Cyclophosphamide (CPA) is the most common alkylating antineoplastic agent, as well as a strong immunosuppressant that is frequently applied to autoimmune diseases and organ transplantation. It is metabolized by cytochrome P450 oxidases (CYPs) to its active metabolite which played a critical role in therapy. CPA has serious and even fatal side effects, and its efficacy and adverse reactions are significantly varied among individuals. In this review, the association of the genetic polymorphisms in the metabolic enzymes and transporters involved in the disposition of CPA with the efficacy and adverse effects of CPA were summarized, thereby providing fundamental reference for further pharmacogenomic study of CPA.
Antineoplastic Agents, Alkylating ; pharmacology ; Cyclophosphamide ; pharmacology ; Humans ; NADPH-Ferrihemoprotein Reductase ; metabolism ; Pharmacogenetics

Objective Study the useful effect of the subjective and objective assessmentscale in fungal‐rhino‐sinusitis (FRS) patients before and after endoscopic sinus surgery ,and thier transition rules .Methods Visual analog scale (VAS) ,sino‐nasal out‐come measures 20 (SNOT‐20) ,Lund‐Mackay CT score and Lund‐Kennedy nasal endoscopy score were used to prospective evaluate 130 cases of FRS patients at the time of before endoscopic sinussurgery ,the 3rd month and the6thmonth after survey ,and correla‐tion analysiswas took between the various scales .Results At the time ofbeforesurgery ,the 3rd month and the 6th month after the endoscopic sinus surgery ,the VAS ,SNOT‐20 ,Lund‐Mackay sinus CT scores and Lund‐Kennedy endoscopic score were significantly correlated (P< 0 .05) ,but At the time ofbeforesurgery ,VAS and Lund‐Kennedy nasal endoscopy scorehas no correlation(P>0 .05) .Except for SNOT‐20 scores at the time of 3rd month had relationship with preoperative scores(P<0 .05) ,there were no sig‐nificant relation of each scales that preoperative scores compared with 3rd month of 6th mouth(P> 0 .05) .The difference ofSNOT‐20 ,VAS ,Lund‐Kennedy nasal endoscopy scorewas statistically significant compared to each other at the time of 3rd month and the 6th month after surgery (P<0 .05) .Conclusion Subjective combined with objective scale can be a better response for patients be‐fore surgery ,which may be helpful for the choosing of operation time;combination of postoperative subjective evaluation with objec‐tive evaluation and following‐up ,may be a more effect way for patient to kmow the outcome after surgery .

Aim Toinvestigatetheeffectofbencyclo-quidium bromide(BCQB)on mucus MUC5AC expres-sion induced by lipopolysaccharide in cultured human nasalepithelialcells(HNECs).Methods Primary culture of human nasal epithelial cells (HNECs)was randomly divided into control group (C,with no treat-ment),LPS group (LPS,with LPS 1 mg · L-1 added in),BCQB low dose group(BCQBL,with LPS 1 mg· L-1 and BCQB 10 -8 mol·L-1 added in),BCQB mid-dle dose group(BCQBM,with LPS 1 mg·L-1 and BC-QB 10 -7 mol·L-1 added in),BCQB high dose group (BCQBH,with LPS 1 mg·L-1 and BCQB 10 -6 mol· L-1 added in)and ipratropium bromide group(IB,with LPS 1 mg·L-1 and IB 10 -6 mol·L-1 added in).Af-ter incubation at 37 ℃with 5% CO2 for 24 h,the ex-pression of MUC5 AC mRNA was detected with Real-time PCR and the expression of MUC5 AC protein in HNECs was detected with Western blot,while the ex-pression of MUC5 AC protein in supernatant was detec-tedwithELISAineachgroup.Results Ascompared with control group,the expression of MUC5 AC mRNA and protein increased significantly in LPS group (each P<0. 01 ).As compared with LPS group,the expres-sion of MUC5 AC mRNA and protein decreased signifi-cantly in each group of BCQB(P<0. 01,P<0. 05), and there was no statistical difference between BCQB high dose group and control group (each P>0. 05 ). Conclusion Bencycloquidiumbromidecansuppress MUC5 AC expression induced by LPS in cultured hu-man nasal epithelial cells,indicating that BCQB may be a new drug for nasal mucous hypersecretion diseases.

Objective To study the bioavailability and bioequivalence of erythromycin ethylsuccinate granules in healthy male volunteers.Methods In a randomized two-period crossover study,20 healthy male volunteers received single 500 mg test and reference formulations of erythromyein ethylsuccinate granules.The plasma concentrations of erythromycin were assayed by microbiological method.Results The parameters of test and reference preparations were as follows:T_(max)(0.86?0.22)and (0.80?0.13)h,C_(max)(2.13?0.64)and(2.16?0.61)mg/L,t_(1/2)(2.04?0.2)and(1.97?0.4)h,AUC_(0-t)(4.96?1.73)and(4.63?1.52)mg?h/L,respectively.There was no significant difference between the two preparations.The rela- tive bioavailahility of the test granules was(109.1?22.8)%.Conclusions The two preparations of erythromycin ethylsucci- nate granules are bioequivalent.

