L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective:To investigate the value of sedation in colonoscopy.Methods:A retrospective cohort study of colonoscopy procedures was performed in our institution. Inclusion criteria: (1) colonoscopy procedures were performed by well-trained gastrointestinal surgeons our institution; (2) medical records were complete and colonoscopy was documented properly by notes, videos, photographs, and traceable pathological reports. Those with incomplete records or performed in other institution were excluded. According to above criteria, clinical data of 49 057 cases of clinic and hospitalization receiving diagnostic or therapeutic colonoscopyat Department of Gastric and Colorectal Surgery, Daping Hospital from July 2007 to February 2017 were collected. Among them, there were 24 638 (50.2%) males and 24 419 females, with mean age of (50.6±14.1) (4 to 98) years. Based on the application of sedation during colonoscopy, patients were divided into the sedation group (39 412 cases, 80.3%) and the non-sedation group (9 645 cases, 19.7%). Clinical characteristics of two groups were compared.Results:The sedation rate increased from 45.6% (369/810) to 94.8% (917/967) from 2007 to 2017. As compared to non-sedation group, a higher proportion of females [51.0% (20 095/39 412) vs. 44.8% (4 324/9 645), χ 2=117.422, P<0.001] and younger median age (50.0 years vs. 51.0 years, Z=-4.774, P<0.001) were found in the sedation group, whose differences were statistically significant. In all the 9645 cases in the non-sedation group, about 5.5% (534) of them terminated the examination because of unbearable discomfort, including 244 (4.6%) males and 290 (6.7%) females (χ 2=20.522, P<0.001). Among all the screening population who were ≥50 years old, there was no significant difference in the polyp detection rate (PDR) between the sedation group and the non-sedation group [26.7% (4 737/17 753) vs. 27.4% (1 093/3 984), χ 2=0.937, P=0.330]. The cecal intubation rate (CIR) in the sedation group was significantly higher than that in the non-sedation group [(85.2% (14 422/16 933) vs. 76.1% (2 803/3 682), χ 2=180.032, P<0.001]. Five cases in the sedation group developed iatrogenic colonic perforation (ICP), with none in the non-sedation group. Conclusions:The application of sedation in colonoscopy is increasingly popular. Sedation can significantly improve CIR in colonoscopy, while it has no positive influence on PDR. Meanwhile, sedation increases the medical expense and may result in higher ICP rate.

Objective:To investigate the value of sedation in colonoscopy.Methods:A retrospective cohort study of colonoscopy procedures was performed in our institution. Inclusion criteria: (1) colonoscopy procedures were performed by well-trained gastrointestinal surgeons our institution; (2) medical records were complete and colonoscopy was documented properly by notes, videos, photographs, and traceable pathological reports. Those with incomplete records or performed in other institution were excluded. According to above criteria, clinical data of 49 057 cases of clinic and hospitalization receiving diagnostic or therapeutic colonoscopyat Department of Gastric and Colorectal Surgery, Daping Hospital from July 2007 to February 2017 were collected. Among them, there were 24 638 (50.2%) males and 24 419 females, with mean age of (50.6±14.1) (4 to 98) years. Based on the application of sedation during colonoscopy, patients were divided into the sedation group (39 412 cases, 80.3%) and the non-sedation group (9 645 cases, 19.7%). Clinical characteristics of two groups were compared.Results:The sedation rate increased from 45.6% (369/810) to 94.8% (917/967) from 2007 to 2017. As compared to non-sedation group, a higher proportion of females [51.0% (20 095/39 412) vs. 44.8% (4 324/9 645), χ 2=117.422, P<0.001] and younger median age (50.0 years vs. 51.0 years, Z=-4.774, P<0.001) were found in the sedation group, whose differences were statistically significant. In all the 9645 cases in the non-sedation group, about 5.5% (534) of them terminated the examination because of unbearable discomfort, including 244 (4.6%) males and 290 (6.7%) females (χ 2=20.522, P<0.001). Among all the screening population who were ≥50 years old, there was no significant difference in the polyp detection rate (PDR) between the sedation group and the non-sedation group [26.7% (4 737/17 753) vs. 27.4% (1 093/3 984), χ 2=0.937, P=0.330]. The cecal intubation rate (CIR) in the sedation group was significantly higher than that in the non-sedation group [(85.2% (14 422/16 933) vs. 76.1% (2 803/3 682), χ 2=180.032, P<0.001]. Five cases in the sedation group developed iatrogenic colonic perforation (ICP), with none in the non-sedation group. Conclusions:The application of sedation in colonoscopy is increasingly popular. Sedation can significantly improve CIR in colonoscopy, while it has no positive influence on PDR. Meanwhile, sedation increases the medical expense and may result in higher ICP rate.

