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1.
Urol Int ; 108(4): 334-338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38537617

RESUMO

INTRODUCTION: The aim of this study was to explore the safety and feasibility of single-port nephroscopy combined with a needle electrode technique to unroof single dorsal simple renal cysts (SRCs). METHODS: This was a retrospective analysis of the clinical data for 18 patients with single dorsal SRCs treated with single-port nephroscopy and a needle electrode technique at Zhongshan City People's Hospital from August 2021 to August 2022. The basic information included the cyst condition, surgical methods and recurrence rate, and follow-up was conducted with CT imaging. RESULTS: The surgery was successful in all 18 patients. The duration of surgery ranged from 24 to 46 min, with an average of 35.83 ± 1.62 min; the intraoperative bleeding volume ranged from 2 to 20 mL, with an average of 9.0 ± 1.3 mL; and the visual analog scale (VAS) score within 24 h after surgery ranged from 1 to 6 points, with an average of 2.72 ± 0.36 points. There were no significant postoperative complications, such as bleeding, urinary fistula, or infection. All drainage tubes were removed on the first day after surgery. After 1 year of postoperative follow-up, 1 patient experienced recurrence, for a recurrence rate of 5.6%. CONCLUSION: Single-port nephroscopy combined with a needle electrode technique is a safe, feasible, and effective minimally invasive surgical approach for treating single dorsal SRCs.


Assuntos
Estudos de Viabilidade , Doenças Renais Císticas , Agulhas , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Doenças Renais Císticas/cirurgia , Doenças Renais Císticas/diagnóstico por imagem , Eletrodos , Resultado do Tratamento , Laparoscopia , Idoso
2.
J Ren Nutr ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615701

RESUMO

OBJECTIVE: Despite adequate dialysis, the prevalence of hyperkalemia in Chinese hemodialysis (HD) patients remains elevated. This study aims to evaluate the effectiveness of a dietary recommendation system driven by generative pretrained transformers (GPTs) in managing potassium levels in HD patients. METHODS: We implemented a bespoke dietary guidance tool utilizing GPT technology. Patients undergoing HD at our center were enrolled in the study from October 2023 to November 2023. The intervention comprised of two distinct phases. Initially, patients were provided with conventional dietary education focused on potassium management in HD. Subsequently, in the second phase, they were introduced to a novel GPT-based dietary guidance tool. This artificial intelligence (AI)-powered tool offered real-time insights into the potassium content of various foods and personalized dietary suggestions. The effectiveness of the AI tool was evaluated by assessing the precision of its dietary recommendations. Additionally, we compared predialysis serum potassium levels and the proportion of patients with hyperkalemia among patients before and after the implementation of the GPT-based dietary guidance system. RESULTS: In our analysis of 324 food photographs uploaded by 88 HD patients, the GPTs system evaluated potassium content with an overall accuracy of 65%. Notably, the accuracy was higher for high-potassium foods at 85%, while it stood at 48% for low-potassium foods. Furthermore, the study examined the effect of GPT-based dietary advice on patients' serum potassium levels, revealing a significant reduction in those adhering to GPTs recommendations compared to recipients of traditional dietary guidance (4.57 ± 0.76 mmol/L vs. 4.84 ± 0.94 mmol/L, P = .004). Importantly, compared to traditional dietary education, dietary education based on the GPTs tool reduced the proportion of hyperkalemia in HD patients from 39.8% to 25% (P = .036). CONCLUSION: These results underscore the promising role of AI in improving dietary management for HD patients. Nonetheless, the study also points out the need for enhanced accuracy in identifying low potassium foods. It paves the way for future research, suggesting the incorporation of extensive nutritional databases and the assessment of long-term outcomes. This could potentially lead to more refined and effective dietary management strategies in HD care.

3.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39000284

RESUMO

African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC50 = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations.


Assuntos
Vírus da Febre Suína Africana , Antivirais , Benzilisoquinolinas , Macrófagos Alveolares , NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Replicação Viral , Animais , Macrófagos Alveolares/virologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Replicação Viral/efeitos dos fármacos , Vírus da Febre Suína Africana/efeitos dos fármacos , Vírus da Febre Suína Africana/fisiologia , Suínos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Benzilisoquinolinas/farmacologia , Antivirais/farmacologia , Febre Suína Africana/virologia , Febre Suína Africana/tratamento farmacológico , Febre Suína Africana/metabolismo
4.
J Cancer Res Clin Oncol ; 150(1): 21, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38244085

RESUMO

PURPOSE: The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive evaluation to inform clinical decision-making. We conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions. METHODS: We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts from inception to June 1, 2023. NMA was performed to calculate and analyze progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events of grade 3 or higher (≥ 3 AEs). RESULTS: Out of the 10,313 manuscripts retrieved, we included 28 RCTs involving 11,680 patients. Regarding PFS and ORR, the combination of trastuzumab with tyrosine kinase inhibitors (TKIs) was more favorable than dual-targeted therapy. If only using trastuzumab, combination chemotherapy is superior to monochemotherapy in terms of PFS. It is important to note that the addition of anthracycline did not result in improved PFS. For patients with hormone receptor-positive HER2-positive diseases, dual-targeted combined with endocrine therapy showed better benefit in terms of PFS compared to dual-targeted alone, but it did not reach statistical significance. The comprehensive analysis of PFS and ≥ 3 AEs indicates that monochemotherapy combined with dual-targeted therapy still has the optimal balance between efficacy and safety. CONCLUSION: Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Mama/metabolismo , Trastuzumab/uso terapêutico , Receptor ErbB-2/metabolismo , Docetaxel , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
J Nat Med ; 78(3): 722-731, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38683298

