Objective To investigate the effect of renal sympathetic denervation (RSD) on the activity of renalase in dogs with chronic heart failure (CHF).Methods After induced by abdominal aorta constriction,dogs were divided into three groups according to whether they underwent double renal artery ablation:2 dogs in control group,2 dogs in sham-operated group (no renal artery ablation),and 5 dogs in RSD group (renal artery ablation).Plasma noradrenaline (NE),B-type natriuretic peptide (BNP),and renalase were determined in 5 dogs with RSD (RSD group),2 control dogs (control group),and 2 shamoperated dogs (sham-operated group).Results NE,BNP and heart rate were significantly higher and renalase was lower in CHF group than those in control group (all P ＜ 0.05).Compared to the control dogs with CHF,the levels of renalase were significantly increased in 6 weeks after RSD [(1 948.78 ±49.19) ng/ml vs (1 847.35 ±20.72)ng/ml,P =0.029],and NE [(166.30 ±7.68)pg/ml vs (181.29 ±8.57)pg/ml],and BNP [(75.10 ± 5.58)lμg/ml vs (89.79 ± 2.04) μg/ml] were decreased in 8 weeks after RSD (all P ＜ 0.05).An decreased trend of the levels of renalase was observed in 8 weeks than in 6 weeks in CHF dogs after RSD,without significant difference (P ＞ 0.05).Conclusions The activity of renalase in dogs with CHF can be affected by RSD.

New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.

CYP2D6 is an important drug-metabolizing enzyme. The polymorphism of CYP2D6 leads to metabolism difference and the different reactions of drugs in the individuals and different races are normal phenomenon in clinical medication. CYP2D6*10 is an important subtype in Asian people and 51.3% Chinese are classified with this subtype. To obtain recombinant active CYP2D6*1/CYP2D6*10 in baculovirus system by optimizing coexpression with CYPOR, and detect their activity to catalyze dextromethorphan, three recombinants pFastBac-CYP2D6*1, pFastBac-CYP2D6*10 and pFastBac-CYPOR were constructed and transformed into DH10Bac cell to obtain the recombinant Bacmid-CYPOR, Bacmid-CYP2D6*1 and Bacmid-CYP2D6*10. And then the recombinant CYP2D6*1 and CYP2D6*10 virus were obtained by transfecting Sf9. Then homogenate protein activity was determined with dextromethorphan as substrate. The multiple of infection (MOI) and its ratio of recombinant CYP2D6 virus to CYPOR virus were adjusted by detecting the activity of the homogenate protein. The Km and Vmax are 26.67 +/- 2.71 micromol x L(-1) (n=3) and 666.7 +/- 56.78 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*1 to catalyze dextromethaphan. The Km and Vmax are 111.36 +/- 10.89 micromol x L(-1) (n=3) and 222.2 +/- 20.12 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*10 to catalyze dextromethorphan. There is significant difference between CYP2D6*1 and CYP2D6*10 for Vmax and Km (P < 0.01). The clearance ratio of CYP2D6*1 is 25.0 and the clearance ratio of CYP2D6*10 is 2.0. The expressed CYP2D6*1 and CYP2D6*10 are useful tools to screen the metabolism profile of many xenobiotics and endobiotics in vitro, which are benefit to understand individual metabolism difference.

OBJECTIVETo explore the effects of principal-subordinate acupoints combination on improving myocardial ischemia, and the gene regulatory pathways for the protection of myocardial ischemia.

METHODSAccording to the random number table method, 70 SPF Wistar male rats were divided into a normal group, a model group, a LY294002 group, an insulin-like growth factors-1(IGF-1) group, a Neiguan group, an acupoint combination group and an acupoint combination + LY294002 group, 10 rats in each one. Rats in the normal group were injected with 0.9% NaCl solution, while rats in the remaining groups were treated with abdominal subcutaneous injection of isoroterenol hydrochloride to establish the rat model of myocardial ischemia. Rats in the LY294002 group and IGF-1 group were treated with injection of LY294002 solution and IGF-1 solution for 14 days. Rats in the Neiguan group were treated with electroacupuncture (EA) at "Neiguan" (PC 6) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination group were treated with EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination + LY294002 group were treated with LY294002 solution for 14 days, and EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) was given before model establishment, once a day for 21 days. EA pretreatment was given before model establishment in all acupuncture groups. The heart rate (HR) and ST segment voltage were detected before and after treatment; the myocardial pathological morphology was observed by HE staining; the expressions of P13K mRNA and Akt mRNA were tested.

