Objective To investigate the protective effect of c-jun N-terminal kinase (JNK)inhibitor SP600125 against acute liver failure in mice.Methods Fifty-five male C57/BL6 mice were divided into control group (n =30) and SP600125 group (n =25).The animals were given an intraperitoneal injection of D-galactosamine (D-GalN,400 mg/kg body weight)/lipopolysaccharide (LPS,30 μg/kg body weight).The control group and SP600125 group were given 10％ dimethyl sulfoxide (15 mL/kg body weight) or SP600125 (75 mg/kg body weight) subcutaneously 12 h and 1 h before D-GalN/LPS administration,respectively.D GalN/LPS induced mouse JNK activation was detected by immunohistochemistry for phospho JNK (p-JNK).D-GalN/LPS induced mouse liver cell apoptosis was detected by immunohistochemistry for Caspase-3 and TdT-mediated-dUTP nick endlabeling (TUNEL).Serum alanine transaminase (ALT) level was tested to assess liver injury.Survival rate of mice within 24 h after D-GalN/LPS administration was observed.The comparison between groups was done by t test and survival rate was analyzed by Kaplan-Meier method.Results JNK activity in liver tissues,as indicated by observation of p-JNK positive cells by immunohistochemistry,was diminished 4 h after D-GalN/LPS administration in SP600125 group.Reduced Caspase-3 activity was observed 6 h after D-GalN/LPS administration in SP600125 group (as indicated in immunohistochemistry by Caspase-3 positive cells).Mice in SP600125 group showed significantly lower TUNEL-positive cell count than control group (43.0±24.5 vs 194.7±73.8; t=9.743,P=0.000).Serum ALT level 6 h after D-GalN/LPS administration was (24.0±54.7) U/L in SP600125 group,which was significantly lower than that in control group [(1234.4±478.4) U/L; t=4.734,P=0.0015].SP600125 also significantly improved the survival rate within 24 h after D-GalN/LPS administration (4/5 vs 1/10； x2=5.225,P=0.0223).Conclusions JNK inhibitor SP600125 exerts protective effects against D-GalN/LPS induced acute liver failure in mice by suppressing JNK activation and hepatocyte apoptosis.

Objective To evaluate the effect of graded management of health in hypertensive populations.Methods Hypertensive adults who were detected in health checkup between January 2008 and June 2011 and with no severe liver or kidney disease,chronic consumptive disease and cancer were enrolled in this investigation.Those with low or modest hypertensive risk received grade 2health management,and those with high or extreme high risk got grade 3health management.At the end of the intervention,50％ participants were randomly selected in each year(1441 in 2008,1508 in 2009,1533 in 2010,and 1601 in 2011) to compare lifestyle modification,blood pressure,blood glucose and blood lipid profiles by using multiDunnett's t test and x2 analyses.Results In both grade 2 and 3 health management groups,compared with baseline,high-salt diet,current cigarette smoking,alcohol consumption and insufficient physical activity were significantly improved after intervention (x2 values were 154.27 and 81.16,52.43 and 9.37,61.40 and 12.13,46.54 and 12.05,respectively; all P ＜ 0.05).Blood glucose in grade 2 health management group and waistline in grade 3 health management group showed no significant change.Body weight,blood glucose,blood lipid profiles and serum creatinine of grade 2 health management group were significantly declined after intervention.In both groups,systolic and diastolic blood pressure were significantly decreased(F values were 13.12 and 56.86,56.86 and 239.89,respectively; all P ＜0.05),and those with normal blood pressure were increased from 28.8％ and 23.4％ to 37.9％ and 28.2％ in grade 2 and 3 health management groups(F values were 12.78 and 22.93,respectively ; all P ＜ 0.05).Conclusion These data suggest the beneficial effects of graded management of health on blood pressure control and reduced risks of cardiovascular disease.

