Acute Toxicity and Hepatotoxicity of Aqueous Extracts of Taxilli Herba from Different Hosts in Zebrafish Model / 中国实验方剂学杂志

Objective:To explore the acute toxicities and hepatotoxicities of aqueous extracts of Taxilli Herba from <italic>Morus alba</italic>， <italic>Toxicodendron</italic> <italic>trichocarpum</italic>， <italic>Camellia oleifera</italic>， <italic>Salix babylonica</italic>， <italic>Melia azedarach</italic>， and <italic>Nerium indicum</italic> against zebrafish model and the effect of different hosts on the toxicity of Taxilli Herba， hoping to provide a theoretical basis for the safe use of Taxilli Herba. Method:The normally developed AB zebrafish at 3-day post fertilization was selected for acute toxicity study. According to the results of preliminary toxicity experiments， the zebrafishes were treated with aqueous extracts of Taxilli Herba from different hosts at six doses， and their mortality was calculated 72 h later. GraphPad Prism 6.0 was used for plotting the dose-toxicity curve， followed by the calculation of their median lethal concentration （LC₅₀） and 10% lethal concentration （LC₁₀）. The gz15Tg/+（AB） liver fluorescent protein transgenic zebrafish with normal development at 4-day post fertilization was applied for the hepatotoxicity study. The zebrafishes were divided into the low-， medium-， and high-dose groups of aqueous extracts of Taxilli Herba from six hosts， the positive control （acetaminophen） group， and the blank （embryo amniotic fluid） group， and then treated with the corresponding drugs. Seventy-two hours later， the liver morphology and fluorescent area changes in zebrafish were observed. And the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. Result:The results of acute toxicity test demonstrated that the LC₅₀ values of water extracts of Taxilli Herba from <italic>M. alba</italic>， <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> were 1.24， 0.94， 0.51， 0.38， 0.11， 0.09 g·L^-1， respectively， and the LC₁₀ values were 0.70， 0.60， 0.35， 0.28， 0.08， 0.07 g·L^-1， respectively. As revealed by hepatotoxicity test， compared with the blank group， the positive control group exhibited liver morphological changes， decreased fluorescent area （<italic>P</italic><0.01）， and elevated ALT and AST activities （<italic>P</italic>< 0.01）， suggesting that acetaminophen was hepatotoxic to zebrafish. However， there was no change in the liver morphology or fluorescent area of zebrafish in the low-， medium-， and high-dose groups of water extracts of Taxilli Herba from <italic>M. alba</italic>， and the ALT and AST activities were decreased. By contrast， the liver morphology and fluorescent areas in the medium- and high-dose groups of water extracts of Taxilli Herba from <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> changed to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）. Besides， the activities of both ALT and AST were also enhanced. These indicated that Taxilli Herba from <italic>M. alba</italic> had no hepatotoxicity to zebrafish， while that from <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> showed varying degrees of hepatotoxicity to zebrafish. Conclusion:The toxicity of Taxilli Herba is host-dependent. Taxilli Herba from <italic>M. alba</italic> has no hepatotoxicity， but that from the other five hosts shows varying degrees of hepatotoxicity. Standardizing the host source may be an important measure to realize the medication safety of Taxilli Herba.

Molecular mechanism of eucommia ulmoides active ingredients treating synovitis of knee osteoarthritis: An analysis based on network pharmacology / 中国组织工程研究

