To explore therapeutic efficacy of androgens and low dose all-trans retinoic acid (ATRA) for myelodysplastic syndrome (MDS) patients, 55 patients of MDS were observed, including 41 cases of refractory anemia (RA), 11 cases of refractory anemia with excess of blasts (RAEB), 2 cases of refractory anemia with excess of blasts in transformation (RAEB-t) and 1 case of chronic myeloic-monocytic leukemia (CMML). These patients received danazol (600 mg/day) or stanazol (6 mg/day) and ATRA (10 mg/day) for at least 3 months. The results showed that according to MDS international working group response criteria, at the end of three months,complete remission (CR) was seen in 1 patient, partial remission (PR) was found in 2 patients. Hematologic improvement: major response (MaR) were seen in 15 patients, minor response (MiR) were seen in 4 patients. The total response rate was 35.8%. In conclusion, danazol or stanazol in combination with low dose ATRA are partialy effective in therapy for patients with low-risk myelodysplastic syndrome.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Androgens ; adverse effects ; therapeutic use ; Anemia, Refractory ; drug therapy ; Anemia, Refractory, with Excess of Blasts ; drug therapy ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Chemical and Drug Induced Liver Injury ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Treatment Outcome ; Tretinoin ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVETo explore the oxidative modification effect and its mechanism of low density lipoprotein (LDL) in hyperlipidemia (HL) rats after treating with tetrahydrobiopterin (BH4).

METHODSFifty four 8-week-old male Wistar rats were used, these 54 rats were randomly divided into control group, high fat diet group (HL group), high fat diet and injected BH4 group (HL + BH4 group), and 18 in each group. The BH4 levels of blood fats and blood serum and its metabolites, the aortic reactive oxygen species, the end product malondialdehyde (MDA) and the LDL oxidation level were all determined by killing 6 experimental rats in each group at the first 8, 16, and 24 weeks of age respectively.

RESULTSTreating with BH4 after 8 and 16 weeks, there was no significant difference in serum lipids among three groups (P > 0. 05); but ROS and MDA decreased significantly (P < 0.01); compared with control and HL groups, the BH4 level of HL + BH4 group increased a lot (P < 0.01); compared with control group, the BH4 content reduced obviously in aortic homogenate of HL group (P < 0.01), but the total petrin levels (TB = BH4 + BH2 + B) had no significant difference (P > 0.05); the serum TBARS formation increased gradually with the increase of week-ages, but compared with HL group, the serum TBARS formation of HL + BH4 group reduced significantly (P < 0. 01).

CONCLUSIONTreating with BH4 can reduced the LDL oxidation, the mechanism may be related to the correct of NOS uncoupling, the reduce of ROS generation and the decrease of LDL lipid peroxidation.

Animals ; Biopterin ; analogs & derivatives ; therapeutic use ; Hyperlipidemias ; blood ; drug therapy ; Lipid Peroxidation ; Lipids ; blood ; Lipoproteins, LDL ; metabolism ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism

OBJECTIVETo observe the expression of vascular smooth muscle cells calcium channel α1C subunit (LTCCα1C) in rats exposed in low temperature.

METHODSCold-induced hypertension was established and blood pressure was measured every two weeks. The mRNA expression of L type calcium channel α1C was determined by RT-PCR.

RESULTSThe blood pressure of the rats exposed to cold environment increased. The blood pressure of experimental groups [(102.8 ± 2.25) mm Hg] began to increase from the first two weeks, compared with the control group [(89.2 ± 3.73) mm Hg], there were significant difference (P < 0.05). The blood pressure of experimental groups were (114.5 ± 4.21), (121.9 ± 3.03) mm Hg respectively at 4, 6 weeks. Compared with the control group, the expression of LTCCα1C mRNA of the cold exposure group increased significantly (P < 0.01). There was a significant correlation between the expression of LTCCα1C mRNA and the blood pressure of the rats (r = 0.86, P < 0.01).

