This study aims to evaluate the prognosis of pathologically node-positive bladder cancer after neoadjuvant chemotherapy, the role of adjuvant chemotherapy in these patients, and the value of preoperative clinical evaluation for lymph node metastases.
Patients who received neoadjuvant chemotherapy followed by partial/radical cystectomy and had pathologically confirmed lymph node metastases between Jan 2007 and Dec 2019 were identified and analysed.
A total of 53 patients were included in the study. The median age was 61 years (range, 34-81) with males comprising 86.8%. Among the 52 patients with post-neoadjuvant/pre-operative CT results, only 33 patients (63.5%) were considered positive for lymph node metastasis. Sixteen patients (30.2%) received adjuvant chemotherapy (AC group), and 37 patients did not (no AC group). With the median follow-up duration of 67.7 months, the median recurrence-free survival (RFS) and the median overall survival (OS) was 8.5 months and 16.2 months, respectively. The 2-year RFS and OS rates were 23.3% and 34.6%, respectively. RFS and OS did not differ between the AC group and no AC group (median RFS, 8.8 vs. 6.8 months, p=0.772; median OS, 16.1 vs. 16.3 months, p=0.479). Thirty-eight patients (71.7%) experienced recurrence. Distant metastases were the dominant pattern of failure in both the AC group (91.7%) and no AC group (76.9%).
Patients with lymph node-positive disease after neoadjuvant chemotherapy followed by surgery showed high recurrence rates with limited survival outcomes. Little benefit was observed with the addition of adjuvant chemotherapy.
Patients with lymph node-positive disease after neoadjuvant chemotherapy followed by surgery showed high recurrence rates with limited survival outcomes. Little benefit was observed with the addition of adjuvant chemotherapy.The aim of this study was to evaluate the tolerability, safety, and pharmacokinetics of single and continuous dose administration of recombinant neorudin (EPR-hirudin, EH) by intravenous administration in healthy subjects, and to provide a safe dosage range for phase II clinical research. Forty-four subjects received EH as a single dose of between 0.2 and 2.0 mg/kg by intravenous bolus and drip infusion. In addition, 18 healthy subjects were randomly divided into three dose groups (0.15, 0.30, and 0.45 mg/kg/h) with 6 subjects in each group for the continuous administration trial. Single or continuous doses of neorudin were generally well tolerated by healthy adult subjects. There were no serious adverse events (SAEs), and all adverse events (AEs) were mild to moderate. Moreover, no subjects withdrew from the trial because of AEs. There were no clinically relevant changes in physical examination results, clinical chemistry, urinalysis, or vital signs. The incidence of adverse events was not significantly related to drug dose or systemic exposure. After single-dose and continuous administration, the serum EH concentration reached its peak at 5 min, and the exposure increased with the increase in the administered dose. The mean half-life (T1/2 ), clearance (Cl), and apparent volume of distribution (Vd) of EH ranged from 1.7 to 2.5 h, 123.9 to 179.7 ml/h/kg, and 402.7 to 615.2 ml/kg, respectively. The demonstrated safety, tolerability, and pharmacokinetic characteristics of EH can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies. Clinical trial registration Chinadrugtrials.org identifier CTR20160444.Diabetic nephropathy (DN) is becoming a research hotspot in recent years because the prevalence is high and the prognosis is poor. Lipid accumulation in podocytes induced by hyperglycemia has been shown to be a driving mechanism underlying the development of DN. However, the mechanism of lipotoxicity remains unclear. Increasing evidence shows that acetyl-CoA carboxylase 2 (ACC2) plays a crucial role in the metabolism of fatty acid, but its effect in podocyte injury of DN is still unclear. In this study, we investigated whether ACC2 could be a therapeutic target of lipid deposition induced by hyperglycemia in the human podocytes. Our results showed that high glucose (HG) triggered significant lipid deposition with a reduced β-oxidation rate. It also contributed to the downregulation of phosphorylated ACC2 (p-ACC2), which is an inactive form of ACC2. Knockdown of ACC2 by sh-RNA reduced lipid deposition induced by HG. Additionally, ACC2-shRNA restored the expression of glucose transporter 4 (GLUT4) on the cell surface, which was downregulated in HG and normalized in the insulin signaling pathway. We verified that ACC2-shRNA alleviated cell injury, apoptosis, and restored the cytoskeleton disturbed by HG. Mechanistically, SIRT1/PGC-1α is close related to the insulin metabolism pathway. ACC2-shRNA could restore the expression of SIRT1/PGC-1α, which was downregulated in HG. Rescue experiment revealed that inhibition of SIRT1 by EX-527 counteracted the effect of ACC2-shRNA. https://www.selleckchem.com/products/Gefitinib.html Taken together, our data suggest that podocyte injury mediated by HG-induced insulin resistance and lipotoxicity could be alleviated by ACC2 inhibition via SIRT1/PGC-1α.
To investigate the willingness of nursing students in Hong Kong and Mainland China to care for the elderly and to identify the factors influencing their willingness.
A correlational and cross-sectional design.
A four-part self-administered questionnaire was utilized to collect data from the undergraduate nursing students in Hong Kong and Mainland China.
The total sample consisted of 820 nursing students, with 481 students in Hong Kong and 339 students in Mainland China. The scores of willingness to care for older people of the two groups were similar (mean score 4.68 versus 4.44), and no significant difference was observed between the students in the two regions (p=.071). A very low proportion of the nursing students in Hong Kong (7.7%) and those in Mainland China (3.6%) ranked caring for older people as their first choice of work. No salient predictors of willingness to care for older people existed for the nursing students in Mainland China.
The total sample consisted of 820 nursing students, with 481 students in Hong Kong and 339 students in Mainland China.