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.

Objective To evaluate the risk factors of failure in pain resolution in chronic pancreatitis(CP)after endoscopic treatment.Methods We undertook a retrospective cohoa study of subjects with pain caused by CP,who underwent endoscopic treatment from January 1997 to December 2006.Cox proportional-hazards model was used for multivariate analysis of the variables that were possibly related to failure of treatment.Results Follow-up data were obtained from 172 patients(114 males and 58 females,mean age 39.4 yr.Pain resolution after endoscopic treatment was achieved in 148(86.0%).Cox proportional-hazards model showed risk factors of failure in pain resolution after endoscopic treatment were onset age(＞36 years,hazard rate(HR)=3.5),mild and moderate abdominal pain before endoscopy(HR=2.4),no decrease in amount alcohol consume(＜50%,HR=1.9)and inappropriate diet(HR=2.8).Conclusion Patients with CP should abstain from alcohol and have low-fat diet,especially for those with pain onset at older ages (＞36 years)and with mild and moderate abdominal pain before endoscopic treatment.

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 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 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 effects of prenatal stress (PNS) on kinetic properties of high-voltage-activated (HVA) Ca(2+) channel in freshly isolated offspring rat hippocampal CA3 pyramidal neurons.

METHODSThe pregnant rats were exposed to restraint stress, and the hippocampal CA3 pyramidal neurons were freshly isolated from the offspring rats to record voltage-gate Ca(2+) channel currents in these neurons using whole-cell configuration of patch-clamp technique.

RESULTSPNS significantly increased HVA calcium current density and integral current but did not alter the steady-state activation and steady-state inactivation properties of HVA Ca(2+) channel in the offspring rat CA3 neurons. The maximal HVA calcium current density was -40.89-/+0.31 pA/pF in the control group (n=10) and -49.44-/+0.37 pA/pF in PNS group (n=8, P<0.01). The maximal integral current of the HVA Ca(2+) channel was 106.81-/+4.20 nA*ms in the control group (n=10) and 133.49-/+2.59 nA*ms in the PNS group (n=8, P<0.01).

CONCLUSIONMaternal exposure to stress during the critical phase of pregnancy may result in long-lasting effects on the ion channels of the hippocampal neurons in the offspring rats.

Animals ; Animals, Newborn ; Calcium Channels ; physiology ; Female ; Hippocampus ; cytology ; Kinetics ; Male ; Membrane Potentials ; physiology ; Patch-Clamp Techniques ; Pregnancy ; Pregnancy Complications ; psychology ; Pyramidal Cells ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Restraint, Physical ; psychology ; Stress, Psychological ; physiopathology

In this study, immunohistochemistry and Western blot were used to determine whether the expression of NF-kappaB in the hippocampus of prenatally stressed offspring rats is gender-dependent. The results were as follows: In the female offspring rats, the expressions of p65 in the hippocampal dentate gyrus in mid-term stress (MS) and late-term stress (LS) groups were significantly less than that in the control group (P<0.01). There was a significant difference between MS and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in MS and LS groups were significantly more than that in the control group (P<0.01). A significant difference was also present between MS and LS groups (P<0.01). In the male offspring rats, the expressions of p65 in the hippocampal dentate gyrus in MS and LS groups were evidently more than that in the control group (P<0.01). There was a significant difference between MS and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in MS and LS groups were significantly less than that in the control group (P<0.05, P<0.01). There was also a significant difference in p65 expression between MS and LS groups (P<0.01). In addition, in the control group the expressions of p65 in the hippocampal dentate gyrus of female offspring rats were significantly more than that of male ones (P<0.01). However, in LS group the expressions of p65 in the hippocampal dentate gyrus of female offspring rats were significantly less than that of male ones (P<0.01). Moreover, there was no significant difference in p65 expression between female and male offspring rats in MS group. In the control group the gender difference in the expression of p50 was only observed in hippocampal CA1 (P<0.01). The expressions of p50 in all regions of hippocampus of female offspring rats were significantly more than that of male ones in LS group (P<0.01). There was no significant difference in p50 expression between female and male offspring rats in MS group. The results of Western blot were similar to those of immunohistochemical study. These results indicate that prenatal stress in different gestational periods significantly affects the expressions of p65 and p50 in hippocampus, and this effect is gender-dependent. This may be one of the mechanisms underlying the gender difference in the ability of learning and memory of the prenatally stressed offspring rats.
Animals ; Female ; Hippocampus ; metabolism ; Male ; NF-kappa B p50 Subunit ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Sex Factors ; Stress, Physiological ; Transcription Factor RelA ; metabolism

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 assess the safety, immunogenicity and efficacy of group A and C meningococcal polysaccharide vaccine (A/C MPV) in response to an outbreak of group C meningococcal disease. Methods A vaccination campaign with A/C MPV was prompted 6 weeks after the use of group A MPV in Laibin city, Guangxi, where an outbreak of group C meningococcal meningitis occurred in 2002.Vaccinees were observed for local and systemic reactions after the vaccination and followed up for the meningococcal disease for 5 years. Blood samples were collected from 71 people in the epidemic and 43 in the non-epidemic areas before and 1 month after the vaccination and examined by ELISA to detect IgG antibodies to group A and C polysaccharides. Results The vaccination coverage was 97%. No significant adverse reactions were observed. The positive rates of group C antibodies after vaccination was between 97.67% and 100% among the populations in the epidemic and non-epidemic areas, as well as among those negative and positive for group C antibodies prior to the vaccination.The geometric mean anti-C concentrations ranged 30.81 μg/ml to 37.44 μg/ml, showing no significant difference between groups. The incidence rate of meningococcal disease in students with timely immunization (218.58/100 000) dropped by 69.02% , when compared to that in those with delayed immunization (705.72/100 000). No clinical cases were identified during the follow-up period of 15 760 person-years. Conclusion The vaccination campaign with the Chinese group A/C MPV seemed successful in controlling the group C meningococcal outbreak.The vaccine was shown to be safe even administered after the group A vaccine only 6 weeks apart. It could induce high levels of antibodies in vulnerable population and significantly increase antibody levels in seropositive individuals, thus providing a protection of at least 5 years.

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