Objective To study the interobserver variabilities and the differential diagnosis value of Breast Imaging Reporting and Data System-Ultrasound (BI-RADS-US) lexicon for small ( ≤ 2 cm) breast nodules. Methods Between January 2009 and December 2011, 289 patients with small (≤2 cm) breast nodules (n=317) were included. According to sizes, the lesions were divided into two groups, i.e., 0-1 cm (n=160) group and 1-2 cm (n=157)group. Each lesion was described independently by 3 radiologists using BI-RADS-US lexicon. Interobserver variabilities were assessed by Kappa test. Chi-square test was used to compare the frequency difference of the descriptors between malignant and benign lesions. Sensitivity, speciifcity, accuracy, positive predictive value and negtive predictive value were calculated. Results (1)Moderate agreements were obtained for lesion shape, orientation, margin, echo pattern, surrounding tissue and calciifcations (κ=0.44, 0.57, 0.48, 0.43, 0.51 and 0.57) in 0-1 cm group. Substantial agreements were obtained for lesion shape, orientation, margin and echo pattern (κ=0.65, 0.61, 0.64 and 0.63) in 1-2 cm group. (2)Irregular shape, non-parallel orientation, non-circumscribed margin, echogenic halo and microcalciifcations were more frequently found in malignant nodules than in benign nodules in 0-1 cm group [52.3% (34/65) vs 20.0% (19/95), 38.5%(25/65) vs 13.7%(13/95), 75.4%(49/65) vs 32.6%(31/95), 18.6%(12/65) vs 0 (0/95) and 10.8%(7/65) vs 2.1%(2/95);χ2=18.19, 13.08, 28.22, 16.39 and 3.95;P=0.000, 0.000, 0.000, 0.000 and 0.047]. Similarly, irregular shape, non-parallel orientation, non-circumscribed margin, echogenic halo, shadowing, changes of Cooper′s ligament and microcalciifcations were signiifcantly more frequent found in malignant nodules than in benign nodules in 1-2 cm group [74.2%(49/66) vs 12.1%(11/91), 36.3%(24/66) vs 5.5%(5/91), 93.9%(62/66) vs 22.0%(20/91), 37.9%(25/66) vs 3.3%(3/91), 30.3%(20/66) vs 7.7%(7/91), 15.2%(10/66) vs 0 (0/91) and 16.7%(11/66) vs 4.4%(4/91);χ2=62.59, 24.21, 79.40, 31.22, 13.73, 12.30 and 6.67;P=0.000, 0.000, 0.000, 0.000, 0.000, 0.000 and 0.010]. (3)In both groups, a good sensitivity was demonstrated (75.4%&93.9%) when using the non-circumscribed margin as a criterion for malignancy, and high speciifcity was achieved in two groups (80.0%-100%and 87.9%-100%) when other descriptors including irregular shape, non-parallel orientation, echogenic halo, shadowing, changes of Cooper′s ligament and microcalciifcations were used as differentiation criteria. Conclusions Good interobserver agreement can be achieved using the BI-RADS-US lexicon in the diagnosis of small breast nodules. Non-circumscribed margin are proved as the most valuable sign for screening malignant breast lesions ≤ 2 cm. High speciifcity was found for irregular shape, nonparallel orientation, echogenic halo, shadowing, Cooper′s ligament changes and microcalciifcations, which can help biopsy and preoperative diagnosis.

OBJECTIVETo investigate the effects of different concentrations of lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), dexamethasone (Dex), and insulin on the mRNA and protein expressions of GPR54 in the MCF7 cell line in vitro.

METHODSMCF7 breasr cancer cells were cultured and treated with different concentrations of LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L). Those treated with culture fluid only served as controls. The mRNA and protein expressions of GPR54 were measured by real-time PCR and Western blot, respectively, after 6, 24, 48, and 72 hours of treatment.

RESULTSCompared with the blank con- trol, LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L) significantly increased the expressions of GPR54 mRNA (P < 0.05) and protein (P < 0.05).

CONCLUSIONLPS, TNFα, IL-6, Dex, and insulin evidently increase the expression of GPR54 in the MCF7 cell line, indicating their influence on the function of gonads by regulating the GPR54 level.

Blotting, Western ; Dexamethasone ; administration & dosage ; pharmacology ; Glucocorticoids ; administration & dosage ; pharmacology ; Gonads ; drug effects ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Insulin ; administration & dosage ; pharmacology ; Interleukin-6 ; administration & dosage ; pharmacology ; Lipopolysaccharides ; administration & dosage ; pharmacology ; MCF-7 Cells ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, G-Protein-Coupled ; drug effects ; genetics ; metabolism ; Receptors, Kisspeptin-1 ; Time Factors ; Tumor Necrosis Factor-alpha ; administration & dosage ; pharmacology

