CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway.

Spinal metastasis (SM) frequently occurs in renal cell carcinoma (RCC) patients. Our preliminary work showed that CX3CL1 plays a positive role in SM. The objective of the present study was to verify whether CX3CL1 activates the downstream pathway by binding to CX3CR1 in RCC cells, ultimately promoting RCC to metastasize to the spine. The expression of CX3CL1 and CX3CR1 in tissue samples was detected by immunohistochemistry and western blotting. ELISA was used to quantify the concentration of CX3CL1 in the serum. The expression level of CX3CR1 in RCC cell lines was also detected. The CellTiter-Glo assay and flow cytometry were used to analyze cell viability and apoptosis of RCC cells. Transwell and wound healing assay were used to analyze the effect of CX3CL1 on the invasion and migration ability of RCC cells. Specific inhibitors were used to interfere with key molecules in the signaling pathway to further explore the signal transduction in RCC cells after CX3CL1 stimulation. The expression of CX3CR1 in SM from RCC was higher than that in limb bone metastases. Among the five RCC cell lines, 786O cells expressed the highest level of CX3CR1. CX3CL1 neither inhibited the proliferation of 786O cells nor promoted the apoptosis of 786O cells. However, it promoted the migration and invasion of RCC cells. After CX3CL1 stimulation, Src and Focal adhesion kinase (FAK) phosphorylation levels increased in RCC cells. Bosutinib and PF-00562271 inhibited Src/FAK phosphorylation and cell motility and invasion triggered by CX3CL1 stimulation. CX3CL1 in the red bone marrow of spinal cancellous bone enhances migration and invasion abilities of RCC cells, thereby promoting RCC metastasize to the spine. The migration and invasion of RCC cells activated by CX3CL1 are at least partially dependent on Src/FAK activation.

Simvastatin Treatment Protects Myocardium in Noncoronary Artery Cardiac Surgery by Inhibiting Apoptosis Through miR-15a-5p Targeting.

Simvastatin treatment is cardioprotective in patients undergoing noncoronary artery cardiac surgery. However, the mechanisms by which simvastatin treatment protects the myocardium under these conditions are not fully understood. Seventy patients undergoing noncoronary cardiac surgery, 35 from a simvastatin treatment group and 35 from a control treatment group, were enrolled in our clinical study. Simvastatin (20 mg/d) was administered preoperatively for 5-7 days. Myocardial tissue biopsies were taken before and after surgery. Apoptosis was detected by TUNEL staining. The expressions of Bcl-2 and Bak in myocardial tissue were detected by immunoblotting. The expressions of miRNA and Bcl-2 mRNA were detected by quantitative real-time polymerase chain reaction assays. Cardiomyocytes were isolated from rat and cultured cells. MiR-15a-5p mimic was transfected into cardiomyocytes, and the Bcl-2 was detected by immunoblotting. TUNEL staining showed significantly less myocardial apoptosis in the simvastatin treatment group when compared with the control treatment group. Protein expression of Bcl-2 was increased in the simvastatin treatment group before surgery, and Bak expression was increased in the control treatment group after surgery. Further comparisons showed that Bcl-2/Bak ratios were reduced in the control treatment group but were not significantly changed in the simvastatin treatment group after surgery. Furthermore, microarray assays revealed that miR-15a-5p was significantly decreased by simvastatin treatment. This was validated by quantitative real-time polymerase chain reaction analysis. MiR-15a-5p was predicted to target Bcl-2 mRNA at nucleotide positions 2529-2536. This was validated by luciferase binding assays. Coincident with the change in miR-15a-5p, the mRNA expression of Bcl-2 was increased in the simvastatin treatment group. MiR-15a-5p mimic significantly inhibited Bcl-2 expression in cardiomyocytes. Our findings strongly suggest that simvastatin treatment preoperatively protected the myocardium in patients undergoing noncoronary artery cardiac surgery, at least in part, by inhibiting apoptosis via suppressing miR-15a-5p expression, leading to increasing expression of Bcl-2 and decreasing expression of Bak.

Outcomes of Transferred Adult Venovenous and Venoarterial Extracorporeal Membrane Oxygenation Patients: A Single Center Experience.

Objectives: Extracorporeal membrane oxygenation (ECMO) patients with or without transport both have high hospital mortality rate and there are few data on adult VA-ECMO transport patients. Hence, this study was designed to analyze factors that affect the outcomes of patients with ECMO transport. Methods: This study retrospectively enrolled 126 ECMO patients transferred from regional hospital to the First Affiliated Hospital of Zhengzhou University by our ECMO team during June 2012 to Sept 2020. Data were calculated and analyzed. Results: The median distance of transportation was 141 (76-228) km, the median transport time consuming was 3 (1.3-4) h, the percentage of complications during transport was 40.5% (except for bleeding on cannula site, and no one death during transport), and the survival rate in hospital was 38.9%. Compared with survivors, the non-survivors were older and showed higher SOFA score, longer time with ECMO assisted, longer time in ICU and in hospital. However, after divided into VA-ECMO and VV-ECMO groups, the older age showed no significant difference between survivors and non-survivors groups of VA-ECMO patients. Moreover, the Cox regression survival analysis showed that higher SOFA score and lactate level indicated higher ICU mortality of VA-ECMO patients while higher SOFA score, higher lactate level, older age and lower MAP after transportation (<70mmHg) indicated higher ICU mortality of VV-ECMO patients. However, there was no significant difference of comorbidities and complications in survivors and non-survivors groups of ECMO patients. Conclusions: The transportation for ECMO patients can be feasible performed although life-threatening complications might occur. The SOFA score and the lactate level could be used to evaluate the risk of ICU mortality of transportation ECMO patients. Besides, lower MAP after transportation (<70mmHg) had potential predictive value for short-term outcome of VV-ECMO patients.

An extensive DeBakey type IIIb aortic dissection with massive right pleural effusion presenting as abdominal pain and acute anemia: particular case report.

We describe the case of a 79-year-old male presented with sudden onset of abdominal pain and mild breathlessness, and complicated acute progressive anemia with haemoglobin which declined from 120 g/L to 70 g/L within five days. An urgent computed tomography angiography showed acute thoracic aortic dissection, DeBakey type IIIb, a dissecting aneurysm in the proximal descending thoracic aorta starting immediately after the origin of the left subclavian artery and extending distally below the renal arteries with evidence of rupture into the right pleural cavity for massive pleural effusion. Plasma D-dimer, brain natriuretic peptide and C reactive protein level were elevated. Our case showed that D-dimer can be used as a 'rule-out' test in patients with suspected aortic dissection. A raised BNP may exert a protective role through anti-inflammatory endothelial actions in the systemic circulation.