RESUMO

We previously demonstrated that ginsenoside Re (G-Re) has protective effects on acute kidney injury. However, the underlying mechanism is still unclear. In this study, we conducted a meta-analysis and pathway enrichment analysis of all published transcriptome data to identify differentially expressed genes (DEGs) and pathways of G-Re treatment. We then performed in vitro studies to measure the identified autophagy and fibrosis markers in HK2 cells. In vivo studies were conducted using ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) models to evaluate the effects of G-Re on autophagy and kidney fibrosis. Our informatics analysis identified autophagy-related pathways enriched for G-Re treatment. Treatment with G-Re in HK2 cells reduced autophagy and mRNA levels of profibrosis markers with TGF-ß stimulation. In addition, induction of autophagy with PP242 neutralized the anti-fibrotic effects of G-Re. In murine models with UUO and AAN, treatment with G-Re significantly improved renal function and reduced the upregulation of autophagy and profibrotic markers. A combination of informatics analysis and biological experiments confirmed that ginsenoside Re could improve renal fibrosis and kidney function through the regulation of autophagy. These findings provide important insights into the mechanisms of G-Re's protective effects in kidney injuries.


Assuntos
Autofagia , Fibrose , Ginsenosídeos , Rim , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Autofagia/efeitos dos fármacos , Animais , Fibrose/tratamento farmacológico , Camundongos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Humanos , Nefropatias/tratamento farmacológico , Masculino , Linhagem Celular , Injúria Renal Aguda/tratamento farmacológico , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Obstrução Ureteral/tratamento farmacológico
6.
Free Radic Biol Med ; 218: 120-131, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583680

RESUMO

Sepsis-induced acute kidney injury (S-AKI) is the most common type of acute kidney injury (AKI), accompanied by elevated morbidity and mortality rates. This study investigated the mechanism by which lipid droplets (LDs) degraded via autophagy (lipophagy)required for RAB7 regulated ferroptosis in the pathogenesis of S-AKI. Here, we constructed the S-AKI model in vitro and in vivo to elucidate the potential relationship of lipophagy and ferroptosis, and we first confirmed that the activation of lipophagy promoted renal tubular epithelial cell ferroptosis and renal damage in S-AKI. The results showed that lipopolysaccharide (LPS) induced a marked increase in lipid peroxidation and ferroptosis, which were rescued by ferrstain-1 (Fer-1), an inhibitor of ferroptosis. In addition, LPS induced the remarkable activation of RAB7-mediated lipophagy. Importantly, silencing RAB7 alleviated LPS-induced lipid peroxidation and ferroptosis. Thus, the present study demonstrated the potential significant role of ferroptosis and lipophagy in sepsis-induced AKI, and contributed to better understanding of the pathogenesis and treatment targets of AKI.


Assuntos
Injúria Renal Aguda , Autofagia , Ferroptose , Peroxidação de Lipídeos , Lipopolissacarídeos , Sepse , Proteínas rab de Ligação ao GTP , proteínas de unión al GTP Rab7 , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/etiologia , Sepse/complicações , Sepse/metabolismo , Sepse/patologia , Sepse/genética , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Ferroptose/genética , Animais , Camundongos , Humanos , Masculino , Gotículas Lipídicas/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
7.
Cell Death Dis ; 15(1): 63, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233375

RESUMO

Acute kidney injury (AKI) constitutes a prevalent clinical syndrome characterized by elevated morbidity and mortality rates, emerging as a significant public health issue. This study investigates the interplay between endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and ER-associated degradation (ER-phagy) in the pathogenesis of AKI. We employed four distinct murine models of AKI-induced by contrast media, ischemia-reperfusion injury, cisplatin, and folic acid-to elucidate the relationship between ER-phagy, ER stress, and apoptosis. Our findings reveal a marked decrease in ER-phagy coinciding with an accumulation of damaged ER, elevated ER stress, and increased apoptosis across all AKI models. Importantly, overexpression of DDRGK1 in HK-2 cells enhanced ER-phagy levels, ameliorating contrast-induced ER stress and apoptosis. These findings unveil a novel protective mechanism in AKI, wherein DDRGK1-UFL1-mediated ER-phagy mitigates ER stress and apoptosis in renal tubular epithelial cells. Our results thereby contribute to understanding the molecular underpinnings of AKI and offer potential therapeutic targets for its treatment.


Assuntos
Injúria Renal Aguda , Retículo Endoplasmático , Animais , Humanos , Camundongos , Injúria Renal Aguda/metabolismo , Apoptose , Autofagia/fisiologia , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia
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