[Proportion and Clinical Significance of γδT17/Th17/Tc17 Cells in Peripheral Blood of Uygur Patients with Chronic Lymphoblastic Leukemia].

OBJECTIVE: To explore the distribution of γδT17/Th17/Tc17 cells in the peripheral blood of Uygur patients with chronic lymphoblastic leukemia (CLL) and clinical significance. METHODS: ELISA method was used to detect the levels of IL-17, IL-23, IL-6, and IFN-γ in the peripheral blood serum of 53 newly diagnosed Uygur patients with CLL and 30 healthy controls. Flow cytometry was used to determine the proportion of γδT/γδT17/Th17/Tc17 cells in the peripheral blood of Uygur CLL patients and controls, and the changes of the abover indexes in CLL Binet staging were observed. RESULTS: Compared with the control group, the proportion of γδT cells, γδT17 cells, and Th17 cells in the peripheral blood of Uygur CLL patients increased significantly （P <0.05）. γδT17 cell proportion in total lymphocytes was significantly higher than Th17 and Tc17 cell proportions（P <0.05）, and proportions of γδT, γδT17 cells increased gradually as the disease progressed. The levels of cytokines IL-17, IL-23, and IL-6 in peripheral blood of Uygur patients with CLL were significantly higher than those in the control group（P <0.05）, while the level of cytokine IFN-γ was significantly lower（P <0.05）. The level of IL-17 in peripheral blood decreased gradually as the disease progressed（P <0.05）. CONCLUSION: γδT and γδT17 are abnormally highly expressed in Uygur CLL , which are related to the stage of disease and participate in the occurrence and development of CLL.

[Expression and Clinical Significance of Helper T Cells 9 and Its Sytokines Interleukin 9 in Chronic Lymphocytic Leukemia].

OBJECTIVE: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL). METHODS: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed. RESULTS: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with ß2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(rs=-0.32，rs=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (rs=0.79，rs=0.54，rs=0.58； rs=0.72，rs=0.63，rs=0.45), but not with WBC, CD4+ T cells and CD8+T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (rs=0.53). CONCLUSION: Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.

[Significance of Tim-3 and Its Ligand Galectin-9 in Th1/Th2 Imbalance in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the significance of Tim-3 and Galectin-9 in Th1/Th2 imbalance in patients with multiple myeloma (MM). METHODS: 55 newly diagnosed MM patients and 20 healthy controls were included. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th1, Th2, Tim-3+Th1 and Tim-3+Th2 cells in peripheral blood. ELISA was used to detect the levels of cytokines IFN-γ and IL-4 in serum, and PCR was used to detect the level of Galectin-9 mRNA. Then the correlations between Galectin-9 mRNA expression and Th-cell subsets and related cytokine levels, as well as the relationship between Tim-3+Th1/Tim-3+Th2 ratio and corresponding clinical features were analyzed. RESULTS: Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was significantly increased (P<0.05), the proportions of Tim-3+Th1 cells, Tim-3+Th2 cells and Tim-3+Th1/Tim-3+Th2 ratio in MM patients were also increased (P<0.05), while the proportion of Th1 cells and Th1/Th2 ratio in MM patients were significantly decreased (P<0.05). The level of cytokine IFN-γ and IFN-γ/IL-4 ratio in MM patients were significantly decreased (P<0.05), while the level of cytokine IL-4 was increased (P<0.05). The mRNA levels of Galectin-9 in MM patients were significantly increased (P<0.05). The levels of Galectin-9 mRNA were positively correlated with Tim-3+CD4+T cells (r=0.663), Tim-3+Th2 cells (r=0.492) and IL-4 (r=0.470), while negatively correlated with IFN-γ (r=-0.593). The ratios of Tim-3+Th1/Tim-3+Th2 in MM patients were positively correlated with ISS stage (r=0.511), osteolytic damage (r=0.556) and chromosome abnormality (r=0.632). CONCLUSION: These results suggest that Tim-3 and Galectin-9 are involved in Th1/Th2 imbalance in MM patients, and the high ratio of Tim-3+Th1/Tim-3+Th2 is associated with poor clinical prognosis.

Identification of key genes and miRNA-mRNA regulatory networks associated with bone marrow immune microenvironment regulations in multiple myeloma by integrative bioinformatics analysis.

