Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports

BACKGROUND Glucose imbalance is common in total parenteral nutrition(TPN).Hypoglycemia seems to be less frequent than hyperglycemia,but it influences the clinical outcome to a greater extent.Therefore,it should be effectively prevented and treated.However,there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury.CASE SUMMARY We present three patients with liver cell injury who developed severe hypo-glycemia during or after TPN infusion.The causes of severe hypoglycemia and glucose-raising strategies were discussed.According to the physiological charac-teristics of the hepatocellular injury,the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases.We simultaneously reduced the dose of insulin and fat emulsion,and increased the dose of glucose in TPN.The blood glucose level was restored to normal range and clinical symptoms were eliminated.CONCLUSION When hypoglycemia occurs during or after TPN in patients with hepatocellular injury,physicians need to simultaneously reduce insulin and fat emulsion,and increase glucose,and correct severe hypoglycemia in time to reduce its adverse consequences.

Prognostic Factors for Mortality in Severe Traumatic Brain Injury at HGZ 46, Villahermosa, Tabasco, Period from March 1, 2021 to December 31, 2022

Introduction: A traumatic brain injury (TBI) is caused by a forceful bump, blow, or jolt to the head or body, or by an object that pierces the skull and interrupts the normal function of the brain. Severe TBI is estimated at 73 cases per 100,000 people. The mortality of severe TBI can be reduced if a timely diagnosis and treatment of the injuries are made through prognostic factors. Objective: To determine the prognostic factors related to mortality in severe traumatic brain injury at the Hospital General de Zona No. 46. Material and Methods: Retrospective, cross-sectional and descriptive study in beneficiaries admitted to the Hospital General de Zona (HGZ) No. 46 of the Mexican Institute of Social Security (IMSS by its acronym in Spanish), with a diagnosis of severe TBI;the possible prognostic factors related to mortality of severe TBI were obtained from their records. Measures of central tendency and chi square were used for data analysis. Results: The study sample consisted of 60 subjects diagnosed with severe traumatic brain injury, of which 5 (8%) were women and 55 (92%) were men, and all 60 (100%) patients died. The average age of the sample was 26 with a standard deviation of 9 years. The variables that had a p value less than or equal to 0.05 were: Mydriasis, seizures, Hyperglycemia, Normoglycemia, Hypothermia and Hypotension. This means that these variables were associated with mortality. Conclusion: Statistical significance is demonstrated in prognostic factors of mortality in severe traumatic brain injury with p < 0.05 in the case of mydriasis, seizures, hyperglycemia, normoglycemia, hypothermia and hypotension.

Clinical Evaluation of Enteral Nutrition+Probiotics in the Treatment of Gastrointestinal Dysfunction After Severe Traumatic Brain Injury

Objective:To evaluate the therapeutic effect of enteral nutrition+probiotics in patients with gastrointestinal dysfunction after severe craniocerebral injury.Methods:From September 2018 to February 2023,80 patients(20-82 years old)with gastrointestinal dysfunction who were admitted to the Intensive Care Unit at the Third People’s Hospital of Xining were included in the study.Their primary condition was severe craniocerebral injury,and all of them received conventional symptomatic treatment.Group A received enteral nutrition+probiotic therapy,whereas group B received enteral nutrition only.The differences in the following indicators were compared before and after treatment:nutritional and biochemical indicators,gastrointestinal function indicators,Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA),APACHE II score,serum procalcitonin(PCT),neutrophil(N)ratio,and C reactive protein(CRP).Result:The nutritional and biochemical indicators in group A were higher than those in group B,P<0.05;the time to first passage of flatus,time to first passage of stool,and bowel sound recovery time in group A were shorter than those in group B,P<0.05;the GCS of group A was higher than that of group B,P<0.05;the SOFA and APACHEⅡscores of group A were not different from those of group B,P>0.05;and the PCT,N ratio,and CRP levels of group A were lower than those of group B,P<0.05.Conclusion:In patients with gastrointestinal dysfunction after severe craniocerebral injury,enteral nutrition+probiotic therapy is highly effective and feasible,as it can optimize various nutritional indicators,shorten the gastrointestinal function recovery time,and reduce the body’s stress response.

