A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma.

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10-7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan-Meier analysis indicated that the "TT" genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 "TT" genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 "TT" genotype.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

[Protective effect and mechanism of Maiwei Yangfei Decoction on pulmonary fibrosis mice based on Nrf2 regulation of oxidative stress].

This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type Ⅲ(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type Ⅰ collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.

[Remedying Effects of a Combined Amendment for Paddy Soil Polluted with Cd for Spring and Autumn Rice].

An in-situ paddy experiment was conducted to study the remedying effects of a combined amendment(calcium carbonate+diatomite+ferric sulfate) on Cd bioavailability in soil and Cd accumulation in rice for spring and autumn rice planted in a certain Cd contaminated paddy soil in Beishan Town, Changsha, Hunan Province. The results showed that:Application of the combined amendment significantly increased soil pH and CEC values in both cultivated seasons, but decreased soil OM contents for the spring rice. During the experiment, the contents of TCLP-extractable Cd and CaCl2-extractable Cd in soil were reduced by 18.0%-33.0% and 5.4%-57.9%, respectively. The Cd contents in brown rice, husk, leave and root for the spring rice decreased by 29.6%-56.1%, 52.1%-54.0%, 18.1%-80.7% and 24.4%-41.6%, respectively, due to application of the combined amendment. There were significant differences in Cd transport capacity between spring rice and autumn rice, and the transportation of soil Cd in autumn rice was smoother than that in spring rice. For the autumn rice, the effects of the combined amendment were not significant(P>0.05), except that the Cd content in husk increased a little after applying 2 g·kg-1 of the combined amendment. Significant positive correlations were found between the Cd contents in brown rice and the contents of TCLP-extractable Cd or CaCl2-extractable Cd in soil. Application of the combined amendment effectively inhibited Cd uptake by rice root and reduced Cd content in brown rice for the spring rice; however, these remedying effects were significantly weakened for the autumn rice due to loss of the combined amendment with the movement of irrigation water in the spring season. Therefore, we suggest that supplement of the combined amendment is necessary between two rice cultivated seasons.

MART-10, the new brand of 1α,25(OH)2D3 analog, is a potent anti-angiogenic agent in vivo and in vitro.

BACKGROUND: Angiogenesis is the hall marker for cancer growth and metastasis. Thus, anti-angiogenesis emerges as a new way to treat cancer. 1α,25(OH)2D3 is recently getting popular due to the non-mineral functions, which have been applied fore cancer treatment. The newly-synthesized 1α,25(OH)2D3 analog, MART-10, has been proved to be much more potent than 1α,25(OH)2D3 regarding inhibiting cancer cells growth and metastasis without inducing hypercalcemia in vivo. In this study, we aimed to investigate the effect of MART-10 and 1α,25(OH)2D3 on angiogenesis in vitro and in vivo. METHODS AND RESULTS: MART-10 and 1α,25(OH)2D3 were able to repress VEGFA-induced human umbilical vein endothelial cells (HUVECs) migration, invasion and tube formation, but not proliferation, with MART-10 much more potent than 1α,25(OH)2D3. The Chick Chorioallantoic Membrane (CAM) assay and matrigeal angiogenesis assay further confirmed the in vivo more potent anti-angiogenesis effect of MART-10. MART-10 inhibited the VEGFA-induced HUVECs angiogenesis process through downregulation of Akt and Erk 1/2 phosphorylation. The VEGFA-VEGFR2 (VEGF receptor 2) axis is the main signal transducing pathway to stimulate angiogenesis. A positive autocrine manner was found for the first time in HUVECs as treated by VEGFA, which induced VEGFA expression and secretion, and VEGFR2 expression. MART-10 and 1α,25(OH)2D3 were demonstrated to be able to repress this positive autocrine manner, thus inhibiting angiogenesis. CONCLUSIONS: MART-10 and 1α,25(OH)2D3 both are effective anti-angiogenesis agents. Given MART-10 is much more potent than 1α,25(OH)2D3 and active in vivo without obvious side effect, MART-10 should be deemed as a promising anti-cancer agent.

[Selection of denitrifying phosphorus-removing bacteria and its characteristic].

Using YG culture medium, combined with the experiments of blue-and white-colored screening, Albert staining and detection of phosphorus removal capacity, seven phosphorus-removing bacterium were isolated from activated sludge collected from aerobic biochemical pool of wastewater treating factory. After nitrate reducing and anoxic culturing experiment, a strain with high capability of denitrifying and phosphorus removing was selected. With the study of its physiology and biochemistry and the analysis of its 16S rRNA gene, this strain was identified as Pseudomonas grimontii, and named of C18. The phosphorus removal rate of C18 was 94.1% under aerobic condition in 24 hours (The phosphorus concentration in supernatant was 38.7 mg/L to 2.28 mg/L). The phosphorus removal rate of C18 was 88.3% under anoxic condition in 24 hours (the phosphorus concentration in supernatant was 44.5 mg/L to 5.21 mg/L), and the denitrifying rate of C18 was 83.4% under anoxic condition in 24 hours (the nitrate concentration in supernatant was 184.2 mg/L to 30.6 mg/L). The optimal temperature of C18 denitrifying and phosphorus removing was 30 degrees C; The optimal pH of C18 denitrifying and phosphorus removing was 7.5.

[Study of temperature correction in the PLS near-infrared quantitative analysis of the wheat].

The influence of sample temperature on the wheat PLS near infrared (NIR) quantitative analysis was studied with 45 wheat seeds. The original spectra of the wheat seeds were measured at different temperatures. The temperature corrections were subtracted from the original spectra of the samples by using the PLS algorithm. The corrected spectra were used to build the mathematical model of the near-infrared quantitative analysis of the wheat. The results show that the influence of sample temperature on the mathematical model can be eliminated effectively when the temperature correction was performed in the calculation, improving the stability and prediction of this mathematical model.