OBJECTIVE: To investigate the effects of different concentrations of thiomersal on apoptosis and autophagy regulation of human leukemia cell lines U937, CEM-C1 and BALL-1. METHODS: The inhibitory effect of thiomersal on the proliferation of U937, CEM-C1 and BALL-1 cells was detected by CCK-8 assay. Annexin V-FITC/PI double staining flow cytometry was used to detect the apoptosis rate. Western blot was used to detect the effects of thiomersal on autophagy signaling pathway and the expression of PI3K, Akt, mTOR, p-mTOR, caspase-3 and LC3-II proteins. RESULTS: Within 24 and 48 hours, thiomersal inhibited the proliferation of U937, CEM-C1 and BALL-1 cell lines in a time and dose-dependent manner (r_{24 h}=0.295, r_{24 h}=0.452, r_{24 h}=0.103; r_{48 h}=0.821, r_{48 h}=0.665, r_{48 h}=0.821), but no significant time and dose-dependent effect was observed at 72 hours. After 48 hours treatment of thiomersal, the apoptosis rate of U937, CEM-C1 and BALL-1 cells increased in a dose-dependent manner (r=0.819, r=0.763, r=0.835). After 48 hours treatment of thiomersal, the expression levels of PI3K, Akt, mTOR and p-mTOR protein in U937, CEM-C1 and BALL-1 cells decreased in a concentration-dependent manner, the R value of U937 cells was -0.975, -0.899, -0.925 and -0.915, respectively, that of CEM-C1 cells was -0.960, -0.920, -0.861 and -0.927, and that of BALL-1 cells was -0.939, -0.911, -0.896 and -0.926,. which suggested that thiomersal-induced apoptosis of U937, CEM-C1 and BALL-1 cells might be due to the inhibition of PI3K/Akt/mTOR pathway. Thiomersal promoted the apoptosis of U937, CEM-C1 and BALL-1 cells via caspase-3 pathway, and the expressions of caspase-3 and LC3-II were up-regulated in a dose-dependent manner (r=0.976, r=0.914; r=0.976, r=0.986; r=0.961, r=0.974). CONCLUSIONS Thiomersal can inhibit the proliferation and promote the apoptosis of U937, CEM-C1 and BALL-1 cells. A certain concentration of thiomersal can down-regulate the expression of PI3K/Akt/mTOR pathway related proteins PI3K, Akt, mTOR and p-mTOR in U937, CEM-C1 and BALL-1 cells, and activate autophagy and apoptosis by down-regulation of PI3K/Akt/mTOR pathway.
Humans ; Thimerosal ; Caspase 3 ; Phosphatidylinositol 3-Kinases ; Autophagy ; Apoptosis ; Leukemia ; Cell Line

Objective To investigate the effect of aerobatic flight on high performance fighter pilots' physiological characteristics and to analyze their work loads in such flight.Methods Ten healthy male military pilots executed 17 aerobatic flights.Electrocardiograph was recorded during flight,and heart rate (HR) and heart rate variability (HRV) were analyzed.Results During aerobatic flight,HR and HRV showed increasing sympathetic nerve regulation.The mean HR,max HR at aerobatic stage was (92.3 ±13.2),(101.2 ±15.9) beats / min and significantly higher than those in other stages respectively(F=58.479,35.209; P＜0.01).The ratio of LF and HF (LF/HF) significantly increased in aerobatic stage,and the difference with that in acrobatic stages were statistic meaning(F=19.893,P＜0.01).Conclusions High performance fighter pilots endure high G and high G onset in aerobatic flight.The increasing sympathetic nerve regulation indicates pilot's high physical and mental workload.

Objective To investigate the effect of aerobatic flight on high performance fighter pilots' physiological characteristics and to analyze their work loads in such flight.Methods Ten healthy male military pilots executed 17 aerobatic flights.Electrocardiograph was recorded during flight,and heart rate (HR) and heart rate variability (HRV) were analyzed.Results During aerobatic flight,HR and HRV showed increasing sympathetic nerve regulation.The mean HR,max HR at aerobatic stage was (92.3 ±13.2),(101.2 ±15.9) beats / min and significantly higher than those in other stages respectively(F=58.479,35.209; P＜0.01).The ratio of LF and HF (LF/HF) significantly increased in aerobatic stage,and the difference with that in acrobatic stages were statistic meaning(F=19.893,P＜0.01).Conclusions High performance fighter pilots endure high G and high G onset in aerobatic flight.The increasing sympathetic nerve regulation indicates pilot's high physical and mental workload.