Effect of Prone Position Ventilation in Patients with Severe Craniocerebral Injury Complicated with Pulmonary Infection

Objective:To investigate the effects of prone ventilation in patients with severe traumatic brain injury combined with pulmonary infection.Methods:A total of 100 patients with severe traumatic brain injury combined with pulmonary infection in the hospital were randomly divided into a prone ventilation group and a conventional ventilation group,with 50 patients in each group.The Glasgow Coma Scale(GCS)score,APACHE II score,sputum culture results,oxygenation indicators,and prognosis were compared between the two groups.Data were processed using SPSS 25.0 statistical software,and t-tests and chi-square tests were used to compare continuous and categorical variables,respectively.Results:The experimental group showed better oxygenation indicators,a lower positive rate of sputum cultures,and reduced intracranial pressure compared to the control group(all P<0.05).Multivariate Cox regression analysis indicated that GCS score,APACHE II score,and prone ventilation were independent risk factors affecting patient prognosis(all P<0.05).Conclusion:Prone ventilation can improve oxygenation,reduce the risk of pulmonary infection,and decrease intracranial pressure in patients with severe traumatic brain injury combined with pulmonary infection,thereby improving patient prognosis.GCS score and APACHE II score can serve as important indicators for prognostic evaluation.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Risk factors and their interactive effects on severe acute pancreatitis complicated with acute gastrointestinal injury

BACKGROUND There are many risk factors for severe acute pancreatitis(SAP)complicated with acute gastrointestinal injury(AGI),but few reports on the interaction between these risk factors.AIM To analyze the risk factors for SAP complicated with AGI and their interactive effects.METHODS We selected 168 SAP patients admitted to our hospital between December 2019 and June 2022.They were divided into AGI group and non-AGI group according to whether AGI was present.Demographic data and laboratory test data were compared between the two groups.The risk factors for SAP with concomitant AGI were analyzed using multifactorial logistic regression,and an analysis of the interaction of the risk factors was performed.RESULTS The percentage of patients with multiple organ dysfunction syndrome,acute physiological and chronic health scoring system II(APACHE II)score,white blood cell count and creatinine(CRE)level was higher in the AGI group than in the non-AGI group.There was a statistically significant difference between the two groups(P<0.05).Logistic regression analysis indicated that an APACHE II score>15 and CRE>100μmol/L were risk factors for SAP complicating AGI.The interaction index of APACHE II score and CRE level was 3.123.CONCLUSION An APACHE II score>15 and CRE level>100μmol/L are independent risk factors for SAP complicated with AGI,and there is a positive interaction between them.

Delta shock index predicts injury severity,interventions,and outcomes in trauma patients:A 10-year retrospective observational study

