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Objective To investigate the influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in patients with severe acute pancreatitis(SAP), and to establish a predictive model. Methods A retrospective analysis was performed for the clinical data of 163 patients who were admitted to the intensive care unit and the emergency intensive care unit due to SAP in The First Affiliated Hospital of Guangxi Medical University from May 2012 to May 2022, and according to the diagnostic criteria for PICS, these patients were divided into PICS group (65 SAP patients with PICS) and non-PICS group (98 SAP patients without PICS). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Variance inflation factor and correlation matrix heatmap were used to evaluate multicollinearity between variables, and Lasso regression and multivariate logistic regression were used to identify independent risk factors and establish a nomogram predictive model. The receiver operating characteristic (ROC) curve, the calibration curve, and the Hosmer-Lemeshow goodness-of-fit test were used for the internal validation of the model, and the decision curve was used to evaluate the clinical practicability of the model. Results The univariate analysis showed that there were significant differences between the PICS group and the non-PICS group in mean arterial pressure, hemoglobin, hematocrit (HCT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), blood urea nitrogen, creatinine, Glasgow coma score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, acute respiratory distress syndrome, acute kidney injury (AKI), acute liver injury, hypovolemic shock, sepsis, intra-abdominal hypertension, intra-abdominal hemorrhage, and multiple organ dysfunction syndrome (all P < 0.05). The Lasso regression analysis showed that related predictive variables included PLR, HCT, APACHE Ⅱ, SOFA, mechanical ventilation, AKI, hypovolemic shock, and intra-abdominal hypertension, and the multivariate logistic regression analysis showed that PLR (odds ratio [ OR ]=1.006, P < 0.05), mechanical ventilation ( OR =4.324, P < 0.05), AKI ( OR =3.432, P < 0.05), and hypovolemic shock ( OR = 6.910, P < 0.05) were independent risk factors for PICS in patients with SAP. Model fitting was performed for the above factors, and bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.874 (95% confidence interval: 0.822-0.925); the calibration curve of the model was close to the reference curve, and the Hosmer-Lemeshow goodness-of-fit test showed that the model was well fitted ( χ 2 =8.895, P =0.351). The decision curve analysis showed that the predictive model had good clinical practicability. Conclusion PLR, mechanical ventilation, AKI, and hypovolemic shock are independent risk factors for PICS in patients with SAP, and the nomogram model established has good discriminatory ability, calibration, and clinical practicability.
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ObjectiveTo investigate the value of early fluid resuscitation endpoints in evaluating blood volume in patients with acute pancreatitis. MethodsA retrospective analysis was performed for the clinical data of 445 previously untreated patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Guangxi Medical University from 2003 to 2016 and had an onset time of less than 24 hours, and according the fluid resuscitation endpoints of mean arterial pressure (MAP), hematocrit (HCT), and blood urea nitrogen (BUN), the patients were divided into standard-reaching group (MAP ＞65 mm Hg, BUN ＜7.14 mmol/L, and HCT ≥0.35 and ≤044, n=219) and non-standard-reaching group (MAP ≤65 mm Hg or BUN ≥7.14 mmol/L or HCT ＞0.44 or ＜0.35, n=226). The standard-reaching group represented normal volume, while the non-standard-reaching group represented insufficient volume. The two groups were compared in terms of symptoms, signs, etiology, severity, complication, and prognosis. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of continuous data between two groups. ResultsCompared with the standard-reaching group, the non-standard-reaching group had significant increases in white blood cell count, BUN, and Computed Tomography Severity Index of the pancreas (Z=-2.85, -6.725, and -2.293, all P＜0.01). As for local complications, compared with the non-standard-reaching group, the standard-reaching group had significantly lower incidence rates of peripancreatic exudation (45.2% vs 54.9%, χ2=4.15, P＜0.05) and pancreatic necrosis (10.0% vs 186%, χ2=6.59, P＜0.05). As for systemic complications, compared with the non-standard-reaching group, the standard-reaching group had significantly lower incidence rates of acute respiratory distress syndrome (ARDS) (0.5% vs 4.4%, χ2=7.26, P＜0.05) and renal dysfunction (1.4% vs 6.6%, χ2=7.95, P＜0.05). The standard-reaching group had significantly lower proportion of patients with severe pancreatitis and hospital costs than the non-standard-reaching group (both P＜0.05). ConclusionFluid resuscitation endpoints can be used to evaluate the blood volume of patients with acute pancreatitis in the early stage after admission, and the patients not reaching the standard of fluid resuscitation tend to develop the complications such as peripancreatic exudation, pancreatic necrosis, ARDS, and renal dysfunction and may have higher hospital costs.
