Osteochondroma of the pubic symphysis causing hematuria: a case report and literature review.

BACKGROUND: Osteochondroma is the most common benign bone neoplasm and is sometimes referred to as osteocartilaginous exostosis. The symptoms caused by osteochondroma are rare, especially the urogenital complications. Therefore, this tumour is sometimes misdiagnosed. CASE PRESENTATION: This report described a 70-year-old woman with hematuria who was initially misdiagnosed with a bladder tumour in the outpatient department by a urologist. However, during cystoscopy, we found that the mass did not resemble a bladder tumor. Multidisciplinary approach with careful analysis of the imaging data suggested the diagnosis of osteochondroma. Open surgical excision of the mass was done and histology confirmed the diagnosis of benign osteochondroma. After 6 months of follow-up, the patient was still asymptomatic. CONCLUSIONS: This case illustrates that hematuria is caused by not only urogenital disease but also osteochondroma. We present this case to draw the attention of clinicians to osteochondroma of the pubic symphysis.

Regulation of ATP-binding cassette subfamily B member 1 by Snail contributes to chemoresistance in colorectal cancer.

Although accumulating evidence has indicated the intimate association between epithelial-mesenchymal transition (EMT) and acquired resistance to chemotherapy for colorectal cancer (CRC), the underlying mechanisms remain elusive. Herein, we reported that Snail, a crucial EMT controller, was upregulated in CRC tissues. Colorectal cancer cells overexpressing Snail were found to be more resistant to 5-fluorouracil (5-Fu). Mechanistic studies reveal that Snail could increase the expression of ATP-binding cassette subfamily B member 1 (ABCB1) rather than the other 23 chemoresistance-related genes. Additionally, knockdown of ABCB1 significantly attenuated Snail-induced 5-Fu resistance in CRC cells. Oxaliplatin increased Snail and ABCB1 expression in CRC cells. Snail and ABCB1 were upregulated in 5-Fu-resistant HCT-8 (HCT-8/5-Fu) cells and inhibition of Snail decreased ABCB1 in HCT-8/5-Fu cells. These results confirm the vital role played by ABCB1 in Snail-induced chemoresistance. Further investigation into the relevant molecular mechanism revealed Snail-mediated ABCB1 upregulation was independent of ß-catenin, STAT3, PXR, CAR and Foxo3a, which are commonly involved in modulating ABCB1 transcription. Instead, Snail upregulated ABCB1 transcription by directly binding to its promoter. Clinical analysis confirms that increased Snail expression correlated significantly with tumor size (P = .018), lymph node metastasis (P = .033), distant metastasis (P = .025), clinical stage grade (P = .024), and poor prognosis (P = .045) of CRC patients. Moreover, coexpression of Snail and ABCB1 was observed in CRC patients. Our study revealed that direct regulation of ABCB1 by Snail was critical for conferring chemoresistance in CRC cells. These findings unraveled the mechanisms underlying the association between EMT and chemoresistance, and provided potential targets for CRC clinical treatment.

Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis.

1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employed to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1). 3. Knockout of aryl hydrocarbon receptor (Ahr) in mice can significantly reverse ANIT-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor knockout significantly reversed ANIT-induced lipid metabolism alteration through regulating the expression of Chka. 4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice.

Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1.

As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of ß-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1 mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.

Plasma nesfatin-1 level is associated with severity of depression in Chinese depressive patients.

