Enzalutamide-Induced Upregulation of PCAT6 Promotes Prostate Cancer Neuroendocrine Differentiation by Regulating miR-326/HNRNPA2B1 Axis.

Our previous studies have demonstrated that Enzalutamide-induced upregulation of long non-coding RNA p21 (lncRNA-p21) facilitates prostate cancer (PCa) neuroendocrine differentiation (NED). Given the important role of lncRNAs in PCa pathogenesis, and given that lots of lncRNAs are dys-regulated in neuroendocrine PCa (NEPC) patients, we next explored the biological function and underlying mechanism of lncRNA-PCAT6 (PCAT6) in mediating Enzalutamide-induced NED. The level of PCAT6 in Enzalutamide-treated PCa cells and NEPC samples were assessed using quantitative RT-PCR (qPCR). The effect of PCAT6 on PCa cell proliferation, invasion, and NED was evaluated through CCK-8, transwell, qPCR, western blot analysis, Xenograft mouse model, and in vivo lung metastasis model. We found that PCAT6 was highly expressed in NE-like cells (PC3, DU145, and NCI-H660) compared with androgen-sensitive LNCaP cells. PCAT6 was also highly expressed in NEPC tissues. Enzalutamide treatment resulted in a significant increase of PCAT6 level in a dose- and time-dependent fashion. Functionally, PCAT6 overexpression promoted NED of C4-2 cells, as evidenced by an increased expression of NE markers (NSE, ChgA, and SYP), whereas PCAT6 knockdown in NCI-H661 cells repressed NED. Furthermore, PCAT6 overexpression promoted PCa cell proliferation and invasion in vitro and in vivo. Mechanistically, PCAT6 functioned as competing endogenous (ce) RNA via absorbing miR-326, thus resulting in a de-suppression of Hnrnpa2b1 target gene. The current results demonstrate that PCAT6 acted as a tumor activator in PCa progression by sponging miR-326 and increasing Hnrnpa2b1 expression and that the PCAT6/miR-326/Hnrnpa2b1 signaling might be a new therapeutic target for PCa.

Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis.

BACKGROUND: Prostate cancer (PCa) is a commonly diagnosed malignant cancer and is the second- highest cause of cancer death in men worldwide. Enzalutamide is the second-generation inhibitor of androgen receptor signaling and is the fundamental drug for the treatment of advanced PCa. However, the disease will eventually progress to metastatic castration-resistant prostate cancer (CRPC) and aggressive neuroendocrine prostate cancer (NEPC) because of androgen-deprivation therapy (ADT) resistance. The aim of the study was to investigate the role of long non-coding RNA (lncRNA) AFAP1-AS1 in ADT resistance. METHODS: Quantitative real-time PCR analysis (qPCR) was used to assess the expression of AFAP1-AS1 in PCa cell lines and tissues. Cell proliferation and invasion were assessed after AFAP1-AS1 knockdown using Cell Counting Kit (CCK)-8 and Transwell assay, respectively. A dual-luciferase reporter gene assay was carried out to validate the regulatory relationship among AFAP1-AS1, microRNA (miR)-15b, and insulin-like growth factor1 receptor (IGF1R). RESULTS: AFAP1-AS1 level was markedly increased in castration-resistant C4-2 cells and NE-like cells (PC3, DU145, and NCI-H660), compared with androgen-sensitive LNCaP cells. Enzalutamide treatment increased the expression of AFAP1-AS1 in vitro and in vivo. Functionally, AFAP1-AS1 knockdown repressed tumor cell proliferation and invasion. Mechanistically, AFAP1-AS1 functioned as an oncogene in PCa through binding to miR-15b and destroying its tumor suppressor function. Finally, we identified that AFAP1-AS1 up-regulated IGF1R expression by competitively binding to miR-15b to de-repress IGF1R. CONCLUSION: AFAP1-AS1 facilitates PCa progression by regulating miR-15b/IGF1R axis, indicating that AFAP1-AS1 may serve as a diagnostic biomarker and therapeutic target for PCa.

Effect of interleukin-1ß and lipoxin A4 in human endometriotic stromal cells: Proteomic analysis.

