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【Objective】 To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization. 【Methods】 A two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) summary data. The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database (version R9). Causal relationship between education level and pancreatitis was explored using the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Heterogeneity and directional pleiotropy were evaluated using Cochran’s Q test and funnel plots. 【Results】 Totally 604 SNPs associated with education level were included. The results provided evidence that there was negative relationship between education level and pancreatitis risk. For acute pancreatitis, OR=0.52, 95% CI: 0.44-0.62, P=2.43×10-14 while for chronic pancreatitis, OR=0.51, 95% CI: 0.41-0.64, P=7.20×10-9. Results from MR-Egger and weighted median analyses obtained the same results. The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization. 【Conclusion】 There is a causal relationship between education level and the occurrence of pancreatitis. The educational level is negatively correlated with the risk of pancreatitis.
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Objective:To analyze the clinical characteristics of acute pancreatitis.Methods:The retrospective case-control study was conducted. The clinical data of 558 patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from June 2015 to June 2023 were collected. There were 352 males and 206 females, aged (46±15)years. Observation indicators: (1) general situations of acute pancreatitis patients; (2) etiology of acute pancreatitis patients; (3) severity of acute pancreatitis patients; (4) chronic diseases in acute pan-creatitis patients; (5) complications in acute pancreatitis patients; (6) subgroup analysis of patients with recurrent acute pancreatitis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Bonferroni correction was used for pairwise comparison. Results:(1) General situations of acute pancreatitis patients. There were significant differences in gender, age, total duration of hospital stay, smoking, and alcohol consumption between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (2) Etiology of acute pancreatitis patients. There were significant differences in gallstones and hyperlipidemia between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (3) Severity of acute pancreatitis patients. Of the 443 patients with first episode of acute pancreatitis and 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pan-creatitis were 320 and 83, 24 and 9, 99 and 23, showing no significant difference between them ( P>0.05). (4) Chronic diseases in acute pancreatitis patients. There were significant differences in com-plication as hyperlipidemia, fatty liver and diabetes between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (5) Complications in acute pancrea-titis patients. There was no significant difference in terms of acute necrotic collection, acute peripan-creatic fluid accumulation, walled-off necrosis, pancreatic pseudocyst, infectious pancreatic necrosis, systemic inflammatory response syndrome, respiratory system complications, circulatory system complications, renal complications, sepsis, abdominal compartment syndrome, or pancreatic ence-phalopathy between the first episode of acute pancreatitis patients and the recurrent acute pancrea-titis patients ( P>0.05). (6) Subgroup analysis of patients with recurrent acute pancreatitis. ① Combination with chronic diseases. Of the 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pancreatitis were 83, 9, 23, and there were 25, 8, 11 cases of them with hyperlipidemia, respectively, showing a significant difference among them ( P<0.05). ② Complications. Of the 115 patients with recurrent acute pancreatitis, there were 44 cases with hyperlipidemia and 71 cases without hyper-lipidemia, and there were significant differences in acute peripancreatic fluid accumulation and renal complications between them ( P<0.05). Conclusions:Recurrent acute pancreatitis is more common in males. Compared with first episode of acute pancreatitis, cases with recurrent acute pancreatitis usually have younger age, shorter total duration of hospital stay, higher proportion of smoking and drinking. The etiology of recurrent acute pancreatitis is composed of lower levels of biliary diseases and higher levels of hyperlipidemia. Patients with recurrent acute pancreatitis have higher proportion of comorbidities as hyperlipidemia, fatty liver and diabetes. There was no signifi-cant difference in the incidence of complications between first episode of acute pancreatitis and recurrent acute pancreatitis. Compared with recurrent acute pancreatitis patients without concomi-tant hyperlipidemia, recurrent acute pancreatitis patients with concomitant hyperlipidemia are more prone to acute peripancreatic fluid accumulation and renal complications.
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【Objective】 To investigate the effects of resveratrol on gemcitabine chemotherapy in pancreatic cancer and the possible molecular mechanism. 【Methods】 Gemcitabine resistant cell lines were screened by continuous low concentration increasing induction. High-throughput RNA-seq was used to analyze the differential expression enrichment pathway, COMET assay was used to detect DNA damage, Western blotting was used to detect related pathway indicators, and Chou-Talalay was used to calculate drug combination synergistic index. AutoDock predicts docking targets for small molecules and proteins. 【Results】 DNA damage repair related pathways were activated in drug-resistant cell lines compared with their parents. Resveratrol enhanced the DNA damage effects induced by gemcitabine (P<0.01). Resveratrol inhibited the expression of PARP1, a key molecule of DNA damage repair, and played a synergic effect with gemcitabine (CI<1). Resveratrol has docking targets with the CAT domain of PARP1. 【Conclusion】 Resveratrol can inhibit PARP1, a key molecule of chemotherapy resistance, and has a synergistic effect with gemcitabine in pancreatic cancer chemotherapy.
