Diagnostic value of magnetic resonance imaging in cesarean scar pregnancy / 第二军医大学学报

Objective To analyze the magnetic resonance imaging (MRI) features of caesarean scar pregnancy (CSP), and to evaluate the diagnosis value of MRI in CSP. Methods The MRI data of 38 patients with clinically and pathologically confirmed CSP were retrospectively analyzed. These patients aged 19 to 50 years old, with one to two previous cesarean sections. The interval between this pregnancy and the last cesarean section was 2 to 11 years, the menopause time was 32 to 90 days, the urine human chorionic gonadotrophin (HCG) were all positive, and the blood β-HCG was 159.7-210 800.0 U/L. Twenty-nine cases were treated due to a small amount of vaginal bleeding after menopause, and nine cases due to abdominal pain. Results On the sagittal T2-weighted image, 38 cases of gestational sacs were clearly showed, of which 28 cases had round or oval morphology, with low signal on T1 and high signal on T2; 10 cases of gestational sacs showed irregular mixed cystic solidity with slightly low signal on T1 and slightly high signal on T2, and the contents were significantly strengthened after the enhancement. In all cases, the cyst wall was intact and located at the scar of the cesarean section of the anterior inferior wall of the uterus. In two cases of MRI grade 0, the gestational sac was located on the scar surface and grew into the uterine cavity without involving the myometrium; in 13 cases of grade 1, the gestational sac slightly invaded the myometrium, but mainly grew in the uterine cavity, with a clear boundary between the gestational sac and the myometrium; in 14 cases of grade 2, the gestational sac was small and completely implanted into the myometrium, the endometrial junction was continuously interrupted, the anterior-inferior wall of the uterus was thin, in the shape of “W” or “U”, without invading the serosa; in nine cases of grade 3, the gestational sac was large, completely implanted into the myometrium and protruded out of the uterine contour, compressing the bladder. Fifteen patients of MRI grade 0 and 1 were mainly treated with methotrexate, mifepristone or misoprostol, and/or ultrasound-guided curettage; 23 patients of grade 2 and 3 were mainly treated with curettage, excision of scar lesions and scar repair. Conclusion The typical MRI features of CSP can guide the clinical treatment decision-making, especially for the choice of operation mode.

Concentration Determination of Voriconazole in Human Plasma by UPLC-MS/MS and Its Clinical Application / 中国药房

OBJECTIVE:To develop a method for concentration determination of voriconazole in human plasma and apply it in the clinic. METHODS:UPLC-MS/MS method was adopted. Using ketoconazole as internal standard,the determination was per-formed on Shim-pack VP-ODS column with mobile phase consisted of water(containing 1‰ formic acid and 2 mmol/L ammonium acetate)-acetonitrile(gradient elution)at flow rate of 0.3 ml/min and column temperature of 40℃.The electrospray ion source,pos-itive ionizing pattern and multiple reaction monitoring were used;the mass transition ion-pairs of voriconazole and internal standard were m/z 351.2→282.2 and m/z 532.1→490.2. RESULTS:The linear range of voriconazole were 1-10 000 ng/ml (r=0.999 5,n=5),and the limit of quantitation was 1 ng/ml;RSDs of inter-day and intra-day were all lower than 10%;method recovery was higher than 90%(RSD<8%),and extraction recovery was higher than 70%(RSD<8%). The plasma concentrations of voriconazole in 10 patients with invasive fungal infection determined by this method were 507.33-7 011.24 ng/ml,and those of 3 patients were outside the recommended treatment concentration range. CONCLUSIONS:The established method is fast,accurate and sensitive,and can be applied for the therapeutic drug monitoring of voriconazole.

A new acorane sesquiterpene from Lysionotus pauciflorus / 中国天然药物

AIM@#To study the chemical constituents of the whole plant of Lysionotus pauciflorus@*METHODS@#Chromatographic separations on silica gel, Toyopearl HW-40F gel, and MCI gel were used to isolate the compounds. The structures were elucidated on the basis of spectral data.@*RESULTS@#Three compounds were obtained and their structures were identified as 3, 10-dihydroxyacoronene (1), bis(2-butylhexyl)phthalate (2) and 3, 5-dimethoxy-4-hydroxy-trans-stilbene (3).@*CONCLUSION@#Compound 1 is a new acorane sesquiterpene, this is the first report of acorane sesquiterpenes from the Lysionotus genus.

