1.Analysis of Clinicopathological Characteristics and Factors Affecting the Prognosis of Patients With Resectable Sarcomatoid Carcinoma of the Bladder
Shiwang HUANG ; Kaipeng JIA ; Chong SHEN ; Huitong CHEN ; Zhe ZHANG ; Zhouliang WU ; Yunkai QIE ; Jianing GUO ; Hailong HU
Journal of Sichuan University (Medical Sciences) 2024;55(5):1085-1091
Objective To investigate the clinicopathological characteristics and the factors affecting the prognosis of patients with resectable sarcomatoid carcinoma of the bladder(SCB).Methods A retrospective analysis was conducted with the clinical data of patients with resectable SCB treated at the Second Hospital of Tianjin Medical University between September 2008 and December 2023.The patients were divided into two groups,a bladder-preserving surgery(BPS)group and a radical cystectomy(RC)group,according to the specific surgical approach used for each patient.Kaplan-Meier survival curves were used to evaluate overall survival(OS)in both groups,and Cox regression models were employed to identify risk factors affecting survival.Results A total of 77 patients with resectable SCB were included.Among them,35 patients(45.5%)underwent BPS,while 42 patients(54.5%)underwent RC.Ki-67 expression≥30%was observed in 91.7%of the patients.A total of 92.2%of the patients was tested positive for cytokeratin(CK)and 98.1%for vimentin.In addition,62.5%and 37.5%of patients had the human epidermal growth factor receptor 2(Her-2)scores of 0 and 1+,respectively.The median follow-up time was 23.2 months(ranging from 0.4 to 164.7 months).The 1-year,3-year,and 5-year survival rates for the BPS group and the RC group were as follows,76.2%vs.84.9%,46.7%vs.61.1%,and 35.6%vs.43.2%,respectively.Multivariate Cox regression analysis revealed that in the RC group,age ≥ 75 years old(hazard ratio[HR]=3.836,95%confidence interval[CI]:1.168-12.595,P=0.027),tumor multiplicity(HR=3.439,95%CI:1.235-9.574,P=0.018),and lack of adjuvant therapy(HR=3.164,95%CI:1.015-9.862,P=0.047)were independent risk factors affecting survival.In the BPS group,female sex was identified as an independent risk factor for survival(HR=3.601,95%CI:1.200-10.804,P=0.022).Conclusion Ki-67,CK,and vimentin are significantly overexpressed in SCB patients,while Her-2 is either unexpressed or expressed at low levels.In the RC group,tumor multiplicity,age ≥75 years,and lack of postoperative adjuvant therapy are independent risk factors for overall survival.Female sex is an independent risk factor affecting prognosis in the BPS group.
2.Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries.
Huitong RUAN ; Yongfang LI ; Cheng WANG ; Yixu JIANG ; Yulong HAN ; Yiwei LI ; Dandan ZHENG ; Jing YE ; Gang CHEN ; Guo-Yuan YANG ; Lianfu DENG ; Ming GUO ; Xingcai ZHANG ; Yaohui TANG ; Wenguo CUI
Acta Pharmaceutica Sinica B 2023;13(5):2202-2218
Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

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