Severe burns may cause intense stress and persistent inflammation, resulting in intestinal mucosal barrier damage. In this study, we evaluated the effects of glutamine (Gln) on intestinal mucus barrier after burn injury. The results showed that glutamine could improve intestinal mucosal blood flow (IMBF), decrease diamine oxidase (DAO) activity, and reduce intestine damage, thereby alleviate intestinal mucous permeability. Severe burn was associated with subsequent decrease in mucus thickness, levels of hexose, sialic acid, and protein. Glutamine administration might partially reverse these changes. Additional experiments showed that supplementation with glutamine could markedly raise the content of glutamine, glutathione (GSH), and ATP in intestinal tissue. Moreover, the levels of mRNA and protein expression of MUC2, intestinal trefoil factor (ITF) were increased remarkably, but contrary to the trend of GRP-78, CHOP. These results suggest that glutamine can improve tissue perfusion and increase energy synthesis in enterocytes, decrease endoplasmic reticulum stress (ERS) and improve mucin and ITF synthesis. Finally, lessen intestinal mucus barrier damage after burn injury.
Although intestinal trefoil factor (ITF) can alleviate the burn-induced intestinal mucosa injury, the underlying mechanisms remains elusive. In this study, we investigated if ITF alters glutamine transport on the brush border membrane vesicles (BBMVs) of the intestines in Sprague-Dawley rats inflicted with 30% TBSA and the underlying mechanisms. We found that ITF significantly stimulated intestinal glutamine transport in burned rats. Mechanistically, ITF enhanced autophagy, reduces endoplasmic reticulum stress (ERS), and alleviates the impaired PDI, ASCT2, and B0AT1 in IECs and BBMVs after burn injury likely through AMPK activation. Therefore, ITF may protect intestinal epithelial cells from burn-induced injury through improving glutamine transport by alleviating ERS.
A radiomics-based explainable eXtreme Gradient Boosting (XGBoost) model was developed to predict central cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC), including positive and negative effects.A total of 587 PTC patients admitted at Binzhou Medical University Hospital from 2017 to 2021 were analyzed retrospectively. The patients were randomized into the training and test cohorts with an 8:2 ratio. Radiomics features were extracted from ultrasound images of the primary PTC lesions. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression were used to select CCLNM positively-related features and radiomics scores were constructed. Clinical features, ultrasound features, and radiomics score were screened out by the Boruta algorithm, and the XGBoost model was constructed from these characteristics. SHapley Additive exPlanations (SHAP) was used for individualized and visualized interpretation. SHAP addressed the cognitive opacity of machine learning models.Eleven radiomics features were used to calculate the radiomics score. Five critical elements were used to build the XGBoost model: capsular invasion, radiomics score, diameter, age, and calcification. The area under the curve was 91.53% and 90.88% in the training and test cohorts, respectively. SHAP plots showed the influence of each parameter on the XGBoost model, including positive (i.e., capsular invasion, radiomics score, diameter, and calcification) and negative (i.e., age) impacts. The XGBoost model outperformed the radiologist, increasing the AUC by 44%.The radiomics-based XGBoost model predicted CCLNM in PTC patients. Visual interpretation using SHAP made the model an effective tool for preoperative guidance of clinical procedures, including positive and negative impacts.
TNF-related apoptosis inducing ligand(TRAIL) is a member of TNF super family.TRAIL could specifically induce apoptosis in broad kinds of tumor cells,but has little side and toxic effects on normal cells.TRAIL has become a hotspot in tumor therapy.Human brain glioblastoma is a common kind of tumor in nervous system accounting for 50%～60% of intracranial tumors;the five-year survival rate is only 20%～30%.In this study,we investigated the inhibitory effects of recombinant human TRAIL on human brain glioblastoma U251 cell line.TRAIL expressed by E.coli system was usually in elementary body form.The functional fragment of human TRAIL(95～281 amino acids) were cloned into the prokaryotic expressing vector pHisSUMO to acquire soluble TRAIL protein.SUMO-hTRAIL fusion protein was induced by IPTG at low temperature and purified by Ni-NTA Agarose.The SUMO tag was removed by SUMO ProteaseⅠdigestion to obtain the mature hTRAIL protein.The MTT assay indicated that the mature hTRAIL protein could significantly inhibit the growth of U251 cell line.The induction was dose-depended and the highest inhibitory rate was 53.9%.Flow cytometry assay showed that the survival rate of control group was 92.2 ± 0.8% and the survival rate of medication administration group was 35.5±1.2%.We concluded that the protein is biologically active and could significantly induce apoptosis in U251 tumor cells.This study provided a platform for TRAIL protein to use in cancer therapy.