BACKGROUND: Nesfatin-1 plays a role in the regulation of emotional states like depression. The aim of this study was to investigate the plasma nesfatin-1levels in Chinese patients with depression and healthy subjects, and to determine the possible association between the plasma nesfatin-1 level and the severity of depression. METHODS: A total of 103 depressive patients and 32 healthy subjects were assessed. According to HAMD-17scores, 51, 18, and 34 patients were enrolled in the mild depression, moderate depression, and severe depression groups, respectively. Plasma nesfatin-1 levels were determined by the ELISA method. Differences between groups were compared and associations between plasma nesfatin-1 and other variables were analyzed. RESULTS: The plasma nesfatin-1 was significantly positively correlated with HAMD-17 score (r = 0.651). Compared with healthy controls (8.11 ± 3.31 ng/mL), the plasma nesfatin-1 level significantly increased in patients with mild depression (11.17 ± 3.58 ng/mL), with moderate depression (16.33 ± 8.78 ng/mL), and with severe depression (27.65 ± 8.26 ng/mL) respectively. Plasma nesfatin-1 level (Odds ratio [OR] = 1.269) was an independent indicator for severe depression by multivariate logistic regression analysis. CONCLUSION: The plasma nesfatin-1 level is positively correlated with the severity of depression. Plasma nesfatin-1 level may be a potential indicator for depression severity.

Diverse ortho-C(sp2)-H Functionalization of Benzaldehydes Using Transient Directing Groups.

Pd-catalyzed C-H functionalizations promoted by transient directing groups remain largely limited to C-H arylation only. Herein, we report a diverse set of ortho-C(sp2)-H functionalizations of benzaldehyde substrates using the transient directing group strategy. Without installing any auxiliary directing group, Pd(II)-catalyzed C-H arylation, chlorination, bromination, and Ir(III)-catalyzed amidation, could be achieved on benzaldehyde substrates. The transient directing groups formed in situ via imine linkage can override other coordinating functional groups capable of directing C-H activation or catalyst poisoning, significantly expanding the scope for metal-catalyzed C-H functionalization of benzaldehydes. The utility of this approach is demonstrated through multiple applications, including late-stage diversification of a drug analogue.

Prospective Evaluation of a Transfusion Policy of RhD-Positive Red Blood Cells into DEL Patients in China.

BACKGROUND: The D antigen is highly immunogenic, requiring only a small quantity of transfused red blood cells (RBCs) to cause alloimmunization in D- immunocompetent recipients. DEL was reported arousing alloimmunization to true Rh- patients. Molecular studies of the RHD gene have revealed that DEL individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. Avoiding immunization with clinically important antibodies is a primary objective in transfusion medicine. METHODS: In order to determine whether pregnant DEL women carrying an RhD+ fetus are at risk of anti-D alloimmunization, 808 Rh- pregnant women with a history of gestations or parturitions who regularly visited hospitals for their prenatal anti-D screening and postpartum care from January 2011 to December 2012 were investigated. Samples were analyzed for DEL by PCR with specific primers, PCR-sequence-specific primers (PCR-SSP), reverse transcription-PCR (RT-PCR), PCRrestriction fragment length polymorphism (PCR-RFLP), and by gene sequencing to characterize different alleles. RESULTS: Among the 808 Rh- pregnant women of our sample, 178 (22.0%) were typed as DEL; 168 DEL samples were confirmed to have the RHD (1,227 G>A) allele, 8 DEL samples were characterized by one base mutation of the RHD (3G >A) allele, and the remaining two DEL samples were determined to carry RHD-CE(4-9)-D or RHD-CE(2-5)-D. The observation of allo-anti-D in two prominent D epitope loss cases confirmed the partial nature of these DEL phenotypes. CONCLUSIONS: In conclusion, evidence is provided that different DEL genotypes code either for partial or complete D antigen expression. It is suggested that the use of RhD+ RBCs in complete D antigen DEL patients does not induce adverse reaction.

Fish consumption and lung cancer risk: systematic review and meta-analysis.