Objective:To explore the association between the changes in ideal cardiovascular health (CVH) indices and the renal function.Methods:The retrospective cohort study consisted of 837 Chinese individuals from Department of Health Management in the Third Xiangya Hospital.The general information,anthropometry and blood biochemistry were obtained for all subjects from 2008 to 2014,respectively.The 6-year changes of 7 ideal CVH metrics defined by American Heart Association and the estimated glomerular filtration rate (eGFR) were calculated.Linear regression analysis was used to study the association between the changes in the ideal CVH metrics and eGFR.Covariance analysis was used to compare the levels of changes in eGFR stratified by variations of the ideal CVH metrics.Results:After 6 years' follow-up,we did not find significant difference in ideal cardiovascular health indexes between 2014 and 2008 [(3.3±1.4) items vs.(3.2±1.3) items,respectively] (P＜0.05).However,the eGFR in 2014 was significantly lower than that in 2008 [(99.8±22.7) mL/(min.1.73 m2)vs (104.3±24.9) mL/(min.1.73 m2),respectively] (P＜0.01).After adjusting for age,sex,history of hypertension and diabetes,and history of drug usage (antihypertensive,cholesterol-lowering and blood glucose-lowering medication),the changes in ideal CVH metrics were positively associated with the changes in eGFR (β=0.701,P＜0.01).With the improved change in ideal CVH metrics from ≤-2 points,-1 point,0 point,1 point to ≥ 2 points,the magnitude of decline in eGFR was gradually decreased,with significant difference (F=21.71,P＜0.01).Conclusion:The changes in ideal CVH metrics are an independent risk factor for changes of eGFR.Positive changes in ideal CVH metrics exert a favorable effect on renal function evolution.

Objective To investigate miR-146a-Smad4 expression during ultraviolet A(UVA)-induced photoaging of human skin fibroblasts (HSFs), and to evaluate effects of up-regulation of miR-146a expression on its target gene Smad4 and cell photoaging. Methods HSFs were isolated from the prepuce, and subjected to primary culture and maintained up to 10th passage. Then, the HSFs were classified into 4 groups: blank control group receiving no treatment, UVA group irradiated with 10 J/cm2 UVA, miR-146a group transfected with a lentiviral vector expressing miR-146a, UVA+ miR-146a group transfected with the lentiviral vector expressing miR-146a followed by UVA radiation. Real time PCR was performed to measure miR-146a expression in HSFs in the UVA group on day 0, 3, 7 and 14 after UVA radiation.Fluorescence microscopy was carried out to estimate transfection efficiency on day 7 and 14 in the miR-146a group after transfection, and real time PCR was performed to quantify miR-146a expression in these cells. Methyl thiazolyl tetrazolium (MTT)assay was conducted to evaluate proliferative activity of HSFs, real time PCR to quantify mRNA expressions of photoaging-related genes p53, p21 and p16, and Western blot analysis to measure Smad4 protein expression in these cells. Statistical analysis was carried out by using repeated-measures analysis of variance and factorial design analysis of variance. Results Repeated-measures analysis of variance showed that the expression of miR-146a decreased over time in both the UVA group and blank control group(F = 213.840, P < 0.01), and significantly lower in the UVA group than in the blank control group (F = 52.55, P < 0.01), with the difference between the two groups increasing over time. After transfection with the lentiviral vector expressing miR-146a-Smad4, HSFs showed a strong fluorescence intensity of miR-146a. The expression level of miR-146a was significantly higher in the miR-146a group than in the blank control group on day 7 and 14 after transfection(10.31 ± 0.17 vs. 8.33 ± 0.13 on day 7, 9.65 ± 0.19 vs. 7.86 ± 0.11 on day 14, F =42.49, P < 0.01), but insignificantly different between day 7 and 14 in the miR-146a group (P > 0.05). Factorial design analysis of variance showed that UVA radiation had an inhibitory effect on the proliferative activity of HSFs (P < 0.01), which was significantly lower in the UVA group than in the blank control group(P < 0.01), and lower in the UVA + miR-146a group than in the miR-146a group (P < 0.01). The lentivirus-mediated up-regulation of miR-146a expression also affected cellular proliferative activity (P < 0.01), which was significantly higher in the UVA + miR-146a group than in the UVA group(P < 0.01), but insignificantly different between the miR-146a group and blank control group(P > 0.05). Real time PCR and Western blot analysis both revealed that UVA radiation could increase the expressions of p53, p21 and p16 mRNAs as well as Smad4 protein(all P < 0.01). Concretely speaking, the expressions of p53, p21, p16 mRNAs and Smad4 protein were all significantly higher in the UVA group than in the blank control group (all P < 0.01), and higher in the UVA +miR-146a group than in the miR-146a group (all P < 0.01), but significantly lower in the UVA + miR-146a group than in the UVA group (all P < 0.01), and insignificantly different between the blank control group and miR-146a group (all P >0.05). Conclusion The expression of miR-146a is inhibited in UVA-induced photoaged HSFs, and its up-regulation may counteract cell photoaging by suppressing Smad4 expression in, and promoting proliferation of, photoaged HSFs.