BACKGROUND Most trauma occurs among young male subjects in Qatar.We examined the predictive values of the delta shock index(DSI),defined as the change in the shock index(SI)value from the scene to the initial reading in the emergency unit(i.e.,subtracting the calculated SI at admission from SI at the scene),at a Level 1 trauma center.AIM To explore whether high DSI is associated with severe injuries,more interventions,and worse outcomes[i.e.,blood transfusion,exploratory laparotomy,ventilator-associated pneumonia,hospital length of stay(HLOS),and in-hospital mortality]in trauma patients.METHODS A retrospective analysis was conducted after data were extracted from the National Trauma Registry between 2011 and 2021.Patients were grouped based on DSI as low(≤0.1)or high(>0.1).Data were analyzed and compared usingχ2 and Student’s t-tests.Correlations between DSI and injury severity score(ISS),revised trauma score(RTS),abbreviated injury scale(AIS),Glasgow coma scale(GCS),trauma score-ISS(TRISS),HLOS,and number of transfused blood units(NTBU),were assessed using correlation coefficient analysis.The diagnostic testing accuracy for predicting mortality was determined using the validity measures of the DSI.Logistic regression analysis was performed to identify predictors of mortality.RESULTS This analysis included 13212 patients with a mean age of 33±14 years,and 24%had a high DSI.Males accounted for 91%of the study population.The trauma activation level was higher in patients with a high DSI(38%vs 15%,P=0.001).DSI correlated with RTS(r=-0.30),TRISS(r=-0.30),NTBU(r=0.20),GCS(r=-0.24),ISS(r=0.22),and HLOS(r=0.14)(P=0.001 for all).High DSI was associated with significantly higher rates of intubation,laparotomy,ventilator-associated pneumonia,massive transfusion activation,and mortality than low DSI.For mortality prediction,a high DSI had better specificity,negative predictive value,and negative likelihood ratio(77%,99%,and 0.49%,respectively).After adjusting for age,emergency medical services time,GCS score,and ISS,multivariable regression analysis showed that DSI was an independent predictor of mortality(odds ratio=1.9;95%confidence interval:1.35-2.76).CONCLUSION In addition to sex-biased observations,almost one-quarter of the study cohort had a higher DSI and were mostly young.High DSI correlated significantly with the other injury severity scores,which require more time and imaging to be ready to use.Therefore,DSI is a practical,simple bedside tool for triaging and prognosis in young patients with trauma.

Pretreatment with a modified St.Thomas'solution in patients with severe upper limb injuries:Four case reports

BACKGROUND This study aims to describe the application of a modified St.Thomas'solution in patients with severe limb injuries.CASE SUMMARY Four patients who sustained a high-energy trauma and underwent complete upper limb amputation were pretreated with a modified St.Thomas'solution before upper limb replantation.After the perfusion solution stopped flowing from the blood vessel,the amputated upper limb amputation was replanted.The patients were instructed to perform functional rehabilitation training after the operation.All 4 patients were followed up for 5 years.All the severed upper limbs survived.Routine re-examination after the operation showed that the function of the affected limb was restored.All the patients were satisfied with the sensory and functional recovery of the affected limb.CONCLUSION The modified St.Thomas'solution can effectively improve the success rate of limb salvage surgery and the recovery of limb function in patients with a severe limb injury.

Early Enteral Combined with Parenteral Nutrition Treatment for Severe Traumatic Brain Injury:Effects on Immune Function,Nutritional Status and Outcomes

Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN)with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patientswith severe traumatic brain injury (STBI).Methods A prospective randomized control trial was carried out from January 2009 to May 2012 inNeurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow ComaScale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were administratedEN, PN or EN＋PN treatments respectively. The indexes of nutritional status, immune function,complications and clinical outcomes were examined and compared statistically.

Pathological changes at early stage of multiple organ injury in a rat model of severe acute pancreatitis

BACKGROUND: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal syndrome characterized by sudden onset, rapid progression and high mortality rate. The damage in peripheral organs may be more severe than that in the pancreas, and can even lead to multiple organ dysfunction. It is critical to recognize early pathological changes in multiple organs. This study aimed to assess the early pathological features of damaged organs in a rat model of SAP. METHODS: Thirty clean grade healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into a model control group (n=15) and a sham-operated group (n=15). The SAP rat model was induced by sodium taurocholate. Samples of blood and from multiple organs were collected 3 hours after operation. We assessed the levels of IL-6, TNF-alpha, PLA2, NO, ET-1, MDA, amylases and endotoxin in blood and observed the early pathological changes in multiple damaged organs. RESULTS: Levels of IL-6, TNF-alpha, PLA2, NO, ET-1 and MDA in serum and of amylase and endotoxin in plasma of the model control group rats were significantly higher than those of the sham-operated group (P<0.01). Different degrees of pathological change were observed in multiple damaged organs. CONCLUSION: Multiple organ injury may occur at the early stage of SAP in rats.

