Enhancing Enzyme Activity and Thermostability of Bacillus amyloliquefaciens Chitosanase BaCsn46A Through Saturation Mutagenesis at Ser196.

Chitosanase plays an important role in chitooligosaccharides (COS) production. We found that the chitosanase (BaCsn46A) of Bacillus amyloliquefacien was a good candidate for chitosan hydrolysis of COS. In order to further improve the enzyme properties of BaCsn46A, the S196 located near the active center was found to be a critical site impacts on enzyme properties by sequence alignment analysis. Herein, saturation mutation was carried out to study role of 196 site on BaCsn46A catalytic function. Compared with WT, the specific enzyme activity of S196A increased by 118.79%, and the thermostability of S196A was much higher than WT. In addition, we found that the enzyme activity of S196P was 2.41% of that of WT, indicating that the type of amino acid in 196 site could significant affect the catalytic activity and thermostability of BaCsn46A. After molecular docking analysis we found that the increase in hydrogen bonds and decrease in unfavorable bonds interacting with the substrate were the main reason for the change of enzyme properties which is valuable for future studies on Bacillus species chitosanase.

High preoperative serum ferritin predicted poor prognosis in non-metastatic colorectal cancer.

OBJECTIVES: To validate the prognostic significance of preoperative serum iron metabolism parameters in non-metastatic colorectal cancer patients treated with curative resection.   Methods: We conducted a prospective cohort study in the Department of Surgical Oncology, WuXi 4th People's Hospital, WuxiChina, between  March 2010 and September 2013.  The relationships of serum iron metabolism parameters with other variables were examined. The prognostic significance was evaluated using the Kaplan Meier curve and Cox proportional hazards regression model.  Results: Five hundred and fourteen patients were eligible for analysis. The levels of the 3 iron metabolism parameters were interdependent. Hemoglobin level was positively correlated with serum iron and transferrin, and was negatively correlated with ferritin. Compared with peri-neural invasion (PNI)-negative patients, PNI-positive patients had higher serum iron (p=0.03) and ferritin levels (p=0.01). Compared with patients with the lowest quartile level of ferritin, patients with the highest quartile level of ferritin had a 2.21 (95% CI: 1.18-4.14) fold increased mortality risk in the univariate and 2.56 (95% CI: 1.10-5.96) in the multivariate Cox proportional hazards models. When stratified by TNM stages, it was only in stage III patients that serum ferritin remained statistically prognostically significant. Conclusions: Preoperative serum ferritin appeared as an independent adverse risk factor in non-metastatic colorectal cancer.

Comparison of central foveal thickness and subfoveal choroidal thickness in healthy pregnancy and pre-eclampsia / 中华眼底病杂志

Objective To compare the central foveal thickness (CFT) and subfoveal choroidal thickness (SFCT) in healthy pregnant women and patients with pre-eclampsia.Methods A prospective control study.Twenty normal subjects,20 healthy pregnant women and 20 patients with pre-eclampsia were included.The difference of gestational weeks between healthy pregnant women and patients with pre-eclampsia was not significant (x2=0.012,P=0.913).The differences of age and spherical equivalent among normal subjects,healthy pregnant women and patients with pre-eclampsia were not significant (x2=1.760,0.087;P=0.413,0.957).All eyes underwent optical coherence tomography examination to measure the CFT and SFCT.Results The mean CFT of normal subjects,healthy pregnant women and patients with pre-eclampsia were (194.40± 16.17),(201.2±17.33),(199.00±15.46) μm,there was no significant difference among the three groups (x2=0.888,P=0.641).The mean SFCT of normal subjects,healthy pregnant women and patients with pre-eclampsia were (263.45±69.66),(330.00±49.20),(373.40±52.00) μm,there was significant difference among the three groups (x2=22.818,P=0.000).The mean SFCT of healthy pregnant women was increased than that of normal subjects (Z=-2.991,P=0.002).The mean SFCT of patients with pre-eclampsia was increased than that of healthy pregnant women (Z=-2.638,P=0.007).Conclusion The mean SFCT of patients with pre-eclampsia is increased than healthy pregnant women.

Comparison of intravitreal injection of conbercept and macular photocoagulation for non-ischemic macular edema secondary to branch retinal vein occlusion / 眼科新进展

Objectlve To assess the clinical effects and safety of intravitreal injection of conbercept and macular photocoagulation for non-ischemic macular edema secondary to branch retinal vein occlusion (BRVO).Methods A total of 50 patients (50 eyes) with non-ischemic macular edema following BRVO were retrospectively analyzed.Patients were divided into 2 groups:ICI group (26 eyes) received intravitreal injection of conbercept,laser group (24 eyes) received standard-of-care grid laser for macular edema.The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were observed before and 1 week,1 month,2 months and 3 months after treatment.Then,the changes in pre-treatment and post-treatment were compared,and the related complications were recorded.Results The difference of BCVA before treatment was not significant between two groups (P ＞ 0.05).BCVA at 1 week,1 month,2 months and 3 months after treatment in two groups were all improved,the differences were statistically significant compared with before treatment (all P ＜ 0.05),and the differences were statistically significant between two groups after treatment (all P ＜0.05).At 3 months after treatment,BCVA of 18 patients (69.23％) in ICI group and 8 patients (33.33％) in ICI group improved 2 lines.The difference of CMT before treatment was not significant between two groups (P ＞ 0.05),CMT at 1 week,1 month,2 months and 3 months after treatment in two groups were all decreased,the differences were statistically significant compared with before treatment (all P ＜ 0.05),and the differences were statistically significant between two groups after treatment (all P ＜0.05).13 eyes received repeat intravitreal injection in ICI group,including 2 eyes at 1 month,7 eyes at 2 months with CMT ＞250 μm,and 3 eyes at 3 months.No severe side effect related with drug and intravitreal injection occurred in the two groups.Conclusion Mean BCVA change and CMT change are significantly greater in the intravitreal injection of conbercept than the standard-of-care grid laser group for the macuiar edema secondary to non-ischemic BRVO.

Antineoplastic properties of nitrogen-containing bisphosphoates / 国际肿瘤学杂志

Nitrogen-containing bisphosphonates exert antitumor activity through induction of apoptosis or inhibition of proliferation, invasion and migration in tumor cells, inhibition of angiogenesis and promotion of immune surveillance. Animal models show that bisphosphonates delay visceral metastasis progression. Both ABCSG-12 and ZOFAST trial have demonstrated that Zoledronate reduced breast cancer recurrence risks. Bisphosphonates are synergistic with a variety of chemotherapeutics, and sequential dosing is more effective, which may be attributable to increased uptake of bisphosphonates by tumor cells after pretreatment with chemotherapeutics. Metronomic administration of bisphophonates after chemotherapy provides bisphosphonates the promising antineoplatic potential.