RESUMO
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.
RESUMO
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.
RESUMO
Objective To systematically study the efficacy and safety of KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRASG12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRASG12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.
RESUMO
Objective: To explore the potential genetic target of Stephania terandra in the therapy for hypertension based on inte-grated pharmacology platform to study the molecular mechanism of Chinese medicines in treating hypertension. Methods: Using the functional prediction modules of integrated pharmacology platform and the functional modules of network construction, the component-target network of Stephania terandra was calculated, and the target network of anti-hypertension was further calculated, and the target molecules related to hypertension were explored. Results: A total of 198 targets related to hypertension were obtained from the hyper-tension prevention. Among them, there were 59 potential action nodes and 20 known action nodes. The nodes with direct action were type-2 angiotensin Ⅱ receptor ( AGTR2), type-1 angiotensin Ⅱ receptor ( AGTR1), prostacyclin receptor ( PTGIR), solute carrier family 12 member 3 (SLC12A3) and endothelin-1 (EDN1). The GO enrichment and KEGG pathway enrichment of Stephania terandra chemical components showed a close correlation with hypertension, and the molecular mechanism of the target was clear. Conclusion:Through the integration of pharmacology platform, the targets of Stephania terandra-disease are deeply explored, and its potential mo-lecular mechanism as well as potential factors is studied.
RESUMO
Background and purpose:Perioperative hypothermia will affect the prognosis of cancer patients. Amino acid infusion can increase the core temperature by endogenous thermogenesis. And the forced-air warming system has gained high acceptance as a measure for rewarming. This study aimed to find out whether amino acid infusion was effective to treat postoperative hypothermia and how well the treatment effect was when compared with the forced-air warming system.Methods:Fifty-seven ASAⅠ orⅡ patients aged 18-60 years undergoing elective esophageal or gastric cancer operation under epidural-general anesthesia and whose core temperature were below 36℃. When admitted to the recovery room wererandomly divided into 3 groups (n=19): GroupⅠ received intravenous infusion of mixed amino acid at a rate of 2 mL·kg-1·h-1 (A); GroupⅡ received a forced-air system (B); groupⅢreceived no therapy (C). Rectal temperature and thermal comfort were recorded per 5 min during the ifrst 1 h and oral temperature and thermal comfort were recorded at the 2, 6 and 24 h. ABG was recorded when patients were admitted to the recovery room and at the ifrst hour.Results:At the ifrst hour, the rectal temperature and thermal comfort of groups A and B were higher when compared with group C (P0.05). At the second and sixthhour, the temperature and thermal comfort of group A were higher when compared with group B and C (P0.05). At the 24th hour, there were no statistically signiifcant differences in the temperature and thermal comfort among the three groups (P>0.05). Conclusion:The rewarming effect of infusion of mixed amino acid is better than that of the forced-air warming system. It is the more effective and convenient method to rewarm the postoperative hypothermia.
RESUMO
Objective To investigate the level and influencing factors of stigma among patients with lung cancer, in order to provide evidence for staff nurses to take pertinent interventions for assisting patients to deal with stigma. Methods Totally 234 hospitalized patients with lung cancer were cross-sectional survey with General Demographic Questionnaire, Disease Information Questionnaire, Chinese version of Cataldo Lung Cancer Stigma Scale (CLCSS-CV). Results The total score of stigma was (72.35±10.85) points. The total scale score and each subscale score was divided by the item number. The mean score of CLCSS-CV was (2.68±0.40) points, the rate of the patients with lung cancer with moderate above stigma was 51.20% (120/234). The patients rated higher scores on the subscales of smoking (2.90±0.58) points, while lower scores on the subscales of discrimination (2.47 ±0.55) points. Multiple stepwise regression analysis showed that the number of children and the clinical stages were influencing factors of lung cancer stigma, where regression coefficients were -0.065, 0.136 respectively, coefficients of determination was 0.178. Conclusions Patients with lung cancer have a moderate or higher level of stigma. The medical staff should communicate with patients, evaluate the psychological status, impose public health education, mobilize the social support for assisting them to deal with stigma.
RESUMO
Objective To supply the fastest and most effective first aid for patients with the least medical workers and within the shortest time after the occurrence of emergent public health accidents by application of emergency management. Methods We carried out retrospective invetigations about 55 great medical succors from the year of 2004 to 2006.Results Application of emergency nursing management played a pivotal role in these 55 great medical succors. The medical workers handled all the emergencies without confusion and a large number of patients got first aid in time. Conclusion It could facilitated the first aid for emergent public health accidents by application of emergency nursing management.
RESUMO
Objective To research and develop a model of the representative active component's content by NIR spectroscopy,so as to realize the on-line quality control of extracting process for multiple herbal medicine system in product scale.Methods The on-line NIR detection of extracting process was used to obtain the NIR spectrum,HPLC detection of the extracts was carried out to determine the content of danshensu,and PLS method was used to establish the relationship between the information of NIR and HPLC.Results The optimum NIR wavelength range was 9 715-7 082 cm-1,R=0.959 4,RMSEC=0.049 4,the average relative error was 7.2%.Conclusion NIR Technique could be used in the on-line quality control of Compound Danshen's extracting process.