BACKGROUND: Studies have shown that the active ingredients of Eucommia ulmoides can inhibit the growth of synovial fibroblasts of arthritis, but the molecular mechanism underlying Eucommia ulmoides treating synovial inflammation of knee osteoarthritis is not yet clear. OBJECTIVE: To investigate the possible molecular mechanism of Eucommia ulmoides ingredients treating synovitis of knee osteoarthritis based on the network pharmacology and bioinformatics. METHODS: The active ingredients and targets of Eucommia ulmoides were screened by using the TCM systematic pharmacological analysis platform (TCMSP). The disease targets corresponding to synovitis of knee osteoarthritis were obtained from Gene Expression Omnibus (GEO). The protein-protein interaction network was constructed by STRING online database, analyzed and showed by the Cytoscape software. Gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of the targets were conducted by R/Bioconductor. The enrichment results were obtained with a significant difference (P < 0.05). RESULTS AND CONCLUSION: A total of 21 active ingredients of Eucommia ulmoides, including eugenol, eucommia glycoside, eucommia liposide A, quercetin, and 25 different expressed genes (7 up-regulated and 18 down-regulated differentially expressed genes) were obtained. The main biological processes of the differentially expressed genes were found different significantly in cytokine activity, cytokine receptor binding and activating transcription factor binding. The hub genes, such as interleukin-6, vascular endothelial growth factor A and chemotactic factor 8, may be regulated by the active ingredients to influence the signal of MAPK/NF-kappa B/Toll-like receptor signaling pathway. Based on the network pharmacology and bioinformatics approach, the study preliminarily validates the molecular mechanism of Eucommia ulmoides for treatment of synovitis of knee osteoarthritis, which may lay a foundation for further pharmacodynamics study and experiment.

Correlation study on chemical constitutes of cardiac glycosides in Taxillus chinensis and its Nerium indicum host by UPLC-Q-TOF-MS/MS / 中国中药杂志

To build up an identification method on cardiac glycosides in Taxillus chinensis and its Nerium indicum host, and evaluate the influence on medicine quality from host to T. chinensis, ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass-mass spectrometry(UPLC-Q-TOF-MS/MS)was applied. The samples of T. chinensis(harvested from N. indicum)and its N. indicum host were collected in field. The samples of T. chinensis(harvested from Morus alba)and its M. alba host was taken as control substance. All samples were extracted by ultrasonic extraction in 70% ethanol. Chromatographic separation was performed on an ACQUITY UPLC HSS T3 C_(18)(2.1 mm×100 mm,1.8 μm)column at 40 ℃. Gradient elution was applied, and the mobile phase was consisted of 0.1% formic acid water and acetonitrile. The 0.5 μL of sample solution was injected and the flow rate of the mobile phase was kept at 0.6 mL·min~(-1) in each run. It was done to identify cardiac glycosides and explore the chemical composition correlation in T. chinensis and its N. indicum host by analyzing positive and negative ion mode mass spectrometry data, elemental composition, cardiac glycoside reference substance and searching related literatures. A total of 29 cardiac glycosides were identified, 28 of it belonged to N. indicum host, 5 belonged to T. chinensis(harvested from N. indicum host), none of cardiac glycoside was identified in T. chinensis(harvested from M. alba host). The result could provide a reference in evaluating the influence in T. chinensis medicine quality from host. It was rapid, accurate, and comprehensive to identify cardiac glycosides in T. chinensis and its N. indicum host by UPLC-Q-TOF-MS/MS.

Chemical Constitutes of Cardiac Glycosides in Scurrula parasitica and Its Nerium indicum by UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective: To establish a method for identifying cardiac glycosides in Scurrula parasitica and its Nerium indicum host by UPLC-Q-TOF-MS/MS. With safflower parasitoids with sweet-scented osmanthus trees as the host and their host osmanthus tree samples used for control, the chemical constituents of the cardiac glycosides were identified by comparison between the cardiac glycoside reference substances and literatures, so as to analyze the correlation between the safflower parasitoid and its host oleander glycoside components,and evaluate the host' s impact on the quality of Taxilli Herba. Method: Samples of S. parasitica (parasitic on N. indicum and Osmanthus fragrans),N. indicum and O. fragrans were collected. Samples of S. parasitica and its O. fragrans host were taken for control. All of the samples were extracted through ultrasonic extraction with 70%ethanol. ACQUITY UPLC HSS T3 C18(2.1 mm×100 mm,1.8 μm) column was adopted with mobile phase A comprising 0.1%formic acid water and mobile phase B comprising acetonitrile for gradient elution. The sample size was 0.5 μL. The flow rate was 0.6 mL·min-1. The column temperature was maintained at 40℃. MassLynx V4.1 software was used to analyze the data. Identification and correlation of chemical constitute of cardiac glycosides in S. parasitica and its N. indicum host were performed through analysis on cardiac glycosides reference substances,relevant literatures,elemental composition of compounds and positive and negative ion mode mass spectrometry data. Result: A total of 26 compounds of cardiac glycoside were identified,including 25 compounds of cardiac glycoside from N. indicum host,and 5 compounds of cardiac glycoside from S. parasitic(parasitic on N. indicum). none of cardiac glycosides were found in S. parasitica (parasitic on O. fragrans ) and its O. fragrans host. Conclusion: It was rapid,accurate and comprehensive to identify cardiac glycosides in S. parasitica (parasitic on N. indicum) and its N. indicum host by UPLC-Q-TOF-MS/MS. S. parasitica itself does not contain cardiac glycosides,its host may impact the quality of S. parasitica by delivering cardiac glycosides, a kind of its characteristic compound.

