According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
Carboxylesterase/metabolism* ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions

Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.

Objective: To explore the effect of Da Chengqitang on the lung index,lung index inhibition rate,lung histological morphology,classification changes of inflammatory cells and mitogen-activated protein kinase (MAPK) signal pathway in mice with allergic asthma.Method: Forty female C57BL/6 mice were randomly divided into normal control group,model group,dexamethasone group (0.005 g·kg^-1) and Da Chengqitang group (19 g·kg^-1).Murine allergic asthma model was established by sensitization and nebulization of ovalbumin (OVA).In brief,asthmatic mice were first sensitized by OVA and Al (OH)₃ mixture ip on day 0 and day 14,and then nebulized by OVA from day 21 to 27.At the same time,each mouse in the dexamethasone and Da Chengqitang groups were intragastrically administered with 0.2 mL corresponding medicine one hour before the nebulization challenge,while the normal control group was given with the same amount of normal saline.On day 28,pulmonary morphology was detected by htoxylin eosin (HE) staining and inflammatory cells from the brachial alveolar lavage fluid were counted by Diff staining.The expression levels of key proteins in MAPK signaling pathway were detected by Western blot.Result: As compared with the normal control group,the lung indexes were significantly increased in model group (P<0.01),showing obvious inflammatory pathological changes,and serious airway inflammation cells exudation (P<0.01),with a predominant percentage of eosinophils,moreover,the expression levels of phosphorylated p38 MAPK and extracellular signal-regulated kinase 1/2(ERK1/2) were increased obviously in asthmatic mice.After treatment by Da Chengqitang,lung indexes and pulmonary inflammation were significantly decreased,with an inhibitory rate of 68.4% for lung indexes,and inflammatory pathology of lung tissues was obviously improved and inflammatory cell exudation was alleviated,with the obviously lower levels of phosphorylated p38 MAPK and ERK1/2 protein.Conclusion: Da Chengqitang based on "Pulmonary Intestinal Treatment" can effectively improve lung inflammation in mice with allergic asthma,which may be related to the expression of phosphorylated p38 MAPK and ERK1/2 protein.

ObjectiveTo investigate the relationship of the characteristics of sperm donors with the results of screening and provide some reference for the screening of sperm donors.

METHODSWe statistically analyzed the screening data about 12 362 sperm donors at the Guangdong Human Sperm Bank from January 2003 to June 2017 and the relationship of the eligibility rate of screening with the donors' age, education, occupation, marriage, and fatherhood.

RESULTSOf the 12 362 sperm donors, 3 968 (32.1%) met the standards of semen quality and 3 127 (25.3%) filled all the requirements of sperm donation. The eligibility rate of screening was 27.7% in the donors aged 20－24 years, 24.3% in those aged 25－29 years, 23.8% in those aged 30－34 years, and 17.5% in those aged =&ge;35 years (P < 0.01); 23.5% in the senior high school students, 24% in the junior college students, 25.9% in the undergraduates, and 30.3% in the postgraduates (P < 0.01); 29.3% in the students versus 22.9% in the others (P < 0.01), 41.5% in the married versus 20.7% in the unmarried (P < 0.01), and 45.6% in the fathers versus 20.9% in the childless husbands (P < 0.01).

CONCLUSIONSA higher eligibility rate of screening was found among the sperm donors aged <35 years or with a bachelor's or higher degree, particularly among students.

Adult ; Humans ; Male ; Semen Analysis ; standards ; Spermatozoa ; Students ; statistics & numerical data ; Tissue Donors ; statistics & numerical data ; Tissue and Organ Procurement ; Young Adult

OBJECTIVETo explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms.

METHODSThe anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK.

RESULTSResveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced.

