Objective To evaluate the impact of PET/CT on the clinical therapeutical strategy of patients with non-small cell lung cancer (NSCLC). Methods Sixty patients with histologically confirmed NSCLC supposed to accept radical radiotherapy or surgical operation were firsthy divided into group A (stage Ⅰ-Ⅱ) and group B (stage Ⅲ) according to CT findings, and the individualized treatment strategy was designed, then restage and compare with different stage and management with initial treatment strategy by PET/CT scanning. Results ①PET/CT scanning restaged the TNM stage in 53.33% (32/60) patients, including 3 of T stage, 23 of N stage and 9 of M stage. Changes of stage occurred in 65.85% (27/41) patients with adenocarcinoma and in 26.32% (5/19) with squamous carcinoma (P＜0.05), while in 34.29 (12/35) with central and 57.14% (20/35) with peripheral NSCLCs (P＜0.05). ②PET/CT scanning resulted in alteration of the managements of NSCLC patients. The management changed from radical into palliative strategy with PET/CT information in 9 (15.00%) patients. In 25 patients who were supposed to accept surgical operation, the treatment changed to radical radiotherapy in 8 (8/25, 32.00%) and to palliative radiotherapy in 5 (20.00%) patients. In 35 patients who were supposed to accept radiotherapy, surgical operation or palliative radiotherapy was finally chosen in 5.71% (2/35) and 11.43% (4/35) patients, respectively. Conclusion PET/CT images can make significant alteration to clinical stage and treatment plan in patients with NSCLC.

By engineering the subsite +1 of cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans, we improved its maltodextrin specificity for 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G) synthesis. Specifically, we conducted site-saturation mutagenesis on Leu194, Ala230, and His233 in subsite +1 separately and gained 3 mutants L194N (leucine --> asparagine), A230D (alanine --> aspartic acid), and H233E (histidine --> glutamic acid) produced higher AA-2G yield than the wild-type and the other mutant CGTases. Therefore, the 3 mutants L194N, A230D, and H233E were further used to construct the double and triple mutations. Among the 7 obtained combinational mutants, the triple mutant L194N/A230D/H233E produced the highest AA-2G titer of 1.95 g/L, which was increased by 62.5% compared with that produced by the wild-type CGTase. Then, we modeled the reaction kinetics of all the mutants and found a substrate inhibition by high titer of L-AA for the mutants. The optimal temperature, pH, and reaction time of all the mutants were also determined. The structure modeling indicated that the enhanced maltodextrin specificity may be related with the changes of hydrogen bonding interactions between the side chain of residue at the three positions (194, 230 and 233) and the substrate sugars.
Ascorbic Acid ; analogs & derivatives ; chemistry ; Glucosyltransferases ; genetics ; metabolism ; Hydrogen Bonding ; Kinetics ; Mutagenesis, Site-Directed ; Paenibacillus ; enzymology ; Polysaccharides ; chemistry ; Protein Engineering ; Substrate Specificity ; Temperature

Objective:To develop a grading prediction model of traumatic hemorrhage volume based on deep learning and assist in predicting traumatic hemorrhage volume.Methods:A retrospective observational study was conducted based on the experimental data of pig gunshot wounds in the time-effect assessment database for experiments on war-traumatized animals constructed by the General Hospital of the Chinese People's Liberation Army. The hemorrhage volume data of the study population were extracted, and the animals were divided into 0-300 mL, 301-600 mL, and > 600 mL groups according to the hemorrhage volume. Using vital signs indexes as the predictive variables and hemorrhage volume grading as the outcome variable, trauma hemorrhage volume grading prediction models were developed based on four traditional machine learning and ten deep learning methods. Using laboratory test indexes as predictive variables and hemorrhage volume grading as outcome variables, trauma hemorrhage volume grading prediction models were developed based on the above fourteen methods. The effect of the two groups of models was evaluated by accuracy and area under the receiver operator characteristic curve (AUC), and the optimal models in the two groups were mixed to obtain hybrid model 1. Feature selection was conducted according to the genetic algorithm, and hybrid model 2 was constructed according to the best feature combination. Finally, hybrid model 2 was deployed in the animal experiment database system.Results:Ninety-six traumatic animals in the database were enrolled, including 27 pigs in the 0-300 mL group, 40 in the 301-600 mL group, and 29 in the > 600 mL group. Among the fourteen models based on vital signs indexes, fully convolutional network (FCN) model was the best [accuracy: 60.0%, AUC and 95% confidence interval (95% CI) was 0.699 (0.671-0.727)]. Among the fourteen models based on laboratory test indexes, recurrent neural network (RNN) model was the best [accuracy: 68.9%, AUC (95% CI) was 0.845 (0.829-0.860)]. After mixing the FCN and RNN models, the hybrid model 1, namely RNN-FCN model was obtained, and the performance of the model was improved [accuracy: 74.2%, AUC (95% CI) was 0.847 (0.833-0.862)]. Feature selection was carried out by genetic algorithm, and the hybrid model 2, namely RNN-FCN* model, was constructed according to the selected feature combination, which further improved the model performance [accuracy: 80.5%, AUC (95% CI) was 0.880 (0.868-0.893)]. The hybrid model 2 contained ten indexes, including mean arterial pressure (MAP), hematocrit (HCT), platelet count (PLT), lactic acid, arterial partial pressure of carbon dioxide (PaCO 2), Total CO 2, blood sodium, anion gap (AG), fibrinogen (FIB), international normalized ratio (INR). Finally, the RNN-FCN* model was deployed in the database system, which realized automatic, continuous, efficient, intelligent, and grading prediction of hemorrhage volume in traumatic animals. Conclusion:Based on deep learning, a grading prediction model of traumatic hemorrhage volume was developed and deployed in the information system to realize the intelligent grading prediction of traumatic animal hemorrhage volume.

