[Fatty acid synthase interacts with signal transducer and activator of transcription 3 to promote migration and invasion in liver cancer cells].

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide. Metastasis is a marker of cancer deterioration in patients with liver cancer and a major cause of death. In order to develop effective therapeutic strategies, it is urgent to study the molecular basis of liver cancer metastasis. Methods: Immunohistochemistry was used to detect the expression of fatty acid synthase (FASN) in HCC. Wound healing and transwell cell invasion assays was used to confirm the role of FASN in liver cancer migration and invasion. Proteins that interacted with FASN were identified using iTRAQ (isobaric tag for relative and absolute quantification). Co-immunoprecipitation (Co-IP) and cellular immunofluorescence analysis were used to assess the interaction between FASN and signal transduction and transcription activator 3 (STAT3). The expression of STAT3, p-STAT3, matrix metalloproteinase (MMP)-2 and MMP-9 was detected after FASN knockdown using Western blot method. Statistical analysis was performed using the t-test. Results: Immunohistochemistry showed that the expression of FASN in HCC tissue was higher than that in adjacent tissues. iTRAQ, Co-IP and immunofluorescence analysis revealed that FASN interacted with STAT3. Western blot analysis showed that the expression of p-STAT3, MMP-2 and MMP-9 decreased after FASN knockdown. Conclusion: FASN may promote the metastasis of liver cancer by interacting with STAT3 and affecting the expression of MMP-2/MMP-9.

[Correlation study of blood drug concentration and nephrotoxicity on high dose methotrexate therapy in suggestion of diagnosis and treatment of childhood acute lymphoblastic leukemia in the 4th revised edition].

Objective: To explore the influence of the 4th revised treatment recommendations in childhood acute lymphoblastic leukemia (ALL) on high dose methotrexate(HD-MTX)-induced nephrotoxicity and MTX blood concentrations. Method: The clinical data from 330 ALL children who received 1 242 courses of HD-MTX therapies from September 2012 to November 2016 was collected. The courses were divided into two groups based on the chemotherapies: original scheme group was treated with the 3rd revised regimen, and new scheme group was treated with the 4th revised regimen. The two groups in acute kidney injury (AKI) and MTX blood concentrations were compared. Result: The incidences of AKI with low risk (LR) and intermediate risk (IR) in new scheme group were significantly lower than those in original scheme group (1.3%(3/229) vs. 7.9%(24/303), 4.9%(10/204) vs. 12.8%(26/203), χ(2)=11.831 and 7.888 respectively, both P<0.05). There was no significant difference in the incidence of AKI with high risk (HR) in the two groups (15.2%(10/66) vs. 10.5%(25/237), χ(2)=1.071, P>0.05). The 48h MTX blood concentrations and the interphase from onste to MTX concentrations decreased to the safe level with LR and IR children in new scheme group were significantly lower than those in original scheme group (0.36(0.08-4.00) vs. 0.44(0.06-32.00) µmol/L, 0.49(0.22-33.00) vs. 0.60(0.18-83.00) µmol/L, 3(2-6) vs. 3(2-11) d, 3(2-11) vs. 3(2-19) d, Z=-5.953, -2.658, -4.490 and -4.729 respectively, all P<0.05). The differences with HR were not observed between the two groups (0.61(0.14-36.00) vs. 0.71(0.11-68.00) µmol/L, 3(2-15) vs. 3(2-13) d, Z=-1.465 and -1.179 respectively, both P>0.05). Conclusion: Decreased renal toxicity and acceleration of MTX excretion may occur when childhood ALL with LR and IR were treated with the 4th revised regimen. However, nephrotoxicity and MTX blood concentrations have no significant differences with HR in the two regimens, and close monitoring are necessary.

Tamsulosin for treatment of lower urinary tract symptoms in women: a systematic review and meta-analysis.

Tamsulosin has been used for the off-label treatment of lower urinary tract symptoms (LUTS) in women. Over the past few years, several randomized controlled trials (RCTs) have reported the clinical effectiveness and safety of tamsulosin for LUTS in women. Therefore, the aim of the present study was to perform a meta-analysis to evaluate the safety and efficacy of tamsulosin in treating LUTS in women, which may resolve some of the current controversies over use of the drug and provide more reliable evidence for the use of tamsulosin. A literature review was performed to identify all published RCTs of tamsulosin for the treatment of LUTS in women. The search included the following databases: PUBMED, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technique Journals Database (VIP) and Wanfang Database. A systematic review and meta-analysis were conducted. Six RCTs studies involving 764 female participants were included in the analysis. Four out of the six RCTs compared tamsulosin with placebo, one RCT compared tamsulosin with prazosin and the other study compared tamsulosin with tamsulosin combined with tolterodine. Two RCTs evaluated total International Prostate Symptom Score (IPSS) and improved total IPSS compared with the placebo (standardized mean difference=-4.08, 95% confidence interval=-5.93 to -2.23, P<0.00001). IPSS (storage symptom score), IPSS (voiding symptom score) and quality-of-life score also showed the similar effects. In addition, tamsulosin improved the Overactive Bladder Questionnaire score when compared with placebo in only one RCT. For urodynamic parameters, tamsulosin improved the average flow rate and the post-void residual volume when compared with prazosin and tolterodine combined with tamsulosin, respectively. Beyond that, the other parameters showed no significant difference between the treatment and control groups. On the basis of the present evidence, tamsulosin is an effective treatment for the relief of LUTS in women when compared with placebo. However, the safety of the tamsulosin remains unknown. Further, well-conducted trials that examine long-term outcomes are required.

[An investigation of trichloroethylene-induced effects on histone methylation in L-02 hepatic cells].

Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis. The further analysis of the function of histone abnormal methylation modifications were done by single cell gel electrophoresis (SCGE) and Western blot analysis of p53 and ɤH2AX. Results: After treatment with TCE for 24 h in L-02 cells, the 36 TCE related histone methylation sites in 28 peptide segments were identified by MS. After treatment with TCE in concentrations of 0 and 8.0 mmol/L in L-02 cells for 24 h, the relative expression level of histone H3K79 me3 were 1.00±0.06, 0.70±0.09 (t=15.01, P=0.015); the relative expression level of histone H3K79 me2 were 1.00±0.05, 0.74±0.07 (t=16.69, P=0.018); the Olive Tail Moment about DNA damage were 1.46±0.28, 3.12± 0.68 (t=15.22, P=0.018); the relative expression levels of p53 were 1.00±0.04, 1.24±0.04 (t=18.71, P= 0.012); and the relative expression levels of ɤH2AX were 1.00 ± 0.03, 1.56 ± 0.11 (t=8.32, P=0 045). Conclusion: TCE can induce changes in the relative expression level of H3K79 me2 and H3K79 me3 in L-02 cell, and induce DNA damage, suggesting that TCE may induce changes in the relative expression level of H3K79 me2 and H3K79 me3 by DNA damage.