The deregulation of microRNAs (miRNAs) and genes in the bone marrow microenvironment have been involved with the pathogenesis of multiple myeloma (MM). However, the exploration of miRNA-mRNA regulatory networks in MM remains lacking. We used GSE125363, GSE125361, GSE47552, GSE2658, GSE136324, GSE16558, and GSE13591 datasets for this bioinformatics study. We identified 156 downregulated and 13 upregulated differentially expressed miRNAs (DEmiRs) in MM. The DEmiRs are associated with the enrichment of pathways mainly involved with cancers, cellular signaling, and immune regulations. We identified 112 hub genes associated with five significant clusters in MM. Moreover, we identified 9 upregulated hub genes (such as IGF1, RPS28, UBA52, CDKN1A, and CDKN2A) and 52 downregulated hub genes (such as TP53, PCNA, BRCA1, CCNB1, and MSH2) in MM that is targeted by DEmiRs. The expression of DEmiRs targeted two hub genes (CDKN2A and TP53) are correlated with the survival prognosis of MM patients. Furthermore, the expression level of CDKN2A is correlated with immune signatures, including CD4+ Regulatory T cells, T cell exhaustion, MHC Class I, immune checkpoint genes, macrophages, neutrophils, and TH2 cells in the TME of MM. Finally, we revealed the consistently deregulated expression level of key gene CDKN2A and its co-regulatory DEmiRs, including hsa-mir-192, hsa-mir-10b, hsa-mir-492, and hsa-mir-24 in the independent cohorts of MM. Identifying key genes and miRNA-mRNA regulatory networks may provide new molecular insights into the tumor immune microenvironment in MM.

[Significance of Tim-3 in The Imbalance of Th17/Treg in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the singnificance of Tim-3 in Th17/Treg balance in patients with multiple myeloma (MM). METHODS: Fifty-six newly diagnosed MM patients and 30 healthy people were enrolled. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th17 and Treg cell, the Th17/Treg ratio, the expression of Tim-3 in Th17 and Treg cells, and the ratio of Tim-3+Th17/Tim-3+Treg cells in two groups. ELISA was used to detect the level of cytokines IL-17 and IL-10. Moreover, to analyze the relationship between Tim-3+Th17/Tim-3+Treg balance and clinical indicator. RESULTS: Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was increased (P<0.05), the ratio of Th17 cells and Th17/Treg in MM patients were higher than those in control group (P<0.05), and the ratio of Treg cells in MM patients was lower than those in control group, which the difference showed no statistically significant (P>0.05), and the level of cytokines IL-17, IL-10 and the ratio of IL-17/IL-10 in MM patients were significant higher than those in the control group (P<0.05). The expression level of Tim-3+Th17 cells and the ratio of Tim-3+Th17/Tim-3+Treg in MM patients were higher than those in control group (P<0.05), while the expression level of Tim-3+Treg cells in MM patients were lower than that in the control group (P<0.05). The ratio of Tim-3+Th17/Tim-3+Treg in MM patients were positive correlated with ISS staging, DS staging, chromosome abnormality and sFLCR (r=0.635, r=0.501, r=0.449, r=0.587). CONCLUSION: The ratios of Th17/Treg, IL-17/IL-10 and Tim-3+Th17/Tim-3+Treg increase in MM patients, among which Tim-3+Th17/Tim-3+Treg is correlated with ISS staging, DS staging, chromosomal abnormalities and sFLCR, which suggesting that Tim-3 is involved in the imbalance of Th17/Treg in MM patients.

[Incidence Analysis of Monoclonal Gammopathy of Undetermined Significance in People over 40 Years of Age].

