Baeyer-Villiger monooxygenases (BVMOs) are important biocatalysts to synthesize a series of valuable esters and lactones. Based on protein sequence alignment and crystal structure analysis, a nonconserved hinge which linked NADPH domain and FAD domain was speculated to play an important role in substrate recognition and catalytic oxidation process. Cyclohexanone monooxygenase (CHMO) was selected as a model. Mutants obtained by homologous replacement of the whole hinge almost completely lost its original catalytic activity, demonstrating that the overall hinge structure was of great importance. Some significant sites were identified to greatly affect the catalytic activity and stereoselectivity by alanine scanning mutagenesis, accompanied by enzyme activity assessments and chiral kinetic resolutions. Altering K153 decreased the activity of the enzyme but enhanced the stereoselectivity. Changing L143 site reduced stereoselectivity but had little effect on enzyme activity. Mutation at L144 site dramatically weakened both activity and stereoselectivity. Subsequently, these corresponding sites in phenylacetone monooxygenase were also illustrated to follow a similar rule, revealing a universal importance of these sites in the BVMO family. These results expanded our understanding of the structure-activity relationship of these enzymes and provided more proofs for future directed evolution of BVMOs.
Amino Acid Sequence ; Catalysis ; Mixed Function Oxygenases ; chemistry ; Models, Molecular ; NADP ; Oxidation-Reduction ; Oxygenases ; chemistry ; Protein Conformation ; Sequence Alignment ; Structure-Activity Relationship ; Substrate Specificity

Fluid Therapy ; Humans ; Rehydration Solutions ; therapeutic use

Histiocytosis, Langerhans-Cell ; diagnosis ; therapy ; Humans ; Practice Guidelines as Topic

From the beginning of the 20th century, Alois Alzheimer, a German doctor, discovered Alzheimer′s disease, so far, the isease-related research has been the focus of researchers all over the world. From Alzheimer's disease to mild cognitive impairment, then to subjective cognitive impairment, the attention phase of the disease is also being advanced. Subjective cognitive impairment, as a stage earlier than mild cognitive impairment, has important implications for the early diagnosis and intervention of Alzheimer′s disease.This article will summarize the research progress of conception and screening instruments for subjective cognitive impairment at home and abroad.

Objective To investigate the effect of early jejunal nutrition combined with enteral infusion of traditional Chinese medicine in the treatment of severe acute pancreatitis.Methods 10 patients with Severe acute pancreatitis were selected as group A,the implementation of the X-line built-jejunal tube through the nose,early enteral nutrition and joint Dachengqi Tom jejunum treatment.10 patients with severe pancreatitis were selected as group B,taken TPN nutrition therapy.Results A group of patients with abdominal pain and bloating relief at the time was better than group B( P ＜ 0.01 ) ; A group of mortality and multiple organ failure was less than the number of cases in group B ( P ＜ 0.01 ).Conclusion The effects of early enteral nutrition combined with enteral infusion of traditional Chinese medicine was more effective than the traditional treatment.

Objective:To compare the effects of XELOX (oxaliplatin + capectabine) regimen and FOLFOX4 (oxaliplatin + calcium leucovorin + fluorouracil) regimen on colon cancer and their influences on serum tumor markers and cytological indexes.Methods:A total of 84 patients with colon cancer treated in Wuhu Hospital of Chinese Medicine of Anhui Province from January 2016 to January 2019 were selected, and the patients were randomly divided into the observation group (XELOX regimen, 42 cases) and the control group (FOLFOX4 regimen, 42 cases) according to the random number table. The efficacy, side effects, the changes of cytological indicators and serum tumor markers before and after chemotherapy between the two groups were compared.Results:The short-term effective rate was 76.19% (32/42) in the observation group and 61.91% (26/42) in the control group, and the difference was not statistically significant (χ 2 = 2.005, P=0.156). The incidence of side effects in the observation group was lower than that in the control group [35.71% (15/42) vs. 59.53% (25/42), χ 2 = 4.773, P = 0.029]. There was no significant difference in the levels of carbohydrate antigen 199 (CA19-9), colon cancer-specific antigen (CCSA-2) and osteopontine (OPN) between the two groups before treatment (all P > 0.05); after treatment, CA19-9, CCSA-2, OPN levels were lower than those before treatment of the two groups (all P < 0.05); after treatment, CA19-9, CCSA-2, OPN levels in the observation group were lower than those in the control group (all P < 0.05). Before treatment, there was no significant difference in the levels of neutrophils to lymphocytes ratio (NLR), platelet-lymphocytes ratio (PLR), and red cell distribution width (RDW) between the two groups (all P > 0.05); the levels of NLR, PLR and RDW after treatment in the two groups were decreased compared with those before treatment (all P < 0.05); NLR, PLR and RDW levels in the observation group after treatment were lower than those in the control group (all P < 0.05). In the observation group, the recurrence rate of 1-year, 2-year, 3-year was 4.76% (2/42), 14.26% (6/42), and 19.05% (8/42), respectively; in the control group, the recurrence rate of 1-year, 2-year, 3-year was 11.90% (5/42), 21.43% (9/42), and 26.19% (11/42), respectively; there was no statistical difference between the two groups (all P > 0.05); in the observation group, the survival rate of 1-year, 2-year, 3-year was 92.86% (39/42), 78.57% (33/42), and 71.43% (30/42), respectively; in the control group, the survival rate of 1-year, 2-year, 3-year was 85.71% (36/42), 69.05% (29/42), and 64.28% (27/42), and there was no statistically significant difference between the two groups (all P > 0.05). Conclusions:XELOX regimen and FOLFOX regimen have similar short-term and long-term effects on patients with colon cancer. They both can decrease the levels of serum tumor markers and cytological indicators of patients, and improve their prognosis, while XELOX regimen has low side effects.

Antitubercular Agents ; pharmacology ; therapeutic use ; Child ; Drug Resistance, Multiple, Bacterial ; Drug Therapy, Combination ; Humans ; Tuberculosis, Multidrug-Resistant ; drug therapy ; microbiology

OBJECTIVE:To investigate the effects and safety of 2 kinds of glucocorticoid administration regimens including 5 d and 15 d on clinical efficacy,pulmonary function,quality of life in elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). METHODS:A total of 160 elderly patients with AECOPD selected from Haikou Forth People's Hos-pital during May 2013-Dec. 2015 were divided into group A and B according to lottery method,with 80 cases in each group. Both groups received symptomatic treatment as eliminating phlegm and relieving asthma,controlling infection,etc. Based on it,group A was given Methylprednisolone sodium succinate for injection,40 mg/d for 15 d;group B was given Methylprednisolone sodium succinate for injection,40 mg/d for 5 d. Clinical efficacies were compared between 2 groups as well as the levels of pulmonary ven-tilation function indexes,blood gas analysis indexes,Spitzer life quality index scale (QLI) scores before and after treatment. The occurrence of ADR was also compared between 2 groups. RESULTS:Total response rate of group A was 92.50%,and that of group B was 90.00%,without statistical significance(P>0.05). Before treatment,there was no statistical significance in the levels of pulmonary ventilation function indexes,blood gas analysis indexes,QLI scores between 2 groups (P>0.05). After treatment, FVC,FEV1,FEV1% and PaO2 of 2 groups were significantly higher than before treatment,while PaCO2 was significantly lower than before treatment,with statistical significance (P<0.05);there was no statistical significance between 2 groups (P>0.05). QLI scores of 2 groups were significantly higher than before treatment,and the group B was significantly higher than the group A, with statistical significance (P<0.05). The incidence of ADR in group B (6.25%) was significantly lower than group A (22.50%),with statistical significance(P<0.05). CONCLUSIONS:Glucocorticoid administration regimen including 5 d and 15 d in the treatment of elderly patients with AECOPD possess the same effects in improving lung function;glucocorticoid administra-tion regimen for 5 d application is superior in effectively improving the quality of life of patients,reducing the risk of ADR,and has clinical value.

Objective To sum up the trend of changes in symptoms of prolonged symptomatic gastroesophageal reflux(GERD), and discuss the relationship between reflux symptoms and the medical treatment in the elderly patients with GERD. Methods 98 elderly GERD patients over 60 years old were followed up for 5 years through questionaires. The changes of reflux symptoms and effect of medication were analyzed. Results Reflux symptoms were improved in 71 subjects (72.4%), disappeared in 10, worsened in 9, and remained unchanged in 18. The symptom improvement rate of medication group was significantly higher than that of non-medication group(P0.05). In 62 subjects who modified their life styles and diet habits, 53 of them had their symptoms improved (85.5%), and 9 of them had their symptoms unchanged (14.5%). Among 98 patients who underwent endoscopic examination, 44 were found to have erosive esophagitis, and were diagnosed as reflux esophagitis(RE). Although the other 54 subjects complained of typical "heart burn" and regurgitation symptoms, no erosive esophagitis was found with endoscopy, and they were regarded designated as having non-erosive reflux disease(NERD). The symptom improvement rate of NERD group was significantly higher than that of RE group(P

Bronchogenic Cyst ; Humans ; Laryngeal Diseases ; Male ; Middle Aged