Objective To evaluate the utility of serum thymidine kinase 1(STK1)in health screening.Methods A total of 8896 adults who participated in health check-up during November 2009 and November 2010 were tested for STK1 by using sensitive chemiluminescence's dot blot assay.Results The level of STK1 of group A(STK1 ＞ 2 pmol/L)was much higher than that of the group B(STK1 ＜ 2 pmol/L)[(5.47 ±4.23)vs(0.62 ±0.48)pmol/L;t =11.90,P =0.00].The STK1 level was not correlated with gender.However,the mean age of individuals in the group A was higher than that in the group B[(48.2 ± 12.0)vs(41.8 ± 12.3)years; t =5.37,P =0.00].The positive detection rate of STK1 was 1.2％(108/ 8896).In the group A,there were 1.9％ pre-or post-treatment malignancy,27.8％ pre-malignant tumor or benign disease,36.0％ nontumorous proliferation disease,14.8％ hepatitis B virus/HP infection,10.2％fatty liver,and 9.3％ other diseases.No pre-treatment malignancy and pre-malignancy were found in the group B.Conclusion STK1 measurement could reflect the situation of cell proliferation and predict the risk of any type of malignancy.

Objective 　Determination of Wilson disease gene mRNA expression in human fibroblast cell strain (Me32aT22/2L) by reverse transcription-polymerase chain reaction (RT-PCR). Methods　Using lipofection reagent, the plasmid vector carrying the Wilson disease gene (pRc/CMV-WD) was transferred into Me32aT22/2L cultured in serum free complement medium. RT-PCR was used to determine WD mRNA expression in Me32aT22/2L. Results　 Wilson disease gene expression was detected in Me32aT22/2L, while no specific signals were detected in untransfected fibroblast. Conclusions　It demonstrated that Me32aT22/2L strain could express the Wilson disease gene, suggesting that Wilson disease gene transfer might develop a new approach to study Wilson disease.

Objecive To explore the medicine packaging improvement based on PAP shelter hospital requirements to fulfill emergency medicine support,Methods The medicine support during rescue was discussed from the aspects of considerations in medicine plan,requirement for emergency medicine,special medicine purchasing and medicine support,and some countermeasures were put forward for improving medicine packaging.Results Its suggested that the optimization of medicine packaging be performed with considerations on medicine property,package capacity,convenience,transport and environmental suitability.Conclusion Emergency medicine support is of importance for disaster medical rescue,and medicine packaging improvement based on PAP shelter hospital requirements contributes to enhancing the efficiency during disaster rescue.

Objective To explore the application value of stepped screening on hypertension with self-report health measurement questionnaire by comparing the accuracy of the different levels of screening. Methods A total of 6 715 subjects with hypertension (average age of 53.47 ± 11.07 years) were selected from those who completed the physical examination in the department of health management in the Third Xiangya Hospital of Central South University for questionnaire survey, routine inspection and special inspection for hypertension. And the patients were divided into four groups based on their hypertension risk levels: the questionnaire survey group, routine inspection group, questionnaire + routine inspection group and questionnaire+routine inspection+special inspection group. The results were compared respectively to calculate the sensitivity, specificity, positive predictive value and coincidence rate of single inspection and joint inspection. Results Nearly 90.00%of the subjects had hypertension associated with the risk factors, while 20.83% of the subjects had hypertension associated with other clinical diseases (the highest percentage was seen in hypertension with diabetes as 14.88%). According to the guidelines of stratification, 3.41% of the patients were at low risk, 23.78% at moderate risk, 47.85% at high risk, and 24.96% at extremely high risk. Sensitivity and specificity of routine inspection were 95.56%and 45.51%in judgment of moderate risk, which became 100.00%and 45.51%after addition of questionnaire survey;as a result, thesensitivity increased. Sensitivity and specificity of routine inspection were 15.03%and 96.28%in judgment of high risk, which became 30.03% and 99.14% after addition of questionnaire survey; as a result, the sensitivity doubled. Sensitivity and specificity of routine inspection were 15.03%and 100.00%in judgment of extremely high risk, and the sensitivity increased to 94.45%after addition of questionnaire survey, while the specificity remained unchanged. Conclusion Addition of questionnaire on the basis of routine physical examination could greatly increase the detection rate of hypertension patients at different risk levels, and increase the sensitivity as well as specificity for detection of moderate risk, high risk and extremely high risk. Therefore, health information and data acquired from the questionnaire and data obtained from the medical inspection equipment are equally important and suggest health management (physical examination) institutions to take questionnaire as a necessary and primary screening in physical examination and chronic disease screening.