OBJECTIVE: To study the distribution of monoclonal gammopathy of undetermined significance(MGUS) in different age, sex and ethnic people over 40 years old. METHODS: Five hundred and ninety-six people(over 40 years old) examened in the Health Examination center of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to September 2017 were selected. Among 596 people, male 310, female 286, Han people 488, and Uygur ethnic people 108. According to age, 596 people were divided into 3 groups, (40-59 years old group, 60-79 years old group, over 80 years old group). First, all samples were screened by capillary serum protein electrophoresis. If the suspected monoclonal bands were found in the electrophoretogram, and then the specific protein types were determined by serum immunofixation electrophoresis. RESULTS: The total incidence of MGUS in 596 screened population was 4.027%. The incidence of MGUS in 40-59 years old group, 60-69 years old group and over 80 years old group were 1.762%, 2.929% and 10% respectively, and the differences among the groups were statistically significant(P<0.05). The incidence of MGUS in male (5.806%) was significantly higher than that in female (2.097%)(χ2=5.177，P<0.05). Binary Logistic regression analysis showed that over 80 years old and male were independent risk factors for MGUS(P=0.001, OR=4.188, 95%CI: 1.814-9.673, P=0.048, OR=2.605, 95%CI: 1.009-6.725). The types of immunoglobulin in patients with MGUS were mostly IgG, IgG(66.7%) was significantly more than IgA (29.2%)(χ2=21.375，P<0.05)，and there was no significant difference in the incidence of MGUS between people with in Kappa and Lambda. CONCLUSION: The age increase and male may increase the incidence of MGUS, the IgG is the most common type of immunoglobcdin in pathogenesis of MGUS, so the early screening should be done.

[Expression of Transcription Factor SOX4 in Acute Myeloid Leukemia and Its Clinical Significance].

OBJECTIVE: To study the expression of SOX4 gene in patients with acute myeloid leukemia (AML) and its correlation with clinical features and prognosis, and to explore the role of this gene in acute myeloid leukemia. METHODS: The real-time guantitative PCR was used to detect the expression level of SOX4 gene in bone marrow of 96 patients with newby diagmsed AML, and the features and prognosis was analyzed. RESULTS: The level of SOX4 expression in the 96 AML patients was significantly higher than that in healthy controls (P<0.01), and the expression of SOX4 gene was not significanly different between M1-M5 (P<0.05). The expression of SOX4 gene was no significanly different between different sex, nationality, and remission after chemotherapy (P>0.05). In AML patients the SOX4 gene expression level did not significantly correlated with the white blood cell count, hemoglobin level, platelet count primitive cell count, reticulocyte count and other laboratory indexes ( P>0.05), while which correlated with the overall survival (OS) (P<0.01) and erent-free survival (EFS) (P<0.05). CONCLUSION: The high expression of SOX4 gene affects the survival time of patients (OS, EFS), suggesting that may be one of the unfavorable prognostic factors for the AML patients.

Perfluorooctane sulfonate-induced testicular toxicity and differential testicular expression of estrogen receptor in male mice.

Perfluorooctane sulfonate (PFOS, CAS#1763-23-1) causes male reproductive toxicities, but the underlying mechanisms are still unclear. In this study, 0, 0.5 and 10mg/kg/day PFOS were given by oral gavage to adult mice for 5 weeks. In the 10mg/kg group, serum testosterone levels decreased significantly. Sperm counts declined which might be associated with the decreased proliferation and increased apoptosis of germ cells. In relation to increased apoptosis, bax, cleaved caspase-9 and cleaved caspase-3 levels elevated significantly, indicating that PFOS induced germ cell apoptosis by activating the mitochondrial pathway. In addition, the increase in levels of testicular estrogen receptor (ER) ß was observed in both 0.5 and 10mg/kg group, whereas a decrease in ERα expression was only observed in 10mg/kg group. These results suggested that the alterations in testicular ERs expression, together with decreased proliferation and increased apoptosis of germ cells, might be involved in PFOS-induced testicular toxicity.

[Expression of Ki-67 in chronic lymphocytic leukemia and its clinical significance].

