Objective To compare the effects of propofol combined with fentanyl or dezocine on painless abortion and the influence on body movement.Methods From July 2016 to May 2017,240 patients with voluntary painless abortion who aged 19-45 years old in the Second People's Hospital of Linhai,were randomly divided into 3 groups according to the digital table ,with 80 cases in each group.D group was given propofol and dezocine ;F group was given propofol combined with fentanyl ;C group was the control group and was treated with propofol intravenous anesthesia,the three groups were given propofol added according to the specific situation.The operative time,recovery time and the total amount of propofol were compared among the three groups ;and the pain visual analogue scale (VAS) at 0min,15min,30min,1h,3h were comparedamong the three groups ;The incidence of respiratory depression and other adverse reactions were statistically analyzed in three groups.Results The operation time,recovery time,the total dosage of propofol in D group were (4.5 ±0.7)min,(1.2 ±0.3)min and (136.8 ±14.5)mg,respectively, which in F group were (4.6 ±0.8)min,(1.3 ±0.2)min and (139.6 ±12.1)mg,respectively,there were no statisti-cally significant differences between the two groups (all P＞0.05).The recovery time and total dosage of propofol in D group and F group were lower than those of C group [(2.4 ±0.6) min,(168.7 ±18.9) mg](t＝25.298,27.287, 11.977,27.287,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h,3h in D group were lower than those in F group and group (t＝34.785,25.044,25.043,22.349,28.622,48.809,42.278,40.000,42.278, 40.000,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h in F group were lower than those of C group(t＝36.978,24.406,19.846,24.406,all P ＜0.05).The incidence rates of nausea,sedentary,respiratory depression,hypotension in D group were 1.3%(1case),2.5%(2cases),1.3%(1case),0.0%(0cases), resperctively,which in F group were 0.0%(0cases),3.8%(3cases),3.8%(3cases),2.5%(2cases),which in D group,F group were lower than those in C group [6.3%(5cases),16.3%(13cases),11.3%(9cases),15.0%(12cases)](χ2＝3.925,3.657,3.925,3.657,5.889,3.152,3.152,3.657,all P＜0.05).Conclusion Propofol combined with dezocine and fentanyl used in painless abortion have good effect ,and the body movement is less ,but propofol combined with dezocine has less postoperative pain degree.

OBJECTIVETo explore the relationship between temperature and non-accidental mortality in Guangzhou, Changsha and Kunming;to evaluate the temperature-related risk of mortality; and thereby to provide scientific evidence for enacting the policy to tackle climate changes.

METHODDaily meteorology data and mortality data were collected in 2006-2009 in Guangzhou, Changsha and Kunming. Distributed lag non-linear model (DLNM) was established and applied in a case-crossover design, which controlled the secular trend of time, to estimate the specified effects of temperature on non-accidental mortality at conditions of lag 0-2, lag 0-18 and lag 0-27 days, respectively.

RESULTAn obvious seasonal periodicity was found in non-accidental mortality in Guangzhou, Changsha and Kunming during 2006-2009. The mortality number was comparatively high in the winters, and some high temperature days in summer; but was comparatively low in springs and autumn. An L-shaped relationship was found between temperature and mortality in Guangzhou and Kunming and a U-shaped relationship was found in Changsha. When daily mean temperature exceeded 28.2 °C, 24.5°C and 23.2°C, as average temperature increase 1°C, non-accidental mortality increased 4.56% (95%CI:2.74%-6.63%), 5.66% (95%CI:0.22%-12.65%) , -3.94% (95%CI:-32.77%-39.01%) , respectively; when daily mean temperature below 24.8°C, 20.0°C and 17.3°C, as average temperature decrease 1°C, the corresponding increase in non-accidental mortality were 3.28% (95%CI:2.41%-4.10%) (lag 0-18 days), 1.35% (95%CI:0.31%-1.77%) (lag 0-2 days) and 2.42% (95%CI:1.08%-3.27%) (lag 0-27 days) , respectively. The effects of hot weather were acute and short term; while the effects of cold weather had a several days delay, but a longer persistence.

