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

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 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 .

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.

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 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

Objective To explore the influence factors of poor myocardial perfusion in patients with ST-segment elevation myocardial infarction( STEMI) after primary percutaneous coronary intervention(PCI). Methods One hundred and forty-three patients with first STEMI who were on admission from April 2010 to May 2014 and underwent primary PCI within 12 hours were enrolled as our subjects. According to the sum-ST-segment resolution(sumSTR)and TIMI myocardial perfusion grade(TMP)after primary PCI,all patients were divided into well myocardial perfusion group( sumSTR ≥ 50% or TMP 2 - 3 grade)and poor myocardial perfusion group(sumSTR < 50% and TMP 0 - 1 grade). The influence factors between two groups were collected and analyzed,including sex,age,pain to balloon time,blood pressure on admission,left ventricular ejection fraction,leucocyte count,neutrophil ratio(NR),high-sensitivity C-reactive protein(hs-CRP),blood lipid,and the history of hypertension,diabetes mellitus. Results The leucocytes count,NR,hs-CRP in patients of poor myocardial perfusion group were(11. 60 ± 3. 57)× 109 / L,0. 84 ± 0. 06 and 9. 80 ± 11. 37 mg/ L,higher than those in well myocardial perfusion group((9. 51 ± 2. 59)× 109 / L,0. 77 ± 0. 11 and(3. 83 ± 5. 58)mg/ L),and the differences were significant(t = 3. 497,P = 0. 001;t = 3. 390,P = 0. 001;t = 3. 973,P < 0. 001). Multiple linear regression analysis showed that neutrophil ratio was independent risk factor of sumSTR in STEMI patient after primary PCI(P = 0. 000). Conclusion The increase of leucocyte count,NR and hs-CRP are related to the poor myocardial perfusion after primary PCI. The increase of neutrophil ratio is an independent risk factor of poor myocardial perfusion.

Objective To investigate the EB virus (EBV) infection and its clinical significance in angioimmunoblastic T-cell lymphoma(AITCL).Methods 62 patients diagnosed as AITCL between 2008 Jan and 2011 Dec were retrospective analyzed.All cases were re-confirmed and classified with the histology and immunology according to 2008 WHO Classification.In situ hybridization of EBV encoded RNA (EBV-EBER) was performed.Clinical characteristics and follow-up data of patients were collected.Results 42 ％ (26/62) AITCL cases were EBER-positive.EBV infection was found to be significant correlation with age over 60 years and poor response to therapy (P =0.025,P =0.049,respectively).However,EBV infection had no relationship with the overall survival,the presence of B symptom and the Ann Arbor stage.Conclusion In AITCL,EBV infection seems not to be associated with the overall survival,B symptom and Ann Arbor stage,but it may have impacts on theraputic response.

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.