Expression of monocyte chemoattractant protein-1 in aqueous humor of patients with primary acute angleclosure glaucoma and its association with the patients' prognosis after trabeculectomy / 眼科新进展

Objective To measure the levels of monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor of patients with acute primary angle-closure glaucoma (APACG),and its correlation with the patients' prognosis after trabeculectomy.Methods This retrospective case-control study included 19 patients with APACG who experienced a failed trabeculectomy (case group) and 57 age-and sex-matched patients with APAGG who underwent successful trabeculectomy (control group).Aqueous humor was collected before trabeculectomy for the detection of MCP-1 levels in the both groups by enzyme-linked immunosorbent assay.And finally,logistic regression analysis was applied to assess the risk factors for failed trabeculectomy.Results The MCP-1 concentration in aqueous humor was (5688.04 ± 2099.99)ng · L-1 in the case group and (2077.57 ± 568.44)ng · L-1 in the control group,and the difference between both groups were significant (P ＜ 0.001).Logistic regression analysis revealed MCP-1 level (OR =1.005;95％ CI =1.001-1.008) and a shallow anterior chamber after surgery (OR =31.430;95％ CI =1.577-57.350) were the independent risk factors for failed trabeculectomy procedures.Conclusion MCP-1 levels in aqueous humor are higher in APACG eyes with failed trabeculectomy than those with successful one during 1-year follow-up,so MCP-1 level is considered as an independent risk factor for failed trabeculectomy.

Effects of Taxilli Herba from different hosts on lowering blood pressure of spontaneously hypertensive rats / 中成药

AIM To observe the effects of Taxilli Herba from six different hosts (Morus alba L.,Salix babylonica L.,Camellia oleifera Abel.,Castanea mollissima B1.,Liquidambar formosana Hance and Nerium indicum Mill.) on lowering blood pressure of spontaneously hypertensive rats (SHR).METHODS SHR were randomly divided into 14 groups,captopril positive group (20 mg/kg),model group,and Taxilli Herba groups of 6 different hosts,and each Taxilli Herba group was further divided into high-dose group (5.9 g/kg) and low-dose group (1.48 g/kg);WKY,in addition,was the blank control.And the 20-day consective correspondence medication was applied to the groups,each with eight rats.The caudal arterial systolic blood pressure (SBP) was measured by tail-cuff method before the administration,and on the 10th day and 20th day of the administration.Anaesthesia was performed at the blood collection 12 h after the last administration;and thus final serum contents of nitric oxide (NO) and changes of superoxide dismutase (SOD) activity,plasmatic contents of angiotensin Ⅱ (Ang Ⅱ) and endothelin-1 (ET-1) were determined.RESULTS From the data before and after administration,an SBP drop among all SHR groups was observed on the 10th day of administration,among which the blood pressure lowering effect by high-dose Taxilli Herba from Morus alba L.was very obvious (P ＜ 0.01);remarkable SBP decrease on the 20th day of administration induced by Taxilli Herba from Salix babylonica L,Liquidambarformosana Hance and Camellia oleifera Abel,and high-dose Taxilli Herba from Morus alba L,low-dose Taxilli Herba from Castanea mollissima B1 were detected (P ＜ 0.01).No significant SBP variation was available between the model group and Taxilli Herba groups after10-day administration;all the Taxilli Herba groups exhibited obvious effect in lowering SBP except Taxilli Herba from Nerium indicum Mill,low-dose Taxilli Herba from Morus alba L.and high-dose Taxilli Herba from Castanea mollissimaBl.after 20-day administration,compared to the model group (P ＜ 0.05).Highdose Taxilli Herba from Morus alba L.and Salix babylonica L significantly decreased plasmatic Ang Ⅱ and ET-1 contents of SHR groups in comparison with the model group (P ＜0.01).High-dose Taxilli Herba from Morus alba L.,Salix babylonica L.and Liquidambarformosana Hance significantly increased serum NO release and superoxide dismutase (SOD) activity (P ＜ 0.01).CONCLUSION Taxilli Herba from the five different hosts,except Nerium indicum Mill,can lower blood pressure,and there exists an effect difference due to the host variation.

