Gut microbiota-derived indole 3-propionic acid partially activates aryl hydrocarbon receptor to promote macrophage phagocytosis and attenuate septic injury.

Sepsis is associated with a high risk of death, and the crosstalk between gut microbiota and sepsis is gradually revealed. Indole 3-propionic acid (IPA) is a gut microbiota-derived metabolite that exerts immune regulation and organ protective effects. However, the role of IPA in sepsis is not clear. In this study, the role of IPA in sepsis-related survival, clinical scores, bacterial burden, and organ injury was assessed in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Aryl hydrocarbon receptor (AhR) highly specific inhibitor (CH223191) was used to observe the role of AhR in the protection of IPA against sepsis. The effects of IPA on bacterial phagocytosis by macrophages were investigated in vivo and vitro. The levels of IPA in feces were measured and analyzed in human sepsis patients and patient controls. First, we found that gut microbiota-derived IPA was associated with the survival of septic mice. Then, in animal model, IPA administration protected against sepsis-related mortality and alleviated sepsis-induced bacterial burden and organ injury, which was blunted by AhR inhibitor. Next, in vivo and vitro, IPA enhanced the macrophage phagocytosis through AhR. Depletion of macrophages reversed the protective effects of IPA on sepsis. Finally, on the day of ICU admission (day 0), septic patients had significantly lower IPA level in feces than patient controls. Also, septic patients with bacteremia had significantly lower IPA levels in feces compared with those with non-bacteremia. Furthermore, in septic patients, reduced IPA was associated with worse clinical outcomes, and IPA in feces had similar prediction ability of 28-day mortality with SOFA score, and increased the predictive ability of SOFA score. These findings indicate that gut microbiota-derived IPA can protect against sepsis through host control of infection by promoting macrophages phagocytosis and suggest that IPA may be a new strategy for sepsis treatment.

Predicting prolonged postoperative length of stay risk in patients undergoing lumbar fusion surgery: Development and assessment of a novel predictive nomogram.

Objective: The purpose of this study was to develop and internally validate a prediction nomogram model in patients undergoing lumbar fusion surgery. Methods: A total of 310 patients undergoing lumbar fusion surgery were reviewed, and the median and quartile interval were used to describe postoperative length of stay (PLOS). Patients with PLOS > P75 were defined as prolonged PLOS. The least absolute shrinkage and selection operator (LASSO) regression was used to filter variables for building the prolonged PLOS risk model. Multivariable logistic regression analysis was applied to build a predictive model using the variables selected in the LASSO regression model. The area under the ROC curve (AUC) of the predicting model was calculated and significant test was performed. The Kappa consistency test between the predictive model and the actual diagnosis was performed. Discrimination, calibration, and the clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using the bootstrapping validation. Results: According to the interquartile range of PLOS in a total of 310 patients, the PLOS of 235 patients was ≤P75 (7 days) (normal PLOS), and the PLOS of 75 patients was > P75 (prolonged PLOS). The LASSO selected predictors that were used to build the prediction nomogram included BMI, diabetes, hypertension, duration of surgery, duration of anesthesia, anesthesia type, intraoperative blood loss, sufentanil for postoperative analgesia, and postoperative complication. The model displayed good discrimination with an AUC value of 0.807 (95% CI: 0.758-0.849, P < 0.001), a Kappa value of 0.5186 (cutoff value, 0.2445, P < 0.001), and good calibration. A high C-index value of 0.776 could still be reached in the interval validation. Decision curve analysis showed that the prolonged PLOS nomogram was clinically useful when intervention was decided at the prolonged PLOS possibility threshold of 3%. Conclusions: This study developed a novel nomogram with a relatively good accuracy to help clinicians access the risk of prolonged PLOS in lumbar fusion surgery patients. By an estimate of individual risk, surgeons and anesthesiologists may shorten PLOS and accelerate postoperative recovery of lumbar fusion surgery through more accurate individualized treatment.

[Apoptosis mechanism of taxol combined with resveratrol on human laryngeal carcinoma Hep-2 cells].

Laryngeal cancer is one of the most common malignant tumors in the respiratory tumors, and its incidence ranks second highest in the respiratory tumors. Resveratrol (Res) is a kind of polyphenols, which can inhibit nucleotides can inhibit the growth of liver cancer cells, gastric cancer cells, pancreatic cells and other tumor cells by inhibiting ribonucleotide reductase in the cells. Taxol (Tax) is a kind of secondary metabolites of Taxus chinensis, which has anti-tumor activity for breast cancer, cervical cancer, ovarian cancer and other tumors by inhibiting cellular microtubule depolymerization. But at present the effects of resveratrol combined with taxol on human laryngeal carcinoma cell strain Hep-2 and their underlying molecular mechanisms are rarely reported. After human laryngeal cancer cell Hep-2 cells were processed with resveratrol (Res) and taxol (Tax), CCK-8 assay was used to evaluate the effect of these two herbs on the proliferation of cancer cells; AO/PI staining and JC-1 were used to detect Hep-1 cells apoptosis; the expression of Bax, Bcl-2, PARP, TRIB3, and XIAP genes was detected by real time quantitative PCR; the activity of caspase-3 and caspase-8 was determined with quantitative fluorescence method. The experimental results showed that compared with Tax, Res medication alone, joint group significantly enhanced inhibition of Hep-2 cells activity, decreased the dosage of Tax, increased the expression of Bax and PARP, TRIB3, reduced the expression of the Bcl-2 and XIAP, and promoted the activity of caspase-3 and caspase-8. The test results showed that compared with the single medication, combined group could significantly increase the inhibitory effect on Hep-2 cells, significantly reduce Tax dosage, increase expressions of Bax, PARP, TRIB3, reduce expressions of Bcl-2, XIAP, and promote activity of caspase-3, caspase-8. This indicated apoptosis of human laryngeal carcinoma cell strain Hep-2 may be induced with Res, Tax, and the combination of these two herbs by mitochondria pathway. It provides valuable clue for further research on combination of Res and Tax for the treatment of laryngeal cancer, and expanding the combined application of Res and Tax.