AIM: Lipoxin A4 (LXA4 ) can function as an endogenous 'breaking signal' in inflammation and plays an important role in the progression of endometriosis. The proteome responses to interleukin-1ß (IL-1ß) or LXA4 in human endometriotic stromal cells (ESC) are not well understood. METHODS: In this study, primary ESC were cultured from ovarian endometriosis tissue. Three groups were established: the control group; the IL-1ß stimulation group; and the IL-1ß and LXA4 incubation group. Proteins were assessed on 2-D polyacrylamide gel electrophoresis (2D-PAGE), and differentially expressed protein spots were further identified on matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MALDI-TOF-MS). Wound healing and transwell assays were performed to assess the migration and invasion of ESC after treatment. RESULTS: In total, 40 differentially expressed protein spots were identified successfully on MALDI-TOF-MS. The proteins identified were related to cell structure, metabolism, signal transduction, protein synthesis and membrane structure, processes that may be involved in the development of endometriosis. Vinculin and IL-4 were further analyzed on western blot and quantitative real-time polymerase chain reaction. Moreover, LXA4 could suppress the migration and invasion of ESC induced by IL-1ß. CONCLUSION: LXA4 may inhibit the progression of endometriosis partly by lowering or raising the effect of IL-1ß, mediated via some inflammation-related proteins (e.g. vinculin) and immune response-related protein (e.g. IL-4) in vitro.

Cyclopropanyldehydrocostunolide LJ attenuates high glucose-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways.

AIMS: The aim of this research was to investigate the effects of cyclopropanyldehydrocostunolide (also named LJ), a derivative of sesquiterpene lactones (SLs), on high glucose (HG)-induced podocyte injury and the associated molecular mechanisms. METHODS: Differentiated mouse podocytes were incubated in different treatments. The migration and albumin filtration of podocytes were examined by Transwell filters. The protein and mRNA levels of MCP-1 were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (q-PCR). Protein expression and phosphorylation were detected by western blot, and the nuclear translocation of NF-κB was performed with a confocal microscope. The gene expression of the receptor activator for NF-κB (RANK) was silenced by small interfering RNA (siRNA). RESULTS: Our results showed that HG enhanced migration, albumin filtration and MCP-1 expression in podocytes. At the molecular level, HG promoted the phosphorylation of NF-κB/p65, IKKß, IκBα, mitogen-activated protein kinase (MAPK) and the nuclear translocation of p65. LJ reversed the effects of HG in a dose-dependent manner. Furthermore, our data provided the first demonstration that the receptor activator for NF-κB ligand (RANKL) and its cognate receptor RANK were overexpressed in HG-induced podocytes and were downregulated by LJ. RANK siRNA also attenuated HG-induced podocyte injury and markedly inhibited the activation of NF-κB and MAPK signaling pathways. CONCLUSIONS: LJ attenuates HG-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways.

Lipoxin A4 regulates expression of the estrogen receptor and inhibits 17ß-estradiol induced p38 mitogen-activated protein kinase phosphorylation in human endometriotic stromal cells.

OBJECTIVE: To study the role of lipoxin A4 (LXA4) in endometriosis. DESIGN: Molecular analysis in human samples and primary human endometriotic stromal cells (ESCs). SETTING: University hospital. PATIENT(S): Forty-nine premenopausal women (30 patients with endometriosis and 19 controls). INTERVENTION(S): Normal and ectopic endometrial biopsies obtained during surgery performed during the proliferative phase of the menstrual cycle; ESCs used for in vitro studies. MAIN OUTCOME MEASURE(S): Levels of LXA4 measured by enzyme-linked immunosorbent assay (ELISA); mRNA levels of the estrogen receptor (ER), progestogen receptor (PR), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR); and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation evaluated by Western blotting. RESULT(S): The LXA4 expression level decreased in ectopic tissue as well as ERα and PR, although the expression of ERß increased in ectopic endometrium compared with the controls. Investigations with correlation analysis revealed the expression of LXA4 was positively correlated with ERα and negatively correlated with ERß in vivo. Moreover, administering LXA4 could augment ERß expression in ESCs and inhibit the 17ß-estradiol-induced phosphorylation of p38 MAPK very likely through ERß. CONCLUSION(S): Our findings indicate that LXA4 regulates ERß expression and inhibits 17ß-estradiol-induced phosphorylation of p38 MAPK, very likely through ERß in ESCs.

Treatment of advanced non-small-cell lung cancer with Chinese herbal medicine by stages combined with chemotherapy.

PURPOSE: To observe the effect of Chinese herbal medicine by stages combined with chemotherapy in treating patients with non-small-cell lung cancer (NSCLC) of stage III or IV. METHODS: Adopting prospective, randomized, controlled, multi-centered trial design, 121 patients enrolled were assigned to the treatment group (n = 65) and the control group (n = 56). All the patients were randomized to receive chemotherapy alone or chemotherapy and Chinese herbal medicine combined (Kangliuzengxiao decoction during chemotherapy and Feiyanning decoction after chemotherapy). The main outcome measures were survival time, Karnofsky score, main clinical symptoms, and adverse reactions. RESULTS: Five patients discontinued from the trial due to oral administration of Iressa after disease progression or other reasons, and 116 patients were evaluable for clinical efficacy with 63 in the treatment group and 53 in the control group. The overall response rate were 15.87% vs. 7.55% (P = 0.170), and the disease control rate were 85.71% vs. 71.70% in the treatment and control group (P = 0.063), respectively. The median survival time was 16.17 months vs. 12.00 months in the treatment and control group (P = 0.165), respectively. In addition, adverse reactions such as leucopenia in the treatment group were less than those in the control group (P = 0.039). CONCLUSIONS: Chinese herbal medicine combined with chemotherapy showed favorable effect in improving quality of life and prolonging survival time on patients with advanced NSCLC.

SB203580, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis by down-regulating proinflammatory cytokines and proteolytic factors in a mouse model.

BACKGROUND: p38 mitogen-activated protein kinase (p38 MAPK), a regulator of inflammation, may play a role in the pathogenesis of endometriosis (EM). We studied the effect of SB203580, a p38 MAPK inhibitor, on the development of EM in a mouse model. METHODS: EM was induced in BALB/c mice by peritoneal injection of endometrium-rich fragments. Mice (n = 15) were injected i.p. for 24 days with SB203580 and 15 mice served as positive controls (EM group). Sham-operated mice received carrier only. Peritoneal fluid (PF) cells were collected for protein/mRNA analysis. Interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins were measured using enzyme-linked immunosorbent assay and mRNAs by RT-PCR. Phosphorylation of p38 MAPK was evaluated by western blotting. RESULTS: SB203580 decreased the weight and size (P < 0.05 versus EM) of endometriotic lesions in BALB/c mice. IL-1ß, TNF-α, MMP-2 and MMP-9 mRNA levels were decreased in peritoneal cells of the SB203580 versus EM group (P < 0.01, P < 0.05, P < 0.05 and P < 0.05, respectively). Concentrations of IL-1ß, TNF-α, MMP-2 and MMP-9 proteins in PF were reduced in the SB203580 versus EM group (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively). Compared with the sham-operated group, phosphorylation of p38 MAPK in the EM group was increased, and this was down-regulated by SB203580 (P < 0.01). CONCLUSIONS: SB203580 may suppress the development of EM by inhibiting expression of proinflammatory cytokines and proteolytic factors. p38 MAPK might play a key role in progression of EM.

[The action of p38 MAP kinase and its inhibitors on endometriosis].

Endometriosis, an oestrogen-dependent disorder, is related to inflammation, p38 Mitogen activated protein kinases (p38 MAPK) can be activated by sex hormone and inflammatory factors, which plays an important role in many cellular reactions such as apoptosis, proliferation, inflammation and stresses, etc. Many studies showed that p38 MAPK was participated directly in regulating the pathogenesis of endometriosis. The special regulatory action of p38 MAPK on sex hormone and inflammation may help us to understand the intricate endometriosis pathological hypothesis. p38 MAPK inhibitors play a key role in the the study of endometriosis, and show great promise for the future. Blocking and regulating the expression of p38 MAPK on the signal transduction pathway level may hope to be a new strategy to prevent and treat endometriosis.

[A retrospective analysis of the six-year data of peritoneal dialysis in a single center].

OBJECTIVE: To investigate the epidemiology, peritoneal dialysis (PD) related complications and survival outcomes of 236 patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) in our center from January, 2004 to November, 2009. METHODS: The data including patient gender, age, time of PD initiation, addresses, types of medical reimbursement, primary diseases, modes of PD catheter placement surgery, types of PD catheter, PD-related complications, and time of drop out were retrospectively analyzed. PD catheter migration rate, peritonitis rate, drop out rate (DOR), length of the time of PD therapy (TOT), and survival rate were calculated and compared with those of patients in other PD centers. RESULTS: The number of newly introduced patients increased gradually in the years from 2004 to 2009. The mean age of newly introduced patients was 47-/+16 years, and patients with age below 60 years accounted for 77.96%. Patients who paid for their own expenses accounted for 67.37% of all, and the rate of these patients decreased gradually. Similar to that in Asian-Pacific region, chronic glomerulonephritis was the most frequent cause of ESRD followed by diabetic nephropathy. The number of patients with chronic glomerulonephritis or obstructive nephropathy as the primary diseases was greater in this center than that reported in the Asian-Pacific region, accounting for 54.66% and 11.02% of all patients, respectively. In contrast, the patients with diabetic nephropathy or benign arteriolar renal sclerosis were less, accounting for 12.29% and 10.17% of all, respectively. PD catheter migration rate (8.05%) and peritonitis rate (1:44.22 patient-months) were both lower than those reported. The patient survival rates at 1, 2, 3 years were 83.65%, 51.59% and 29.81%, respectively, lower than those of other centers in the developed countries but higher than the mean levels in China. DOR decreased gradually to 11.56% in 2009, and TOT increased to 23.61 months. CONCLUSION: The above characteristics of the patients are related to many factors, including the "PD first" principle, high prevalence of urinary calculosis in the primary source regions of most patients, preventive partial omentum resection in some patients, education and follow-up for patients, and increased expense cover by medical insurance.

[Frequent peritoneal dialysis-related peritonitis: clinical characteristics, risk factors and treatments].

OBJECTIVE: To identify the clinical characteristics and risk factors of frequent peritoneal dialysis (PD)-related peritonitis. METHODS: A retrospective analysis was conducted in the peritonitis patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in our hospital. Frequent PD-related peritonitis was defined by two or more onsets in one year, and the patients with only one onset served as the control group. The clinical and laboratory data of the two groups were compared and the risk factors of PD-related peritonitis analyzed. RESULTS: Forty-four episodes of peritonitis were recorded in the 16 patients with frequent PD-related peritonitis, as compared to 53 episodes in the 45 control patients. Compared with those in the control group, the patients with frequent peritonitis had significantly higher blood pressure (P0.05). Variables identified to be associated with an increased likelihood of frequent PD-related peritonitis included hemoglobulin<70 g/L (OR=0.135, P

Change of proinflammatory cytokines follows certain patterns after induction of endometriosis in a mouse model.

OBJECTIVE: To examine the change in proinflammatory cytokines in the pathologic processes of endometriosis in mice. DESIGN: A dynamic study on a murine model of endometriosis. SETTING: Medical school. ANIMAL(S): Female BALB/c mice. INTERVENTION(S): Endometriosis was induced by injecting endometrial fragments of syngenic mice into the peritoneal cavity of model mice; in control group, phosphate-buffered saline instead of fragments was injected. The peritoneal fluid and the endometriotic lesions were harvested 1 to 21 days after the induction. MAIN OUTCOME MEASURE(S): The endometriotic lesions were weighed, the gene and protein levels of some proinflammatory cytokines, including interleukin 1beta, tumor necrosis factor alpha, vascular endothelial growth factor, and monocyte chemoattractant protein 1, were determined by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULT(S): The levels of these cytokines reached the first peak on the first day and no endometriotic lesions were found. The lesions began to appear on the second day, presenting red color during the initial 6 days, and then they turned dark-red, brown, or bluish. The adhesion took place on the 9th day, and all the lesions evolved into white or transparent cysts on the 15th day. Corresponding to these changes, the second and the third peaks were identified during the 3rd-6th day and the 12th-15th day, respectively. CONCLUSION(S): The change pattern of cytokines over time might bear some relationship with the development and progression of the endometriosis.

15-Epi-lipoxin A(4) inhibits the progression of endometriosis in a murine model.

OBJECTIVE: To examine the pro-resolution actions of 15-epi-lipoxin A(4) (LXA(4)) on endometriotic lesions, on the concentrations and activities of matrix metalloproteinases (MMP-2 and MMP-9) in murine endometriosis. DESIGN: Prospective, vehicle-controlled experimental study. SETTING: Animal research facility. ANIMAL(S): BALB/c mice. INTERVENTION(S): Endometriosis (EM) was induced in 30 mice. Fifteen of them were administered LXA(4) for 24 days (LXA(4) group), whereas the other 15 served as a control group (EM group). Another 15 sham-operated mice (sham-operated group) were treated with vehicles. MAIN OUTCOME MEASURE(S): The weight of the endometriotic lesions was measured. The concentrations, mRNA, and activities of MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and gelatin zymography, respectively. RESULT(S): Compared with EM group, the weight of the endometriotic lesions was decreased, the concentrations of MMP-2 and MMP-9 dropped, the mRNA levels of MMP-2 and MMP-9 in the peritoneal fluid cells and the endometriotic lesions were reduced, and the activities of MMP-2 and MMP-9 were inhibited in the LXA(4) group. CONCLUSION(S): LXA(4) may inhibit the progression of endometriosis possibly by lowering the concentrations and the activities of MMP-2 and MMP-9.

[Association of CTLA-4 + 49A/G and CT60 gene polymorphism with type 1 diabetes and thyroid autoimmunity].

OBJECTIVE: To investigate the association of CTLA-4 + 49A/G and CT60 gene polymorphisms with type 1 diabetes (T1DM) and thyroid autoimmunity. Subjects Three hundred thirty-two T1DM patients and 476 controls were recruited in the study. METHOD: The CTLA-4 + 49 A/G and CT60 polymorphisms of CTLA-4 gene were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were determined by radioimmunoassay. Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) were measured by radioligand immunoassay. RESULTS: (1) The CTLA-4 + 49 A/G polymorphism was significantly associated with T1DM complicated with thyroid autoimmunity (OR = 2.43, P < 0.01) and with T1DM alone (OR = 1.66, P < 0.05). (2) The CTLA-4 CT60 polymorphism was also significantly associated with T1DM complicated with thyroid autoimmunity (OR = 2.67, P < 0.01) and with T1DM alone (OR = 1.60, P = 0.02). (3) T1DM with thyroid autoimmunity was characterized by a significantly higher frequency of CTLA-4 CT60 GG genotype (77.8% vs 62.3%, P < 0.05) and GADA (77.8% vs 57.4%, P < 0.05) compared to the patients without thyroid antibodies. CONCLUSION: CTLA-4 + 49 A/G and CT60 gene polymorphism confers genetic susceptibility to type 1 diabetes, particularly in patients with thyroid autoimmunity.

[Dual regulation of cell cycles by Shuanghuang Shengbai Granule in Lewis-bearing mice with chemotherapy-induced myelosuppression and its mechanism].

OBJECTIVE: To explore the dual regulatory effects of Shuanghuang Shengbai Granule, a compound traditional Chinese herbal medicine, on cell cycle in Lewis-bearing mice with chemotherapy-induced myelosuppression. METHODS: Thrity Lewis-bearing mice were randomly divided into control group, untreated group and treated group. A model of myelosuppression was established by peritoneal injection of cyclophosphamide to Lewis-bearing mice. Mice in the treated group were treated with Shuanghaung Shengbai Granule for 6 days. Cell cycle progressions of cells collected from bone marrow and tumor tissues were assayed by flow cytometry, and proliferation index (PI) was also calculated. Expressions of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6) and cyclin D1 in bone marrow and tumor tissues were detected by Western blotting and immunohistochemical method. RESULTS: Percentages of bone marrow and tumor cells in G0/G1 phase in the untreated group were lower than those in the control group; however, the PI of untreated group was higher than that of the control group. The expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues in the untreated group were increased as compared with the control group. Compared with the untreated group and the control group, the percentage of bone marrow cells in G0/G1 phase was decreased, and the PI of bone marrow cells and the expressions of CDK4, CDK6 and cyclin D1 were increased in bone marrow in the treated group. However, the percentage of tumor cells in G0/G1 phase in the treated group was increased, and the PI of tumor cells and the expressions of CDK4, CDK6 and cyclin D1 in tumor tissues were decreased as compared with the untreated and control groups. CONCLUSION: Shuanghuang Shengbai Granule may have a function of cell cycle dual regulation in Lewis-bearing mice with chemotherapy-induced myelosuppression by regulating the expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues.

Regulation by 1, 25-dihydroxy-vitamin D3 on altered TLRs expression and response to ligands of monocyte from autoimmune diabetes.

BACKGROUND: Altered Toll-like receptors (TLRs) expression and response of monocyte may be associated with insulin sensitivity, obesity and diabetes. METHODS: Peripheral blood monocytes were respectively collected from 23 healthy controls, 16 type 1 diabetes mellitus (T1DM), and 18 latent autoimmune diabetes in adults (LADA). CD14, TLR2 and TLR4 expression were analyzed by flow cytometer. Moreover, the effect of 1, 25-dihydroxy-vitamin D3 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation concentration of NF-kappaB-p65 and associated cytokine production. RESULTS: Monocytes showed significantly higher surface CD14 and TLR4 expressions from LADA and lower CD14 expression from T1DM than controls. TLRs ligands decreased monocyte CD14 expression in T1DM but increased in LADA. Monocyte hyperresponsiveness to ligands was modulated by 1,25(OH)(2)D3 to similar concentration, as compared to controls. CONCLUSIONS: Monocytes from T1DM and LADA showed similar cellular reactivity towards ligands and 1,25(OH)2D3 was observed to restore this defect to a certain extent in vitro.

Modulation of monocyte hyperresponsiveness to TLR ligands by 1,25-dihydroxy-vitamin D3 from LADA and T2DM.

To investigate the differences of Toll-like receptors (TLRs) expression and response of monocyte and modulation of 1,25-dihydroxy-vitamin D3 on monocyte activity. Peripheral blood monocytes were collected from 23 healthy controls, 18 latent autoimmune diabetes in adults (LADA), and 22 type 2 diabetes mellitus (T2DM), respectively. CD14, TLR2 and TLR4 expression were analyzed. Moreover, the effect of 1,25-dihydroxy-vitamin D3 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation level of NF-kappaB-p65 and associated cytokine production. Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. Activation of NF-kappaB and amounts of IL-1beta and TNF-alpha production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH)(2)D3 to similar level, as compared to controls. The modulation of 1,25(OH)(2)D3 on monocytes makes us to consider more potency of vitamin D3 as therapy in LADA and T2DM.

[Using MSR model to analyze the impact of gene-gene interaction with related to the genetic polymorphism of metabolism enzymes on the risk of breast cancer].

OBJECTIVE: To identify the interactions of susceptive genes with related to the genetic polymorphism of metabolism enzymes (CYP1A1, GSTT1 and GSTM1) and their impacts on the risk of breast cancer; and to test the feasibility of using Multifactor Dimensionality Reduction (MDR) model in analyzing gene-gene interactions. METHODS: A paired case-control study, matched by age and menstruate state, was conducted. From December 2003 to September 2004, 78 pairs of people with and without breast cancers were investigated. The variant genotypes of CYP1A1 Msp I and GSTT1/M1 were identified by PCR-RFLP and multiplex PCR assays. The gene-gene interactions were analyzed with the MDR model. Based on the result of the MDR model, a conditional logistic regression model was constructed as the final cause-effect interpretative model. RESULTS: The interaction between CYP1A1 Msp I variant genotype (vv) and GSTT1 null genotype gave the best MDR model with statistical significance (Sign Test, P = 0.05). The model Testing Balance Accuracy was 0. 5920. The Cross-Validation consistency was 10/10. The final conditional logistic regression based on the MDR model showed that passive smoking, abortion and gene-gene interaction were risks of breast cancers, with an OR (95% confidence interval) of 12.234 (1.7459-85.7279), 4.554 (1.3250-15.6507) and 9.597 (1.5783-58.3599), respectively. CONCLUSION: The MDR model may be an effective method for estimating risks of breast cancers due to gene-gene and gene-environment interactions. The gene-gene interaction with related to the genetic polymorphism of metabolism enzymes (CYP1A1 and GSTT1) may increase the risk of breast cancer by disturbing the metabolism of estrogen.

[Cochlear implantation with suprameatal approach in Chinese children].

