Objective:To explore the clinical efficacy of targeted interventional embolization therapy by a multidisciplinary team for the hemorrhagic shock caused by acute pelvic fracture or/and acetabular fracture.Methods:A retrospective study was conducted to analyze the data of 63 patients with hemorrhagic shock caused by pelvic fracture or/and acetabular fracture who had been admitted to Department of Orthopaedics, The Second Hospital of Shanxi Medical University from January 2015 to July 2022. There were 44 males and 19 females with an age of (39.6±15.6) years, and 23 pelvic fractures, 35 acetabular fractures, and 5 pelvic and acetabular fractures. The time from injury to targeted interventional embolization therapy was 2.67 (2.00, 3.33) hours. All the patients were treated with targeted interventional embolization therapy by a multidisciplinary team involving orthopedics, interventional medicine, general surgery, and urology. The shock index and lactate level within 12 hours after therapy, 24-hour urine output, and incidence of complications 3 weeks after therapy were recorded.Results:No bleeding was found again in the 63 patients after embolization. Within 12 hours after therapy, the shock index was ≤1.0, indicating the shock was corrected. Within 12 hours after targeted interventional embolization therapy, the shock index (0.70±0.46) and lactate value [(2.03±1.35) mmol/L] in the 63 patients were significantly lower than those before therapy [(1.76±0.56) and (4.53±1.74) mmol/L] ( P<0.05). The 24-hour urine output [(50.26±20.38) mL/h] was significantly higher than that before therapy [(21.56±1.27) mL/h] ( P<0.05). Two patients experienced poor blood circulation in the distal skin of the great toe, which was relieved after treatment with blood circulation promotion and anticoagulation. Three patients developed necrosis of the hip soft tissue, which was cured after multiple times of debridement and anti-infection treatments. One patient with severe injury died from multiple organ dysfunction. Conclusions:The targeted interventional embolization therapy can not only diagnose the bleeding location in patients with hemorrhagic shock caused by pelvic fracture or/and acetabular fracture, but also timely and accurately carry out hemostatic treatment to correct shock. Moreover, a multidisciplinary team can help patients avoid multiple surgeries and decrease their pain and financial loss.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).