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Acute pancreatitis (AP) is a common gastrointestinal disease and may lead to local complications and even multiple organ failure, and the pathogenesis of AP involves self-digestion of trypsin, inflammatory response, and microcirculation disturbance. This article introduces the role of pyroptosis in the pathogenesis of AP and briefly describes the activation pathway of pyroptosis, inflammasome, and the mechanism of action of effector molecules in inducing damage to the pancreas and extra-pancreatic organs. It is believed that the regulation of pyroptosis plays an important role in the pathogenesis of AP, which provides new ideas for the prevention and treatment of AP.
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ObjectiveTo investigate the clinical features of severe acute hypertriglyceridemic pancreatitis (HTGP). MethodsA retrospective analysis was performed for the clinical data of 179 patients with moderate severe pancreatitis (MSAP) or severe acute pancreatitis (SAP) who were admitted to The First Affiliated Hospital of Guangxi Medical University from January 2013 to June 2016. According to the etiology, these patients were divided into severe biliogenic acute pancreatitis (biliogenic AP) group with 68 patients, severe alcoholic acute pancreatitis (alcoholic AP) group with 39 patients, severe acute HTGP group with 45 patients, and severe acute pancreatitis group with other causes (other group) with 27 patients. Related data of the patients with clear causes in the former three groups were recorded, including demographic data, blood triglyceride (TG) level on the first day of admission, cause, pancreatic necrosis, systemic complications ［acute respiratory distress syndrome (ARDS), acute renal injury, hypotension, and disseminated intravascular coagulation (DIC)］, and related clinical outcomes (admission to the intensive care unit, length of hospital stay, and mortality rate). In order to investigate the influence of TG concentration on the prognosis of AP patients, the patients were divided into normal blood lipid group with 82 patients, mild dyslipidemia group with 52 patients, moderate dyslipidemia group with 28 patients, and severe dyslipidemia group with 17 patients, according to the TG level on the first day of admission, and the incidence rates of systemic complications, pancreatic necrosis, and clinical outcomes were analyzed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, the chi-square test was used for comparison of categorical data between groups, and the Spearman rank correlation test was used for correlation analysis. ResultsBiliary tract disease remained the leading cause of SAP (38%), followed by hypertriglyceridemia (25%). As for systemic complications, the HTGP group had a significantly higher incidence rate of ARDS than the biliogenic AP group and the alcoholic AP group (P=0.014 and 0022). In the groups with different TG levels, the incidence rates of ARDS and acute renal injury were positively correlated with TG level (r=0.966 and 0.982, P=0.004 and 0.019). ConclusionThe HTGP group has a higher incidence rate of ARDS than the biliogenic AP group and the alcoholic AP group, and the risk of ARDS and acute renal injury tends to increase with the increasing TG level.
