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1.
肾脏是人体最重要的排泄器官。肾单元近端小管细胞具有多种药物转运体和代谢酶,在药物及其代谢物处置中发挥关键作用。近端小管细胞中主要转运体包括有机阴离子转运体、有机阳离子转运体、有机阳离子/肉毒碱转运体、多药及毒素外排转运蛋白、P-糖蛋白、乳腺癌耐药蛋白和多药耐药相关蛋白;主要代谢酶包括细胞色素P450酶,UDP-葡萄糖醛酸基转移酶、磺酸基转移酶、谷胱甘肽S-转移酶。肾脏转运体和/或代谢酶介导药物相互作用(DDIs)是临床关注的重要问题。肾脏转运体和代谢酶存在密切协作关系,在肾脏也存在多种相互作用现象(包括转运-转运相互作用,代谢-代谢相互作用和转运-代谢相互作用),其显著影响药物肾脏处置、临床疗效和肾毒性。本文系统阐述了这些相互作用对药物及其代谢物的肾脏排泄、药动学、DDIs和肾毒性的影响。今后需要进一步阐明肾脏转运-代谢相互作用机制,将有助于研究体内药物肾脏处置和DDIs,促进临床合理用药。 相似文献
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《Value in health》2022,25(3):331-339
ObjectivesClinical artificial intelligence (AI) is a novel technology, and few economic evaluations have focused on it to date. Before its wider implementation, it is important to highlight the aspects of AI that challenge traditional health technology assessment methods.MethodsWe used an existing broad value framework to assess potential ways AI can provide good value for money. We also developed a rubric of how economic evaluations of AI should vary depending on the case of its use.ResultsWe found that the measurement of core elements of value—health outcomes and cost—are complicated by AI because its generalizability across different populations is often unclear and because its use may necessitate reconfigured clinical processes. Clinicians’ productivity may improve when AI is used. If poorly implemented though, AI may also cause clinicians’ workload to increase. Some AI has been found to exacerbate health disparities. Nevertheless, AI may promote equity by expanding access to medical care and, when properly trained, providing unbiased diagnoses and prognoses. The approach to assessment of AI should vary based on its use case: AI that creates new clinical possibilities can improve outcomes, but regulation and evidence collection may be difficult; AI that extends clinical expertise can reduce disparities and lower costs but may result in overuse; and AI that automates clinicians’ work can improve productivity but may reduce skills.ConclusionsThe potential uses of clinical AI create challenges for health technology assessment methods originally developed for pharmaceuticals and medical devices. Health economists should be prepared to examine data collection and methods used to train AI, as these may impact its future value. 相似文献
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Since their inception in the 1960s–70s, mesenchymal stem/stromal cells (MSCs) have gained interest because of their differentiation potential, anti-inflammatory effects, and immune-modulating properties. Both cell-based and cell-free MSC treatments show healing capacity in injured tissues. Cell-based treatment comprises MSCs and all secreted products, whereas cell-free treatments include only the secreted products. MSCs are therapeutically administered to many damaged organs owing to their efficacy. Specifically, the eye is a unique organ system to study the effects of MSCs, as treatment is easily applied and measured owing to its external location. The eye holds an immune-privileged status, wherein inflammation and immune responses are innately down-regulated. As excessive inflammation in the cornea often leads to fibrosis and irreversible corneal hazing, many studies have investigated the anti-inflammatory and immune-modulating capacities of MSCs. Decades of research suggest that MSCs modulate the immune response by secreting cytokines, growth factors, and extracellular matrix proteins that inhibit the infiltration of inflammatory cells following injury and promote a healing phenotype via M2 macrophage polarization. MSCs have also shown trans-differentiation potential into cornea-specific cell types during the wound healing process, such as corneal epithelial, stromal, or endothelial cells. This review discusses recent investigations of MSC treatment in the cornea, focusing on therapeutic efficacy, mechanisms, and future directions. 相似文献
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目的探讨辅助生殖技术中女方经阴道超声取卵手术导致泌尿系损伤的临床特点及诊断、处理措施。方法回顾性分析广西壮族自治区生殖医院2012年至2020年辅助生殖技术女方取卵手术中发生泌尿系损伤的临床资料、疾病类型、发现时机、诊治情况、预后及处理措施。结果 44 144例取卵手术中,发生泌尿系损伤20例,发生率为0.045%。其中膀胱损伤19例,输尿管损伤1例。在膀胱损伤中,术中发现1例,术后发现18例,输尿管损伤为术后发现。其中有8例是在进行了胚胎移植术后才发现,最终有4例获得妊娠。全部的病例经对症处理、膀胱冲洗和(或)膀胱镜检查、止血等治疗后,均痊愈。结论在辅助生殖技术中女方取卵手术损伤虽小,但要注意防范泌尿系损伤发生的风险,及时发现并处理,利于辅助生殖技术的后续治疗。 相似文献
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《Clinical lung cancer》2022,23(6):467-476
BackgroundImmune checkpoint inhibitor (ICI) monotherapy is more effective than cytotoxic chemotherapy in improving overall survival (OS) among patients with advanced-stage non-small cell lung cancer (NSCLC). Recently, chemotherapy combined with ICI has been found to yield good outcomes. However, ICI monotherapy is still considered an important treatment option. Data on long-term progression-free survival (PFS) and OS in real-world settings are limited.Patients and MethodsThis was a multicenter retrospective observational study. A total of 435 consecutive patients histologically diagnosed with advanced, metastatic, or recurrent NSCLC treated with ICI monotherapy were enrolled in this study from December 2015 to December 2018. Clinical data were collected from electronic medical records and pharmacy databases.ResultsThe PFS and OS of the patients were 3.4 and 13.0 months, respectively. The objective response and disease control rates were 22.8% and 54.9%, respectively, and the 4-year survival rate was 17.9%. Multivariate analyses revealed that elder patients (>70 years), good Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, programmed death-ligand 1 tumor proportion score (PD-L1 TPS) of ≥ 50%, absence of bone metastasis, and presence of immune-related skin toxicity, which is an immune-related adverse event, were correlated with good PFS. Moreover, good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good OS.ConclusionsThe 4-year survival rate was 17.9%. Good ECOG PS score, PD-L1 TPS of ≥ 50%, absence of bone metastasis, and presence of skin toxicity were correlated with good PFS and OS. 相似文献
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