Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.

Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS. Bioinformatics analysis indicated that RCC1 is highly expressed and correlated with poor prognosis in STS. Functional studies showed that RCC1 knockdown significantly inhibited the cell cycle transition, proliferation and migration of STS cells in vitro, and the growth of STS xenografts in mice. Mechanistically, we identified Skp2 as a downstream target of RCC1 in STS. Loss of RCC1 substantially diminished Skp2 abundance by compromising its protein stability, resulting in the upregulation of p27Kip1 and G1/S transition arrest. Specifically, RCC1 might facilitate the nucleo-cytoplasmic trafficking of Skp2 via direct interaction. As a result, the cytoplasmic retention of Skp2 would further protect it from ubiquitination and degradation. Notably, recovery of Skp2 expression largely reversed the phenotypes induced by RCC1 knockdown in STS cells. Collectively, this study unveils a novel RCC1-Skp2-p27Kip1 axis in STS oncogenesis, which holds promise for improving prognosis and treatment of this formidable malignancy.

Total tubeless percutaneous nephrolithotomy without artificial hydronephrosis in preschool children: Three case reports.

RATIONALE: Indwelling ureteral catheter, double J tube, or nephrostomy tube are routine procedures for percutaneous nephrolithotomy (PCNL) in children. There are a few cases in which PCNL has been performed in children without any additional instruments being left in place. PATIENT CONCERNS: In this study, 3 children were treated for hematuria and complicated with different degrees of urinary tract infection. All of them were diagnosed as upper urinary tract calculi by abdominal computed tomography. DIAGNOSIS: Three preschoolers were diagnosed with upper urinary tract calculi before surgery, one with no hydronephrosis and the other 2 with different degrees of hydronephrosis. INTERVENTIONS: After preoperative evaluation, all the children successfully completed PCNL without indwelling ureteral catheter, double J tube, or nephrostomy tube. OUTCOMES: The operation was successful and there were no residual stones observed during postoperative review. The operating times for the children were 33 minutes, 17 minutes, and 20 minutes, and the intraoperative bleeding volumes were 1 mL, 2 mL, and 2 mL. The catheter was removed on the second day after the operation, the postoperative review of the abdominal computed tomography or ultrasound did not indicate any stone residue, and there were no fever, bleeding, and other related complications after the operation. LESSONS: We believe that total tubeless PCNL without artificial hydronephrosis can be achieved in the preschool population.

One-stage tubeless percutaneous nephrolithotomy for asymptomatic calculous pyonephrosis.

BACKGROUND: In recent years, the safety and effectiveness of one-stage percutaneous nephrolithotomy (PCNL) for the treatment of calculous pyonephrosis have been proven. In order to further reduce postoperative pain and hospital stay, we first proposed and practiced the idea of one-stage tubeless percutaneous nephrolithotomy for calculous pyonephrosis. METHODS: A retrospective analysis was performed of case data of 30 patients with asymptomatic calculous pyonephrosis treated in our center with one-stage PCNL from January 2016 to January 2021. Patients were routinely given 20 mg of furosemide and 10 mg of dexamethasone sodium phosphate injection intravenously at the beginning of anesthesia. Among them, 27 patients successfully underwent one-stage tubeless percutaneous nephrolithotomy, while 3 cases were given indwelling nephrostomy tubes because of proposed second-stage surgery or the number of channels was greater than or equal to 3. All patients were operated on by the same surgeon. RESULTS: Preoperatively, 11 of 30 patients (8 men and 22 women) had positive urine bacterial cultures, and all were given appropriate antibiotics based on drug sensitivity tests. All patients completed the surgery successfully. The mean operative time was 66.6 ± 34.7 min, the mean estimated blood loss was 16.67 ± 14.34 mL and the mean postoperative hospital stay was 5.0 ± 3.1 days. The mean postoperative hospital stay was 4.6 ± 2.5 days among the 27 patients with one-stage tubeless percutaneous nephrolithotomy. Of the 3 patients with postoperative fever, 2 had the tubeless technique applied. One patient with 3 channels was given renal artery interventional embolization for control of postoperative bleeding. None of the 30 patients included in the study developed sepsis. The final stone-free rate was 93.3% (28/30) on repeat computed tomography at 1 month postoperatively. The final stone-free rate was 92.6% in the 27 patients undergoing one-stage tubeless percutaneous nephrolithotomy (25/27). CONCLUSIONS: One-stage tubeless PCNL is an available and safe option in carefully evaluated and selected calculous pyonephrosis patients.

Financing elderly people's long-term care needs: Evidence from China.

Confronted by accelerated population aging, China is establishing a long-term care (LTC) system. This study discusses challenges and recommendations for financing China's LTC system. On the basis of the data on elderly people's self-care ability from the Chinese Longitudinal Healthy Longevity Survey, we calculate the size of the elderly population that need LTC for the period from 2015 to 2030 and analyse the increasing tendency of LTC expenses by considering the impact of price increase. We also analyse the local governments' financial capacity for LTC support by comparing the expense level to the fiscal revenue. The study found that aging will double the LTC expenses by 2030. Therefore, this study suggests the establishment of an LTC insurance system that allocates LTC expenses, which are currently borne by individuals and families, more fairly among the government, individuals, and families. Moreover, with the current LTC reforms, implemented primarily by local governments in China, we believe that the central government should bear some of the fiscal responsibility by conducting fiscal transfers to partially support undeveloped regions that are establishing an LTC system.

Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma.

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemo- or radiotherapy prior to surgical resection. Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7 ± 61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P < 0.01). In contrast, the protein level of p27 was significantly lower in ESCC than in normal squamous epithelium (182.0 ± 69.0 vs 266.4 ± 28.0, P < 0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0 ± 42.3 vs 83.0 ± 66.5, P < 0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8 ± 31.7 vs 98.4 ± 84.8, 32.0 ± 19.0 vs 54.1 ± 53.7, 206.2 ± 61.5 vs 123.5 ± 68.3, respectively, all P < 0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r = 0.270, 0.233 and -0.311, respectively, all P < 0.05). CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.

Expression of thymidylate synthase and glutathione-s-transferase pi in patients with esophageal squamous cell carcinoma.

AIM: To investigate the expression of thymidylate synthase (TS) and glutathione-s-transferase pi (GST-pi) in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS: Immunohistochemical methods were used to detect the expression of TS and GST-pi in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in 28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-pi expression and clinicopathologic factors was examined. RESULTS: The expression of TS and GST-pi was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples (P < 0.05). The expression level of TS was not only significantly lower in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%, P < 0.05), but was also significantly higher in samples from male patients (46.51%) than from female patients (18.75%, P < 0.05). GST-pi was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P < 0.05). The expression level of GST-pi was also significantly higher in well-differentiated carcinomas (65.63%) than in poorly-differentiated carcinomas (35.00%, P < 0.05). CONCLUSION: The expression of TS and of GST-pi may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of TS and reduced expression of GST-pi.