The 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare disease. The clinical characteristics and gene mutation of 2 late-diagnosed 17-OHD patients with testicular tumor admitted to our hospital from March 2018 to February 2019 were analyzed retrospectively. The two 17-OHD patients were female (46, XY). Laparoscopic abdominal exploration found undeveloped testicles in grey-yellow or grey-red in the groin and iliac fossa. The testicles were removed and showed malignancy in pathology study. Sequencing of the CYP17A1 gene identified c.1247G>A/c.1427T>C and c.985_987delTACinsAA/c.1306G>A complex heterozygous mutations. Taking together, the possibility of 17-OHD should be considered in patients with hypertension, hypokalemia, adrenal adenomatoid hyperplasia together with 46, XY gonadal dysplasia, so as to make early diagnosis and treatment, and avoid dysplastic testicular turning to malignancy.

Genistein and its monoglucoside derivatives play important roles in food and pharmaceuticals fields, whereas their applications are limited by the low water solubility. Glycosylation is regarded as one of the effective approaches to improve water solubility. In this paper, the glycosylation of sophoricoside (genistein monoglucoside) was investigated using a cyclodextrin glucosyltransferase from Penibacillus macerans (PmCGTase). Saturation mutagenesis of D182 from PmCGTase was carried out. Compared with the wild-type (WT), the variant D182C showed a 13.42% higher conversion ratio. Moreover, the main products sophoricoside monoglucoside, sophoricoside diglucoside, and sophoricoside triglucoside of the variant D182C increased by 39.35%, 56.05% and 64.81% compared with that of the WT, respectively. Enzymatic characterization showed that the enzyme activities (cyclization, hydrolysis, disproportionation) of the variant D182C were higher than that of the WT, and the optimal pH and temperature of the variant D182C were 6 and 40℃, respectively. Kinetics analysis showed the variant D182C has a lower K_m value and a higher k_cat/K_m value than that of the WT, indicating the variant D182C has enhanced affinity to substrate. Structure modeling and docking analysis demonstrated that the improved glycosylation efficiency of the variant D182C may be attributed to the increased interactions between residues and substrate.
Cyclodextrins ; Genistein ; Glucosyltransferases/metabolism* ; Glycosylation ; Kinetics

To investigate the clinical and genetic characteristics of patients with idiopathic hypogonadotropic hypogonadism (IHH), the clinical data of 23 patients with IHH were retrospectively analyzed. Gene analyses were accomplished with whole-exome sequencing (WES) and Sanger sequencing. Functional prediction of mutation sites was conducted using two bioinformatics platforms, SIFT and Polyphen. Among the 23 patients with IHH, 9 patients carried prokinin 2 (PROKR2) gene mutations including 4 missense mutations (p.W178S, p.Y113H, p.A103V, p.R164Q), and 1 frameshift mutation (p.D42delinsDED), the remaining 14 cases were found negative in gene sequencing. Functional prediction showed that the above mutations may affect protein function suggestive of a pathogenic role of PROKR2 mutation in the patients. There were no significant differences in the levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol between the IHH patients with PROKR2 gene mutation and those without. PROKR2 gene mutation might associated with IHH, and the mutations reported in the present study could enrich the pathogenic spectrum of genes.

The large scale production and indiscriminate use of plastics led to serious environmental pollution. To reduce the negative effects of plastics waste on the environment, an approach of enzymatic degradation was put forward to catalyze plastics degradation. Protein engineering strategies have been applied to improve the plastics degrading enzyme properties such as activity and thermal stability. In addition, polymer binding modules were found to accelerate the enzymatic degradation of plastics. In this article, we introduced a recent work published in Chem Catalysis, which studied the role of binding modules in enzymatic hydrolysis of poly(ethylene terephthalate) (PET) at high-solids loadings. Graham et al. found that binding modules accelerated PET enzymatic degradation at low PET loading (< 10 wt%) and the enhanced degradation cannot be observed at high PET loading (10 wt%-20 wt%). This work is beneficial for the industrial application of polymer binding modules in plastics degradation.
Polyethylene Terephthalates/metabolism* ; Polymers ; Plastics ; Ethylenes

Objective: To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 μg/L influences the efficacy of adjuvant therapy. Methods: A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis. Results: Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m² and body surface area was (1.6±0.2) m². Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration <1100 μg/L and 53 patients with plasma concentration ≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 μg/L and two with plasma concentration ≥1100 μg/L. One recurrent patient with plasma concentration <1100 μg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 μg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 μg/L, and 96.6% in patients with plasma concentration ≥1100 μg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 μg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242). Conclusions IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 μg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.