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Objective To explore the expression and function of myosin light streptokinase (MLCK) in small intestine mucosa of acute necrotizing pancreatitis (ANP) rats.Methods Fifty-six male SD rats were randomly assigned to control group and ANP group.A rat model of ANP was reproduced by retrograde injection of 4％ sodium taurocholate into the biliopancreatic duct,while the control group underwent a sham operation.The rats were sacrificed at 6th,12th,24th,48th hour after ANP induction.Serum amylase、TNF α,IL 1β,diamine oxidase (DAO) were measured.The pathological scores in the pancreas and small intestine were observed.The ultrastructure and tight junction (TJ) changes in the small intestine mucosa were observed with an electron microscope.The localization and expression of MLCK in small intestine mucosa was determined by immunohistochemistry method.Results Compared to the control group,the serum amylase,TNF-α,IL-1 β,DAO level,in the ANP group were all significantly increased;[(4 978 ± 1 574) U/L vs (1 176 ± 124))U/L,(47.88 ± 15.85) μg/L vs (17.24 ± 1.99) μg/L,(132.48 ± 68.54) μg/L vs (23.51 ± 6.44) μg/L,(95.96 ± 30.84)μg/L vs (38.06 ± 17.73)U/L at 12 h],and the pathology scores of pancreas and small intestine were both significantly elevated [12 h:(12.2 ± 1.80) vs (4.68 ± 0.35),(2.58 ± 0.52) vs (0.58 ±0.26)] (P ＜0.05);the MLCK protein expression in small intestine mucosa was significantly increased in ANP group (12 h:0.1863 ± 0.0230 vs 0.1636 ± 0.0049),and the difference was statistically significant (P ＜0.05).The small intestine ultrastructure was seriously damaged and TJ was widened significantly in ANP Group.Conclusions The increased serum TNF alpha and IL-1β concentration and DAO activity and up-regulated MLCK protein expression in small intestine mucosa may damage the integrity of tight junction of intestinal epithelial cell and cause intestine mucosa barrier dysfunction.
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Objective To observe the expression of adrenomedullin (ADM) mRNA in hepatic tissue of rats with acute necrotizing pancreatitis (ANP) complicated with hepatic injury.Methods Sixty-four SD rats were randomly divided into control group and ANP group with 32 rats in each group.In ANP group,ANP model was induced by retrograde injection of 5％ sodium taurocholate into biliopancreatic duct of rats.Rats in control group only received sham operation and pancreas manipulation.All the rats were sacrificed at 3,6,12,24 h after the operation.The serum levels of amylase,alanine aminotransferase (ALT),aspartate aminotransferase (AST) and ADM were detected.Pathological changes in pancreatic and hepatic tissue were examined.The expressions of ADM mRNA in hepatic tissue were evaluated by fluorescence quantitative PCR.Results The serum concentrations of amylase,ALT,AST were (7229 ±968),(174.2 ±28.0),(657.7 ± 139.0) U/L,which were significantly higher than those in control group [(2036 ± 292),(104.3 ± 22.1),(419.7 ± 86.3) U/L],and the difference between the two groups was statistically significant (P ＜ 0.05 or P ＜0.01).Pathological injury of pancreas and liver tissue in ANP gradually aggravated with time,and the pathological scores at 12 h were (11.60 ± 1.51),(2.60 ± 0.89),which were significantly higher than those in control group (1.20 ± 0.77,0),and the difference between the two groups was statistically significant (P＜0.01).The serum concentrations of ADM in ANP group increased at 3 h after ANP induction,and reached (38.53 ± 6.25)pg/ml at 12 h,which was significantly higher than that in control group [(28.99 ±3.92)pg/ml] ; the concentrations of ADM in liver tissue increased at 3 h after ANP induction,and reached (3.00 ± 1.49) at 6 h,which was significantly higher than that in control group (1.04 ± 0.20),and the difference between the two groups was statistically significant (P＜0.05 or P＜0.01).Conclusions The expression of ADM mRNA in rat 's hepatic tissue increases in the early stage of ANP,and the serum concentration of ADM also increases.
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Objective To investigate the roles of toll like receptor7 (TLR7) and toll like receptor 9 (TLR9) in the pathogenesis of acute pancreatitis.Methods AR42J cells were treated by lipopolysaccharide at different dosages (0,1,10,100 mg/L),and cell model of acute pancreatitis in vitro was established.AR42J cells without lipopolysaccharide treatment were as control.Cells and culture supernatant were collected after 24 hours cultivation.TLR7,TLR9 mRNA and protein expressions were detected by RT-PCR and Western Blot,and levels of TNF-α,IL-10 in culture supernatant were measured by ELISA.Results The TLR 7 mRNA expression levels in control group,1,10,100 mg/L lipopolysaccharide group were 0.12 ± 0.09,0.28 ± 0.06,0.49 ± 0.04,0.78 ± 0.04,and the TLR9 mRNA expression levels were 0.06 ± 0.02,0.32 ± 0.03,0.56 ± 0.14,0.84 ± 0.12; the TLR7 protein expression levels were 0.04 ± 0.01,0.26 ± 0.05,0.49 ±0.04,0.77 ±0.16,and the TLR9 protein expression levels were 0.10 ±0.14,0.62 ±0.23,1.21 ± 0.26,1.75 ± 0.13 ; the TNF-α levels in culture supernatant were (8.01 ± 5.32),(25.64 ± 8.71),(49.06 ± 10.23),(75.83 ± 6.65) ng/L,and the IL-10 levels were (155.54 ± 25.47),(105.16 ± 10.49),(69.36 ± 8.19),(14.07 ± 9.06)ng/L.The expression levels of TLR7 and TLR9's mRNA,protein in cell,as well as the levels of TNF-α in culture supernatant increased with the lipopolysaccharide concentration,while the levels of IL-10 in culture supernatant decreased with the lipopolysaccharide concentration,and the difference among these groups was statistically significant (P ＜ 0.01).Conclusions The expressions of TLR7 and TLR9 in AR42J cells treated by using lipolysaccharide are obviously up-regulated,and it suggests that TLR7 and TLR9 may be vital in the pathogenesis of acute pancreatitis.