There is evidence pointing to a possible role of diet on cancer etiology. Prior studies evaluating the relationship between fish consumption and lung cancer risk reported inconclusive results. The aim of this study was to achieve a comprehensive assessment of the relationship between fish consumption and lung cancer risk through systematic review and meta-analysis. Case control and cohort studies up to September 1, 2012 about fish consumption and lung cancer risk were confirmed by an online search. Separate relative risk (RR) or odds ratio (OR) estimates with 95% confidence interval (CI) of the relationship between lung cancer risk and fish consumption level from the included articles were combined by Stata11.0 software. Publication bias was evaluated by Egger's linear regression test and funnel plot. Twenty articles (17 case-control and 3 cohort studies) comprising 8799 cases of lung cancer and 17,072 noncases were included in the final analysis. The pooled results from all studies indicated that high fish consumption was significantly associated with a decreased risk of lung cancer (pooled RR: 0.79; 95% CI: 0.69-0.92). There was heterogeneity among the studies (I(2) = 73%, P < 0.05). Pooled RR in case control and cohort studies were 0.76 (95% CI: 0.63-0.91) and 0.95 (95% CI: 0.73-1.24), respectively. Omission of any single study had little effect on the combined risk estimates. This article had no publication bias. This study identifies a significant association between fish consumption and lung cancer, confirming a protective role of fish in lung cancer. More well-designed prospective studies are required to further verify the effect of fish consumption on lung cancer.

Hemostatic function and transfusion efficacy of apheresis platelet concentrates treated with gamma irradiation in use for thrombocytopenic patients.

BACKGROUND: During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia. METHODS: 20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (α), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed. RESULTS: No differences could be found in hemostatic function parameters (MA, R, and α) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s). CONCLUSIONS: This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable.

Blockade of Discoidin Domain Receptor 2 as a Strategy for Reducing Inflammation and Joint Destruction in Rheumatoid Arthritis Via Altered Interleukin-15 and Dkk-1 Signaling in Fibroblast-Like Synoviocytes.

OBJECTIVE: This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR-2), a putative fibrillar collagen receptor, in inflammation promotion and joint destruction in rheumatoid arthritis (RA). METHODS: In synovial tissue from patients with RA and from mice with collagen antibody-induced arthritis (CAIA) (using Ddr2-/- and DBA/1 mice), gene and protein expression levels of DDR-2, interleukin-15 (IL-15), and Dkk-1 were measured by quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast-like synoviocytes (FLS) was conducted via small interfering RNA. Interaction between the long noncoding RNA H19 and microRNA 103a (miR-103a) was assessed in RA FLS using RNA pulldown assays. Cellular localization of H19 was examined using fluorescence in situ hybridization assays. Chromatin immunoprecipitation and dual luciferase reporter assays were applied to verify H19 transcriptional and posttranscriptional regulation by miR-103a. RESULTS: DDR2 messenger RNA (mRNA) expression was significantly associated with the levels of IL-15 and Dkk-1 mRNA in the synovial tissue of RA patients (r2 = 0.2022-0.3293, all P < 0.05; n = 33) and with the serum levels of IL-15 and Dkk-1 in mice with CAIA (P < 0.05). In human RA FLS, activated DDR-2 induced the expression of H19 through c-Myc. Moreover, H19 directly interacted with and promoted the degradation of miR-103a. CONCLUSION: These results indicate a novel role for activated DDR-2 in RA FLS, showing that DDR-2 is responsible for regulating the expression of IL-15 and Dkk-1 in RA FLS and is involved in the promotion of inflammation and joint destruction during pathophysiologic development of RA. Moreover, DDR-2 inhibition, acting through the H19-miR-103a axis, leads to reductions in the inflammatory reaction and severity of joint destruction in mice with CAIA, suggesting that inhibition of DDR-2 may be a potential therapeutic strategy for RA.

