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.

[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.

Effect of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with erectile dysfunction.

OBJECTIVE: To evaluate the effect and clinical significance of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with Erectile dysfunction (ED). METHODS: Eighty patients with hyperlipidemia complicated with ED who were treated at The Second Hospital of Hebei Medical University from January 2019 to June 2020 were selected. Using a completely randomized design experimental method, these 80 patients were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. The control group was treated with a single drug, atorvastatin calcium, while the experimental group was given tadalafil orally on the basis of the control group for 3 months. Changes in the levels of inflammatory factors such as IL-6, TNF and CRP, adverse drug reactions, changes in hemodynamic indicators such as HSV, LSV, PSV, HCT and ESR before and after treatment, as well as changes in sexual function after treatment were compared and analyzed between the two groups. RESULTS: TNF-a, CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with statistically significant differences (p<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (p=0.18). After treatment, hemodynamic indexes and sexual function indexes of the experimental group were significantly improved compared with those in the control group, with statistically significant differences (p<0.05). CONCLUSION: A significant improvement effect can be achieved by tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with ED. At the same time, the combination of the two has synergism on inflammatory factors and blood rheology, and the incidence of adverse reactions is not significantly increased.

[Transumbilical single-port laparoscopy combined with improved double hernia needles for pediatric hydrocele].

OBJECTIVE: To compare the clinical effect of transumbilical single-port laparoscopy combined with improved double hernia needles with that of traditional open surgery in the treatment of hydrocele in children. METHODS: We retrospectively analyzed 35 cases (54 sides) of pediatric hydrocele treated by transumbilical single-port laparoscopy combined with improved double hernia needles (laparoscopy group). We recorded the operation time, intraoperative blood loss, hospital stay, scrotal edema, and postoperative complications and compared them with those of another 46 cases (58 sides) treated by traditional open surgery (open surgery group) during the same period. RESULTS: The laparoscopy group showed a significantly shorter operation time, less intraoperative blood loss, milder scrotal edema, and fewer hospital days than the open surgery group (all P<0.05). However, no statistically significant difference was found in the incidence of postoperative complications between the two groups (P>0.05). Subcutaneous emphysema developed in 2 patients in the laparoscopy group, which disappeared after 1－3 days of oxygen inhalation and other symptomatic treatment, while scrotal hematoma occurred in 1 and incision fat liquefaction in 2 patients in the open surgery group 3 days postoperatively, which healed after debridement suture and daily dressing, respectively. The patients were followed up for 3－6 months, which revealed no late complications in the laparoscopy group but 1 case of unilateral recurrence and 2 cases of offside recurrence in the open surgery group, all cured by laparoscopic internal ring ligation. CONCLUSIONS: Transumbilical single-port laparoscopy combined with improved double hernia needles is superior to traditional open surgery for the treatment of pediatric hydrocele and therefore deserves clinical generalization.