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Objective To investigate the clinical value of the Classification of acute pancreatitis2012.Methods Medical records and clinical data of patients with acute pancreatitis (AP) who were admitted to First Affiliated Hospital of Guangxi Medical University between October 2009 and September 2012 were retrospectively reviewed and analyzed.Patients were divided into mild acute pancreatitis (MAP),moderately severe acute pancreatitis (MSAP),and severe acute pancreatitis (SAP) groups according to the Classification of acute pancreatitis-2012.The number of improved and cured patients,length of hospital stay,hospitalization costs,rate of ICU admission,length of ICU stay,incidence of SIRS,and length of SIRS continue,Ranson scores,APACHE Ⅱ scores,computed tomographic severity index (CTSI) scores among the 3 groups were compared.Results One hundred and sixty-six patients with AP (119 males and 47 females) were included,and 76 were MAP,65 MSAP and 25 SAP.The average interval between AP onset and hospital admission was (2.27 ± 1.46) d.The number of improved and cured patients,length of hospital stay,hospitalization costs,rate of ICU admission,length of ICU stay,incidence of SIRS,and length of SIRS continue,Ranson scores,APACHE Ⅱ scores,CTSI scores increased with the severity of AP.The corresponding values in SAP group were 21 cases (84.0％),(23.8 ± 13.6) d,(53900 ± 30260) Yuan,48.0％ (12/25) and (5.76 ± 13.8) d,96.0％ (24/25) and (5.00 ± 2.40) d,(3.76 ± 1.30) score,(8.52 ± 4.24) score,(5.44 ± 3.48) score.Seventy-nine patients developed local complications,among them 34 was acute peripancreatic fluid collection,45 was acute necrosis collection.The incidence of acute necrosis collection in SAP group was significantly higher than that in MSAP group (68.0％ vs 44.6％,P =0.047),but the incidence of acute peripancreatic fluid collection in SAP group was significantly lower than that in MSAP group (16.0％ vs 46.2％,P =0.016).Organ failure occurred in 42 patients,among them 35 cases were respiratory failure,2 cases were renal failure,and 5 cases were respiratary and renal failure.The incidence of organ failure in SAP and MSAP group was 100％ and 26.2％,the difference between the two groups was statistically significant (P ＜ 0.05).Conclusions Classification of acute pancreatitis-2012 is a simple and convenient system,which can predict the severity of AP and appropriate for clinical application.
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Objective To observe the expression of ghrelin and growth hormone secretagogue receptor (GHSR) in pancreas of rats with acute necrotizing pancreatitis (ANP),and investigate the role of ghrelin in the pathogenesis of ANP.Methods Seventy SD rats were randomly divided into ANP group (n =35) and control group (n =35).ANP model was induced by retrograde injection of 4％ sodium taurocholate into the biliary and pancreatic duct.Rats in the control group underwent laparotomy with gentle pancreas manipulation only.At 3,6,12,24,48 h after ANP induction,the rats were sacrificed,and the serum level of amylase was determined,pathological changes in pancreatic tissue were routinely observed and scored.The expressions of ghrelin mRNA,protein and GHSR mRNA,protein in pancreas were evaluated by RT-PCR and Western blot.Results Serum amylase level began to increase at 3h after sodium taurocholate injection and reached the peak value at 6 h [(8244 ± 2950) U/L],which was significantly higher than that in control group (P ＜ 0.05).Pancreatic injuries was aggravated with time,the pathologic score at 24 h was (11.91 ± 1.31) score,which was significantly higher than (3.12 ± 1.60) score in the control group.The expressions of ghrelin mRNA and GHSR mRNA in pancreas of ANP group were increased gradually with time,and were significantly higher than those of control group at all time points,at 48 h,1.29 ±0.64 vs 0.58 ±0.05 and 0.94 ±0.16vs 0.19 ±0.03,P ＜ 0.05.The expressions of ghrelin protein and GHSR protein in pancreas of ANP group were significantly higher than that in control group at 12,24,48 h.at 48 h,3.05 ± 0.48 vs 2.18 ± 0.23 and 2.34 ± 0.32 vs 1.55 ± 0.10 (P ＜ 0.05).Conclusions The expressions of ghrelin mRNA,protein and GHSR mRNA,protein of pancreas are significantly increased in rats of ANP,and are associated with the severity of ANP.
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Objective To investigate the expression of pancreatic thioredoxin-1 (TRX-1) in rats with acute necrotizing pancreatitis (ANP) and the effect of pretreatment of melatonin on its expression. Methods Male Spraque-Dawley rats (n = 12) were randomly divided to ANP group, melatonin group, control group with 24 rats in each group. The rats in ANP group received three intraperitoneal injections of 25 ml/kg body weight 6% L-arginine at an interval of 1 h to induce ANP. The rats in melatonin group received intraperitoneal injections of 25 ml/kg body weight 6% melatonin 30 min before ANP induction; rats in ANP group and control group received intraperitoneal injections of same amount of saline. Rats were sacrificed at 6 h, 12 h and 24 h after ANP induction. The serum level of amylase was measured and the pathological evaluation of pancreatic tissues was performed. The concentrations of malondialdehyde (MDA) and myeloperoxidase (MPO) in pancreatic tissues were measured. The expressions of TRX-1 protein were detected by immunohistochemistry and the expressions of TRX-1 mRNA in pancreatic tissues were determined by RT-PCR.Results In ANP group, serum level of amylase, MDA, MPO, TRX-1 mRNA and TRX-1 protein in pancreatic tissues were (3 012 ±1 425) U/L, (4.13 ± 1. 85)nmol/mg prot,(7.45 ± 1.26)nmol/mg prot, 0.68 ±0. 18, 66.8 ±8. 1, while they were (1 835±499)U/L, (3.03 ±2.12) nmol/mg prot, (5. 32 ± 1.06) nmol/mg prot, 0.50±0.09, 80. 29 ±8. 14, respectively in melatonin group, the values in melatonin group were significantly lower thanthose in ANP group (P < 0.05). The peak value of TRX-1 mRNA and TRX-1 protwein expressions shifted from 12 h after ANP induction in ANP group to 6 h after ANP induction in melatonin group. Conclusions The expression of pancreatic TRX-1 protein and TRX-1 mRNA in rats with ANP was significantly increased. Melatonin pretreatment could promote pancreatic tissues to express TRX-1 protein and TRX-1 mRNA, and may be protective for pancreatic tissues damages.
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Objective To investigate the effects of recombinant human interleukin(IL)-10 on serum interleukin-1? in L-arginine-induced acute necrotizing pancreatitis of rats.Methods Ninty-two Sprague-Dawley rats were randomly divided into three groups.Group A(n=36) and Group I(n=32) received three intraperitoneal injections of 6% L-arginine(1.0 mg/g) at hourly intervals.Group I(n=32) was treated with 10,000 unites of intraperitioneal recombinant human IL-10 at the 2nd,5th and 8th hour after the last injection of L-arginine.Group C(n=24) received saline alone.Rats were killed at the 4th,12th,24th and 36th hour after the last L-arginine injection.Serum interleukin-1? and amylase were assayed.Pancreatic tissues were examined histopathologically by microscopy.Results Serum amylase,interleukin-1? and pancreatic histopathological scores in group A increased significantly after L-arginine injection(P