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ObjectiveTo reveal the intervention effect of Dahuang Mudantang on pancreatic injury in rats with acute pancreatitis （AP） of dampness-heat in large intestine syndrome and explore its possible mechanism based on network pharmacology. MethodNinety-six SPF-grade Wistar rats were randomly divided into the following six groups： a blank group， a model group， low-， medium-， and high-dose Dahuang Mudantang groups （3.5， 7， and 14 g·kg-1）， and a Qingyi Lidan granules group （3 g·kg-1）， with 16 rats in each group. The AP model of dampness-heat in large intestine syndrome was induced in rats except for those in the blank group by "high-temperature and high-humidity environment + high-sugar and high-fat diet + retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct". The blank and model groups received equal volumes of distilled water by gavage， while the treatment groups were administered Dahuang Mudantang or Qingyi Lidan granules 1 hour before modeling， and 12 and 24 hours after modeling. Samples were collected 1 hour after the last administration. The general conditions of the rats were observed. The AP model of dampness-heat in large intestine syndrome was evaluated. Serum amylase （AMS） and C-reactive protein （CRP） levels were determined using biochemical methods. Pancreatic tissue morphology was observed using hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict potential targets of Dahuang Mudantang in the intervention in AP， and molecular biology technique was used to verify relevant targets. ResultCompared with the blank group， the model group exhibited lethargy， unkempt fur， loose and foul-smelling stools， elevated anal temperature with arching and twisting reactions， significantly increased serum levels of AMS and CRP （P<0.05）， abnormal pancreatic ductules， disordered interlobular spaces， and inflammatory cell infiltration in histopathological examination， as well as pathological changes including pancreatic acinar cell swelling， congestion， and necrosis. Compared with the model group， the treatment groups showed varying degrees of improvement in general survival conditions， reduced twisting reactions， visibly improved stool characteristics， reduced pancreatic tissue edema and necrosis， decreased serum AMS and CRP levels （P<0.05）， with the high-dose Dahuang Mudantang group showing the most pronounced effects （P<0.05）. Network pharmacology prediction indicated that hederagenin， β-sitosterol， and quercetin were the most widely connected active compounds with disease targets. Protein-protein interaction （PPI） network analysis revealed that protein kinase B （Akt）， tumor protein P53 （TP53）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， transcription factor （JUN）， vascular endothelial growth factor α （VEGFα）， interleukin-1β （IL-1β）， and vascular cell adhesion molecule-1 （VCAM1） were key targets in the "drug-disease" interaction. KEGG enrichment analysis suggested that the response of the mitogen activated protein kinase （MAPK） signaling pathway might be a core mechanism for DHMDT in the intervention in AP. Molecular biology analysis showed that compared with the blank group， the model group had significantly increased levels of TNF-α， IL-6， and VCAM-1 in pancreatic tissue （P<0.05）， as well as significantly elevated expression levels of p38 mitogen-activated protein kinase （p38 MAPK）， mitogen-activated protein kinase-activated protein kinase 2 （MK2）， and human antigen R （HUR） genes and proteins （P<0.05）. Compared with the model group， the treatment groups exhibited decreased levels of TNF-α， IL-6， and VCAM-1 in pancreatic tissue （P<0.05）， reduced expression levels of p38 MAPK， MK2， and HUR genes and proteins， with the high-dose Dahuang Mudantang group showing the most pronounced effects （P<0.05）. ConclusionDahuang Mudantang activates and regulates the p38 MAPK/MK2/HUR signaling pathway to suppress the release of inflammatory factors， thereby improving pancreatic injury.
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ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank， model， low-， medium-， and high-dose （3.5， 7， 14 g·kg-1， administrated by gavage） Dahuang Mudantang， and octreotide （1×10-5 g·kg-1， subcutaneous injection） groups （n=20）. The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling， and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase （AMS） and C-reactive protein （CRP） in the serum. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to measure the expression levels of HMGB1， RAGE， inhibitor of NF-κB kinase （IKK）， and NF-κB suppressor protein α（IκBα）in the colon tissue. ResultThe rats in the model group showed poor general survival， writhing response， reduced frequency of defecation， and dry stool. The symptoms of rats in the model group were mitigated in each treatment group， and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group， the model group had elevated AMS and CRP levels （P<0.05）， which were lowered by Dahuang Mudantang （P<0.05）， especially that at the high dose （P<0.05）. Compared with the normal group， the modeling elevated that levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Such elevations were lowered by Dahuang Mudantang （P<0.05）， and the high-dose group and the octreotide group showed better performance （P<0.05）. The modeling caused necrotic， congested， and destructed pancreatic and colonic tissues， which were ameliorated by the drugs， especially high-dose Dahuang Mudantang. Compared with the normal group， the modeling up-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）. Compared with the model group， Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）， and the high-dose Dahuang Mudantang demonstrated the best performance （P<0.05）. Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status， reduce inflammation， and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.
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@#Objective To investigate the effect of low-flow inhaling NO for short time on postoperative cardiac and pulmonary functions in infants with congenital ventricular septal defect complicated with severe pulmonary hypertension. Methods Forty-five patients with congenital ventricular septal defect complicated with severe pulmonary hypertension from May 2014 to May 2016 in our hospital were enrolled. There were 19 males and 26 females, whose age ranged from 1 to 22 months (average age: 7.2±14.4 months) and weight ranged from 2.7 to 10.5 kg (average weight: 6.8±3.6 kg). The patients were randomly divided into three groups (n=15 in each): the blank group, the prior inhalation group and the posterior inhalation group. The blank group did not inhale NO, and the prior inhalation group inhalated NO for 10 min after tracheal and intubation. After the opening of the aorta, the posterior inhalation group inhaled NO for 10 min. The concentration of NO was 20 × 10–6. The pressure ratio of pulmonary circulation/systematic circulation, heart index and oxygenation index were calculated and the troponin value of the three groups was monitored 10 min after returning to intensive care unit (ICU) and postoperatively 1 h, 3 h and 24 h. Differences among above indicators between three groups were compared. Results The troponin value of the posterior inhalation group within 3 h increased most, followed by the blank group and the prior inhalation group. Postoperatively 1 h and 3 h, the troponin value of the prior inhalation group was significantly less than that of the blank group and posterior inhalation group (P<0.01) and the value on postoperative 24 h in each group was lower than that on postoperative 3 h. The cardiac index of prior inhalation group was higher than that of the blank group and the posterior inhalation group at each time point. Postoperatively 3 h and 24 h as well as 10 min after returning to ICU, the cardiac index in prior inhalation group was significantly higher than that of the posterior inhalation group (P<0.05). The pressure ratio of pulmonary circulation/systematic circulation of posterior inhalation group increased more than that of blank group; the differences in two groups were significant between postoperative 3 h and 10 min after returning to ICU (P<0.01). There was no statistical significance in the pressure ratio on postoperative 24 h and 10 min after returning to ICU (P>0.05) in three groups. The index of oxygenation of the prior inhalation group was higher than that of the blank group and the posterior inhalation group and statistically different from that of posterior inhalation group (P<0.05). Conclusion Inhaling NO 10 min preoperatively can reduce the injury to the heart and lung function effectively, but the result is the opposite when inhalating NO 10 min after aorta opening.
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Objective To summarize the experiences and results of completed surgical treatment for double outlet of right ventricle in 135 cases.Methods From May 2007 to May 2012,135 cases with double outlet of the right ventricle,males are 79 cases,female are 56 cases,age from 25 days to 12 years,weigh is 3.5-30.0 kg,underwent surgical procedure.There were 89 cases subaortic ventricular septal defect,33 cases doubly committed ventricular septal defect,repaired VSD with introventricular tunnel and relive right ventricle outflow tract directly with pericardial patch.There are 8 cases subpulmonary (Taussing-Bing)VSD,5 received Rastelli procedure,3 received arterial switch procedure and repaird VSD.There are 5 cases noncommited VSD,3 received Rastelli procedure,2 received arterial switch procedure and repaired VSD.Results Four cases died in the early postoperative period,with a mortality of 3.70％.1 case with subpulmonary VSD was performed arterial switch procedure and repaired VSD.1 case with noncommited VSD,2 cases with subaortic VSD(with pulmonary stenosis) were performed repaired VSD with introventricular tunnel and relive right ventricle outflow tract directly with pericardial patch.1 case with noncommited VSD was performed Rastelli procedure.Conclusion The anatomic type,especially the position of ventricular septal defect,correlates with surgical strategy significantly.