OBJECTIVE: To investigate the expression of nuclear antigen Ki-67 in CLL patients and realationship of Ki-67 expression with other clinical parameters. METHODS: Twenty-Six confirmed cases of CLL were analysised retrospectively. The immhnohistochemical method was carried out to examine the expression of Ki-67 in bone marrow cells, the flow cytometer was used to detect ZAP70 (Zeta chain-associated protein), CD38 and other markers, additionally, a panel of probes RB1 (13q14), ATM (11q22.3), P53 (17p13.1) and CSP12 (+12) FISH were perfomed to detect the cytogenetic abnormalities. RESULTS: Out of 26 patients, 15 cases (57.7%) showed positive expression of Ki-67, 11 cases (42.3%) showed negative expression of Ki-67, the average rate of Ki-67 positive expression was (10.86±7.36)%. The level of Ki-67 did not relate with sex, age, Hb, platelet, ZAP70, ATM. ß2-MG, IgHV and P53, but related to the Rai staging (P=0.01, r=0.517), CD38 (P=0.02, r=0.469), 13q14 (P=0.021, r=-0.48), and there was statistically significant difference (P<0.05). CONCLUSION: The Ki-67 level is higher in progressive stage of CLL and the Ki-67 expression is related with Rai staging, CD38, 13q14. The expression level of Ki-67 may be used as indicator for evaluation of CLL prognosis and guiding treatment for this disease.

[mRNA Expressions of T-bet, GATA-3, ROR γt and Foxp3 in peripheral blood of patients with chronic lymphocytic leukemia in different stages].

OBJECTIVE: This study was to investigate the mRNA expression of T-bet, GATA-3, ROR γt and Foxp3 mRNA in peripheral blood of patients with chronic lymphocytic leukemia (CLL) in different stages and explore their potential role in the pathogenesis and clinical diagnosis. METHODS: A total of 46 newly diagnosed and untreated patients with CLL was chosen as patient group, including 16 patients in the stage of Binet A, 15 in the stage of Binet B, and 15 in the stage of Binet C; 20 healthy persons were selected as controls. The quantitative fluorescence PCR was adopted to detect the mRNA expression of T-bet, GATA-3, RORγt and Foxp3 in peripheral blood mononuclear cell (PBMNC). RESULTS: (1) The expression of T-bet mRNA in patient group was lower than that in normal controls (P < 0.05), while the mRNA expression of GATA-3 mRNA, ROR γt, Foxp3 in CLL patients group were higher than that in normal controls (P < 0.05), and the ratio of T-bet/GATA-3 and RORγt/Foxp3 in CLL in patient group were lower than that in normal controls(P < 0.05); (2) The later the stage, the higher the mRNA expression of GATA-3 and Foxp3. The mRNA expression of GATA-3 in stage Binet B and stage Binet C of CLL patients were higher than that in stage Binet A (P < 0.05),and the mRNA expression of Foxp3 in stage Binet C was higher than that in stage of Binet A and Binet B (P < 0.05); the later the stage, the lower the ratio of T-bet/GATA-3 and RORγt/Foxp3. The ratio of T-bet/GATA-3 in stage of Binet A CLL patients was higher than that in stage Binet C (P < 0.05) and the ratio of RORγt/Foxp3 in stage of Binet A and stage of Binet B were higher than that in stage Binet C (P < 0.05). CONCLUSION: This study found in the level of transcription factors in CLL patients that with the process of disease, the balance shifts from Th1/Th2 and Th17/Treg to Th17 and Treg, and Treg cell may play a critical immunosuppressive role in the development of CLL.

[Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens].

This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 ± 0.09)×10(9)/L] was significantly lower than that in DA group [(0.21 ± 0.16)×10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 ± 5.31)d was much longer than that in DA group (9.17 ± 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.

Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population.

The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally linked to germ cell apoptosis, which may affect human infertility, but very little is known on how common polymorphisms in these genes may influence germ cell apoptosis and the risk of male infertility. Thus, this study was designed to test whether three previously described polymorphisms 72Arg>Pro (rs1042522) and the Ex2+19C>T (rs2287498) in TP53, and the 5' untranslated region (5' UTR) 309T>G (rs937283) in MDM2, are associated with idiopathic male infertility in a Chinese population. The three polymorphisms were genotyped using OpenArray assay in a hospital-based case-control study, including 580 infertile patients and 580 fertile controls. Our analyses revealed that TP53 Ex2+19C>T and MDM2 309T>G polymorphisms are associated with male infertility. Furthermore, we detected a nearly statistically significant additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility (P(interaction)=0.055). In summary, this study found preliminary evidence, demonstrating that genetic variants in genes of the TP53 pathway are risk factors for male infertility.

Involvement of IGF-I signaling pathway in the regulation of steroidogenesis in mouse Leydig cells treated with fenvalerate.

Exposure to fenvalerate has been shown to be associated with decreased steroid hormone production by mouse Leydig tumor cells (MLTC-1) in our previous study and the interference with cAMP-PKA pathway cannot explain this inhibitory effect completely. In this study, the same cell line was used to investigate the potential involvement of insulin-like growth factor I (IGF-I) signaling pathway in the downregulation of steroidogenesis by fenvalerate. Results showed that fenvalerate treatment decreased IGF-I secretion significantly which was consistent with the reduced expression of IGF-I mRNA. Then inhibitors of the two downstream pathways of IGF-I were added to the medium. The addition of LY294002 (inhibitor of phosphatidylinositol (PI)-3-kinase) did not alter the declining trend of progesterone production with increasing dosages of fenvalerate treatment while the addition of UO126 (inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2)) markedly attenuated this trend, which strongly indicated the possible involvement of pathway ERK1/2. In addition, phosphorylation of ERK1/2 was also suppressed by fenvalerate. The results suggest that the mechanism by which fenvalerate decreased steroid hormone production might involve the impairment of IGF-I signal pathway by attenuating the IGF-I production and ERK1/2 phosphorylation.

[Stratification therapy in patients with acute promyelocytic leukemia after a complete remission by all-trans retinoic acid].

OBJECTIVE: To explore an efficacious protocol for the patients with acute promyelocytic leukemia (APL) after a complete remission (CR) by all-trans retinoic acid (ATRA). METHODS: A total of 32 APL patients with an induction of CR by ATRA at our hospital from January 2000 to October 2007 received conventional standard chemotherapy as a consolidation regimen. Stratified according to age, those under 50 years old received an intermediate dose of cytarabine(IDAra-C)and over 50 years old non-IDAra-C regimen. Maintenance regimen: all patients received ATRA, arsenic trioxide (As2O3) and 6-mercaptopurine (6-MP) + methotrexate (MTX) alternately and sequentially for 3 years. The efficacy and side effects of these chemotherapies were observed. RESULTS: The median follow-up was 72 (40 - 124) months. The 5-year disease-free survival (DFS) rates of under 50 years old and over 50 years old were 94.7% and 92.3% respectively. The difference was statistically insignificant (P > 0.05). One patient relapsed after a consolidation therapy and so did another on a maintenance regimen. Thirty patients achieved a constant CR. And 16 of 30 patients completed chemotherapy beyond 5 years and survived disease-free. The 5-year DFS rate of 32 patients was 93.8%. CONCLUSION: After the achievement of CR with ATRA, all APL patients have a higher rate of DFS after stratification. The side effects are generally mild. Thus a stratification therapy is both feasible and efficacious.

[Comparison of immunological reconstitution and related complications after HLA-matched and HLA haploidentical peripheral blood hematopoietic stem cell transplantation].

OBJECTIVE: To explore the difference of immune function and relationship with main complications after HLA-matched and HLA haploidentical allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT). METHODS: Sixty-seven patients undergoing HLA-matched (n = 33) or HLA haploidentical (n = 34) allo-PBSCT during the same time period in our hospital from June 2004 to December 2007 were included in this study. Indirect immunofluorescence assay was employed to detect lymphocyte subsets before transplantation and on month 1, 3, 6, 12 and 18 after transplantation and the lymphocyte subsets of 100 healthy people were used as normal control. The comparison of immunological reconstitution and relationship with main complications was carried out with statistical analysis. RESULTS: (1) Comparison of the 67 patients with normal controls showed that CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+) at month 1, CD(4)(+), CD(4)(+)/CD(8)(+) at month 3 and CD(4)(+) at month 6 after PBSCT were lower. CD(8)(+) at month 3 and month 6 were higher. (2) The immune function was not statistically different between HLA haploidentical and HLA-matched allo-PBSCT (P > 0.05). (3) The immune function of patients with and without severe infection was not statistically different (P > 0.05). (4) The immune function of patients with chronic graft-versus-host disease (cGVHD) between HLA haploidentical and HLA-matched allo-PBSCT groups was not statistically different. The immune function of patients without cGVHD in two groups was not statistically different (P > 0.05). (5) The immune function of patients with or without relapse was not statistically different (P > 0.05). CONCLUSIONS: HLA-haploidentical PBSCT conditioning including antithymocyte globulin without in vitro T cell depletion is feasible and safe. The immunological reconstitution, incidence of severe infection, incidence of relapse and treatment-related mortality are not significantly different between HLA-matched and HLA haploidentical allo-PBSCT.

