Objective To explore the effects of melatonin (MT) on the expression of interleukin (IL)-10,interleukin-6 and interleukin-8 as well as the inflammatory reaction and nerve repair after acute spinal cord injury (SCI).Methods One hundred and eight Sprague-Dawley rats were randomly divided into a spinal cord injury group (group A),an MT treatment group (group B) and a sham operation group (group C),each with 36 rats.SCI models were established in the rats of groups A and B using a version of Allen's weight drop method (50gcf at the T12 level).Group C had removal of the lamina only.Ten minutes later,group A was injected with 5％ ethanol in saline (the MT solvent) and group B with 100 mg/kg of melatonin preparation.At 6,12,18 and 24 hours,IL-6,IL-8 and IL-10 levels in serum were detected in 6 rats of each group.At 18 hours post-surgery,spinal cord specimens were taken from 6 rats of each group for hematoxylin eosin staining,morphological examination and immunohistochemical SP detection of IL-10 expression.Results The specimens of group A showed inflammatory reaction and ulceration at 48 h; groups B and C had no ulcers.Group B showed the highest levels of IL-10 in serum and IL-10 mRNA in the spinal cord,while group C showed the lowest level.The differences were statistically significant.Group A had the highest levels of IL-6 and IL-8 and group C had the lowest.The difference between group B and groups A and C was significant.The morpho-logical observation showed that after melatonin treatment the IL-10 levels in the spinal cord's central canal and around the gray matter improved.Conclusions Melatonin can improve nerve lipid peroxidation and inflammatory reaction in the treatment of spinal cord injury by increasing IL-10 expression and inhibiting IL-6 and IL-8 expression.

Objective: To construct effective short hairpin RNA (shRNA) recombinant plasmids targeting humanDystrophin Dp71 gene, and evaluate their interference effciency. Methods: hTree pairs of siRNA sequences targeting human Dp71 gene and one pair of control siRNA sequence were designed, synthesized, and then inserted into the pRNAT-U6.1/Neo vector. hTe shRNA recombinant vectors were evaluated by enzyme digestion and sequencing. Dp71-shRNA and control shRNA plasmids were transfected into human normal gastric epithelial cells (GES-1) and humanbronchial epithelium (HBE). Western blot was used to evaluate its interfering effciency. Results: Restriction enzyme digestion and sequencing showed that the Dp71-shRNA vectors were successfully constructed. Western blot displayed that Dp71 protein expression was reduced to a signiifcant degree atfer transfection with the 3 Dp71-shRNA plasmids, and Dp71-shRNA2 plasmid inhibit the Dp71 expression most effciently. Conclusion: Dp71-shRNA vectors have been successfully constructed. The 3 Dp71-shRNA plasmids can inhibit Dp71 expression in GES-1 and HBEC, with Dp71-shRNA2 plasmid displaying the highest inhibition effciency.

Air Pollution, Indoor ; analysis ; China ; Environmental Monitoring ; Humans ; Surveys and Questionnaires

Objective To evaluate the impacts of air temperature on years of life lost(YLL) among the residents in Guangzhou and Zhuhai,Guangdong province. Methods Daily mortality and meteorology data in Guangzhou and Zhuhai were collected,and distributed lag non-linear model (DLNM)was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature(0-1 days)and extreme low temperature(0-13 days)situation in Guangzhou and Zhuhai were analyzed respectively. Results The average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day,while the cold effect reached the peak at 5th days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged ≥65 years than in people aged <65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai. Conclusion The effects of high and low temperatures on YLL were obvious,and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations.

Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

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.

Purpose: Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. Materials and Methods: Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. Results: CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. Conclusion CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L⁻¹, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L⁻¹ respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.

Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m^-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m⁻² may be more sensitive to compound hot extreme.