Relation of MBL ExonI 54 and NFκB1-94ins/del ATTG Polymorphism with Fever during Neutropenia in Patients with Acute Leukaemia after Chemotherapy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the correlation between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia (AL) (except M3) after first chemotherapy in Chinese Han population.</p><p><b>METHODS</b>Blood samples obtained from 76 fever patients with AL during neutropenia episodes were detected to analyse single nucleotide polymorphism (SNP) in the MBL ExonI 54 and NFκB1-94ins/del ATTG gene, and analyse the correlation between above-mentioned 2 polymorphisms and fever during neutropenia of AL patients after chemotherapy.</p><p><b>RESULTS</b>In 76 patients, no correlation were found between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy (P > 0.05). No significant relation were found in sex, age, underlying disease, disease status or degrees of neutropenia in febrile neutropenia between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism (P > 0.05). However, patients with MBL ExonI 54 mutation presented longer febrile duration with a median of 5 days compared to 3 days of patients with wildtype MBL ExonI 54 genotype (P < 0.05).</p><p><b>CONCLUSIONS</b>There is no clear correlation between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy. However, the patients with MBL ExonI 54 mutation have been observed to present a longer febrile duration.</p>

The relationship of telomere and telomerase activity with outcome of aplastic anemia after immunosuppressive therapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the changes of telomere length and telomerase activity in patients with aplastic anemia (AA), and relationship with immunosuppressive therapy (IST) efficacy, to explore the pathogenesis of AA and the role of telomere length in evaluating immunosuppressive therapy efficacy.</p><p><b>METHODS</b>71 cases of AA patients between September 2010 and March 2013 were enrolled into this study. 3 ml peripheral blood specimens from this cohort of patients were collected to test the telomere length in peripheral blood mononuclear cell (PBMNC) with flow-FISH and detect telomerase activity with TRAP-PCR-ELISA method.</p><p><b>RESULTS</b>Telomere length and age showed negative correlation (b=-0.387, P=0.001) in normal control, NSAA and SAA + VSAA groups, telomere length became shorter with the growth of age, and normal control group telomere length decreased along with the age growth slightly greater than the other two groups (NSAA, SAA+VSAA). Besides the effect of age on telomere length, no significant difference was observed between NSAA and SAA+VSAA groups (P=0.573), and NSAA, SAA+VSAA (30.957 ± 4.502,29.510 ± 5.911)groups were significantly shorter than normal control group (51.086±10.844) (P<0.01). Telomere length in NR group (25.357±4.848)was significantly lower than normal control group (51.086 ± 10.844) (P=0.005), telomere length in CR(32.808 ± 4.685)/PR groups (30.334±4.464) compared with normal control group had no significant difference (P=0.517, P=0.254). Telomere length below 29.21% obviously decreased outcomes of IST. Telomerase activity had significant difference (χ²=20.385, P<0.01). The telomerase activity had no significant difference in terms of age and gender in three groups, multiple comparison found that telomerase activities in SAA + VSAA (0.324±0.178) (P<0.01), and NSAA (0.234±0.175) groups (P=0.002) were significantly higher than normal control group (0.107±0.083).</p><p><b>CONCLUSION</b>Telomere length of PBMNC in AA patients was significantly shortened than normal control group with telomerase activity increased, and telomere shorted more apparently in NR group, these patients should adjust the treatment as early as possible. Telomeres could predict the curative effect of IST.</p>

Effect of acupoint catgut embedding on height of adolescents with spleen qi deficiency / 中国针灸

<p><b>OBJECTIVE</b>To observe the effect of acupoint catgut embedding on height of adolescents with spleen qi deficiency.</p><p><b>METHODS</b>Three hundred voluntary adolescents with spleen qi deficiency syndrome who want to increase height were stratified according to sex first, and then randomly divided into an observation group, a control group and a placebo group, 100 cases in each group. The observation group was treated with acupoint catgut embedding at Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21) etc. The control group was treated with oral administration of Lysine Dicalcium Phosphate particles, and the placebo group was treated with oral administration of flour capsule. The height was measured and the therapeutic effects were detected after treatment of 3 months and 6 months respectively.</p><p><b>RESULTS</b>The total effective rate of 95.0% (95/100) in the observation group was superior to that of 49.0% (49/100) in the control group and 0 (0/100) in the placebo group (both P < 0.05). The height increased more obviously in the observation group than that of the control group and the placebo group, there were significant differences among three groups (all P < 0.01).</p><p><b>CONCLUSION</b>Acupoint catgut embedding can increase the height and improve the symptoms of the adolescents with slow growth caused by spleen qi deficiency.</p>

Antiangiogenic activity of thalidomide in vitro mediated by cytochrome CYP2C19 / 中国实验血液学杂志

This study was aimed to investigate the effect of metabolic system in human hepatic cell microsome on antiangiogenic in vitro activity of thalidomide used in treating multiple myeloma and to explore the role of cytochrome CYP2C19. Human umbilical cord vein endothelial cells (hUCVECs) were treated with thalidomide alone or thalidomide co-incubated with human hepatic cell microsome. Cell proliferation ability was assessed by MTT assay, cell cycle analysis and detection of apoptosis were carried out by flow cytometry (FCM), migration activity of hUCVECs was determined by modified Boyden chamber and differentiation of hUCVECs was assayed by tube formation test. The results showed that thalidomide alone had no obvious direct effect on hUCVEC viability or apoptosis, mild effect on cell migration and no effect on tube formation. However, when co-incubated with human hepatic cell microsome, thalidomide significantly inhibited the hUCVECs viability. At 100 microg/ml, thalidomide co-incubated with human hepatic cell microsome, the proliferation ability of hUCVECs decreased by (11.7 +/- 3.9)%, apoptosis cells increased by 27.2%, the cell migration was down-regulated significantly, and the tube formation was obviously inhibited. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was added into the co-incubation mixture, the effects of thalidomide on cell proliferation ability, apoptosis, migration and tube formation decreased. It is concluded that effect of human hepatic cell microsome is required for thalidomide's antiangiogenic activity in vitro and cytochrome CYP2C19 may be involved in the antiangiogenic effect of thalidomide.

Prognostic impact of heart block during transcatheter closure of ventricular septal defect / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the prognostic impact of heart block during the transcatheter closure of ventricular septal defect (VSD).</p><p><b>METHODS</b>Forty three patients developed complete left or right bundle branch block (CLBBB, CRBBB), incomplete left or right bundle branch block (ILBBB, IRBBB), and atrioventricular block (AVB) during and within 1 week post procedure were followuped at 1, 6, 12, 24, 36, 48 and 60 months post procedure. Electrocardiogram, dynamic electrocardiogram and transthoracic echocardiography were made.</p><p><b>RESULTS</b>Bundle branch block and atrioventricular block were detected in 26 patients (CLBBB n = 4, CRBBB n = 5, ILBBB n = 2, IRBBB n = 10 and third-degree AVB n = 5) during the transcatheter closure of VSD, and in 17 patients (CLBBB n = 5, CRBBB n = 2, first-degree AVB n = 3, second-degree I-type AVB n = 1 and third-degree AVB n = 6) within 1 week post procedure. Heart block disappeared in 33 patients (76.7%) before discharge, in 37 patients (86.1%) at 1 month and in 41 patients (95.4%) at 6 months post procedure. CLBBB or CRBBB was seen in two cases at 24 months after closure. There was no heart failure and serious cardiac dilatation during follow up.</p><p><b>CONCLUSION</b>The heart block occurred during the periprocedure period of transcatheter closure of VSD was a benign phenomenon without prognostic importance.</p>

Establishment of a bortezomib-resistant myeloma cell line and differential proteins analysis by MALDI-OF-MS / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish a bortezomib-resistant myeloma cell line and to investigate its mechanism.</p><p><b>METHODS</b>Bortezomib-resistant NCI-H929 cell line (NCI-H929B) was obtained by stepwise increasing extracellular concentrations of bortezomib over a period of 8 months. The biological characteristics of NCI-H929 and NCI-H929B were observed. Proteins from NCI-H929B cell and NCI-H929 cell were extracted, run on two-dimensional gel electrophoresis. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and mass spectrometry (MS) were used to identify proteins. Western blot was used to further verify differential proteins.</p><p><b>RESULT</b>Bortezomib-resistant cell line NCI-H929B was established. NCI-H929B exhibits a 23.5-fold level of resistance to bortezomib as compared to the parental cell line NCI-H929. There were no significant differences in cellular biology of cell growth curve and cell cycle distribution between NCI-H929 and NCI-H929B cell lines.Whole proteins of NCI-H929 and NCI-H929B myeloma cell lines were extracted by two-dimensional gel electrophoresis. Gel-image analysis revealed that there were 17 differential protein spots. A total of 14 differential protein spots were successfully identified by MALDI-TOF-MS. The result of Western blot was consistent with 2-DE.</p><p><b>CONCLUSION</b>A bortezomib-resistant human myeloma cell line NCI-H929B was successfully established. The differentially expression of proteomes may be useful for study of the bortezomib-resistant mechanisms and the molecular markers of MM.</p>

Effect of cytochrome CYP2C19 on the anti-myeloma activity of thalidomide in vitro / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of human liver microsome on anti-myeloma activity of thalidomide (TH) in vitro and identify the role of cytochrome CYP2C19 in it.</p><p><b>METHODS</b>Human multiple myeloma (MM) cell lines U266, NCI-H929, RPMI 8226, LP-1 and CZ-1 were treated with TH or TH pre-incubated with human liver microsome. Cell viability was detected by MTT assay, and cell cycle and apoptosis by flow cytometry (FCM).</p><p><b>RESULTS</b>TH treatment had no direct effect on cell viability at concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, the viabilities of the 5 MM cell lines were 96.2% - 103.7%, 96.3% - 103.7% and 97.9% - 106.5% respectively, being no significant difference from that of control (P > 0.05). However, when preincubated with human liver microsome, TH significantly inhibited the cell viability with a dose-dependent manner. At concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, TH pre-incubated with human liver microsome led to 12.2% - 22.9%, 25.9% - 36.4% and 34.9% - 46.3% decreases of cell viability, respectively (P < 0.05). TH at concentration of 100 microg/ml pre-incubated with human liver microsome caused an increase of 18.5% - 32.5% in apoptosis cells. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was added in the incubation system, the inhibition of cell viability by TH was weakened. At concentrations of 5 micromol/L and 10 micromol/L, omeprazole reversed the cell viability by 7.5% - 21.9% and 19.1% - 38.3%, respectively (P < 0.05).</p><p><b>CONCLUSION</b>Treatment of TH with human liver microsome is essential for its anti-myeloma activity in vitro, and cytochrome CYP2C19 is involved with this metabolism process.</p>

The impact of autologous stem cell transplantation on the prognosis in multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) and its impact on the prognosis of MM.</p><p><b>METHODS</b>Retrospective analysis was performed in 28 patients with MM (group A) treated with ASCT in our hospital from October 1998 to February 2007, compared with those not received ASCT in the same time period including 23 patients with near complete response (nCR) or better (group B) and 25 patients with partial response (PR) (group C). The duration of response (DOR), time to progression (TTP) and overall survival (OS) were compared by Kaplan-Meier method in the 3 groups.</p><p><b>RESULTS</b>Eight patients without nCR or better (7 in PR and 1 in MR) after ASCT achieved CR (2 cases) and nCR (5 cases). Complete response (CR) rate was 10.7% (3 cases) and 42.9% (12 cases) before and after ASCT respectively in group A. DOR was 33 months for group A, 17 months for group B and 18 months for group C, and TTP was 45, 43 and 28 months respectively. After a median follow-up of 30 months, patients in group A and in group B had a trenel of longer OS than in group C although there was no statistically significant difference.</p><p><b>CONCLUSIONS</b>ASCT can further enhance the response, prolong the DOR and TTP and probably OS, and therefore improve the quality of life in MM. MM patients not achieved good response by non-ASCT therapy may benefit from ASCT.</p>

Effect of CYP2C19 gene polymorphism on efficacy of thalidomide-based regimens for the treatment of multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the distribution of different genotypes of CYP2C19 in multiple myeloma (MM), and investigate the effect of its polymorphism on efficacy of thalidomide-based regimens for the treatment of MM and discuss the role of antiangiogenesis in MM.</p><p><b>METHODS</b>The CYP2C19 genotype of 92 patients with multiple myeloma was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The incidence of poor metabolizer (PM) in MM was compared with that in healthy Chinese people. After they were treated with thalidomide-based regimens, the response rate was compared between extensive metabolizers (EMs) and PMs.</p><p><b>RESULTS</b>Of 92 patients, 18 (19.5%) were PMs, which was comparable to that in healthy ones. The response rates in EMs and PMs were 62.6% and 33.3%, respectively (P < 0.05). When patients were grouped by treatment regimens, the response rate in EMs was significantly higher than that in PMs (60.8% vs. 27.3%) for the thalidomide-dexamethasone group, and similar results were observed for the thalidomide-chemotherapy group (65.2% vs. 42.7%) though there was no statistical difference (P > 0.05).</p><p><b>CONCLUSION</b>CYP2C19 genotype has no difference between MM patients and healthy person, but exhibits an effect on the treatment efficacy of thalidomide for MM. The lower response rate observed in PMs is possibly due to the reduced activity to inhibit angiogenesis by thalidomide.</p>

Comparison among four kits in detection of anti-SARS-CoV IgG in sera of SARS patients / 中华流行病学杂志

<p><b>OBJECTIVE</b>To compare the sensitivity and specificity of four kits for detection of anti-severe acute respiratory syndrome (SARS)-CoV IgG in sera of SARS patients.</p><p><b>METHODS</b>Anti-SARS-CoV IgG was detected in 99 serial sera from 18 SARS patients and in 123 negative reference sera, using two enzyme linked immunosorbent assays (EIA No. A and No. B) and two indirect immunofluorescence assays (Australian IFA and Euroimmun IFA).</p><p><b>RESULTS</b>Anti-SARS-CoV IgG was not detected in sera collected from SARS patients at the first week after onset by any of the four kits, however, it was detectable in sera obtained at the second week of illness by EIA No. B, and two IFA, but not by EIA No. A, with the positive rates of 57.1% (4/7), 57.1% (4/7) and 42.9% (3/7), respectively. The anti-SARS-CoV IgG was first determined in sera on the 9th day by Euroimmun IFA, 12th day by EIA No. B, 13th day by Australian IFA, and 16th day by EIA No. A. The positive rates of antibody on the 3rd week after onset were 84.2% (16/19), 94.7% (18/19), 78.9% (15/19) and 52.6% (10/19) respectively. They were identical since the 4th week after the disease onset. Through detection of 123 negative reference sera, the specificity of EIA No. A and two IFA was 100%, with exception of 94.9% for EIA No. B.</p><p><b>CONCLUSION</b>The sensitivity and specificity of the two IFAs were relatively higher than that of the two EIAs. The quality of the two homemade EIAs should be improved.</p>