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.</p><p><b>METHODS</b>Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.</p><p><b>RESULTS</b>The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).</p><p><b>CONCLUSIONS</b>These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.</p>

Inducing apoptosis and reversal effect of nilotinib in combination with tetrandrine on multidrug resistance of K562/A02 cell line / 中国实验血液学杂志

This study was aimed to investigate the relevance of nilotinib in combination with tetrandrine (Tet) on reversing multidrug resistance and inducing apoptosis of K562/A02 cell line and its mechanism. Methyl-thiazol tetrazolium (MTT) assay was employed to examine the pharmacological effect of nilotinib or Tet alone on K562/A02 cell line, the IC(50) of daunorubicin (DNR) on K562/A02 cell line treated with nilotinib and Tet was calculated; the flow cytometry (FCM) was employed to detect the apoptosis rate of K562/A02. The expression of bax/survivin mRNA was determined by RT-PCR, and the expression of bax/survivin protein was assayed by Western blot. The results showed that after being treated by 5 nmol/L nilotinib or 1.0 µml/L Tet for 48 hours, IC(50) of DNR to K562/A02 was 5.71 ± 0.72 mg/L or 6.52 ± 0.43 mg/L, respectively, while in their combined treatment, IC(50) decreased to 3.12 ± 0.13 mg/L. Nilotinib or Tet alone could increase DNR-inducing apoptosis rate of K562/A02 cell, while the apoptosis rate of K562/A02 increased remarkably in combination treatment of nilotinib with Tet. After being treated with 5 nmol/L nilotinib or 1.0 µml/L Tet alone for 48 hours, the expressions of bax mRNA and BAX protein was up-regulated, while both effects were more obvious in combination treatment of nilotinib with Tet. Treatment with 5 nmol/L nilotinib or 1.0 µmol/L Tet alone for 48 hours down-regulated the expression of survivin mRNA and its protein, while treatment of nilotinib in combination with Tet had more significant effect on down-regulation of their expression. It is concluded that the K562/A02 cells are resistant to DNR, nilotinib or Tet alone both can partially reverse resistance of K562/A02 cells to DNR, increase the apoptosis rate of K562/A02 cells. Combination of nilotinib with Tet shows obvious synergistic action, mechanism of which may associate with up-regulation of bax mRNA and BAX protein expressions and down-regulation of survivin mRNA and its protein expressions.

Detection of single nucleotide polymorphisms of mthfr and dpyd genes in leukemia cell lines K562 and K562/A02 / 中国实验血液学杂志

This study was purposed to detect single nucleotide polymorphisms (SNP) of 2 pharmacokinetics-related genes in K562 and K562/A02 cell lines. Leukemia cell line K562 and its resistant line K562/A02 were cultured, the genomic DNA was isolated by QIAamp DNA Blood Mini kit, primers were designed, the related DNA fragments were amplified by PCR. The SNP genotyping of mthfr gene rs1801131, rs1801133 and rs2274976 and dpyd gene rs1801159, rs1801160 and rs17376848 was performed by means of matrix assisted laser desorption ionization-time of flight mass spectrometry method (MALDI-TOFMS). The results showed that the genotype of mthfr gene locus 1801131 was AC, rs1801133 was CC, rs2274976 was GG, genotype of dpyd gene locus 1801159 was GG, rs1801160 was GG, rs17376848 was AA in both K562 and K562/A02 cell lines. It is concluded that the above-mentioned loci of mthfr and dpyd genes in K562 and K562/A02 cell lines are not expressed differently.

Effects of 5-bromotetrandrine and daunorubicin on apoptosis and expression of survivin in K562/A02 cells / 中国实验血液学杂志

The aim of this study was to investigate the potential benefit of combination therapy with 5-bromotetrandrine (5-BrTet) and daunorubicin (DNR) on chronic leukemia. The apoptosis of K562/A02 cells treated by DNA, BrTet and BrTet combined with DNR for 48 hours was detected by flow cytometry; the expressions levels of survivin mRNA and protein K562/A02 cells treated by DNR, BrTet and BrTet combined with DNR and in untreated K562 cells for 48 hours were measured by RT-PCR and Western blot respectively. The results showed that the combination of BrTet with DNR increased apoptotic rate of K562/A02, down-regulated the expression levels of survivin mRNA and protein in K562/A02 cells as compared with blank control and cells treated by BrTet or DNR alone, the survivin expression in K562/A02 cells was higher than that in K562 cells. It is concluded that the combination of BrTet with DNR can effectively reverse the multidrug resistance of K562/A02 cells, promote the apoptosis of K562/A02 cells, the mechanism of which may be related with down-regulation of survivin expression. Survivin may be a target for the treatment of MDR in hematopoietic malignancies.