CONCLUSIONRepeated cold exposure can establish cold-induced hypertension, and the level of vascular smooth muscle cells LTCCα1C expression increase.

Animals ; Blood Pressure ; Calcium Channels, L-Type ; metabolism ; Cold Temperature ; adverse effects ; Hypertension ; Muscle, Smooth, Vascular ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear.

METHODSThe left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation (SO) group, myocardial infarction model (MI) group, and MI-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin (HE) stained tissue. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 (MMP-2), and tissue matrix metalloproteinase inhibitor-2 (TIMP-2). Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation.

RESULTSThe model of heart failure was established and the results of HE staining and Masson's trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the MI group showed a significantly increased expression of type I and type III collagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/TIMP-2 ratio. Compared with the MI group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang II-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio.

CONCLUSIONSThese data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.

Animals ; Atorvastatin Calcium ; Collagen ; biosynthesis ; Disease Models, Animal ; Female ; Fibrosis ; Heart Failure ; drug therapy ; pathology ; Heptanoic Acids ; pharmacology ; therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Matrix Metalloproteinase 2 ; genetics ; Myocardial Infarction ; complications ; Myocardium ; pathology ; Pyrroles ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; Ventricular Remodeling ; drug effects

Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

BACKGROUNDThe purpose of this study was to investigate the feasibility of avoiding axillary lymph node dissection (ALND) for patients with only one sentinel lymph node (SLN) metastasis. The characteristics and predictive factors for non-sentinel lymph node (NSLN) metastasis of patients with single positive SLN were also analyzed.

METHODSPatients with no and only one SLN metastasis (0/n and 1/n group, n &ge; 2) were selected from 1228 cases of invasive breast carcinoma, who underwent axillary dissection in Shandong Cancer Hospital between November 1999 and December 2011, to compare the characteristics of NSLN metastasis between them. For the 1/n group, the factors that influenced the NSLN metastasis were analyzed by univariate and multivariate analysis.

RESULTSDifferences of the NSLN metastasis between the 0/n and the 1/n groups were significant (P < 0.001). There was no significant difference between the axillary lymph node metastasis on level III in 1/n group and 0/n group (P = 0.570). When the total SLN number was &ge; 4 and with one positive case, the NSLN metastasis was not significantly different from that in the 0/n group (P = 0.118). In the 1/n group, clinical tumor size (P = 0.012), over-expression of Her-2 (P = 0.003), tumor grade (P = 0.018) and the total number of SLN (P = 0.047) significantly correlated with non-SLN metastasis. Clinical tumor size (P = 0.015) and the expression of Her-2 (P = 0.01) were independent predictive factors for non-SLN metastasis by the Logistic regression model.

CONCLUSIONUnder certain conditions, breast cancer patients with single SLN metastasis could avoid ALND.

Adult ; Aged ; Breast Neoplasms ; complications ; pathology ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Middle Aged ; Sentinel Lymph Node Biopsy

OBJECTIVESTo detect the sexual hormone level in semen of patients with idiopathic azoospermia and oligospermia, and further analyze the relationship between sexual hormone and idiopathic azoospermia and oligospermia.

METHODS50 male patients with idiopathic azoospermia, 50 in idiopathic oligospermia and 50 male controls with normal sperm density were selected. The sperm density and sexual hormone in semen were detected respectively by routine semen analysis and chemical luminescence technique.