Circulating miRNAs as biomarkers for severe acute pancreatitis associated with acute lung injury

AIM To identify circulating micro(mi)RNAs as biological markers for prediction of severe acute pancreatitis(SAP) with acute lung injury(ALI).METHODS Twenty-four serum samples were respectively collected and classified as SAP associated with ALI and SAP without ALI, and the mi RNA expression profiles were determined by microarray analysis. These mi RNAs were validated by quantitative reverse transcriptionpolymerase chain reaction, and their putative targets were predicted by the online software Target Scan, mi Randa and Pic Tar database. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(commonly known as KEGG) were used to predict their possible functions and pathways involved.RESULTS We investigated 287 mi RNAs based on microarray data analysis. Twelve mi RNAs were differentially expressed in the patients with SAP with ALI and those with SAP without ALI. Hsa-mi R-1260 b, 762, 22-3 p, 23 b and 23 a were differently up-regulated and hsa-mi R-550 a*, 324-5 p, 484, 331-3 p, 140-3 p, 342-3 p and 150 were differently down-regulated in patients with SAP with ALI compared to those with SAP without ALI. In addition, 85 putative target genes of the significantly dysregulated mi RNAs were found by Target Scan, mi Randa and Pic Tar. Finally, GO and pathway network analysis showed that they were mainly enriched in signal transduction, metabolic processes, cytoplasm and cell membranes.CONCLUSION This is the first study to identify 12 circulating mi RNAs in patients with SAP with ALI, which may be biomarkers for prediction of ALI after SAP.

Dynamic changes in peripheral blood-targeted miRNA expression profiles in patients with severe traumatic brain injury at high altitude

Background:The aim of this work is to detect and compare the peripheral blood mi RNA expression profiles in patients with severe traumatic brain injury(s TBI)2,12,24,48,and 72 h after injury at high altitude and to predict the target genes of differential expressed mi RNAs.Methods:Twenty s TBI patients from high-altitude areas were randomly selected according to the inclusion and exclusion criteria and were divided into five groups:the 2-h group,12-h group,24-h group,48-h group,and 72-h group.Peripheral blood mi RNA expression profiles were detected using real-time quantitative PCR(q RT-PCR).Results:The expression levels of mi R-18 a,mi R-203,mi R-146 a,mi R-149,mi R-23 b,and mi R-let-7 b in peripheral blood showed significant differences between the 2-h group and the 12-h group.The expression levels of mi R-203,mi R-146 a,mi R-149,mi R-23 b,and mi R-let-7 f in peripheral blood were up-regulated in the 24-h group.In the 48-h group,the expression levels of mi R-181 d,mi R-29 a,and mi R-18 b were upregulated.In the 72-h group,the expression levels of mi R-203,mi R-146 a,mi R-149,mi R-23 b,and mi R-let-7 f changed.The main target genes of the differentiation expressed mi RNAs were genes that regulate inflammatory responses,apoptosis,and DNA damage/repair.Conclusions:mi RNAs may be involved in the pathogenesis of s TBI by dynamically regulating the target genes that regulate inflammatory responses,apoptosis,and DNA damage/repair pathways.

Pathogenesis of acute lung injury in rats with severe acute pancreatitis

BACKGROUND: Acute lung injury (ALI) is the most common and severe complication of severe acute pancreatitis (SAP). The elucidation of the mechanism of ALI contributes to the diagnosis and treatment of the illness. In this study, we studied the pathogenesis of ALI in rats with severe acute pancreatitis. METHODS: The rats were sacrificed at 1, 3, 5, 6, 9 and 12 hours after the establishment of the model of SAP. Pancreas and lung tissues were obtained for pathological study, and examination of microvascular permeability and myeloperoxidase (MPO) examination. The gene expressions of tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the pancreas and lung tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: After the establishment of the SAP model, the degree of pancreatic and lung injury increased gradually along with the gradual increase of MPO activity and micro-vascular permeability. Gene expressions of TNF-α and ICAM-1 in the pancreas rose at 1 hour and peaked at 7 hours. In contrast, their gene expression in the lungs rose slightly at 1 hour and peaked at 9-12 hours. CONCLUSION: An obvious time window existed between SAP and lung injury, which is beneficial to the early prevention of the development of ALI.