RESULTSAfter modeling, HR and ST segment voltage in all intervention groups were higher than those in the normal group (all P < 0.01); after the intervention, the HR and the ST segment voltage in the acupoint combination group, IGF-1 group and IGF-1 group were improved (P < 0.01, P < 0.05), which was more significant in the acupoint combination group and Neiguan group (all P < 0.01). As for the myocardial pathological morphology, obvious myocardial ischemia was observed in the model group, and that in the LY294002 group was the most serious, and that in the acupoint combination+ LY294002 group was moderate. After intervention, the myocardial pathological damage in the IGF-1 group, Neiguan group and acupoint combination group was significant improved, which was more significant in the IGF-1 group and acupoint combination group. As for the expression of PI3K mRNA and Akt mRNA, compared with normal group, the expression of PI3K mRNA was increased in the remaining groups after modeling (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0. 01). The expression of Akt mRNA in the LY294002 group and acupoint combination + LY294002 group was reduced (P < 0. 01, P < 0.05), while that in the remaining groups was increased (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0.01).

CONCLUSIONThe principal-subordinate acupoints combination could improve heart rate and ST segment voltage in rats with chronic myocardial ischemia, reduce myocardial pathological damage, which is superior to single selection of "Neiguan" (PC 6). The PI3K/Akt signaling pathway may be involved in the regulation mechanism of principal-subordinate acupoints combination for the protection of chronic myocardial ischemia.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Chronic Disease ; therapy ; Electroacupuncture ; Electrocardiography ; Heart Rate ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Myocardial Ischemia ; enzymology ; pathology ; physiopathology ; therapy ; Myocardium ; pathology ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Rats, Wistar

There is a great diversity for cellulolytic microbes in nature and the strategies they use to digest cellulose. In addition to the cultured cellulolytic microbes, there are still a great number of microbes being not readily culturable in natural environments, which may represent great potential for identifying novel cellulases and their encoding genes. The rise of metagenomics and metaproteomics provides essential technologic tools to dig up these resources and significant progress has been made so far. This review gives an insight into some relative results that have arisen from the meta-genomic or proteomic analysis of definitive uncultured microbe communities. Their potential role in elucidating the process and mechanisms of cellulose degradation in natural environment from the point of "community system microbiology" is also discussed.
Bacteria ; enzymology ; genetics ; Cellulases ; genetics ; metabolism ; Cellulose ; metabolism ; Cloning, Molecular ; Environmental Microbiology ; Genome, Bacterial ; Metagenomics

Objective:To investigate the relationship between sleep quality and slow-flow in patients with acute coronary syndrome during percutaneous coronary intervention(PCI) and its impact on clinical prognosis.Methods:200 patients with ACS hospitalized in the cardiology department of Guangzhou First People's Hospital from January 2017 to October 2018 were selected. The Pittsburgh Sleep Quality Index (PSQI) was measured before elective PCI, and the sleep breathing of patients was monitored by micro motion sensitive mattress sleep monitoring system (MSMSMS). The patients were divided into normal sleep group (68 cases, PSQI≤7 points) and sleep disorder group (132 cases, PSQI>7 points). The levels of plasma endothelin-1 (ET-1) and nitric oxide (NO) were measured. The " slow-flow" that took place during PCI were also recorded. Major cardiac adverse events (MACE) of patients took placed during 12 months follow-up periods were recorded and compared between two groups.Results:Compared with normal sleep group, patients in sleep disorder group had higher ratio of sleep apnea-hypopnea syndrome (SAHS), hypoxemia and lower deep sleep (25.00% vs 10.29%, 25.76% vs 11.76%, 66.67% vs 48.53%, all P<0.05); lower level of NO and higher level of ET-1 [(28.65±3.26)μmol/L vs (30.24±4.08)μmol/L; (21.17±3.08)pg/ml vs (18.90±2.95)pg/ml, P<0.05]; more slow-flow events took place during PCI in sleep disorder group than normal sleep group (16.67 vs 5.88%, P<0.05); After 12 months of follow-up, Kaplan-Meier survival analysis showed patients of the two groups had significantly different cumulative non-events survival rates (19.70% vs 7.35%, Log rank=5.06, P=0.025). Conclusions:Sleep disorder increase the slow-flow phenomenon during PCI in patients with ACS and affect the clinical prognosis.

Objective To develop a peer support demand scale for patients with malignant tumor, and to test its reliability and validity,so as to provide an assessment tool for evaluating demand of peer support in patients with malignant tumor.Methods Guided by peer support theory,with theoretical review and qualitative interview,item pool of the peer support demand scale was preliminarily made. After a two-round expert consultation and preliminary scale investigation,first draft of the items was determined. 300 patients with malignant tumor were surveyed by the first draft of the scale,so that reliability and validity of the scale were tested.Results In the peer support demand scale for patients with malignant tumor,4 factors with 21 items were included,namely demands on peer support understanding,emotion,information and evaluation,The cumulative variance contribution rate was 59.684%. The content validity (S-CVI) was 0.920. Cronbacha′s α coefficient of the internal consistency reliability was 0.815,and the retest reliability was 0.824. Conclusions Content validity and internal consistency reliability are within acceptable range,which makes it basically qualified and can be used for investigation on patients with malignant tumor about their peer support demands.

Molecular engineering of cellulases can improve enzymatic activity and efficiency. Recently, the Carbohydrate-Active enZYmes Database (CAZy), including glycoside hydrolase (GH) families, has been established with the development of Omics and structural measurement technologies. Molecular engineering based on GH families can obviously decrease the probing space of target sequences and structures, and increase the odds of experimental success. Besides, the study of cellulase active-site architecture paves the way toward the explanation of catalytic mechanism. This review focuses on the main GH families and the latest progresses in molecular engineering of catalytic domain. Based on the combination of analysis of a large amount of data in the same GH family and their conservative active-site architecture information, rational design will be an important direction for molecular engineering and promote the rapid development of the conversion of biomass.
Catalytic Domain ; genetics ; Cellulase ; chemistry ; genetics ; Directed Molecular Evolution ; methods ; Evolution, Molecular ; Glycoside Hydrolases ; chemistry ; genetics ; Protein Engineering ; methods

Objective To explore the demand of peer support in tumor patients, to provide the basis for the construction and improvement of peer support systems for cancer patients. Methods Self-designed questionnaire was used to investigate the demand of peer support in 94 tumor patients.Results Results showed that among the 94 patients surveyed, 46. 8% of them had received peer support; up to 77. 6% of the patients were willing to accept peer support; three aspects of patients′ demand for peer support in a descending order were emotional demand ( 72. 34%) , information demand ( 68. 9%) and evaluation requirements ( 56. 6%) . Conclusions Tumor patients need peer support, and peer support development has a broader space.

Objective:To explore the construction and effect of biobank in biological research in nursing field.Methods:Through the establishment of a biological research plan for nursing in Affiliated Jinhua Hospital, Zhejiang University School of Medicine, the biobank in biological research for nursing was constructed from aspects of biological samples, instruments and equipment, operating software, biobanking team formation, personnel training and standardized process formulation.Results:In August 2020, the Nursing Department and Central Laboratory of Affiliated Jinhua Hospital, Zhejiang University School of Medicine established a biobank for biological research in the nursing field, formed a biobank team, conducted personnel training and formulated standardized procedures. From December 1, 2020 to June 30, 2021, biological samples were collected from 264 gastric cancer patients and 56 healthy controls, mainly including whole blood, serum and urine.Conclusions:The construction of biobank for biological research in nursing field can collect abundant biological samples, which lays a foundation for subsequent independent biological research in nursing field.