RESULTSThe values of LH were (5.19 +/- 0.67) IU/L and (4.77 +/- 0.68) IU/L, and those of FSH were (1.90 +/- 0.79) IU/L and (2.27 +/- 0.25) IU/L in idiopathic azoospermia and oligospermia respectively, and the values of LH and FSH were (2.19 +/- 0.22) IU/L and (1.61 +/- 0.14) IU/L in normal control group respectively. There were significant differences in the values of LH and FSH between idiopathic azoospermia and normal control group(P < 0.01 or P < 0.05). The values of PRL were (6.25 +/- 0.51) ng/ml and (6.33 +/- 0.34) ng/ml, and those of T were (1.51 +/- 0.12) ng/ml and (1.68 +/- 0.71) ng/ml in idiopathic azoospermia and oligospermia respectively, and the values of PRL and T were (6.36 +/- 0.32) ng/ml and (1.83 +/- 0.09) ng/ml in normal control group respectively. There were no significant difference in the values of PRL between idiopathic azoospermia, oligospermia and normal control group, but there were significant differences of T between idiopathic azoospermia and normal control. Compared with 0.84 +/- 0.20 in normal control, the values of T/LH were 0.35 +/- 0.09 and 0.29 +/- 0.04 in idiopathic oligospermia and azoospermia respectively and there were significant differences(P < 0.05).

CONCLUSIONSThe changes of LH, FSH and T values may be one of the reasons that cause the dysfunction of spermatogenesis and sperm maturation in patients with idiopathic azoospermia and oligospermia. The study of semen hormone may lead to new strategies in the treatment to azoospermia and oligospermia.

Adult ; Azoospermia ; metabolism ; Case-Control Studies ; Follicle Stimulating Hormone ; analysis ; Humans ; Luteinizing Hormone ; analysis ; Male ; Middle Aged ; Oligospermia ; metabolism ; Semen ; chemistry ; Sperm Count ; Testosterone ; analysis

OBJECTIVETo study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD).

METHODSTwenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected.

RESULTSThere were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene.

CONCLUSIONSASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.

Adult ; Aged ; CD3 Complex ; metabolism ; Epstein-Barr Virus Infections ; pathology ; Female ; Follow-Up Studies ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Granzymes ; metabolism ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Killer Cells, Natural ; pathology ; Lymphoproliferative Disorders ; drug therapy ; genetics ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Poly(A)-Binding Proteins ; metabolism ; RNA, Viral ; metabolism ; Retrospective Studies ; Survival Rate ; T-Cell Intracellular Antigen-1 ; T-Lymphocytes ; pathology ; Young Adult

This study was purposed to explore the expression of glucosylceramide synthase (GCS) in human leukemia cells and its relationship with multidrug resistance. RT-PCR was used to analyze peripheral blood samples from 53 leukemia patients with multidrug resistance/non-resistance, and to detect the expression level of GCS gene in HL-60 cells and HL-60/ADR cells, the expression level was compared with the level of mdr-1. The expressions of GCS protein and P-gp protein in HL-60 cells and HL-60/ADR cells were assayed by Western blot analysis. The results showed that the relative optical density ratio of GCS gene amplified bands in samples of leukemia patients with drug-resistance was significantly higher than that in samples of leukemia patients with drug non-resistance group (P < 0.05), meanwhile the significant enhancement of optical density value of GCS gene amplified bands accompanied by high expression of mdr-1 gene. Their correlation showed positive (P < 0.01, r = 0.6). The GCS mRNA and protein were overexpressed in HL-60/ADR cells, and their expression levels were obviously higher than that in HL-60 cells, meanwhile the expression of mdr-1 mRNA and P-gp also significantly increased in HL-60/ADR cells. It is concluded that the high level of GCS in leukemia patients possibly is associated with multidrug resistance of leukemia cells.
ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Glucosyltransferases ; metabolism ; Humans ; Leukemia ; enzymology ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Cells, Cultured

Objective To investigate the effect of topiramate in the treatment of intractable epilepsy in children. Methods 120 cases with intractable epilepsy from May 2012 to May 2017 were randomly divided into 2 groups, the control group used antiepileptic drug treatment, study group combined application of anti epileptic drugs targeted nursing application. Results The clinical effect of the treatment group was better than that of the control group (P< 0.05). The frequency of epileptic seizure in the treatment group was significantly higher than that in the control group (P<0.05). Conclusion In the treatment of intractable epilepsy in children, the application of topiramate in the treatment of basic care is helpful to improve the effect of treatment, the effect is ideal, and should be further popularized in clinical practice.