administered into nude mice bearing A549 tumors. Dynamic MR imaging was carried out to measure the signal and T2 value of the tumor. The control material was also administered into control group of nude mice, and dynamic magnetic resonance imaging was performed. The T2 value of the tumor in both groups were recorded and compared.

RESULTSBoth the in vitro and in vivo experiments proved the targeting ability of targeted probe. Compared with control material, the targeting probe had higher combining ability with tumor cells.

CONCLUSIONMR molecular imaging of tumor can be realized by using targeting magnetic nanoparticles.

Adenocarcinoma ; diagnosis ; pathology ; Animals ; Cell Line, Tumor ; Dextrans ; metabolism ; Drug Delivery Systems ; Feasibility Studies ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; metabolism ; Humans ; Image Enhancement ; methods ; Lung Neoplasms ; diagnosis ; pathology ; Magnetic Resonance Imaging ; methods ; Magnetics ; Magnetite Nanoparticles ; Male ; Mice ; Mice, Nude ; Molecular Imaging ; Nanoparticles ; Neoplasm Transplantation ; Recombinant Proteins ; metabolism

AIMTo develop limited sampling strategy (LSS) for estimation of C(max) and AUC(0-t) and assessing the bioequivalence of two pioglitazone hydrochloride (PGT) preparations.

METHODSHealthy subjects (n = 20), enrolled in a bioequivalence study, were received 30 mg PGT po of reference or test formulation. The plasma concentration of PGT was determined by the validated HPLC method. A multiple linear regression analysis of the Cmax and AUC(0-t) against the PGT concentration for the reference formulation was carried out to develop LSS models to estimate these parameters. The models were internally validated by the Jackknife method and externally validated using simulated sets generated by Monte Carlo method. The best model was employed to assess bioequivalence of the two PGT formulations.

RESULTSThe linear relationship between pharmacokinetics parameters and single concentration point was poor. Several models for these parameters estimation met the predefined criteria (r2 > 0.9). The Jackknife validation procedure revealed that LSS models based on two sampling times (C1, C2.5 and C1.5, C2.5 for C(max); C1.5, C9 and C2.5, C9 for AUC(0-t) predict accurately. Mean prediction errors (MPE) were less than 3%, and mean absolute prediction error (MAE) were less than 9%. The prediction error (PE) beyond 20% was less than 5% of total samples. Model external validation by Monte Carlo simulated data indicated that the most informative sampling combinations were C1.5, C2.5 for C(max), and C1.5, C9 for AUC(0-t), respectively. MPE and MAE of the proposed models were less than 5% , and 9% respectively. The PE beyond 20% was less than 5% of the total. Bioequivalence assessment of the two PGT formulations, based on the best LSS models, provided results similar to those obtained using all the observed concentration-time data points, and indicated that the two PGT formulations were bioequivalent.

CONCLUSIONThe LSS method for bioequivalence assessment of PGT formulations was established and proved to be applicable and accurate. Thus, it could be considered appropriate for PGT bioequivalence study with inexpensive cost of sampling acquisition and analysis. Key words: pioglitazone hydrochloride; limited sampling strategy; Monte Carlo simulation; bioequivalence

Administration, Oral ; Adult ; Area Under Curve ; Chromatography, High Pressure Liquid ; Humans ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Sample Size ; Therapeutic Equivalency ; Thiazolidinediones ; administration & dosage ; blood ; pharmacokinetics

AIMTo determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).

METHODSTwenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile.

RESULTSMDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population.

CONCLUSIONThe MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.

Administration, Oral ; Adult ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Exons ; Genes, MDR ; genetics ; Genetics, Population ; Genotype ; Humans ; Male ; Mouth ; metabolism ; Polymorphism, Genetic

OBJECTIVETo evaluate the effects of microscopic observation drug susceptibility (MODS) in detecting susceptibility of Mycobacterium tuberculosis (MTB) onto four first line anti-tuberculosis drugs.

METHODThe 24-hole cell culture plates were used to test drug susceptibility of MTB on liquid medium, and the best detecting condition of MODS assay was probed; 66 clinical isolates susceptibility to streptomycin (S), isoniazid (H), rifampin (R) and ethambutal (E) were evaluated by using MODS assay and Lowenstein-Jensen (L-J), thereafter, all the inconcordance of isolates between MODS and L-J were tested for the minimal inhibitory concentrations (MIC).

RESULTSConcordance rate of the susceptibility to S, H, R and E in 66 clinical isolates detected by MODS and L-J was 97.0%, 90.9%, 95.5% and 86.4% respectively. If the results obtained by L-J were taken as a golden standard, the sensitivity, specificity, positive and negative predictive value (PPV and NPV) as well as accuracy of susceptibility test to S detected by MODS was 96.0%, 97.6%, 96.0%, 97.6% and 97.0%; 100%, 85.4%, 81.0%, 100% and 90.9% to H; 96.2%, 95%, 92.6%, 97.4% and 95.5% to R; 73.7%, 91.5%, 77.8%, 89.6% and 86.4% to E. There were 20 inconsistent results of 16 isolates by comparing MODS with L-J, and MIC yielded 16 results of those 14 isolates showing identical results with those of the MODS, while 4 results of other 4 isolates identical with L-J.

CONCLUSIONMODS method simultaneously provides drug susceptibility to S, H, R and E. MODS might be one of the rapid tools to diagnosing multidrug-resistant tuberculosis as it is rapid, simple, inexpensive and has high concordance with L-J drug susceptibility test.

Bacteriological Techniques ; methods ; Drug Resistance, Multiple, Bacterial ; Microbial Sensitivity Tests ; methods ; Mycobacterium tuberculosis ; drug effects ; Predictive Value of Tests ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant ; microbiology

OBJECTIVETo evaluate serum-vascular endothelial growth factor (S-VEGF) in the differentiation of solitary pulmonary nodule (SPN).

METHODSSerum level of VEGF of 68 patients with SPN was measured by ELISA kit, and compared with the control group of 20 normal subjects. The nodules were diagnosed by operation and pathology.

RESULTSThe median level of S-VEGF was 42.5 (range from 10 to 170) pg/ml in the control, 44 (range from 18 to 360) pg/ml in benign nodule group and 75 (range from 18 to 890) pg/ml in lung cancer group, with significant difference observed between the nodule group and control (P < 0.01), and between the lung cancer group and the benign nodule group (P < 0.05), but not between the benign nodule group and the control. In addition, when S-VEGF in different pathologic types of the limited number of lung cancer patients were compared, no significant difference was observed.

CONCLUSIONS-VEGF is valuable in the differential diagnosis of solitary pulmonary nodule. An elevated S-VEGF level >or= 100 pg/ml in patients with SPN may strongly speak for a malignant nodule. Operation is suggested.

Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms ; blood ; diagnosis ; Male ; Middle Aged ; Solitary Pulmonary Nodule ; blood ; blood supply ; diagnosis ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells.

METHODSFifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot.

RESULTSCompared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01).

CONCLUSIONSExtract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.

Animals ; Cathepsin B ; metabolism ; Cystatin C ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hydrogen Peroxide ; Lutein ; pharmacology ; Macular Degeneration ; prevention & control ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Inbred C57BL ; Pigment Epithelium of Eye ; drug effects ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Xanthophylls ; pharmacology ; Zeaxanthins