Objective: To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion (I/R) in rats. Methods: Adult male Sprague-Dawley rats, weighing 250-320 g, were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups (n=10 each) by a random number table method: control group (C group), I/R group and dexmedetomidine group (DEX group). The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion, lungs were subjected to 60-min suspension of ventilation and perfusion, followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group, dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope) and ultrastructure (using an electron microscope), and the alveolar damage rate (IAR) was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β), IL-18 and gasdermin D (GSDMD) protein and mRNA was detected by Western blot or by real-time polymerase chain reaction. Results: Compared with C group, the W/D ratio and IAR in lung tissues were significantly increased, and the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups (P<0.05). Compared with I/R group, the W/D ratio and IAR in lung tissues were significantly decreased, the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was down-regulated (P<0.05), and the pathological changes were significantly attenuated in DEX group. Conclusion The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyroptosis.

OBJECTIVE To systematically evaluate the efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis， and to provide evidence-based reference for clinical treatment. METHODS Randomized controlled trials （RCTs） about denosumab （trial group） versus bisphosphonates （control group） in the treatment of osteoporosis were retrieved from PubMed， Embase， Medline， the Cochrane Library， Chinese Journal Fulltext Database， Chinese Science and Technology Journal Database， Wanfang database from January 2012 to December 2022. After the data extraction of included clinical studies， the quality of included studies was evaluated with Cochrane Handbook for Systematic Review 5.1.0， and meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCTs were included， involving 3 145 patients. Meta-analysis showed that the improvement rate of lumbar bone mineral density （BMD） [MD＝1.78， 95%CI（1.13， 2.43）， P＜0.000 01]， femoral neck BMD [MD＝1.26， 95%CI （1.08， 1.45）， P＜0.000 01] and total hip BMD [MD＝1.16，95%CI（0.93，1.39），P＜0.000 01] in trial group were significantly better than control group. C-terminal telopeptide of type Ⅰ collagen after 6 months [MD＝－0.09， 95%CI （－0.16， －0.02）， P＝0.01] and N-terminal propeptide of type Ⅰ collagen after 12 months [MD＝－9.07， 95%CI （－11.22， －6.92）， P＜ 0.001] in trial group were significantly higher than control group. There was no statistical difference in the fracture incidence rate after 12 months [OR＝1.02， 95%CI （0.67，1.54）， P＝0.92] and the incidence of adverse reaction [OR＝0.99， 95%CI （0.67，1.46）， P＝0.97] between 2 groups. CONCLUSIONS Denosumab has more advantages in improving BMD and bone metabolism， compared with bisphosphonates.