CONCLUSIONSExtreme cold and hot temperature could increase the risk of non-accidental mortality in Guangzhou, Changsha and Kunming. The effects of cold weather had a several days delay, but a longer persistence.

China ; epidemiology ; Climate Change ; Cross-Over Studies ; Humans ; Mortality ; Seasons ; Temperature

OBJECTIVETo explore the impact of the socio-economic factors on the temperature-mortality association in different cities in southern China.

METHODSDaily mortality registration data, meteorological data and air pollution data of the cities as Changsha and Kunming during 2006-2009, and cities as Guangzhou and Zhuhai during 2006-2010, were collected to explore modifying effects, stratified by age, gender, education and place of death, of socio-economic factors on the association between temperature and mortality, by distributed lag non-linear model. The accumulative effect of temperature-mortality were separately analyzed in each city, under the high temperature (0-3 days) and low temperature (0-20 days) situation. The association between temperature and mortality was evaluated by general linear threshold model. The above process was firstly adopted to analyze the impact in single city and then Meta analysis was applied to analyze the impact in several cities by effect-combine.

RESULTSThe relationship between temperature and mortality in the four cities showed nonlinearity. The minimum mortality risk was separately 23.5 °C, 20.5 °C, 25.0 °C and 26.0 °C in Changsha, Kunming, Guangzhou and Zhuhai. The results of effect-combine showed that low-temperature (RR = 1.67, 95%CI:1.54-1.80) has a higher gross effect than high-temperature (RR = 1.11, 95%CI:1.01-1.18) on population. With the age increasing, risk of death increased both under high and low temperature situation, and the effect of low temperature was greater (RR = 1.83, 95%CI:1.65-2.04) for the elderly than it of high temperature (RR = 1.17, 95%CI:1.03-1.33). The mortality risk among females (cold and hot effects(95%CI) were 1.75(1.57-1.97) and 1.11(0.99-1.25), respectively)was higher than it among males (cold and hot effects(95%CI) were 1.59(1.45-1.77) and 1.11(1.03-1.19), respectively). Whereas the mortality risk on higher education population was significantly higher (cold and hot effects (95%CI) were 1.89(1.48-2.45)and 1.34(1.19-1.48), respectively) than it on other educated people.

CONCLUSIONAge, gender, educational level and place of death showed modifying effects on the association between temperature and mortality. The elderly, women and highly educated people were vulnerable to the temperature influence on mortality.

Aged ; Air Pollution ; China ; Cold Temperature ; adverse effects ; Female ; Hot Temperature ; adverse effects ; Humans ; Male ; Mortality ; Nonlinear Dynamics ; Risk ; Socioeconomic Factors

Objective To estimate the effect of daily diurnal temperature range (DTR) on mortality in different areas in China.Methods A time series study using the data collected from 66 areas in China was conducted,and Meta-analysis was used to analyze the estimates of associations between DTR and daily mortality.Modifying effects of extremely low and high DTR-mortality relationship by season and socioeconomic status (SES) were also evaluated respectively.Cumulative excess risk (CER) was used as an index to evaluate the effects.Results The information about 1 260 913 registered deaths were collected between 1 January 2006 and 31 December 2011,we found the relationship between extreme DTR and mortality was non-linear in all regions and the exposure-response curve was J-shaped.In central and south areas of China,the result indicated the obvious acute effect of extremely high DTR,and the mortality effect in central area (CER=5.1％,95％CI:2.4％-7.9％) was significant higher than that in south area (CER=4.5％,95％CI:1.7％-7.3％).Regarding to the modification of seasons,the cumulative mortality effect of DTR in cold season (CER=5.8％,95％CI:2.5％-9.2％) was higher than that in hot season (CER=3.1％,95％CI:1.1％-5.1％).Generally,deaths among the elderly (≥75 years) were associated more strongly with extremely high DTR.Conclusions The mortality effects of extremely DTR in different areas and seasons showed different characteristics,that in central area and in cold season it was significantly stronger.After modified by season and SES,DTRs were the greatest threat to vulnerable population,especially to the elderly (≥75 years).Therefore,more attention should be paid to vulnerable groups and protection measures should be taken according to the local and seasonal conditions.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.