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Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.
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Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.
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AIM: To establish an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method to determine the distribution of deuterosuccinylcholine chloride (
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Objective@#To discuss the effect of high-density fat-binding SVF-GEL in female facial lipofilling.@*Methods@#This is a retrospective study including 32 female patients, received facial fat transplantation during June 2017 to June 2018 in Yichun College. Each patient underwent high-density fat-binding SVF-GEL transplantation for facial surgery. Patients′satisfaction with the surgery and the rate of secondary surgery was evaluated. Fat was harvested from the inner thigh, centrifuged at 1200 g for 3 min, and the liquid was removed. The upper 2/3 part is prepared for SVF-GEL, for further used in delicate lipofilling in eyelid, tear groove and nasolabial groove. The lower 1/3 high density fat was used for volume restoration, such as forehead, temporal area and cheek.@*Results@#All patients had significant improvements in facial contours with mild swelling and short recovery time. The satisfaction rate was 68.8%(22/32), and the second operation rate was 15.6%(5/32).@*Conclusions@#High-density fat-binding SVF-GEL transplantation can achieve good results in correcting facial volume loss.
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Objective@#To investigate the safety and efficacy of radiofrequency ablation (RFA) with percutaneous iohexol-ethanol injection (PIEI), compared with RFA plus transcatheter arterial chemoembolization (TACE) for patients with primary liver cancer(PLC)in high-risk locations.@*Methods@#From January 2012 to December 2014, 54 patients with PLC in high-risk locations were enrolled. They were divided into Group A (RFA combined with PIEI) and Group B (RFA plus TACE). The efficacy and adverse events were assessed.@*Results@#54 patients had 74 lesions in high-risk locations. There were 26 cases with 40 lesions in Group A, and 28 cases with 34 lesions in Group B. The complete ablation rate of Group A was significantly higher than that of Group B (92.5% vs 70.6%, P=0.014). The two-year local tumor progressionrateand two-year overall survival rate were similar between these two groups (Group A 20.0% vs Group B 38.2%, P=0.083; 90.3% vs 84.3%, P=0.523). Furthermore, the surgery-related severe adverse events of Group A (7.1%, one case of liver abscess and one case ofhematobilia) were more common than that of Group B (0%, P=0.491). No significant differences were found in common adverse events including fever, pain, elevation of aminotransferase and bilirubin.@*Conclusions@#Compared with RFA plus TACE, RFA plus PIEI resulted inbetter complete ablation rate in patients with primary liver cancer in high risk locations. Prospective, randomized, controlled trials are warranted for further evaluation.
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This article disussed the common moral defects of cosmetic medical organization,cosmetic patients and their relatives,society,news media and so on in the cosmetic dispute respectively,and the difficult ethical problems left by the disposals of current sociol system and law to cosmetic medical dispute.