Objective: To investigate the effects of long-term exposure to silica dust on serum CC16 and KL-6 levels. Methods: The patients with stage I silicosis who were hospitalized in our hospital from April 2016 to April 2017 were treated as silicosis group. The silica dust exposed workers without silicosis who were taken the physical examination in our hospital were taken as a dust-exposed group. The healthy control group comes from in the same period of community physical examination did not touch the dust. The levels of CC16 and KL-6 in serum of all subjects were determined by enzyme-linked immunosorbent assay (ELISA) , and the levels of CC16 and KL-6 in serum were compared in three groups. Results: Compared with the control group, the serum levels of CC16 in the silicosis group (P<0.01) and the dust-exposed group (P<0.01) were significantly lower. Compared with the control group, the level of serum KL-6 in the silicosis group was significantly decreased (P<0.01) compared with the control group, while the level of KL-6 in the serum of the dust-exposed group was significantly increased (P<0.01) . The ROC area of CC16 for diagnosis of silicosis was 0.92 (P<0.01) , with a sensitivity of 81.37%, specificity of 92.63% and Kappa value of 0.74. Conclusion Long-term exposure to silica dust may lead to a decrease in serum CC16 levels. Reduced serum CC16 levels may be useful in identifying the diagnosis of silicosis.

Objective To estimate the dietary diversity,overweight and obesity of the rural adults aged 18-65 years in Jilin Province by diet diversity score(DDS),and to analyze the association between dietary diversity and overweight,obesity.Methods A representative sample of 674 rural residents was selected by a multistage sampling method from Jilin Province in 2012 June to July. A validated semi-quantitative food-frequency questionnaire was used to assess the usual food intake. The height and body weight were measured and the body mass index (BMI)was calculated. Logistic regression analysis was applied to calculate the risk of overweight and obesity for different DDS,after adjusted for mixed factors.Results 62.4% people in rural scored ≥6 while 1 1.8% people in rural scored ≤3.The detection rate of obesity of the rural adults in Jilin Province was higher than the mean level in China .For rural adults with moderate and adequate diversity score, the risk of overweight and obesity was 0.946 and 0.816 times the risk of overweight and obesity of the rural adults with pool diversity score. Conclusion Diet diversity of the rural adults in Jilin Province is low.The risk of overweight and obesity is high;the risk of obesity is decreased with the increasing of diet diversity level.

Background and purpose: Trichostatin A (TSA), an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture, is a potent and specific inhibitor of histone deacetylase (HDAC). This study was aimed to investigate the influence of trichostatin A on the growth of human lung adenocacinoma cells in vitro, and to explore the mechanisms involved. Methods: MTT assay was employed to evaluate the inhibitory effect of TSA (0.1, 0.2,0.4 μmol/L) on the growth of human NCI-H1299 cancer cells. The cell cycle distribution and apoptotic ratio were determined by flow cytometry. The acetyl level of histone H4 after TSA treatment was detected by Western blot;the mRNA level of Bax,Bcl-2,p21 and cyelinBl was measured by Real-time PCR. Results: TSA inhibited the growth of NCI-H1299 cells in a dose-and time-dependent manner. Flow cytometry showed that the cells were blocked at G_2/M phase and cell apoptosis was increased compared to the control. TSA significantly increased the acetyl level of histone H4, induced p21 and Bax expression, and inhibited the expression of cyclin BI and Bcl-2. Conclusion: TSA inhibits the growth of lung cancer cells in vitro through inducing cell apoptosis and cell cycle arrest, which might be related to its regulatory effects on the acetyl blot of histone and the expression of p21, Bax, Bcl-2 and cyclinBl.

Bone metastases in advanced lung cancer patients are common and affect the life quality seriously. So early diagnosis and appropriate treatments are important. The methods of diagnosis include X-ray, CT, MRI, ECT and PET, which are different in sensitivity and specificity. The gene microarray technique is another advance for detecting micrometastasis. The gene analysis also can help understanding the biological characteristics of the primary tumor. The treatment of bone metastases in lung cancer is various, including systemic and local therapeutic means. Surgery is often used to prevent or treat the compressions and bone fractures. Radiotherapy is one of the most effective methods of pain relief. Diphosphonate provides a new convenient and effective way of alleviative treatment. In addition, supportive and symptomatic treatments should be keep in mind.