Correlation between epidermal growth factor receptor mutations and the expression of estrogen receptor-ß in advanced non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) mutations are more common in non-small cell lung cancer (NSCLC) and in female patients of East Asian origin. Therefore, the present study investigated the presence of EGFR mutations in advanced NSCLC, and assessed its correlation with clinicopathologic factors, including the expression of estrogen receptor-ß (ER-ß) and patient prognosis. The present study performed a retrospective analysis of 83 patients with stage IIIB-IV NSCLC. The expression of ER-ß and p53 were examined using immunohistochemical methods. EGFR mutations were evaluated using the amplification refractory mutation system. The expression of ER-ß and p53 were detected in 37 (45.6%) and 48 (57.8%) of the patient tumors, respectively. EGFR mutations were identified in 36 (45.4%) cases. EGFR mutations were more frequently observed in ER-ß-negative tumors (26/46; 56.5%), compared with ER-ß-positive tumors (10/37; 27%). The expression of ER-ß was significantly associated with EGFR mutations with an odds ratio (OR) of 0.241 (P=0.029). However, no significant correlation was observed between the expression of p53 and mutations in EGFR (OR=1.792; P=0.340). In addition, the expression of ER-ß and lymph node metastasis were associated with poor prognosis, whereas EGFR mutations were significantly associated with favorable prognosis in terms of progression-free survival rates. However, there was no prognostic significance associated with the expression of p53. In conclusion, the expression of ER-ß was significantly correlated with the presence of EGFR mutations. The expression of ER-ß and mutations of EGFR were found to be prognostic factors for survival rates in patients with advanced NSCLC.

[Disequilibrium linkage between the polymorphism in exons 2, 3 and 4 of the MICA gene and HLA-B antigen of patient with ankylosing spondylitis].

OBJECTIVE: To investigate the association between the exons 2 to 4 of the MICA gene and ankylosing spondylitis (AS). METHODS: By PCR-SSOP, DNA samples from 56 AS patients and 112 random healthy individuals, as normal control were genotyped to analyse the polymorphism in exons 2, 3, 4 of the MICA alleles. RESULTS: MICA*008 was dominant in MICA allele,accounted for 32.14% and 30.36% in AS patients and normal controls respectively. The frequency of MICA*007 was significantly increased in AS patients, when compared with normal controls (chi-square=10.18, P<0.05, RR=2.50). No difference was found in the other MICA alleles. The haplotype analysis revealed that there were the strong linkage disequilibrium between MICA and HLA-B of AS patients, and normal controls. There was a difference in MICA*007-B27 between two groups (chi-square=18.46, P<0.05, RR=7.47). Both HLA-B27 and MICA*007 were strongly associated with AS. Stratified analysis showed that HLA-B27 was significantly relative to AS,while it was not found between MICA*007 and AS. CONCLUSION: The increased frequency of MICA alleles may be due to its strong linkage disequilibrium with HLA-B27.

[Inducing Effect of Modified Cytokine Cocktail on Dendritic Cells].

OBJECTIVE: To investigate the inducing effect of 'modified' cytokine cocktail on the dendritic cell maturation and migration capability. METHODS: PBMNC were isolated from human peripheral blood stem cell (PBSC) by using density gradient centrifugation, the immature DC (imDC) were induced by using GM-CSF and IL-4 in vitro. Total A549 RNA was transfected into imDC by using electroporation, which was stimulated to matuation by the "gold standard" cytokine cocktail and "modified" cytokine cocktail, respectively. The expression of DC surface markers (CD11c, HLA-DR, CD80, CD83 and CD86) and chemokine receptor (CCR5, CCR7 and CXCR4) were detected by flow cytometry; the mRNA expression levels of DC chemokine receptor (CCR2, CCR5, CCR7, CXCR3 and CXCR4) and chemokine (CCL2, CCL3, CCL5, CCL19, CCL21, CXCL10 and CXCL12) were detected by RT-PCR. RESULTS: As compared with "gold standard cytokine cocktail", the "modified" cytokine cocktail-induced DC expressed higher levels of surface markers (CD11c, HLA-DR, CD80, CD83 and CD86), chemokine receptors (CXCR4) and chemokine (CCL2, CCL3, CCL5, CCL19, CCL21, CXCL10 and CXCL12). CONCLUSION: The "modified" cytokine cocktail can more effectively induce the DC maturation, enhace the migratory capability of DC and more generate the immunostimulatory DC, when compared with the "gold standard" cytokine cocktail effect.

Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization.

Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti-tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or ß-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs-induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs-up-regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells.

Involvement of TP53 and TP16 expression in human papillomavirus-associated non-small cell lung cancer.

Human papilloma virus (HPV) infection has previously been reported to be associated with TP53 and TP16 expression in Japanese and Taiwanese patients with lung cancer, but data for advanced non-small cell lung cancer (NSCLC) patients is limited. The present study examined the association between HPV infection and TP53 and TP16 expression in Chinese patients with advanced NSCLC. HPV DNA was detected in 20 out of 83 (24%) lung tumors, and was observed more frequently in non-smokers, patients with lymph node metastasis, and patients with poorly differentiated tumors (P=0.048, P=0.044 and P=0.024, respectively). Thirteen (65%) out of 20 HPV-infected tumors were positive for TP53 expression while eight (40%) were positive for TP16 expression. Multivariate analysis revealed that poor differentiation alone (OR=0.163) was an independent predictive factor of HPV infection in NSCLC. TP16-positive patients had a significantly longer survival time when compared with TP16-negative patients (P<0.001, log-rank test), a trend a not observed for TP53. Our results suggest that TP53 and TP16 protein expression is not associated with the expression of HPV DNA, but that TP16 expression may be an independent prognostic factor of long survival in advanced NSCLC.

Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma.

Previous studies have demonstrated an association between human papillomavirus (HPV) and mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer patients; however, few studies have investigated this association in advanced lung adenocarcinoma patients undergoing gefitinib treatment. The present study investigated the association between HPV and EGFR mutations in advanced lung adenocarcinoma patients. A total of 95 advanced lung adenocarcinoma patients were enrolled in the study. The HPV infection status and presence of EGFR mutations in tumor tissue was evaluated. Patient clinical characteristics were also determined and compared with HPV infection and EGFR mutation status to analyze their impact on progression-free survival. HPV DNA was identified in 27/95 (28.4%) lung adenocarcinoma tumors and was most common in patients with lymph node metastasis (P=0.016). A total of 44/95 (46.3%) cases exhibited EGFR mutations, which were predominantly observed in female patients and non-smokers. The presence of HPV DNA was significantly associated with EGFR mutations (P=0.012) and multivariate analysis also revealed that HPV DNA was significantly associated with EGFR mutations (odds ratio=3.971) in advanced lung adenocarcinoma. Patients with both HPV infections and EGFR mutations exhibit a marked decrease in the risk of lung cancer progression when compared with those without HPV infection or EGFR mutations (adjusted HR=0.640; 95% confidence interval: 0.488-0.840; P=0.001). HPV infection was significantly associated with EGFR mutations in advanced lung adenocarcinoma patients. Furthermore, patients with HPV infections exhibited the longest progression-free survival times, which may be due to good response to tyrosine kinase inhibitor- or platinum-based-adjuvant therapy in these patients. Patients with EGFR mutations exhibited a better prognosis when compared with those exhibiting wild-type EGFR, regardless of HPV status.

Blockage of tropomyosin receptor kinase a (TrkA) enhances chemo-sensitivity in breast cancer cells and inhibits metastasis in vivo.

Hyper-activation of the Neurotrophin Receptor Signaling contributes to the development and metastasis of breast cancer. The inhibition of growth factor-dependent growth of breast cancer cell demonstrated a promising way for cancer therapy. In this study, the signaling pathway of tropomyosin receptor kinase A (TrkA) had been investigated for the role it played in the proliferation of chemo-resistance of breast cancer cells. Small interference RNA (siRNA) was used to down-regulate the expression of TrkA in breast cancer cell and tumor xenograft mice model. Our results indicated that siRNA mediated down-regulation of TrkA lead to the proliferation inhibition of cancer cells and arrested cells cycle at G0/G1 phase via inactivation of NF-κBp65. Application of TrkA siRNA to cancer cell also increased the chemo-sensitivity to paclitaxel, and further promoted apoptosis in cancer cell through the activation of caspase-3. Moreover, TrkA siRNA increased the efficacy of paclitaxel and decreased the incidence of lung metastasis in tumor xenografted mice. In sum, these results indicate that TrkA signaling plays an important role in breast cancer chemo-resistance and metastasis. It could be a potential pharmacologic target to enhance the effectiveness of chemo-therapy for breast cancer.