This study is to screen the Chinese herbal compounds which could inhibit the production of Abeta and investigate the underlying mechanism. Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial. The cell models which used could overexpress Abeta and beta-secretases or Abeta and gamma-secretases. Extracellular Abeta was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 micromol x L(-1)), separately. Then the compounds were selected which could inhibit extracellular Abeta and their best concentration ranges were decided, too. Furthermore, the cell viability and apoptosis rate, the level of intracellular Abeta, beta and gamma-secretases were determined after the cell models treated with different concentrations of selected compounds. The results showed that 4 of the 10 compounds could reduce the level of extracellular Abeta; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 micromol x L(-1), respectively. Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Abeta were more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of beta and gamma-secretases, with the maximum inhibiting rates of 78.2% and 80.3%, respectively. In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit the expression and secretion of Abeta, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the beta and gamma-secretase activities, respectively.
Amyloid Precursor Protein Secretases ; metabolism ; Amyloid beta-Peptides ; antagonists & inhibitors ; Apoptosis ; Benzyl Alcohols ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Glucosides ; pharmacology ; Humans ; Monoterpenes ; pharmacology ; Phenanthrenes ; pharmacology ; Saponins ; pharmacology

A novel member of extremely halophilic archaea, strain AJ2, was isolated from Ayakekum Lake located in Altun Mountain National Nature Reserve of Xinjiang Uygur Autonomous Region in China. The strain AJ2 requires at least 10% (w/v) NaCl and grows 10% to 30% (optimum at 20%). Phylogenetic analysis based on 16S rDNA sequence comparison revealed that strain AJ2 clustered to three Natrinema species with less than 97.7% sequence similarities, suggesting AJ2 is a novel member of Natrinema. A bacteriorhodopsin-encoding (bop) gene was subsequently detected in the AJ2 genome using the polymerase chain reaction technique. The cloning and sequencing of a 401 base pairs fragment indicated the deduced amino acid sequence of bop from AJ2 is different from that reported for bacteriorhodopsins. This is the first reported detection of a bop gene in Natrinema.
Bacteriorhodopsins ; genetics ; metabolism ; Cell Proliferation ; Gene Expression Profiling ; Genome, Archaeal ; Halobacteriaceae ; classification ; isolation & purification ; physiology ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity

ObjectiveTo investigate the diagnostic significance of different pathology techniques (Immunohistochemistry and ISH)to detect EBV on bone marrow biopsy tissues of hemophagocytic syndrome. Methods Histological,immunohistochemicalandinsituhybridizationwereusedtostudythe hemophagocytic features and expression of LMP-1,EBER and other markers.Results25 out of 51 cases (49.0 ％)showed an active proliferation growth pattern while other 12 cases(23.5 ％)demonstrated a deterioration morphological character compared with their same age group. The left 14 cases (27.5 ％) showed a normal myeloproliferative pattern. 91.4 ％ (32/35) expressed CD68/KP-1 and 89.5 ％ (17/19) cases expressed CD68/PG-M1, which showed an abnormal increase of monocytes. 26 out of 51 cases (51.0 ％) were positive for EBER,while EBER and immunohistochemistry on LMP-1 were detected simultaneously in 41 cases.The EBER were positive in 19 cases(46.3 ％)but none for LMP-1(P =0.000).ConclusionHypoplasia or hemophagocytic features could be detected on bone marrow biopsy tissues of hemophagocytic syndrome, which might be slightly difficult to diagnose. So immunohistochemistry would be essential. Meanwhile, the detection of EBER is more helpful than LMP-1 for diagnosis.

Objective To study the clinicopathologic features and explore the potential prognostic factors of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).Methods 86 patients diagnosed with MALT lymphoma were retrieved and divided into 2 subgroups according to the location of tumor,namely gastric (32 cases) and non-gastric (54 cases) subgroup.Histological characteristics were reassessed on hematoxylin-eosin staining slides,and immunophenotypic features were determined by immunohistochemical staining.Interphase fluorescence in-situ hybridization (FISH) was carried out to detect the cytogenetic abnormalities.Results There were no significant difference of clinical behavior,histology,and immunophenotype between gastric and non-gastric subgroups.In addition,FISH detected t(14;18) in 9 ％ (4/45) and t(11;18) in 12 ％ cases (6/50) respectively.Among the 20 cases treated with H pylori (HP) eradication,a significantly lower remission rate was observed in cases with bcl-10 (20 ％) nuclear expression or those harboring t(11;18) (33 ％) compared with those in the negative group (73 ％,91％)(x2 =3.842 and 4.639,P =0.035 and 0.031,respectively).For the 35 non-gastric patients with follow-up data,males (35 ％) and patients older than 60 yrs (25 ％) tended to have a lower remission rate as compared to females (60 ％) and those younger than 60 yrs (63 ％) (x2 =3.905 and 7.373,P =0.048 and 0.007,respectively).Moreover,progression-free survival rate was significantly lower in patients with higher stage (ⅢⅣ) (25 ％) and without t(14;18) (50 ％) than that in patients with stage Ⅰ-Ⅱ (52 ％) and with t(14;18)(75 ％).The differences had statistical significance (x2 =4.207 and 4.363,P =0.040 and 0.037,respectively).Conclusion MALT lymphoma in general is an indolent B-cell non-Hodgkin’ s lymphoma which more frequently occurs in the elderly people.Differences in the response to treatment or the prognosis are observed between gastric and non-gastric MALT lymphoma patients.