Qingyi decoction protects against myocardial injuries induced by severe acute pancreatitis

BACKGROUND We studied the protective effects of Qingyi decoction(QYD)(a Traditional Chinese Medicine)against severe acute pancreatitis(SAP)-induced myocardial infarction(MI).AIM To study the function and mechanism of QYD in the treatment of myocardial injuries induced by SAP.METHODS Ultrasonic cardiography,hematoxylin and eosin staining,immunohistochemistry,qRT-PCR,western blot,enzyme-linked immunosorbent assays,and apoptosis staining techniques were used to determine the effects of QYD following SAP-induced MI in Sprague-Dawley rats.RESULTS Our SAP model showed severe myocardial histological abnormalities and marked differences in the symptoms,mortality rate,and ultrasonic cardiography outputs among the different groups compared to the control.The expression of serum cytokines[interleukin(IL)-1?,IL-6,IL-8,IL-12,amyloidβ,and tumor necrosis factor-α]were significantly higher in the SAP versus QYD treated group(P<0.05 for all).STIM1 and Orai1 expression in myocardial tissue extracts were significantly decreased post QYD gavage(P<0.001).There was no significant histological difference between the 2-aminoethyl diphenylborinate inhibitor and QYD groups.The SAP group had a significantly higher apoptosis index score compared to the QYD group(P<0.001).CONCLUSION QYD conferred cardio-protection against SAP-induced MI by regulating myocardial-associated protein expression(STIM1 and Orai1).

Protection effect of triptoKde to Kver injury in rats with severe acute pancreatitis

BACKGROUND: The high mortality of patients with severe acute pancreatitis (SAP) is due to multiorgan dysfunction. The mechanisms of SAP are still obscure. The aim of this study was to investigate the role of nuclear factor-kappa B (NF-κB) activation in rats with SAP associated with liver injury and the protection effect of triptolide against liver injury in rats with SAP. METHODS: Ninety Wistar rats were randomly divided into three groups (n =30 each group) : severe acute pancreatitis (group P) , treatment with triptolide ( group T), and sham operation (group S). SAP models were induced by retrograde injection of 5% sodium taurocholate to the pancreatic duct. After the model was successfully established, no treatment was given to group P. In group T, triptolide (0. 05 mg/ml) was injected intraperitoneally (0.2 mg/kg). In group S, the abdominal walls of rats were opened, sutured , but not treated. The rats -were sacrificed after operation at 2, 6, and 12 hours, respectively. The serum levels of amylase (AMY) , alanine aminotransferase (ALT), tumor necrosis factor-alpha ( TNF-α) and interleukin-6 (IL-6 ) were determined at three time points (10 rats for each time point). Liver tissues were obtained to detect the activity of NF-κB and to observe their pathological changes with light and electron microscopes. RESULTS: The serum levels of AMY and ALT were higher in groups P and T than in group S. The serum AMY levels were significantly lower in group T than in group P at 12 hours after operation. The serum ALT levels were significantly lower in group T than in group P at 6, 12 hours after operation. At the three time points, the levels of TNF-α and IL-6 in groups P and T increased more significantly than in group S. In group T they were decreased more significantly than in group P at the three time points. In groups P and T, NF-κB activity in liver tissue increased more significantly than in group S at the three time points. The activity of NF-κB was higher in group P than in groups S and T at the three time points. Liver pathological damages were milder in group T than in group P under light and electron microscopes. CONCLUSIONS: NF-κB plays an important role in the pathogenesis of liver injury in rats with SAP. Triptolide can reduce pathological damage to the liver. Its mechanism is to inhibit the activity of NF-κB and to decrease the release of inflammatory mediators.

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.

Therapeutic effects of Caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis

AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）. METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severity of ALl in SAP.CONCLUSION： Caspase-1 activation, and overproduction of IL-1β and IL-18 play an important role in the course of ALI, and Caspase-1 inhibition is effective for the treatment of ALI in experimental SAP.

Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP). METHODS: One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-α, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation. RESULTS: The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P < 0.05) higher in treated group than in model group [66.67% vs 100%; 0.00 (0.02)% and 0.00 (0.04)% vs 0.00 (0.00)%, respectively]. The serum CREA content was markedly lower in octreotide-treated group than in model group at 3 h and 6 h (P < 0.01, 29.200 ± 5.710 μmol/L vs 38.400 ± 11.344 μmol/L; P < 0.05, 33.533 ± 10.106 μmol/L vs 45.154 ± 17.435 μmol/L, respectively). The expression level of renal Bax protein was not significantly different between model group and treated groups at all time points. The expression level of renal Bcl-2 protein was lower in Baicalin-treated group than in model group at 6 h [P < 0.001, 0.00 (0.00) grade score vs 3.00 (3.00) grade score]. The Bcl-2 expression level was lower in octreotide-treated group than in model group at 6 h and 12 h [P < 0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P < 0.05, 57.50 (22.50) and 52.50 (15.00) μmol/L vs 65.00 (7.50) μmol/L; P < 0.01, 57.50 (27.50) and 45.00 (12.50) μmol/L vs 74.10 (26.15) μmol/L, respectively]. The plasma endotoxin content and serum BUN content (at 6 h and 12 h) were lower in treated groups than in model group. The contents of IL-6, ET-1, TNF-α (at 6 h) and PLA2 (at 6 h and 12 h) were lower in treated groups than in model group [P < 0.001, 3.031 (0.870) and 2.646 (1.373) pg/mL vs 5.437 (1.025) pg/mL; 2.882 (1.392) and 3.076 (1.205) pg/mL vs 6.817 (0.810) pg/mL; 2.832 (0.597) and 2.462 (1.353) pg/mL vs 5.356 (0.747) pg/mL; 16.226 (3.174) and 14.855 (5.747) pg/mL vs 25.625 (7.973) pg/mL; 18.625 (5.780) and 15.185 (1.761) pg/mL vs 24.725 (3.759) pg/mL; 65.10 (27.51) and 47.60 (16.50) pg/mL vs 92.15 (23.12) pg/mL; 67.91 ± 20.61 and 66.86 ± 22.10 U/mL, 63.13 ± 26.31 and 53.63 ± 12.28 U/mL vs 101.46 ± 14.67 and 105.33 ± 18.10 U/mL, respectively]. CONCLUSION: Both Baicalin and octreotide can protect the kidney of rats with severe acute pancreatitis. The therapeutic mechanisms of Baicalin and octreotide might be related to their inhibition of inflammatory mediators and induction of apoptosis. Baicalin might be a promising therapeutic tool for severe acute pancreatitis.

Effect of resveratrol on microcirculation disorder and lung injury following severe acute pancreatitis in rats

AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP). METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate l mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum. Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally. Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination. Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR. RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology: high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs 8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs50.03±0.03 mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2?7.8 g/ L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs 0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10), dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05). CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).

Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis

AIM： To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis （SAP）.METHODS： SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 （ET-1）, nitrogen monoxidum （NO）, phospholipase A2 （PLA2）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） in plasma were determined. The histological changes of multiple organs were observed under light microscope.RESULTS： The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 （1.10）, 2.58 （0.70）, 2.54 （0.71） vs 0.20 （0.04）, 0.30 （0.30）, 0.22 （0.10） at 3, 6 and 12 h in ascites/body weight ratio; 1582 （284）, 1769 （362）, 1618 （302） （U/L） vs 5303 （1373）, 6276 （1029）, 7538 （2934） （U/L） at 3, 6 and 12 h in Amylase; 0.016 （0.005）, 0.016 （0.010）, 0.014 （0.015） （EU/mL） vs 0,053 （0.029）, 0.059 （0.037）, 0.060 （0.022） （EU/mL） at 3, 6 and 12 h in Endotoxin; 3.900 （3.200）, 4.000 （1.700）, 5.300 （3.000） （ng/L） vs 41.438 （37.721）, 92.151 （23.119）, 65.016 （26.806） （ng/L） at 3, 6 and 12 h in TNF-α, all P 〈 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain.CONCLUSION： This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAR