A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Clinical characteristics and prognostic analysis of pancreatic enzyme abnormalities in children / 中华实用儿科临床杂志

Objective:To investigate the etiology, prognosis and clinical characteristics of abnormal serum amylase and lipase in children.Methods:This study was a retrospective study.A total of 7 813 children older than 28 days who had their serum amylase and lipase detected in Hunan Children′s Hospital from August 2017 to August 2020 were included as the study subjects.Children with acute and chronic pancreatitis were excluded.The age, gender, impatient department, imaging exams, discharge outcomes, main diagnosis, diagnostic ICD10 code, and the highest values of serum amylase and lipase during hospitalization were collected through the medical record system.According to the levels of serum amylase and lipase, the children were divided into 3 groups.Patients in group A had normal serum amylase and serum lipase levels.The serum amylase or lipase levels of patients in group B was 1 to 3 times higher than that of group A. The serum amylase or lipase levels in group C was 3 times higher than that of group A. Group B and group C had abnormal pancreatic enzyme levels.According to the prognosis, patients were divided into the survival group and the death group.The relationship of the occurrence of abnormal serum amylase and lipase levels with the age, sex, disease type and prognosis of children was analyzed.Results:The ratio of abnormal trypsin in male and female was 11.5% and 12.9%, respectively.The number of children with abnormal pancreatic enzyme levels in the 28 day -1 year old group, >1-3 years old group, >3-6 years old group, >6 -12 years old group and > 12 year old group were 37 cases (4.6%), 185 cases (15.4%), 199 cases (10.5%), 431 cases (13.9%), and 94 cases (11.7%), respectively.The mortality rate was 1.6% (112/6 867 cases) in group A, 5.2% (32/617 cases) in group B, and 7.6% (25/329 cases) in group C. The mortality risk of group B and C was both higher than that of group A. Compared with group A, the OR (95% CI) of group B and group C was 3.30 (2.21-4.93) and 4.96 (3.17-7.77), respectively.In group C, the top five diseases were parotitis (26.4%), cholangiectasis (11.6%), choledochal cysts (8.5%), gastroenteritis (4.5%) and sepsis (3.3%). Conclusions:Pancreatic enzyme abnormalities in children are associated with adverse prognosis.Pancreatic enzyme abnormalities are more prone to occur in children aged >1-3 with mumps, digestive diseases and congenital digestive system structural deformities.In addition, children with sepsis are also easy to present pancreatic enzyme abnormalities.Clinical attention should be paid to the possibility of secondary pancreatic damage in children with sepsis.

A model study of cecal ligation and perforation for the development of sepsis-induced pancreatic injury / 中国小儿急救医学

Objective:To investigate the changes of inflammatory factors, serum amylase and lipase and pancreatic damage at different time points after establishment of cecal ligation and perforation in a rat model of sepsis, which provides a stable and reliable animal model for the study of pancreatic injury following sepsis in children.Methods:Sixty male SD rats were randomly divided into 6 h group, 12 h group, 24 h group and 48 h group in control group, sham group and cecal ligation and puncture (CLP) group.Rat model of sepsis was established by cecal ligation and perforation in CLP group, the sham group was treated with sham operation, and rats in control group were not treated.The levels of interleukin (IL)-1β, IL-10, amylase and lipase in each group were detected, and pancreatic tissue was taken for HE staining.Results:In this model, the 48 h survival rate of rats in the CLP group was 70%.With the prolongation of postoperative time in the CLP group, pancreatic tissue congestion, cell edema, and inflammatory cell infiltration gradually worsened.The pathological changes of pancreatic tissue in the Sham group were mild.The expression levels of IL-1β in CLP group and sham group increased first and then decreased, and reached the peak at 12 h. The expression levels of IL-1β in CLP group were significantly higher than those in control group and sham group at all time points( P<0.05). The expression level of IL-10 showed a gradually increasing trend, reaching a peak at 48 h. The expression level of IL-10 in CLP group was significantly higher than that in control group and sham group at all time points( P<0.05), which in sham group was significantly higher than that in control group( P<0.05). Serum amylase and lipase in CLP group showed an upward and then downward trend, reaching the peak at 24 h. The serum amylase levels at 24 h and 48 h were significantly higher than those in control group and sham group( P<0.05). Serum amylase levels in sham group were significantly different from those in control group at 12 h, 24 h and 48 h( P<0.05). Serum lipase level at 12 h, 24 h and 48 h was significantly higher than that in control group and sham group( P<0.05). There was no significant difference in serum lipase between sham group and control group( P>0.05). Conclusion:After CLP modeling, IL-1β, IL-10 elevation and pancreatic pathological changes appeared at the early stage, and the pathological changes gradually increased with time.Significant differences in serum amylase and lipase began to appear at 24 h and 12 h respectively.

Management of pancreatic trauma in adult patients: a single centre experience

Background: Pancreatic trauma is very rare and its management is complex. The aim of this study was to report our experience in the management of pancreatic trauma.Methods: All patients who were admitted with pancreatic trauma from May 2017 to May 2019 were reviewed retrospectively. Demographic data and baseline characteristics were recorded. Grading of pancreatic trauma was carried out according to the American Association for surgery for Trauma (AAST). Data were represented by frequency and mean.Results: A total of 24 patients were admitted with pancreatic trauma in the study period. Road traffic accident (n=17) was the leading cause followed by falls (n=5) and assault (n=2). Out of 24 patients, 3 patients had grade I pancreatic injury, 6 patients had grade II AAST injury, 9 patients had grade III injury and 6 patients had grade IV injury. No patients had grade V injury. Mean hospital stay was 12.3±4.2 days. One patient with grade 2 injury underwent surgery for liver laceration, all others were managed conservatively. Patients with grade 3 and 4 injuries were managed conservatively. One patient with grade 3 injury required, cystogastrostomy for pseudocyst 1 month after the index admission. Two patients of grade 4 injury underwent surgery, one patient for traumatic pseudocyst after 1 month and another patient for bleeding pseudoaneurysm of gastroduodenal artery 1 month after trauma. No patient underwent pancreatectomy. There was no mortality in the study population.Conclusions: Pancreatic trauma can be managed conservatively irrespective of the grade of injury in haemodynamically stable patients.

Pancreatic Manifestations in Inflammatory Bowel Disease: A Review Article / 胃肠病学

Some of the patients with inflammatory bowel disease (IBD) can develop symptoms originated from extragastrointestinal organs and systems, and are called extraintestinal manifestations (EIMs). EIMs may be associated with IBD-related injuries or being drug-induced. These manifestations may occur before, after or simultaneously with the diagnosis of IBD. EIMs may detrimentally impact patient's functional status and quality of life. This article reviewed the pancreatic manifestations in patients with IBD and its underlying pathophysiology. EIMs may complicate the course of IBD. The clinicians must pay real attention to EIMs for facilitating the early diagnosis and treatment.

NADPH oxidase participates in pancreatic injury in rats with acute hypertriglyceridemic pancreatitis by regulating Akt/GSK3 β pathway / 中华急诊医学杂志

Objective To investigate the aggravation of pancreatic tissue injury in rats with acute hypertriglyceridemic pancreatitis and the possible role of NADPH oxidase(NOX).Methods Thirty SPF rats were randomly(random number)divided into five groups: N group,H group,NLAP group,HLAP group and HAPO group.AMY,TG,TC and FFA levels were detected.The pathological changes of pancreas were observed under light microscope and the ultrastructural changes of pancreatic acinar cells were observed by TEM.Serum levels of MDA,SOD,LM-1β,TNF-α and LDH were detected.The expression of NOX4,p-Akt and p-GSK3β in pancreas was detected by immunofluorescence,and the expression of NF-κB and TNF-α in pancreas was detected by immunohistochemistry.Results Intraperitoneal injection of P-407 could significantly increase the levels of serum TG,TC and FF A in rats.After acute pancreatitis induced by L-Arg,the levels of serum AMY in the NLAP and HLAP groups were significantly increased,while Apocynin could significantly decrease the level of serum AMY.Compared with the NLAP group,the pathological injury of pancreatic tissue in the HLAP group was more serious,the level of inflammatoty mediators was significantly increased,and the cell necrosis was more serious.After inhibiting NOX,the activation of Akt/GSK3β pathway was regulated and the pancreatic injury was improved.Conclusion In HTGP,NOX aggravates pancreatic injury by regulating the activation of Akt/GSK3 β pathway.Inhibition of NOX expression can play a protective role in pancreas injury of HTGP..

NADPH oxidase participates in pancreatic injury in rats with acute hypertriglyceridemic pancreatitis by regulating Akt/GSK3 β pathway / 中华急诊医学杂志

Objective@#To investigate the aggravation of pancreatic tissue injury in rats with acute hypertriglyceridemic pancreatitis and the possible role of NADPH oxidase (NOX).@*Methods@#Thirty SPF rats were randomly (random number)divided into five groups: N group, H group, NLAP group, HLAP group and HAPO group. AMY, TG, TC and FFA levels were detected. The pathological changes of pancreas were observed under light microscope and the ultrastructural changes of pancreatic acinar cells were observed by TEM. Serum levels of MDA, SOD, IL-1β, TNF-α and LDH were detected. The expression of NOX4, p-Akt and p-GSK3β in pancreas was detected by immunofluorescence, and the expression of NF-κB and TNF-α in pancreas was detected by immunohistochemistry.@*Results@#Intraperitoneal injection of P-407 could significantly increase the levels of serum TG, TC and FFA in rats. After acute pancreatitis induced by L-Arg, the levels of serum AMY in the NLAP and HLAP groups were significantly increased, while Apocynin could significantly decrease the level of serum AMY. Compared with the NLAP group, the pathological injury of pancreatic tissue in the HLAP group was more serious, the level of inflammatory mediators was significantly increased, and the cell necrosis was more serious. After inhibiting NOX, the activation of Akt/GSK3β pathway was regulated and the pancreatic injury was improved.@*Conclusion@#In HTGP, NOX aggravates pancreatic injury by regulating the activation of Akt/GSK3 β pathway. Inhibition of NOX expression can play a protective role in pancreas injury of HTGP..

Sepsis-induced endocrine damage / 中国小儿急救医学

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.Proper endocrine adjustment is required for self-protection of the body during stress conditions; however, decompensation is harmful.It has been proved that violent stress response caused by sepsis can lead to endocrine decompensation and is harmful to children during clinical course and prognosis.

Role of Therapeutic endoscopy vs surgery in the management of traumatic pancreatic injury – A tertiary referral center experience

Background: Pancreatic injury remains a complicated condition requiring an individualized case by case approach to management. In this study, we aim to analyze the varied presentations and treatment outcomes of traumatic pancreatic injury in a tertiary care center. Materials and methods: All consecutive patients hospitalized at our center with traumatic pancreatic injury between 2013 and 2017 were included. The American Association for Surgery of Trauma (AAST) classification was used to stratify patients into five grades of severity. Outcome parameters were then analyzed based on the treatment modality employed. Results: Of the 35 patients analyzed, 26 had an underlying blunt trauma with the remaining 9 presenting due to penetrating injury. Overall in-hospital mortality was 28%. 19 of these patients underwent exploratory laparotomy with the remaining 16 managed non-operatively. 9 patients had severe injury (>grade 3) – of which 4 underwent endotherapy, 3 had stents placed and one underwent an endoscopic pseudocyst drainage. Among those managed non-operatively, 3 underwent a radiological drainage procedure. Conclusion: Mortality rates were clearly higher in patients managed operatively. This is likely a result of significantly higher degrees of major associated non-pancreatic injuries and not just a reflection of surgical morbidity. Despite this, surgical management remains the mainstay of therapy, especially in higher grades of pancreatic injury. However we would like to emphasize that endoscopic intervention definitely remains the preferred treatment modality when the clinical setting permits. This is especially applicable in cases of main pancreatic duct injury with ascites as well as pseudocysts.

The protective effect of nuclear factor-E2-related factor 2 in secondary pancreatic injury in sepsis / 中国小儿急救医学

Sepsis is a major cause of secondra y pancreatic injury in critically ill children.A lagr e number of inflammatoyr m ediators werer elesa ed after acute ijn ury of the pancreas,which may aggravate the inflammatory reaction and the stress reaction.Nuclear factor E2-related factor 2(Nrf2),an important protec-tive transcription factor,could activate the expression of more than 500 genes.Most of the genes have the function of cytoprotection.Studise have dem onts rated that Nrf2 plays a certain role in cytoprotection,such as regulating the inflammatory response,anti-oxidative stress,improving mitochondrial functoi n and decreasing toxic protein aggregation.This review explored the protective mechanism of Nrf2 in pancreatic injury caused by sepis s.

Significance of pancreatic stone protein in pancreatic injury and sepsis / 临床儿科杂志

Pancreatic stone protein (PSP) is the product of exocrine pancreas mainly synthesized and secreted by the pancreas acinar cells, a small amount secreted by gastrointestinal cells. PSP is one of stress protein family members secreted in the pancreas. PSP increased in acute and chronic pancreatitis, diabetes, inlfammatory bowel disease and gastrointestinal tumors. In recent years, some studies showed that PSP has potential clinical value in pancreatic injury and sepsis. In this article, we reviewed the progress of pancreatic stone protein in pancreatic injury and sepsis.

Analysis of related factors for hyperamylasemia in critically ill children / 中华急诊医学杂志

Objective To analyze the clinical features of the hyperamylasemia in critically ill children and investigate the related risk factors in order to provide the basis for prevention and treatment. Methods A total of 1036 critically ill children admitted in pediatric intensive care unit (PICU)from April,2011 to Oct,2012 were studied.They were divided into the high amylase group (n=82)and the normal group (n=954).According to the outcomes,the high amylase group was divided into survival group (n=61 ) and death group (n =21 ).The related risk factors of the occurrence and outcome of hyperamylasemia were analyzed by univariate and multivariate Logistic regression.Results There were statistically significant differences in rates of coagulation disorders, convulsions, disturbance of consciousness,pediatric critical illness score (PCIS)≤80,multiple organ dysfunction (MODS)≥3, sepsis,shock,and lactic acid (LA),procalcitonin (PCT),blood glucose (BG)between the high amylase group and the normal group (P3.Adjusted ORs confidence intervals of them were 1.662 (1.236-2.234),1.042 (1.025-1.060),1.612 (1.411-1.843),3.219 (1.311-7.905),3.411 (1.370-8.494),respectively. The hyperamylasemia's prognostic risk factors were PCT,C-peptide,PCIS ≤80,MODS >3,shock. Adjusted ORs confidence intervals of them were 1.066(1.021-1.113),1.437(1.017 ~2.030),16.137 (1.876-138.836),10.437(1.528-71.925),20.928(1.938-226.009),respectively.Conclusions The severity of the disease,the levels of LA,PCT,BG in critically ill children were positively correlated to the occurrence of hyperamylasemia.The severity of the disease,the incidence of organ failures,the levels of PCT,C-peptide combined shock in children with hyperamylasemia were positively correlated to the prognosis of hyperamylasemia.

Discussion on multiple organ dysfunction syndrome involved with pancreas injury / 中华急诊医学杂志

Objective To explore the clinical characteristics of multiple organs dysfunction syndrome (MODS) complicated with injury of pancreas.Methods A prospective study was carried out.From January 2011 to December 2012,a total of 69 patients with MODS in Department of Medical Intensie Care Unit,Fujian Provincial Hospital,Fujian Medical University were divided into 2 groups at admission.Patients of group A were suffered from MODS complicated with pancreas injury while patients of group B had MODS without complicatios.They were compared and evaluated by acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score,6-hour clearance rate of lactic acid,incidence of shock,fluid resuscitation in the first 24 and 48 hours,bladder pressure and 28-day accumulative mortality.Results APACHE Ⅱ score in group A was significantly higher than that in group B (P ＜ 0.01).Compared with group B,the 6-hour clearance rate of lactic acid was lower,the incidence of shock increased obviously,and larger volume of fluid resuscitation was needed in the first 24 and 48 hours in the group A (P ＜ 0.05).Bladder pressure,incidence of feeble bowel sounds and the mortality in the group A were higher than those in group B,but the difference had no statistical significance (P＞0.05).Conclusions MODS complicated with pancreas injury is more severe than MODS without complications thereby resulting in higher incidence of shock and the poorer response to fluid resuscitation.

Current management of pancreatic trauma.

Background: Although pancreatic trauma is uncommon, it poses a diagnostic and therapeutic challenge. Any delay in diagnosis raises morbidity and mortality. This study highlights the current management and outcome in patients of pancreatic trauma at a single tertiary care center. Methods: This is a retrospective analysis of prospectively collected data of 24 patients diagnosed to have pancreatic trauma. Collected data was analyzed for age, gender, mechanism of injury, hemodynamic status at presentation, initial serum amylase levels, CECT abdomen findings, AAST-OIS grade of pancreatic injury, injury to other organs, management, complications and outcome. Results: The mean age of these 24 patients was 25 years; 19 were male and 5 females. The mechanisms of pancreatic trauma included blunt abdominal trauma in 21 (87.5%) cases and penetrating injury in 3 (12.5%). Seven (29.16%) patients were managed by non-operative management and 17 (70.83%) underwent surgery. Complications were more frequent in the operative group as compared to the non-operative group. Neither endocrine deficiency nor any mortality was noted in the non-operative management group; while there were 2 cases of endocrine deficiency and 3 mortalities in the operative group. Conclusions: Pancreatic trauma is more common in young male patients and more commonly inflicted by motor vehicles accidents. Low grade blunt pancreatic injury in hemodynamically stable patients and selected patients with high grade blunt pancreatic injury can be managed successfully by non-operative management with no increase in morbidity or mortality and most patients with high grade blunt pancreatic injury and those having penetrating injuries need surgical intervention.

Surgical experience and clinical outcome of traumatic pancreatic injury

BACKGROUNDS/AIMS: Traumatic pancreatic injury is rare and various surgical procedures can be applied according to the severity of injury. We reviewed our experience of pancreatic injury and investigated the clinical outcome. METHODS: Fifty-six patients were treated conservatively or with surgery for pancreatic injury at the Department of Surgery, Korea University Medical Center of Korea University College of Medicine from January 2001 to February 2012. RESULTS: Forty-one men and 15 women were included (mean age, 32 years; range, 5-66 years). Twelve patients were hypotensive at admission. According to the American Association for the Surgery of Trauma grade, 15 patients were grade I, 16 were grade II, 10 were grade III, 13 were grade IV, and one patient was grade V. A total of 41 patients underwent exploratory surgery. Complications developed in 35 patients, and 19 patients demonstrated intra-abdominal abscesses associated with pancreatic leakage. Four mortalities occurred. More adult patients (n=42) required intensive care than that of pediatric patients (n=14) (p=0.03). However, more pediatric patients had hyperamylasemia at admission (p=0.023). A significantly higher proportion of patients in the hypotensive group had blunt abdominal injuries, associated extra-abdominal injuries, combined intra-abdominal injuries, longer ICU stays, and a higher mortality rate. CONCLUSIONS: Associated intra-abdominal and extra-abdominal injuries are frequent in patients with traumatic pancreatic injury. Despite the complication rate, most patients recovered. Mortalities were associated with combined injuries being placed into bleeding, hypovolemic shock, and multiorgan failure.

Pancreatic trauma: an analysis of 148 cases / 中华肝胆外科杂志

Objective To explore the early diagnosis, option of the surgical procedures, preven-tion and treatment of the complications in patients with pancreatic trauma.Methods All patients with pancreatic trauma during the past 20 years were studied retrospectively in respect of sex, age, cause of injury, grade by AAST, style of operation, therapeutic efficacy, complications and factors for death etc.Statistical analysis was made with Chi-square test.Results In all 148 cases of the present series, 132 underwent surgical interventions including simple suture or external drainage alone, distal pancre-atectomy, distal pancreaticojejunostomy or other internal drainage, diverticularization, Whipple's pro-cedure, and Damage Control Surgery (DCS) etc.Postoperative morbidity was 27.83% with a signifi-cant difference of the incidence of pancreatic fistula between pancreas grade Ⅲ-Ⅴ injuries and grade Ⅰ-Ⅱ(P＜0.01).The mortality rate was 11.49%.The cause of the deaths was mainly massive bleed-ing due to severe associated injuries(76.47%).Among various grades, the difference of the mortality was not significant (P＞0.05).Conclusion To improve the survival rate, it is important to control massive hemorrhage from associated injuries precedes dealing with pancreas trauma.Selection of surgi-cal procedures should be based on whether the main duct is injured.The removing of devitalized tis-sue, adequate external and internal drainage are essential for treatment of pancreatic injuries.Early recognition of pancreatic injury and correct choice of surgical procedures may obviously decrease the in-cidence of postoperative complications.

Mechanisms of pancreatic injury induced by long-term high-fat diet intake in rats / 中华肝胆外科杂志

Objective To clarify the involvement of the free fatty acids(FFA)and lipid peroxida-tion in rat pancreatic tissue during the development of pancreatic injuries inducecd by long-term high-fat diet.Mehtods The male Sprague-Dawley rats (n=72) were randomized into 6 groups (n=12).One group (group control) received standard chow for 18 weeks, the other five groups (group HFD) were fed with a high-fat diet respectively for 2, 4, 6, 10 and 18 weeks.Serum TG and TCH, the his-topathological changes, pancreatic malondialdehyde (MDA) content, superoxide dismutase (SOD) ac-tivity and the concentration of free fatty acids in pancreatic tissues were examined.Pancreatic fibrosis was assessed using Sirius Red staining.The expression of desmin, a smooth muscle actin (α-SMA), platelet-derived growth factor receptor type β (PDGFRβ) and transforming growth factor131 (TGFβ1) was determined with immunohistochemistry.Results Pancreatic MDA content, the number of desmin and α-SMA positive cells were significantly increased in all the HFD groups.The FFA content, PDGFRβ, and TGFβ1 in pancreatic tissues increased in rats of 2, 4 and 6 week HFD groups accompa-nied with typical histological alternations including edema, capillary vessels hyperplasia, and focal aci-nar degeneration, vaculation of acinar and islet cells.In 6, 10 and 18 weeks HFD groups, the lesions had progressed and acinar cell atrophy, fatty replacement, deposition of hemosiderin, and interstitial collagen deposition were observed.Conclusions The increased amounts of FFA and lipid peroxidant in pancreatic tissues are associated with pancreatic cell injuryies and synthesis of collagen by activated PSCs during the chronic high-fat diet intake.

Role of extracellular regulated kinase signal transduction pathway in the pathogenesis of acute necrotizing pancreatitis / 中华胰腺病杂志

Objective To investigate the changes of extraceUular regulated kinase 1/2 (ERK1/2) phosphorylation and assess the effects of blocking the ERK1/2 phosphorylation on rats with acute necrotizing pancreatitis (ANP). Methods The ANP model was induced by retrograde injection of 5% sodium tanrocholate into the biliary and pancreatic duct. 5 rats were treated as normal control. Other 75 Sprague-Dawley (SD) rots were randomly divided into sham operations(SO) group (n =25), ANP group (n =25) and PD98059 group (n =25). The rats were sacrificed at 15 min, 30 min, 1 h, 3 h and 6 h after ANP induction, the blood and pancreatic sample were taken. Pathological changes of pancreas were observed with light microscope and scored. The serum level of TNF-α and IL-1β was determined by ELISA. MPO activities in pancreas were measured by enzyme chemistry assay. Western blotting was performed to determine the phosphorylations of ERK1/2 in the pancreas homogenates. Results There was no significant pathologic changes in rats of SO group;but significant injuries occurred in ANP group, the pathologic score at 3 h was 9.9 ± 0.4;the extent of injuries attenuated in PD98059 group, the pathologic score at 3 h was 4.0 ± 0.4 (P < 0.05). The serum levels of TNF-α at 3 h in SO, ANP and PD98059 groups were (65.8 ± 20.5) pg/ml, (286.5 ± 50.3) pg/ml, (180.4±32.9)pg/ml, respectively;the serum levels of IL-1β at 3 h in SO, ANP and PD98059groups were (85.8 ± 25.5) pg/ml, (293.8 ± 46.3) pg/ml, (200. 5 ± 33.6) pg/ml, respectively;MPOactivities in pancreas were (0. 19 ± 0.02)U/g, (0.61±0.05)U/g, (0.52±0.03) U/g, and the values in ANP and PD98059 groups were significantly higher than those in SO group, while the values in PD98059 group were significantly lower than those in ANP group (P < 0.01). The expression of ERK1/2 phosphorylation in normal pancreas was 1100 ± 141, the expressions of ERK1/2 phosphorylation in ANP group at 15 min, 30 min were 5300 ± 486, 5621 ± 384, respectively;the expressions began to decrease 1 h later and returned the similar level as SO group at 6 h;the expressions of ERK1/2 phosphorylation in PD98059 group at 15 min, 30 rain were 4200 ± 370, 3600 ± 290, respectively;which were signifieanfly lower than those in ANP group (all P value < 0. 01). Conclusions The ERK1/2 signal transduetion pathway plays an important role in the pathogenesis of ANP. Inhibition of ERK1/2 phosphorylation by PD98059 may decrease the production of IL-1β, TNF-α and pancreatic MPO, attenuate the extent of pancreatic pathologic injuries.

Diagnosis and Treatment of 42 Cases of Multiple Injuries with Pancreatic Injury / 华中科技大学学报（医学）（英德文版）

In order to summarize the clinical diagnosis and treatment methods for 42 cases of mul- tiple injuries with pancreatic injury, a retrospective analysis on 42 cases of multiple injuries with pancreatic injury from January 1990 to January 2006 was carded out in our hospital. Most cases were associated with hemopneumothorax and rib fractures (52.3%), shock (50%), multiple fractures (47.6%), and severe brain injury (26.1%). In 42 cases, one case died of severe hemorrhagic shock, and the remaining 41 cases (97.6%) were cured (including 40 cases receiving surgical operation and one case receiving the conservative treatment). Postoperative complications occurred in 16 cases (21 cases/times): pancreatic fistula (5 cases/times) and incisional wound infection (5 cases/times), in- tra-abdominal infection (3 cases/times), stress ulcer (3 cases/times), pleural effusion (3 cases/times), pulmonary infection (one case) and wound dehiscence (1 case). The principle therapy of multiple in- juries with pancreatic injury is to rescue life, followed by active treatment to prevent injuries which giving rise to the abnormal respiratory and circulatory functions, management of cerebral hernia and other injuries which endangers life at last, and the pancreatic injury to increase the survival rate and survival quality.

Isolated Pancreatic Injury in Case of Blunt Trauma Abdomen.

A 25 year old man presented three days after an episode of blunt trauma abdomen (cycle handle injury) with complaint of abdominal pain and vomiting.At admission he had tachycardia, tenderness in epigastrium, and increase serum amylase. USG showed pancreatic swelling and free fluid in abdomen. CECT abdomen could not be performed. Exploratory laparotomy revealed pancreatic injury with slough. Capsulorrhaphy with drainage of lesser sac was done. Postoperatively he did not relieved, then CECT abdomen done on 8th postoperative day showed transaction of pancreas at neck. Relaparotomy with necrosectomy with drainage was done on next day. Distal pancreatectomy could not be performed due to edema. Patient was discharged with drain in situ draining 400 ml of clear fluid and again operated 2 months later. Distal pancreatectomy with splenectomy was done, patient was discharged uneventfully.