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OBJECTIVE@#To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP).@*METHODS@#A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence.@*RESULTS@#The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05).@*CONCLUSIONS@#The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.
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Humans , Polymorphism, Single Nucleotide , Prospective Studies , Vitamin D-Binding Protein/genetics , Acute Disease , Pancreatitis/genetics , Genotype , PrognosisABSTRACT
Objective:To investigate the therapeutic effect of exosomes divided from bone marrow mesenchymal stem cell (BMSC) on pancreatic cancer in vivo through regulation of tumor-associated macrophages (TAM) polarization.Methods:Ten male C57BL/6 mice weighing approximately 20 g, ages 4 weeks, were used for BMSC exosomes extraction and PKH26 labelling. Thirty female SPF BALB/c-nu/nu nude mice weighing approximately (18.56±0.85) g, ages 4-6 weeks, were adopted for pancreatic carcinoma models. The models were randomly divided into 3 groups with 10 in each: control group (injected with PBS through tail vein), portal vein treatment group (injected with exosomes in PBS through portal vein), tail vein treatment group (injected with exosomes in PBS through tail vein). After the models were executive 8 weeks later, the percentage of PKH26 positive-exosomes in pancreas tissue was quantified by flow cytometry technique. The volume of the primary pancreatic tumor, the tumor volume of inhibitory rate, the number of metastatic nodule, and the ascitic fluid were assess. Also, the weight of liver and the tumor weight were evaluated. The expression of M1 and M2 macrophage-activate biomarkers and the content of pancreatic cancer marker B7-H4 tumor carbohydrate antigen 199 in peripheral blood was detected. Moreover, the expression of Survivin and matrix metalloproteinase-9 (MMP-9) in pancreatic cancer tissue cells was also detected.Results:There was no significant difference for the tumor volume of inhibitory rate between portal vein treatment group (72.4±21.6)% and tail vein treatment group (70.1±20.7)% ( t=0.24, P=0.811). Compared with control group, the volume of the primary pancreatic tumor, the weight of liver, the tumor weight, the number and rate of liver metastatic nodule, the ascitic fluid, and the number of other metastatic nodule were totally lower in the 2 treatment groups with significant difference (all P<0.05). Compared with the control group, iNOS and CD68 in portal vein treatment group and tail vein treatment group were increased, while Arginase, CD206, B7-H4, tumor carbohydrate antigen 199, Survivin and matrix metalloprotein-9 were decreased, with statistically significant differences (all P<0.05). Conclusion:Exosomes derived from BMSC can inhibit the polarization of TAM to the M2 phenotype and induce their polarization to the M1 phenotype, thereby suppressing the proliferation, invasion and migration of pancreatic cancer.
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Objective:To investigate the therapeutic effects and mechanism of bone mesenchymal stem cells(BMSCs)transplantation in the pancreas injury of chronic pancreatitis of rats.Methods:Based on the transplantation methods, all the rats were divided into 5 groups with 10 rats in each: control group, model group, submesopancreas treatment group, portal vein treatment group, tail vein treatment group. The pancreatic fibrosis and pathological score were evaluated. The percentage of PKH26, Pax4, Ngn3 positive-BMSCs in the pancreas, the percentages of double-labeled cells (PKH26 + /Pax4 + , PKH26 + /Ngn3 +) and the expression of α-SMA, collagen type I and III, IL-10 in pancreas were detected. Results:The pancreatic fibrosis and pathological score in treatment group were significantly lower than that of model group (both P<0.05). There was no significant difference of pancreatic fibrosis and pathological score in the other 3-treatment group ( P>0.05). The expression of PKH26, Pax4 and Ngn3 in tissues were much higher in the treatment group compared with model group and control group with significant differences (all P<0.05). There was no significant difference for Pax4 and Ngn3 in pancreas among the other 3-treatment group ( P>0.05). There were double-labeled cells (PKH26 + /Pax4 + , PKH26 + /Ngn3 +) with no significant differences among 3 treatment group ( P>0.05). The expression of α-SMA, collagen type I and III in tissues was lower in treatment group compared with model group with significant difference (all P<0.05), while the level of IL-10 in pancreatic tissue was higher in treatment group compared with model group with significant difference ( P<0.05). There was no significant difference for the expression of α-SMA, collagen type I, collagen type III and IL-10 in tissues among the 3 treatment group (all P>0.05). Conclusions:BMSCs have the therapeutic effects in the treatment of chronic pancreatitis. For the mechanism, the recruitments and engraftment of BMSC contributed to the injury of pancreatic tissue, BMSCs’ promotion to the pancreatic differentiation, and the inhibition of CP inflammation by autocrine or paracrine function.
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Objective To analyze CT findings in adhesive intestinal obstruction caused by different adhesion pattern.Methods Clinical data of 83 adhesive intestinal obstruction cases proved by laparotomy were reviewed.Before surgery two experienced abdominal radiologists randomly double blindly inspected and evaluated the CT findings,as to whether there was intestinal obstruction,the severity of obstruction,the site of obstruction,the adhesion type of obstruction and the diagnosis of strangulated intestinal obstruction,the consensuses were accomplished by discussion.Results The accuracy of diagnosis was 100％ for the existence of obstruction,the severity of obstruction and the site of obstruction.There were intra-abdominal hernia caused by intestinal adhesion (44 cases),a cluster of loop (12 cases),bowel twisted angle (8 cases),the intestine and abdominal adhesions (6 cases),intestinal adhesion contracture stenosis (5 cases),adhesive band compression (4 cases),intestinal volvulus caused by adhesion (1 case).The accuracy,sensitivity,specificity,positive predictive value and negative predictive value of CT in diagnosing strangulated intestinal obstruction were 78％,47％,100％,100％,73％,respectively.Conclusion CT can clearly diagnose different adhesion pattern leading to ileus and ensuing strangulation.