Objective:To evaluate the effect of paclitaxel on the mast cell-CCL2-macrophage axis in rats with pulmonary hypertension.Methods:Thirty SPF-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 180-220 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), pulmonary hypertension group (group PH), and paclitaxel group (group PTX). The model of pulmonary hypertension was established by subcutaneous injection of monocrotaline 60 mg/kg in rats.At 25 days after establishing the models, paclitaxel 2 mg/kg was injected via the tail vein once every four days, for 4 times in total in group PTX.The equal volume of normal saline was injected in the remaining 2 groups.The mean pulmonary artery pressure (mPAP) was performed at 40 days after establishing the model.The heart was removed and dried, the right ventricle (RV) and left ventricle plus ventricular septum (LV+ S) was weighed, and the Fulton index [RV/(LV+ S)] was calculated.The inferior lobe of left lung was taken, the ratio of media wall thickness of pulmonary vessels was calculated by HE staining, the number of Tryptase + , CD68 + , CD163 + , and Ki67 + cells was recorded by immunohistochemistry, the mean value was calculated, the percentage of Ki67-positive cells in blood vessels was recorded, and the proportion of muscularized blood vessels was calculated.The content of CCL2 was measured by enzyme-linked immunosorbent assay, and the expression of cleaved caspase-3 and Cyclin D1 was detected by Western blot. Results:Compared with group C, the mPAP, Fulton index, ratio of media wall thickness, proportion of muscularized blood vessels, the number of Tryptase + , CD68 + and CD163 + cells and percentage of Ki67 + cells were significantly increased, and the expression of cleaved caspase-3 was down-regulated in PH and PTX groups ( P<0.05), the expression of Cyclin D1 was significantly up-regulated in group PH ( P<0.05), and no significant change was found in group PTX ( P>0.05). Compared with group PH, the mPAP, Fulton index, ratio of media wall thickness, percentage of muscularized blood vessels, the number of Tryptase + , CD68 + and CD163 + cells and percentage of Ki67 + cells were significantly decreased, the expression of CCL2 and Cyclin D1 was down-regulated, and the expression of cleaved caspase-3 was up-regulated in group PTX ( P<0.05). Conclusion:The mechanism by which paclitaxel alleviates pulmonary hypertension is related to inhibiting the mast cell-CCL2-macrophage axis in rats.

BACKGROUND: After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU). METHODS: This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy. RESULTS: Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ± 0.6 days vs. 2.0 ± 0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9-36.7] mg/L vs. 44.8 [95%CI: 26.9-63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D -lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups. CONCLUSION: Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR. TRIAL REGISTRATION ChiCTR-INR-17013093.
Humans ; Hepatectomy ; Vena Cava, Inferior/surgery* ; Liver ; Laparoscopy ; Fluid Therapy