Objective To investigate the effects of high intensity flight on physiological indices and subjective evaluation of flight work load of high performance fighter pilot.Methods Five healthy male military pilots executed 22 high intensity flights in one day.Electrocardiograph was recorded during flight,and heart rate and heart rate variability (HRV) were analyzed.Flight work load and subjective fatigue feeling were evaluated by pilots themselves.Results During high intensity flight,heart rate and HRV showed an apparent circadian rhythm.Heart rate,low frequency normalized unit (LFnu) and ratio of low and high frequency (LF/HF)in night time were lower than those in day time,but high frequency normalized unit (HFnu).There was no obvious subjective fatigue feeling commented by pilots.Conclusions High intensity flight of high performance fighter pilots has some effects on physiological indices,but no flight fatigue so far.Rational disposition of flight and adequate aeromedical support could be beneficial to pilot's recovery and the alleviation of flight fatigue.

Objective To investigate the effects of high intensity flight on physiological indices and subjective evaluation of flight work load of high performance fighter pilot.Methods Five healthy male military pilots executed 22 high intensity flights in one day.Electrocardiograph was recorded during flight,and heart rate and heart rate variability (HRV) were analyzed.Flight work load and subjective fatigue feeling were evaluated by pilots themselves.Results During high intensity flight,heart rate and HRV showed an apparent circadian rhythm.Heart rate,low frequency normalized unit (LFnu) and ratio of low and high frequency (LF/HF)in night time were lower than those in day time,but high frequency normalized unit (HFnu).There was no obvious subjective fatigue feeling commented by pilots.Conclusions High intensity flight of high performance fighter pilots has some effects on physiological indices,but no flight fatigue so far.Rational disposition of flight and adequate aeromedical support could be beneficial to pilot's recovery and the alleviation of flight fatigue.

Objective To determine the risk factors related to tuberculosis infection among people living with HIV/AIDS and to develop strategies for preventing the co-infection.Methods A 1:2matched nested case-control study was carried out to analyze the influencing factors of tuberculosis among people living with HIV/AIDS.Results 1018 people living with HIV/AIDS were followed up for one year with a total number of 736.75 person-years,among them 62 tuberculosis cases were diagnosed.The incidence density of tuberculosis among people living with HIV/AIDS was 8.42 persons per 100 person-years.Factors as education level(OR=0.483),vaccination history of Bacille Calmette Guerin(OR=0.561),CD_4~+ count T-lymphocyte(OR=0.356),unemployment(OR=1.976),living alone(OR=2.646),and smoking(OR=2.215)were significantly related to the prevalence of tuberculosis among people living with HIV/AIDS.Conclusion High education level,with vaccination history of Bacille Calmette Guerin and high level of CD_4~+ T-lymphocyte count were protective factors while being unemployed,living alone,and smoking habit were risk factors related to the prevalence of tuberculosis among people living with HIV/AIDS.

OBJECTIVETo investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type I(PC-1), as well as to explore the relationship between the genotype and phenotype.

METHODSThe whole coding region of the KRT16 and KRT6A genes were amplified by long-range polymerase chain reaction (PCR). Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorphism. PCR products were directly sequenced to detect the mutation.

RESULTSNo mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at codon 465 (TAC to CAC) which substitutes tyrosine (Y) by histidine (H). In the sporadic patient, codon 171 (AAC) was mutated to GAC, which changes the asparagines (N) to aspartic acid (D). No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations.

CONCLUSIONThe mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Female ; Humans ; Keratin-6 ; genetics ; Male ; Molecular Sequence Data ; Mutation ; Pachyonychia Congenita ; genetics ; Pedigree