[Non-T-cell depleted HLA haploidentical peripheral blood stem cell transplantation for hematological malignancies: report of 36 cases].

OBJECTIVE: To analyze the clinical outcome of human leukocyte antigen (HLA) haploidentical peripheral blood stem cell transplantation (PBSCT) from related donors for hematological malignancies. METHODS: Thirty-six patients with hematological malignancies, with a median age of 25 (11-48) years, were transplanted with PBSC from an HLA-haploidentical family donors: 7 were 1 locus mismatched and 29 were 2-3 loci mismatched. The recipients received myeloablative conditioning regimen, in combination with different immunosuppressants according to the degree of HLA disparity followed by non-T-cell depleted PBSCT. The median number of CD34+ cells were 11 (4.16-21.00) x 10(6)/kg. RESULTS: All patients achieved sustained, full donor-type engraftment. Fifteen patients (41.7%) developed grade I-II aGVHD. Among 29 patients followed up more than 18 months, 17 (58.6%) developed cGVHD. There was no statistical difference in decrease and recovery of T, B and NK cell subsets after transplantation between HLA haploidentical group and HLA identical PBSCT group. The median follow-up duration was 15 (4 -69) months. Five patients (13.9% ) relapsed. The 2-year probability of leukemia-free survival (LFS) was 82.2%. CONCLUSION: Non-T-cell depleted HLA-haploidentical PBSCT is safe and feasible for patients with hematological malignancies after myeloablative conditioning regimen combined with intensive immunosuppressants.

Fenvalerate inhibits progesterone production through cAMP-dependent signal pathway.

Fenvalerate is a widely used synthetic pyrethroid insecticide and is known to impede the male reproductive function. However, the mechanisms remain to be elucidated. In this study, mouse Leydig tumor cells (MLTC-1) were used to investigate the effects of fenvalerate on progesterone production. Fenvalerate treatment inhibited progesterone secretion induced by human chorionic gonadotropin (hCG), cholera toxin (CT) or forskolin and decreased cAMP levels induced by hCG, but not by CT or forskolin, which suggested a repaired site on the upstream components of G protein or G protein per se by fenvalerate in the cAMP-mediated signal pathway. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse fenvalerate-suppressed progesterone synthesis, indicating that fenvalerate interfered with the downstream molecules of cAMP. In addition, fenvalerate decreased steroidogenic acute regulatory protein (StAR) mRNA and protein levels, and also profoundly inhibited the activity of P450 side chain cleavage enzyme (P450scc) which was consistent with the decreased expression of P450scc mRNA and protein in MLTC-1 cells. These results suggested that fenvalerate might inhibit progesterone production by attenuating cAMP generation and inhibiting StAR expression and P450scc activity.

4-Alkylphenols and related chemicals show similar effect on the function of human and rat estrogen receptor alpha in reporter gene assay.

Alkylphenols (APs) are widely used as important industrial materials and have attracted lots of attention because of their potential estrogenic activities. In this study, we developed human estrogen receptor alpha (hERalpha) and rat estrogen receptor alpha (rERalpha) mediated reporter gene assays and compared the estrogenic activity of APs and related chemicals based on the two ERalpha. Human breast cancer cell line MCF-7 was co-transfected with Gal4-fused hERalpha and corresponding reporter plasmid; African green monkey kidney cell line CV-1 was co-transfected with rERalpha and reporter gene. Both assays showed acceptable response to natural estrogen 17beta-estradiol (E2) with EC50 of 0.16 nM and 4.7 nM. Then the estrogenic activity of 4-APs, 4-phenylphenol and bisphenol-A were evaluated and compared with the effects of E2. The data suggested that test APs and related chemicals possessed weakly estrogenic activity and the activity of test APs increased with the increase of substituent size. This structure-activity relationship helped to infer the activity of chemicals with similar feature. Furthermore, test APs showed similar effect on the function of hERalpha and rERalpha. This consistency helped to extrapolate in vivo rodent data to human being when performing risk assessment of endocrine disruptors.