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Objective To investigate the inhibitory effect of Allicin on the apoptosis of hippocampal neurons induced by lead in rats.Methods Sixty male Sprague-Dawley rats aged 3 weeks were randomly divided into 6 groups,10 rats in each group,which were low dose group(A-L),medium-dose group(A-M) and high dose (A-H) Allicin group and lead exposure group (Pb group),dimercaptosuccinic acid (DMSA) group and blank control group.The blank control group animals were treated with ultrapure water,and the other 5 groups received 1.0 g/L lead acetate aqueous solution instead of ultrapure water after 20 days and they were treated them with compounds by oral gavage.The doses of Allicin in group A-L,A-M group and A-H group were 2.7 mg/kg and 5.4 mg/kg,and 10.8 mg/kg,respectively.The DMSA dose was 10.8 mg/kg,and the Pb group was given 9 g/L saline.After the model was established,the rats were sacrificed to collect whole blood and hippocampus.Blood lead and tissue lead concentrations were measured,and the level of apoptosis in hippocampus was observed by TUNEL staining.The levels of cysteine-containing aspartate-specific proteases (caspase)-3,caspase-9,poly adenosine diphosphate-ribose polymerase (PARP) mRNA and caspase-3,caspase-9,PARP activated protein and cytochromes C distribution in the hippocampus cells were detected by using real-time quantitative PCR (qPCR),Western blot,and immunofluorescence staining.Results (1) Lead levels in the blood lead and hippocampus of rats in A-L group,A-M group and A-H group [(190.54±11.33) μg/L,(0.28 ±0.03) μg/L;(159.55 ±16.94) μg/L,(0.22 ±0.06) μg/L;(l16.62 ±8.85) μg/L,(0.19 ±0.01) μg/L] were lower than those in Pb group [(271.34 ±21.23) μg/L,(0.31 ±0.04) μg/L],and there were significant differences (all P ＜ 0.05).The blood lead and hippocampal lead levels in the DMSA group [(50.12 ± 7.44) μg/L,(0.15 ± 0.03) μg/L] were lower than those in the A-L group,A-M group and A-H group.(2) The results of TUNEL staining showed that the apoptosis levels of hippocampus in A-L group,A-M group and A-H group were lower than that in Pb group [(2.81 ±0.17)％,(2.08 ±0.28)％,(1.33 ±0.08)％ vs.(4.23 ±0.17)％],and there were significant differences (all P ＜ 0.05);the apoptosis level of hippocampus in the DMSA group [(2.63 ± 0.32) ％] was higher than that in the A-M group and the A-H group,which was lower than that in the Pb group.(3) qPCR results showed that the levels of caspase-3,caspase-9 and PARP mRNA in A-H group were down-regulated compared with Pb group (1.07 ± 0.05,1.02 ± 0.02,1.11 ± 0.02 vs.1.34 ± 0.02,1.26 ±0.05,1.93 ± 0.07).The differences were statistically significant (P ＜ 0.05).The expression levels of caspase-3 and PARP mRNA in A-L group and A-M group were down-regulated (1.21 ± 0.05,1.43 ± 0.12,1.16 ± 0.02,1.20 ± 0.06 vs.1.34 ± 0.02,1.93 ± 0.07),and there were significant differences (all P ＜ 0.05),and there was no significant change in caspase-9 mRNA;the mRNA levels of caspase-3,caspase-9 and PARP in A-H group (1.07 ± 0.05,1.02 ± 0.02,1.11 ± 0.02) were lower than those in DMSA group (1.14 ± 0.02,1.15 ± 0.08,1.32 ±0.05).(4) Western blot results:compared with Pb group,the expression levels of activated caspase-3,caspase-9 and PARP protein in A-H group were down-regulated (A-H group:0.44 ± 0.15,0.58 ± 0.25 and 0.31 ±0.19,0.23 ±0.07 vs.Pb group:0.69 ±0.13,0.72 ±0.22 and 0.55 ±0.21,0.43 ±0.10),the expression of activated caspase-9 protein in A-M group was lower than that in Pb group (A-M group:0.59 ±0.18 vs.Pb group:0.72 ± 0.22),and there were significant differences (all P ＜ 0.05);the expression of activated caspase-3 and RARP protein in A-H group was lower than that in DMSA group.(5) Fluorescence staining showed that the expression of cytochrome C in cytoplasm of A-L group,A-M group and A-H group were significantly lower than that of Pb group and DMSA group.Conclusion Allicin can inhibit the apoptosis of hippocampus cells in rats with lead poisoning through mitochondrial pathway.The effect of Allicin on apoptosis inhibition may be better than DMSA.
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Objective To summarize the methods of diagnosing and treating solid-pseudopapillary neoplasm of pancreas SPN so as to provide reference for its early clinical diagnosis.Methods We collected the clinical data of 62 patients with pathologically confirmed diagnosis of SPN treated in the First Affiliated Hospital of Xi'an Jiaotong University between Feb.2004 and Sep.2014.Then we retroactively analyzed and summarized the clinical characteristics,diagnosis and treatment of the disease.Results Among the 62 patients,55 were female and 7 were male;the mean age was (31.58±12.67) years old.The clinical features showed no specificity and the tumor was mostly detected upon physical check-up.The tumor was seen to be located mostly in the body and tail of the pancreas,and the average maximum diameter was (7.81±3.54)cm.We did not find obvious abnormality in routine pre-operative blood test results or liver and kidney functions.The imageological examination indicated tumor occupation in the pancreas.All the patients underwent surgical resection with no complications or death and had a good recovery after operation.Pathological diagnosis after operation was SPN without metastasis in lymph modes.Until the last time we followed up all the patients,we found relapse in two patients (3.2％).Conclusion SPN is a tumor that tends to affect young and middle-aged females.The malignancy grade of SPN is low,and patients with this disease show no specificity in clinical manifestation.The imageological examination is of vital importance in diagnosing SPN and surgical resection is an effective way to treat SPN.