Objective To evaluate the effects of penehyclidine hydroehloride as an atropine alternative on angioearpy and glandular secretions when premedieated in ketamine complex total intravenous anesthesia(TIVA)in children.Methods Forty patients aged 3-10 years undergoing ketamine and propofol complex TIVA were randomly divided into two groups.Penehyclidine hydrochloride(group P,n=20)or atropine(group A,n=20)was premedicated intramuscularly 30 min before anesthesia.Heart rate(HR),mean arterial pressure(MAP),breath rate(R)and the amount of saliva secretion(SS)were recorded before premedication(0 min),10 min,20 min,30 min,60 min and 150 min after.Results (1)SS reduced significantly 20 min,30 min and 60 min after premedication in both groups(P＜0.01),and in 150 min,it was still in a significantly reduced level in group P(P＜0.01),which was significantly lower than that in group A(P＜0.01).(2)MAP,HR and R in group P showed no significant differences before and after premedication(P＞0.05).But in group A,HR increased significantly at 20 min,30 min and 60 min after premedication(P＜0.05 or＜0.01),MAP increased significantly at 30 min and 60 min after premedication(P＜0.01),and meanwhile of them were also significantly higher than those in group P(P＜0.05 or＜0.01).Conclusions Penehychdine hydrochloride can effectively reduce respiratory glandular secretion with longer persistence,and nearly has no influence on HR and blood pressure,which suggests it could be a superior to atropine alternative as an anesthesia premedication in children.

Objective:To explore the effects of human-derived fibrin glue on prevention of postoperative complications of endoscopic submucosal dissection (ESD) in early esophageal squamous cancer and precancerous lesions.Methods:A total of 210 patients with early esophageal squamous cancer or precancerous lesions who underwent ESD at Department of Gastroenterology, Zhongda Hospital Affiliated to Southeast University from April 2017 to April 2020 were included in this retrospective study. Seventy-three cases (79 esophageal lesions) where human-derived fibrin glue was used before retrieving endoscope were included in the observation group, while 137 cases (156 esophageal lesions) where fibrin glue was not used were included in the control group. The postoperative complications and pain were compared between the two groups.Results:Clinical data including general information, longitudinal length, Paris type, pathological type, invasion depth, circumferential range, area of resection, duration of operation and local steroid used were similar between the two groups ( P>0.05). The incidences of perforation, delayed bleeding and esophageal stenosis in the observation group were 2.7% (2/73), 1.4% (1/73), and 16.4% (12/73), respectively, and were 2.9% (4/137), 1.5% (2/137), and 13.1% (18/137), respectively in the control group. There were no significant differences between the two groups ( P>0.05). The incidence of postoperative pain in the observation group was 53.4% (39/73), which was significantly lower than that in the control group of 70.8% (97/137) ( χ2=6.302, P=0.012). The incidences of mild, moderate and severe pain in observation group on the day of ESD were 9.6% (7/73), 6.8% (5/73) and 5.5% (4/73), respectively, and 27.0% (37/137, χ2=8.724, P=0.003), 17.5% (24/137, χ2=4.554, P=0.033) and 0.7% (1/137, χ2=2.805, P=0.094), respectively in the control group. The incidences of mild, moderate and severe pain in the observation group on the first day after the operation were 26.0% (19/73), 5.5% (4/73) and 6.8% (5/73), respectively, and 29.2% (40/137, χ2=0.237, P=0.626), 14.6% (20/137, χ2=3.912, P=0.048) and 4.4% (6/137, χ2=0.193, P=0.660), respectively in the control group. The corresponding incidences on the second day after the operation were 5.5% (4/73), 0 and 1.4% (1/73) in the observation group and 19.0% (26/137, χ2=7.087, P=0.008), 2.9% (4/137) and 0 in the control group, respectively. Conclusion:Human-derived fibrin glue shows no obvious preventive effect on post-ESD bleeding, perforation or stenosis in early esophageal cancer and precancerous lesions. However, it can significantly reduce the incidence of ESD-related postoperative pain, especially the incidences of mild and moderate pain.