A large number of chemotherapeutic drugs, utilized in the treatment of advanced metastatic clear cell renal cell carcinoma, are typically prone to poor biocompatibility, lack of targeting specificity, and high toxicity, which mostly leads to unsatisfactory clinical outcomes. As a new drug delivery pathway, nanoliposomes have the advantages of simplifying metabolism, reducing drug side‐effects, and providing specific targeting, which can potentially improve the therapeutic effect toward tumor therapy. In this study, a clinically integrated nanoliposome containing Sertraline Hydrochloride and indocyanine green (ICG), here named as Ser/ICG@Lip, was successfully synthesized by film‐dispersion and hydration–sonication methods. The photoacoustic imaging and near‐infrared fluorescence imaging capabilities of this novel nanoliposome were validated in vitro. The high encapsulation rate of Sertraline Hydrochloride and ICG ensured the safety and therapeutic efficacy of the particle. Moreover, our results suggest that chemo‐photothermal combination therapy can be more effective than single photothermal or chemotherapy treatments against malignant tumor cells. This is the first study introducing Sertraline Hydrochloride as a liposome‐encapsulated chemotherapeutic agent, containing photothermal capabilities, for the treatment of metastatic renal clear cell cancer cells. This novel drug system has potential to evolve into an alternate treatment method for metastatic clear cell renal cell carcinoma.
Purpose Hyperuricemia is a common disease that may lead to gout, renal damage, and cardiovascular events. Oral medication is the main treatment for hyperuricemia patients when lifestyle intervention fails. An evaluation of the safety of various urate‐lowering therapies (ULTs) is integral to clinical decision‐making. We constructed a network meta‐analysis (NMA) to evaluate the safety of oral ULTs. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched up to April 1, 2021, for randomized controlled trials that examined the safety of ULTs. The language restriction was English. The three outcomes used to assess the safety of uric acid lowering medications were treatment‐related adverse events, liver damage, and major adverse cardiovascular events (MACE). Results Thirty‐two trials enrolling 23,868 individuals were included in the study. In terms of treatment‐related adverse events, there were no statistically significant differences between five uric acid lowering medications and placebo: allopurinol (risk ratio (RR): 1.08; 95% credible interval (CrI): 0.91, 1.29), febuxostat (RR: 1.05; 95% CrI: 0.89, 1.25), lesinurad (RR: 1.19; 95% CrI: 0.85, 1.67), lesinurad combined with xanthine oxidase inhibitor (XOI, RR: 1.05; 95% CrI: 0.83, 1.32), and topiroxostat (RR: 1.01; 95% CrI: 0.83, 1.23). Topiroxostat likely increases risk of liver damage (RR: 2.65; 95%CI: 1.24, 5.70; NNH: 33.40) as compared with placebo. With regard to MACE, there were no statistically significant differences between three uric acid lowering medications and placebo: allopurinol (RR: 0.63; 95% CrI: 0.36, 1.34), febuxostat (RR: 0.69; 95% CrI: 0.38, 1.66), and lesinurad combined with XOI (RR: 0.56; 95% CrI: 0.23, 1.85). The rankings of different interventions were depicted by cumulative ranking curve (SUCRA). Conclusions Through NMA, we provide some evidence for the safety of ULTs. We found no statistically significant differences in their effects on treatment‐related adverse events and MACE. However, topiroxostat likely increases the risk of liver damage.
BackgroundWe assessed levels of circulating amino acids in different etiologies of chronic kidney disease (CKD) and the association of amino acids with risk factors of CKD progression.Material/MethodsHigh-performance liquid chromatography-based analysis was used to determine amino acid profiles in patients with diabetic nephropathy (DN, n=20), hypertensive nephropathy (HN, n=26), and chronic nephritis (CN, n=33), and in healthy controls (HC, n=25).ResultsAll 3 types of CKD patients displayed decreased serum levels of serine, glycine, GABA, and tryptophan compared with healthy controls. Moreover, serine and tryptophan were positively correlated with glucose in DN cohorts. Total cholesterol was positively correlated with tryptophan levels in the DN cohort and negatively correlated with serine levels in the CN cohort. In the HN cohort, glycine was negatively correlated with triglyceride levels, and systolic blood pressure (SBP) was negatively correlated with GABA levels.ConclusionsPatients with different etiologies of CKD have significantly different amino acids profiles, and this indicates specific supplementary nutritional needs in CKD patients.
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