Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis.

Cuproptosis, a new type of copper-induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib-resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM-regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.

[Correlation of environment temperature with the incidence of testicular torsion].

Objective： To explore the influence of environment temperature on the incidence of testicular torsion. METHODS: We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from December 2013 to December 2020. According to the local environment temperature on the day of onset, we divided the patients into groups A (below 0℃), B (0－10℃), C (10－20℃) and D (above 20℃), and compared the incidence rates of testicular torsion among the four groups, followed by correlation analysis. RESULTS: The incidence rate of testicular torsion was 12.8% (n = 22) in group A, 35.5% (n = 61) in B, 34.9% (n = 60) in C and 16.9% (n = 29) in D, the highest at 0－10℃ in group B, with statistically significant difference among the four groups (χ2 = 29.07, P <0.001). Spearman correlation analysis indicated that the incidence of testicular torsion was negatively correlated with the environment temperature (r = －0.261, P <0.01), with no statistically significant difference among different seasons (χ2 = 5.349, P >0.05), but higher in autumn and winter than in the other two seasons. CONCLUSION: The incidence of testicular torsion is negatively correlated with the environment temperature, elevated when the temperature decreases, but has no statistically significant difference among different seasons, though relatively higher in autumn and winter.

[Application of Intraoperative Transesophageal Echocardiography in the Treatment of Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus].

Objective To investigate the value of intraoperative transesophageal echocardiography (TEE) in the diagnosis and treatment of renal cell carcinoma with inferior vena cava tumor thrombus. Methods Ten patients of renal cell carcinoma with inferior vena cava tumor thrombus treated in the Second Hospital of Hebei Medical University from January 2017 to January 2021 were selected.TEE was employed to locate the position of the tumor thrombus,determine the occlusion point of the inferior vena cava,count the intraoperative tumor thrombus shedding rate,examine the tumor thrombus resection integrity,and measure blood loss and other indicators,on the basis of which the application value of TEE in the operation of renal cell carcinoma with inferior vena cava tumor thrombus was evaluated. Results All the 10 patients had completed the operations successfully,including 8 patients of open operation and 2 patients of laparoscopic operation.TEE showed tumor thrombi clearly,and all the tumor thrombi were completely removed.There was no tumor thrombus shedding during the operation.The blood loss varied within the range of 300-800 ml,with the mean of (520.0±193.2) ml.The grade III tumor thrombi in 2 patients and the grade I tumor thrombus in 1 patient diagnosed before operation were reduced to grade Ⅱ and upgraded to grade Ⅱ,respectively,by TEE.One patient had no floating tumor thrombus at the end of tumor thrombus before operation,and the blocking position was adjusted in time with the assistance of TEE to avoid the shedding of the floating tumor thrombus. Conclusion TEE can accurately determine and dynamically monitor the location and shape of inferior vena cava tumor thrombus,which provides an important reference and has a significant clinical value in the operation of renal cell carcinoma with inferior vena cava tumor thrombus.