Gene expression in patients with myelodysplastic syndrome / 中国实验血液学杂志

This study was aimed to investigate the expression of c-FLIPL, c-FLIPS and DLK1 mRNA in the patients with myelodysplastic syndrome (MDS) and its clinical significance. The mRNA expression of c-FLIPL, c-FLIPS and DLK1 in bone marrow mononuclear cells (BMMNC) of 16 patients with MDS and 3 controls were detected by RT-PCR. The results indicated that the expression of DLK1 mRNA was up-regulated in MDS, including RA and RAEB, as compared with controls (p < 0.05). There was no significant difference in expression of DLK1 between RA and RAEB patients (p > 0.05); the expression of c-FLIPL mRNA both in RA and RAEB patients was higher than that in controls (p < 0.05). There was no significant difference in expression of c-FLIPL between RA and RAEB patients (p > 0.05); the expression of c-FLIPS mRNA was not significantly different between MDS patients and controls (p > 0.05), but its expression in RAEB patients was significantly higher as compared with RA patients and controls (p < 0.05). It is concluded that the mRNA expressions of DLK1, c-FLIPL and c-FLIPS in MDS patients are abnormal, some of which may be useful as an important indicator for the evaluation of development in MDS.

Test of activated plasma clotting time to assess efficacy of platelet transfusion / 中国实验血液学杂志

The study was aimed to investigate the value of activated plasma clotting time (APCT) for estimating the efficacy of platelet transfusion therapy. There were twenty patients with hematological diseases, who received transfusion of platelet, involved in the test. APCT was determined before and after transfusion of these patients, then APCT was contrasted with corresponding CCI and PPR. The results showed that 1 hour and 24 hour APCTs were shortened obviously. APCT before transfusion was (103.7 +/- 11.3) seconds, but the 1 hour and 24 hour APCTs were shortened to (60.0 +/- 9.7) seconds and (68.5 +/- 9.8) seconds respectively (P < 0.01). According to the judging criteria of CCI and PPR (CCI and PPR values at 1 and 24 hours after transfusion are < 7500, < 5000 and < 30%, < 20% respectively, the transfusion is invalid), two patients received invalid transfusion. Their 1 and 24 hour CCIs were 7415, 2966 and 6913, 4988 respectively. Their 1 and 24 hour PPRs were 28.0%, 11.2% and 25.2%, 14.1% respectively. One patient's PPR reached the standard of invalid transfusion, but his CCI showed a valid transfusion he received. Two patients' PPR reached the standard of invalid transfusion, but their 1 hour CCI reached the standard of valid transfusion, and their 24 hour CCI reached the standard of invalid transfusion. It is concluded that APCT reflects the variations of quantity and quality of platelet simultaneously, and can evaluate precisely the efficacy of platelet transfusion.

Effects of platelet-derived membrane microparticles on the proliferation and apoptosis of human umbilical vein endothelial cells / 中国实验血液学杂志

This study was purposed to investigate the effects of platelet-derived membrane microparticles (PMP) on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVEC). Different concentrations of thrombin were adopted to activate the platelets so as to release PMPs. Flow cytometry (FCM) was adopted to evaluate the efficiencies of different concentrations of thrombin to release PMPs. By using the HUVEC cultivated in vitro as vector, the effects of PMPs on the proliferation and apoptosis of HUVEC were investigated by MTT and FCM. The results showed that the efficiencies releasing PMPs from platelets activated by 2.0, 1.5, 1.0, 0.5 U/ml thrombin were 28.7, 47.7, 50.1 and 43.9% respectively; PMPs induced proliferation of HUVEC in a dose dependent manner. At the concentration of 40 microg/ml PMPs, the proliferation rate of HUVEC was 1.8 +/- 0.3 times as much as blank control, the proliferation rate in group of vascular endothelial growth factor was 1.9 +/- 0.5 times of as much as blank control, there was no statistic difference (p > 0.05). The PMPs inhibited HUVEC apoptosis. Compared with the apoptosis rate of control (9.4 +/- 0.5)%, apoptosis rate in PMP group (40 microg/ml) was (3.9 +/- 0.4)% (p < 0.05). The addition of VEGF (10 microl/ml) did not successfully prevented apoptosis of HUVEC with apoptosis rate of (8.0 +/- 0.8)%. It is concluded that platelets activated by 1 U/ml thrombin gets the best efficiency of PMP release, which stimulates proliferation of HUVEC and inhibits its apoptosis.

Effects of platelet-derived membrane microparticles on angiogenesis in chick chorioallantoic membranes / 中国实验血液学杂志

This study was purposed to investigate the angiogenesis effect of platelet-derived membrane microparticles (PMPs) in chick chorioallantoic membranes (CAM). Thrombin were adopted to activate the platelets and then PMPs were obtained. PMPs were isolated by high speed centrifugation. Flow cytometry (FCM) was adopted to evaluate the efficiency of thrombin to produce PMPs and BCA method was adopted to evaluate the content of PMPs. PMPs were put into CAM and the effects of PMPs on angiogenesis in CAM were observed. The results indicated that after incubation for 72 hours at the concentration of 80 microg/ml PMPs, the vessel nets in a 'spoked-wheel' pattern were shown around mixed fibrous filter membranes, number of vessel ramification was 112.5 +/- 11.31 and ratio of vessel area/CAM area was 6.19 +/- 1.29%, but there were not localized allantoic vessels developing in the control group, the number of vessel ramification and ratio of vessel area/CAM area in control group were 82.6 +/- 8.05 and 1.78 +/- 0.33 respectively, so there was significant difference between PMP and control groups. In above mentioned conditions, the number of vessel ramification and ratio of vessel area/CAM area in VEGF group were 128.4 +/- 10.02 and 7.44 +/- 1.36 respectively, so there was no difference between PMP and VEGF groups. It is concluded that PMPs show promotive effect on the formation of capillaries in chick chorioallantoic membranes.

Platelet-derived microparticles stimulate proliferation of granulocyte-macrophage progenitor cells from umbilical cord blood / 中国实验血液学杂志

This study was aimed to investigate the effect of platelet-derived microparticles (PMP) on stimulating the proliferation of granulocyte-macrophage progenitors (CFU-GM) from umbilical cord blood. Different concentrations of thrombin were adopted to activate the platelets for releasing PMP. Flow cytometry was adopted to evaluate the efficiencies of different concentrations of thrombin to produce PMP. Umbilical cord blood mononuclear cells (MNC) were obtained from healthy donors and the MNC were isolated by Ficoll density gradient centrifugation. MNC were cultured in 2.7% methylcellulose containing different concentration of PMP and colonies were counted under an inverted microscope after 7 days. The result showed that the release rate of PMP activated by 2.0, 1.5, 1.0 and 0.5 U/ml thrombin were 28.7%, 47.7%, 50.1% and 43.9% respectively. The PMP enhanced colony formation in dose-dependent manner. The number of colonies per 2 x 10(5) MNCs in groups of PMP at different concentrations (10, 50 and 100 microg/ml) were 119.8 +/- 32.2,142.8 +/- 45.2 and 180.8 +/- 85.1 respectively. The number of colonies in the groups of PMP at 100 microg/ml and 50 microg/ml were statistically significant when compared with control group (103.0 +/- 24.8) (P < 0.05). The number of colonies per 2 x 10(5) MNC in the group of PMP (10 microg/ml) was 119.8 +/- 32.2 which was higher than that in control group, but there was no statistical significance between two groups. It is concluded that platelet activated with 1.0 U/ml thrombin can get the best release efficiency of PMP and PMP can enhance the proliferation of granulocyte-macrophage progenitor cells of umbilical cord blood.

Biweekly-Regimens of Paclitaxel Combined with Cisplatin in the Treatment of Advanced Non - small Cell Lung Cancer / 中国药房

OBJECTIVE:To evaluate the efficacy and toxicity of paclitaxel combined with cisplatin in the treatment of advanced non-small cell lung cancer(NSCLC) by weekly-,biweekly- and three-weekly-regimens.METHODS:180 patients who had been confirmed by pathology and cytology as having NSCLC(Ⅲ～Ⅳstage) were enrolled into the study and divided to three groups:Biweekly - regimen(n= 60):paclitaxel 80 mg?m~(-2) plus cisplatin 40 mg?m~2 ivgtt on day 1 and day 8 in every 21 days;Weekly- regimen(n= 60):paclitaxel 55 mg?m~(-2) plus cisplatin 30 mg?m z ivgtt on day 1,8,and 15 in every 28 days;Three - weekly regimen(n = 60):paclitaxel 160 mg?m~(-2) plus cisplatin 80 mg?m~(-2) ivgtt on day 1 in every 21 days.Serum concentrations of paclitaxel at 3,12,24 h after administration were determined,and the efficacy and toxicity after two- cycle treatment were evaluated.RESULTS:The overall response rates of weekly-,biweekly -and three weekly regimens were 43.1%,35.8%and 34.0%respectively,showing no statistical differences among groups,but the incidence of main toxicities of biweekly-regimen was lower as compared with the other regimens.CONCLUSION:Biweekly -regimen is optimal for the treatment of advanced NSCLC with mild toxicity,which deserves to be applied in clinical practice.

Chronopharmacology of Gemcitabine in the Treatment of Non-small Cell Lung Cancer / 中国药房

0.05) but the incidence of toxicities in Group B was higher than in the other two groups. CONCLUSION:Comparatively speaking,Gemcitabine administered at 8 ∶ 00 was proved to be safer and more effective as compared with the other two groups in the treatment of NSCLC.