RESUMEN
Background: Single-cell RNA sequencing (scRNA-seq) enables specific analysis of cell populations at single-cell resolution; however, there is still a lack of single-cell-level studies to characterize the dynamic and complex interactions between osteoporotic vertebral compression fractures (OVCFs) and Kümmell's disease (KD) in the osteoimmune microenvironment. In this study, we used scRNA-seq analysis to investigate the osteoimmune microenvironment and cellular composition in OVCFs and KD. Methods: ScRNA-seq was used to perform analysis of fractured vertebral bone tissues from one OVCF and one KD patients, and a total of 8,741 single cells were captured for single-cell transcriptomic analysis. The cellularity of human vertebral bone tissue was further analyzed using uniform manifold approximation and projection. Pseudo-time analysis and gene enrichment analysis revealed the biological function of cell fate and its counterparts. CellphoneDB was used to identify the interactions between bone cells and immune cells in the osteoimmune microenvironment of human vertebral bone tissue and their potential functions. Results: A cellular profile of the osteoimmune microenvironment of human vertebral bone tissue was established, including mesenchymal stem cells (MSCs), pericytes, myofibroblasts, fibroblasts, chondrocytes, endothelial cells (ECs), granulocytes, monocytes, T cells, B cells, plasma cells, mast cells, and early erythrocytes. MSCs play an immunoregulatory function and mediate osteogenic differentiation and cell proliferation. The differentiation trajectory of osteoclasts in human vertebral bone tissue was also revealed. In addition, ECs actively participate in inflammatory infiltration and coupling with bone cells. T and B cells actively participate in regulating bone homeostasis. Finally, by identifying the interaction of ligand-receptor pairs, we found that immune cells and osteoclasts have bidirectional regulatory characteristics, have the effects of regulating bone resorption by osteoclasts and promoting bone formation, and are essential for bone homeostasis. It is also highlighted that CD8-TEM cells and osteoclasts might crosstalk via CD160-TNFRSF14 ligand-receptor interaction. Conclusion: Our analysis reveals a differential landscape of molecular pathways, population composition, and cell-cell interactions during OVCF development into KD. OVCFs exhibit a higher osteogenic differentiation capacity, owing to abundant immune cells. Conversely, KD results in greater bone resorption than bone formation due to depletion of MSCs and a relatively suppressed immune system, and this immune imbalance eventually leads to vertebral avascular necrosis. The site of action between immune cells and osteoclasts is expected to be a new therapeutic target, and these results may accelerate mechanistic and functional studies of osteoimmune cell types and specific gene action in vertebral avascular necrosis and pathological bone loss diseases, paving the way for drug discovery.
RESUMEN
Objective: To investigate the therapeutic effect of phenylephrine combined with goal-directed fluid therapy (GDFT) in elderly patients undergoing total hip arthroplasty. Methods: From June 2018 to May 2019, a total of 80 patients, age > 70 years, scheduled for total hip arthroplasty at Guangzhou Red Cross Hospital in China were consecutively included in this prospective randomized controlled trial. The patients were divided into 2 groups of 40 patients each by the random number table method. Patients in the control group were given GDFT alone, and patients in the experimental group were given phenylephrine combined with GDFT. The duration of surgery, blood loss, intraoperative urine output, and fluid input were analyzed. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI) and stroke volume variation (SVV) were compared in the 2 groups at different times: before surgery (T0), after induction (T1), before bone cement placement (T2), after bone cement placement (T3) and after surgery (T4). Lactate, oxygenation index and cerebral oxygen uptake rate were compared perioperatively. Meanwhile, the incidence of abdominal distension, nausea and vomiting, pulmonary infection and cognitive dysfunction within 7 days after surgery were compared. Results: The intraoperative fluid input in the experimental group was significantly lower than in the control group (P < .05). In T1 and T3, heart rate (HR) and stroke volume variability (SVV) in the control group were significantly higher than in the experimental group (P < .05), but mean arterial pressure (MAP) and cardiac index (CI) were significantly lower than in the experimental group (P < .05). The intraoperative lactic acid in the control group was significantly higher than in the experimental group (P < .05). In addition, we found that the intraoperative oxygenation index and the postsurgical oxygenation index in the control group decreased by 86.86% and 87.49%, respectively, compared with the preoperative values (P < .05). In addition, at T1 and T3, HR and SVV in the control group were significantly higher than T0 (P < .05), while MAP and CI were significantly lower than T0 (P < .05). In the experimental group, there was no significant difference in HR, SVV, MAP or CI at any time points compared with those of T0 (P < .05). The oxygenation index in the control group was lower than before surgery (P < .05). There was no significant difference in urine volume or brain oxygen uptake between the 2 groups (P < .05). Conclusion: Phenylephrine combined with GDFT can be used in elderly patients undergoing hip arthroplasty to reduce fluid input and improve intraoperative hemodynamic stability, to reduce the occurrence of postoperative related complications.