<i>Background:</i> Whether laparoscopy with CO<sub>2</sub> pneumoperitoneum affects the peritoneal metastasis of gastric cancer is a pressing question. In light of the important impact change in peritoneal macrophage function has on the peritoneal metastasis of gastric cancer, this study investigated the change in peritoneal macrophage function in gastric cancer in the CO<sub>2</sub> pneumoperitoneum environment, as well as its effect on the peritoneal metastasis of gastric cancer. <i>Methods:</i> An orthotopic transplantation model of murine forestomach carcinoma was established using the 615 mouse line. The mice bearing tumors were randomly divided into four groups (30 mice each group): anesthesia alone, laparotomy, mini-laparotomy, and CO<sub>2</sub> insufflation. After the operation, peritoneal macrophages were collected from 6 mice in each group and cultured. The phagocytosis of neutral red by macrophages and the levels of NO, TNF-α, IL-10, and VEGF produced by macrophages were measured after 12, 24, 48, and 72 h of culture. The remaining mice were observed after 2 weeks for the rate of peritoneal metastasis of forestomach carcinoma cells and the total weight of implanted nodules. <i>Results:</i> In the laparotomy group, 4 mice died intraoperatively and 2 died in the CO<sub>2</sub> insufflation group. The uptake of neutral red by peritoneal macrophages and the levels of NO, TNF-α, IL-10, and VEGF secreted by peritoneal macrophages in the laparotomy group and mini-laparotomy group after 12 h of culture were all significantly higher than those in the anesthesia-alone group (p < 0.05). The corresponding levels in the CO<sub>2</sub> insufflation group after 12 h were all significantly lower than those in the anesthesia-alone group (p < 0.05). There were no significant differences among the four groups at 24, 48, and 72 h after culture. Comparing with those in the laparotomy group, the uptake of neutral red by peritoneal macrophages and the levels of NO, TNF-α, IL-10, and VEGF secreted by peritoneal macrophages in the CO<sub>2</sub> insufflation group were all significantly lower after 12 h of culture (p < 0.05), but did not differ significantly at 24, 48, and 72 h of culture (p > 0.05), and did not differ significantly in the mini-laparotomy group at all the time (p > 0.05). The rate of peritoneal metastasis of mouse forestomach carcinoma was 50% in the laparotomy group, 45.83% in the mini-laparotomy group, and 45.45% in the CO<sub>2</sub> insufflation group; this difference was not statistically significant (p > 0.05). The total weight of implanted nodules of mouse forestomach carcinoma was 1.02 ± 0.38 g in the laparotomy group, 0.97 ± 0.41 g in the mini-laparotomy group, and 0.93 ± 0.45 g in the CO<sub>2</sub> insufflation group, which was not a statistically significant difference (p > 0.05). <i>Conclusion: </i>CO<sub>2</sub> pneumoperitoneum neither significantly changes the phagocytosis and cytokine secretion functions of peritoneal macrophages in gastric cancer-bearing mice nor significantly promotes peritoneal metastasis of gastric cancer.
[Objective] To investigate the effect of 5-aza-2′-deoxycytidine(DAC)in proliferation of ovarian cancer cell lines and expression of tumor specific antigen MAGE,BAGE and GAGE.[Methods] Ovarian cancer cell lines were treated with DAC in co-culture,the growth curves were observed,the cell cycle was detected by flow cytometry,the MAGE,BAGE,GAGE gene expression patterns were measured by RT-PCR before and after DAC treatment.[Results] The growth of most cells were stopped in G0 phases after DAC treatment,the levels of MAGE,BAGE,GAGE gene expressions after DAC treatment were higher than before.[Conclusion] DAC has an inhibitive effect on the ovarian cancer cell lines,and can elevate the expression of tumor specific antigen gene.
Background: Deep vein thromboembolism (DVT) is a common postoperative complication with high morbidity and mortality rates. However, the safety and effectiveness of using prophylactic anticoagulants for preventing DVT after spinal surgery remain controversial. Hence, it is crucial to predict whether DVT occurs in advance following spinal surgery. The present study aimed to establish a machine learning (ML)-based prediction model of DVT formation following spinal surgery.Methods: We reviewed the medical records of patients who underwent elective spinal surgery in the Third Affiliated Hospital of Zunyi Medical University from January 2020 to December 2022. We finally selected the clinical data of 500 patients who met the criteria for elective spinal surgery. The Boruta-SHAP algorithm was used for feature selection, and the SMOTE algorithm was used for data balance. The related risk factors of DVT after spinal surgery were screened and analyzed. Five ML algorithm models were established. The data of 150 patients treated at the Affiliated Hospital of Zunyi Medical University from July 2023 to October 2023 were used for the external verification of the model. Area under the curve (AUC) value, geometric mean (G-mean), sensitivity, accuracy, specificity, and F1-score were used to evaluate the performance of the models.Results: The results showed that activated partial thromboplastin time (APTT), age, body mass index (BMI), serum creatinine (Crea), anesthesia time, rocuronium dose, and propofol dose were the seven important characteristic variables to predict DVT after spinal surgery. For the first time, the present study found that an increase in the doses of rocuronium and propofol injections during the surgery can significantly reduce DVT formation following the surgery. Among the five ML models established in this study, the Random Forest Classifier (RF) showed superior performance to other models in the internal validation set. This model showed an AUC value of 0.768, accuracy of 73%, specificity of 87.6%, and G-mean of 0.707. RF also showed good results in the external verification set, with an AUC value of 0.726.Conclusion: Seven preoperative and intraoperative variables were included in our study to develop an ML-based predictive model for DVT formation following spinal surgery, and this model can be used to assist clinical evaluation and decision-making.
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