OBJECTIVE: To investigate the technique of the suprameatal approach for cochlear implantation in Chinese profound sensory hearing loss children. METHODS: Suprameatal approach for cochlear implantation were used in 50 cases (total 53 ears) with profound sensory hearing loss from May 2005 to January 2007. The electrode was passed through the suprameatal tunnel and went between the incus and chorda tympani into the scala tympani. RESULTS: Electrodes were completely inserted in 51 ears. There were no postoperative complications in all cases. Although the long effect need to be observed, all cases received better hearing and speech development benefit from cochlear implantation in the follow-up period. Among the 50 cases, 26 had speech perception in the open condition; 18 patients could speak short sentences although not clearly; and 6 patients learned to speak individual words only. CONCLUSIONS: The suprameatal approach was found to be a simple and safe technique that does not need mastoidectomy and avoid endangering the facial nerve and the chorda tympani. It enables wide exposure of middle ear and is especially suitable for cases with narrow facial recess or anteriorly located facial nerve.

[Study on the relationship between organochlorine pesticides and level of residues in serum and daily foodstuff].

OBJECTIVE: To study the contents of organochlorine pesticides in human bodies and residues in serum of populations with non-occupational exposure as well as to study the relationship between organochlorine pesticides in foodstuff and residues levels in serum. METHODS: A cross-section study was conducted. 107 men and 142 women who were all healthy and living in the communities were investigated from Mar. 2004 to Jul. 2004. Level of daily food exposure was estimated through questionnaires while DDTs and HCHs serum levels were detected by EC-ECD. The relationship between organochlorine pesticides contents in foods and residues in serum were analyzed by ridge regression. RESULTS: Fresh fish was positively correlated to men's serum level of beta-HCH and p,p'-DDT (beta = 0.1266 and beta = 0.0595) while vegetables and fruits were negatively correlated to women's serum level of beta-HCH (beta = -0.1066). Soybean was negatively correlated to women's serum level of p,p'-DDE and p,p'-DDT (beta = -0.0965 and 3 = -0.0581). Alcohol consumption was negatively correlated to men's serum level of beta-HCH and p,p'-DDE and women's serum level of p,p'-DDE (beta = -0.1315, beta = -0.1599 and P = -0.1128).Salted meat was negatively correlated to men's serum level of beta-HCH and p, p'-DDT (P = -0. 066 and P = - 0.0569). CONCLUSION: In this study, fresh fish might increase the body burden of organochlorine pesticides and residues while alcohol might promote the excretion of organochlorine pesticides. Pickled meat and vegetal foodstuff might contain low-level of organochlorine pesticides and residues.

[Study on serum organochlorines pesticides (DDTs) level, CYP1A1 genetic polymorphism and risk of breast cancer: a case control study].

OBJECTIVE: To study the potential effect of gene-environment interaction between CYP1A1 and serum dichlorodiphenyldichloroethane (DDT) levels on the risk of breast cancer in women, in China. METHODS: A case-control study was conducted. From Dec. 2003 to Sep. 2004, 104 women with histologically confirmed breast cancers and 154 noncancerous controls from a community were enrolled in this study. Risk factors information of breast cancer was investigated by a questionnaire. Serum p, p'-dichlorodiphenyldichloroethane (p, p'-DDT) and 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels were tested by GC-ECD. CYP1A1 m2 gene type was tested by allele special-PCR method. RESULTS: Serum DDT levels of case and control were (36.90 +/- 79.41) ng/ml and (50.60 +/- 150.70) ng/ml respectively. Serum 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels of case and control were (7.43 +/- 11.10) ng/ml and (8.96 +/- 11.30) ng/ml respectively. No statistically significant differences were found between the two groups with geometric mean t-test (P > 0.05). Compared with women who had homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 homozygous variant genotype [odds ratio (OR) = 2.61, 95% confidence interval (CI): 1.00 - 6.80]. Among premenopausal women, compared with women with homozygous wild-type of CYP1A1 genotype (Ile/Ile) and low serum DDT level (DDT serum level < or = 42.93 ng/ml), women with at least one variant allele of CYP1A1 m2 genotype and high serum DDT level (DDT serum level > or = 42.93 ng/ml) had higher risk of breast cancer (OR = 4.35, 95% CI: 1.140 - 16.950). CONCLUSIONS: CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer while DDT exposure might have increased the risk of breast cancer among premenopausal women with CYP1A1 m2 variant genotype.