Objective To investigate the survival of patients with painful chronic panereatitis and evaluate the risk factors for mortality in these patients.Methods This was a historical cohort study,subjects ≥18 yr with painful chronic pancreatitis who were treated in our center from Feb.1997 to July 2007 were enrolled.A life-table method was used to estimate the probability of the cumulative survival rate.COX proportional-hazards model was used for multivariate analysis.Results Follow-up data were obtained from 346 patients (87.2%) with the ratio of male/female was 2.4:1.The age of first admission and first symptom onset was (47±14)years and (43±15 ) years.The mean follow-up period was ( 34.3±27.1 ) months.Alcoholic origin accounted for 22.2% of all the patients,while biliary origin was 26.0%.The overall mortality rate was 9.8% (34/346),which happened (62.5±61.1 ) months after abdominal pain was present.The causes of mortality included pancreatic cancer and cancers of other sites.The cumulative survival rate estimated at 2 years was 96.3%,at 5 years 93.6% and at 10 years 86.4%.COX proportional-hazards model suggested age at onset (≥51 years),no improvement of abdominal pain or increased frequency of pain,active smoking,and no diarrhea were associated with increased mortality,and the corresponding hazard rates (HR) were 3.4,3.5,4.2,2.8 and 17.7,respectively.Conclusions The mortality rate of painful chronic panereatitis in China was lower than those reported outside China.The main cause of mortality was pancreatic cancer.Great caution shall be placed on patients with age at onset ≥51 yr,no improvement of abdominal pain,increased frequency of pain,active smoking and no diarrhea.

Objective To investigate the incidence of diabetes mellitus and risk factors for the disease in chronic pancreatitis (CP) patients.Methods A historical cohort study on subjects with painful CP who were admitted to hospital from Jan.1997 to July 2007 were conducted.A life-table method was used to estimate the cumulative probability of the development of diabetes mellitus once clinical onset of abdominal pain.Cox proportional-hazards model was used for multivariate analysis of the variables including age,sex,drinking and smoking habits,etiological factor,presence of pancreatic masses,pancreatic calcifications,measure of intervention,diarrhea,weight loss and degree of pain.Results Data were obtained from 354 patients (239 males,mean age at onset of pain (38.1±17.6) years;alcoholic origin 18.1%) with painful CP.The mean follow-up period was (45.2±32.9)months.The rate of diabetes mellitus in CP patients was 16.1%.There was a high incidence (29.8%)of diabetes mellitus 1 year before the episodes of abdominal pain.The cumulative risk of diabetes mellitus in subjects 5 and 10 years after the episodes of pain was 9.3% and 20.7%,respectively.Cox proportional-hazards model selected smoking (＞10 pack years) (hazard rate (HR)= 3.3),mild abdominal pain (HR=5.2),weight loss (HR = 2.6) and pancreatic calcifications (HR = 2.2) as variables identifying subjects with diabetes mellitus in patients with painful CP before they were performed therapeutic endoscopy or surgical intervention.Smoking (＞10 pack years) (HR = 3.0),weight loss (HR= 2.8) and distal pancreatectomy (HR =7.3) were identified with an increased risk of diabetes mellitus in these cases after they received therapeutic endoscopy or surgical intervention.Conclusion The risk factors of diabetes mellitus for CP appears to be independent of smoking (＞10 pack years),mild abdominal pain,weight loss,pancreatic calcifications and distal pancreatectomy.

Objective To investigate the incidence and risk factors of pancreatic cancer in patients with painful chronic pancreatitis (CP). Methods Three hundred and ninty-seven patients with painful CP were recruited between Jan. 1997 to July 2007. A life-table method was used to estimate the cumulative probability of the incidence of pancreatic cancer. Cox proportional-hazards model was used for multivariate analysis of the variables including age, sex, drinking and smoking habits, etiological factor, presence of pancreatic masses, pancreatic calcifications, measure of intervention, diabetes mellitus, diarrhea, weight loss and degree of pain. Results Of 397 patients,346 (87.2%) were follow-up for (34.3±27.1)months with 244 males and 102 females(2.4 :1). The mean age of the patients were (47.7 ±13. 7) years and alcoholic origin accounted for 22. 2%. The incidence of the pancreatic cancer was 8.1 % (28/346). There was a high incidence of cancers during the 4 years after the episodes of abdominal pain. The cumulative risks of pancreatic cancer 1, 5 and 10 years after the episodes of pain were 5 %, 5.6% and 11.6% respectively. Cox proportional-hazards model selected age at onset (≥51 years) [hazard rate(HR) = 3. 1], pancreatic calcifications ( HR = 4.1) ,pancreatic masses ( HR = 7. 1 )], no improvement of abdominal pain ( HR = 3. 8), increased frequency of pain (HR= 6.8), no diarrhea (HR= 15.3) as variables identified with pancreatic cancer in painful CP patients. Conclusions Pancreatic cancer should be suspected in patients with CP. The risk factors of pancreatic cancer are age at onset (≥ 51 years), pancreatic calcifications, pancreatic masses, no improvement of abdominal pain, increased frequency of pain and no diarrhea.