CONCLUSIONOur findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Cell Culture Techniques ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flow Cytometry ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; pathology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; Stilbenes ; pharmacology ; T-Lymphocytes ; drug effects ; enzymology ; ultrastructure ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To investigate the control status of iodine deficiency disorders (IDD) in the highrisk areas of Gansu province,and to provide a scientific basis for development of effective preventive measures.Methods Twelve counties with high-risk areas of IDD in Gansu province were selected into the survey in 2007 -2009.All patients with suspected cretinism born after the first of January,1997 were enrolled in the study from the 12 counties.Meanwhile,three townships were chosen in each of the 12 counties,two villages were taken in each township,40 children aged 8 to 10 in each village primary school were selected to carry out thyroid examination by B-ultrasonography and palpation,urinary iodine(UI) test,and intelligence quotient(IQ) test; 30 women of childbearing age were selected in each village to fill in the questionnaire,and to test their urinary and salt iodine,and the local salt-related situation was investigated.Results In the 12 high-risk counties,7 were diagnosed as new cretinism cases from a total of 120 suspected cases of cretinism.The goiter rate of children aged 8 - 10 by Bultrasound was 6.8％(290/4281 ),5 counties had goiter rates higher than 5％,of which 3 counties had goiter rates higher than 10％.The average IQ of children was 82.38.The median urinary iodine(MUI) of children was 180.34 μg/L,the ratio of UI ＜ 50 μg/L was 11.0％(482/4383).The MUI of women of childbearing age was 175.91 μg/L,the ratio of UI ＜ 50 μg/L was 16.5％(126/762).MUI of women of childbearing age was less than 100.0 μg/L in Xiahe and Dongxiang counties,which were 95.24 μg/L and 66.30 μg/L,respectively.The coverage rate of iodized salt in 8 of the 12 counties was more than 95％,and that of the remaining four counties was ＜ 85％,of which the coverage rates of iodized salt were only 39.2％ (47/120)and 66.7％ (120/180),respectively,in Guanghe and Dongxiang counties.Fourteen point nine percent (206/1380) of the residents complained that iodized salt was not convenient to buy and 87.7％ (1210/1380) complained that the current price of these salts exceeded the accepted range.Only 29.9％(413/1380)of the housewives knew how to prevent IDD.Conclusions Impact factors of IDD in high-risk areas are widespread.The monitoring of IDD in high-risk areas should be strengthened.Effective measures should be taken to ensure adequate iodine nutrition of people at risk.At the same time,iodized salt-based comprehensive prevention measures should be strengthen and a long-term effective control strategy of IDD should be established.

Objective To master the status in control of iodine deficiency disorders (IDD) in Gansu province and to provide the basis for development of control strategies. Methods One county which reached the national standardization of IDD elimination was selected randomly from each of 14 cities of Gansu province in 2009, then one town was selected respectively from five directions (east, south, west, north, and central) of the above selected counties. One village was chosen from every town which was selected for investigating household iodized salt and iodized salt sales network. At the same time the thyroid of children was examined, their urinary iodine (UI) was determined, the intelligence quotient(IQ) values of children were measured and health education was surveyed in one primary school which was chosen in each of the selected town. Results A total of 1420 edible salt samples were tested;the weighted iodized salt coverage rate and the weighted qualified iodized salt rate were 99.53% and 98.15 respectively. Urine samples were collected from 1761 children included in the study. The urinary iodine median was 225.87 μg/L. The urinary iodine medians were at optimal levels in five counties, over the optimal levels in seven counties and at excessive levels in two counties. A total of 3051 children aged 8 - 10 were randomly selected for thyroid examination. The weighted thyroid goiter rate(TGR) of children was 1.9%, and TGR was higher than 5% only in Hoaggu county. IQ of 2815 children was tested and the mean IQ was 105.3, except for the country of Zhuoni and Kangle, the mean IQ of other counties were over 100. The average score of health education was 3.2.Children of 57.08% (1229/2153) knew that iodine deficiency could lead to mental retardation, 71.76% (1544/2153) knew that iodine deficiency could cause thyroid goiter, 68.04%( 1465/2153 ) knew that eating iodized salt was the best method for IDD prevention and control and 61.82%(1331/2153) informed their families of the benefits of eating iodized salt. Each town had one agency selling iodized salt and each village had one more retail store with iodized salt, but 73.5%(75/102) of the stores without license for the sales. Conclusions Great progress has been made on the prevention and control of IDD in Gansu province. The qualified iodized salt consumption rate has reached the national standard for IDD elimination, TGR has decreased markedly, the urinary iodine levels in more counties are over the optimal levels and iodized salt distribution network is basically sound. But progress in health education is uneven.

Objective To explore the application effect of self-made scene video in the nursing of neonatal care. Methods Totally, 273 pregnant woman who participate in our school neonatal care operation technique teaching (including newborns bath, neonatal touch newborn babies, swimming, the umbilical plexus nursing, neonatal replacement urine pad, hip replacement urine mat of nursing six content) were divided into two groups: the observation group 147 pregnant woman, adopt scene video teaching mode; The control group 126 pregnant women, uses the multimedia teaching mode. Compare two sets of pregnant women neonatal care operation technology situation master. Results Teaching effect in observation group was better than control group (Z=-9. 115, P＜0. 01). Mastery of neonatal care operation technology in observation group is also better than in control group (Z =-6. 43, P ＜ 0. 01). Conclusions Scene video help maternal to grasp the neonatal care operation technology, security baby safety and worth of being generalized.

Adult ; Child ; China ; epidemiology ; Female ; Humans ; Iodine ; deficiency ; urine ; Male ; Thyroid Diseases ; epidemiology ; etiology