Baicalin inhibits autophagy induced by influenza A virus H3N2.

Baicalin, a natural product isolated from Scutellariaradix, has been reported to have significant in vivo and in vitro anti-influenza virus activity, but the underlying mechanism remains poorly understood. In this study, we found that baicalin inhibited autophagy induced by influenza virus A3/Beijing/30/95 (H3N2) in both A549 and Ana-1 cells. The results showed that H3N2 induced autophagy by suppressing mTOR signaling pathway, which however could be significantly inhibited by baicalin. Baicalin could suppress the expression of Atg5-Atg12 complex and LC3-II, and attenuate autophagy induced by starvation. Thus, the inhibition of autophagy induced by virus may account for the antiviral activities of baicalin against H3N2. Autophagy may be a potential marker in developing novel anti-influenza drugs.

Sexual function improvement in association with serum leptin level elevation in patients with premature ejaculation following sertraline treatment: a preliminary observation.

The objective of our work was to evaluate the effect of sertraline hydrochloride on serum levels of leptin and sexual function in patients with premature ejaculation (PE). A total of 124 patients with a history of PE at least 6 months, aged 20-50 years, were treated with sertraline hydrochloride. One hundred and four age-matched normal males without a history of PE were included control subjects and were untreated. Before and after the 8 week experiment, sexual performance parameters including the intravaginal ejaculation latency time (IELT) and the Chinese premature ejaculation index (CIPE) were collected from both PE patients and control subjects through a questionnaire survey and analyzed. Serum levels of leptin were measured. Correlations of serum leptin with Body Mass Index (BMI) were analyzed. Before sertraline treatment, serum levels of leptin were significantly higher (32.9 vs 8.8 µg/L, p<0.001) but IELT and CIPE score were significantly lower (54 vs 590, p <0.001; 8.7 vs 22.3, p <0.0001) in PE patients than control subjects. After 8 weeks of treatment with sertraline, serum levels of leptinl in PE patients were decreased markedly to 8.0 µg/L, which was not significantly different from the levels in control subjects (p >0.05); and IELT and CIPE score in PE patients were increased to the values similar to those in control subjects. The sensitivity and specificity values were 87.5% and 96.3% for leptin as a diagnosis target. These observations suggest sertraline as a selective serotonin reuptake inhibitor may offer an effective option for treating premature ejaculation.

Association between hemorrhagic fever with renal syndrome epidemic and climate factors in Heilongjiang Province, China.

The purpose of this study was to quantify the relationship between climate variation and transmission of hemorrhagic fever with renal syndrome (HFRS) in Heilongjiang Province, a highly endemic area for HFRS in China. Monthly notified HFRS cases and climatic data for 2001-2009 in Heilongjiang Province were collected. Using a seasonal autoregressive integrated moving average model, we found that relative humidity with a one-month lag (ß = -0.010, P = 0.003) and a three-month lag (ß = 0.008, P = 0.003), maximum temperature with a two-month lag (ß = 0.082, P = 0.028), and southern oscillation index with a two-month lag (ß = -0.048, P = 0.019) were significantly associated with HFRS transmission. Our study also showed that predicted values expected under the seasonal autoregressive integrated moving average model were highly consistent with observed values (Adjusted R(2) = 83%, root mean squared error = 108). Thus, findings may help add to the knowledge gap of the role of climate factors in HFRS transmission in China and also assist national local health authorities in the development/refinement of a better strategy to prevent HFRS transmission.