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1.
Nat Immunol ; 24(11): 1813-1824, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37813965

RESUMEN

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.


Asunto(s)
Citofagocitosis , Macrófagos del Hígado , Humanos , Fagocitosis/genética , Galectinas/genética , Galectinas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo
2.
Eur J Nucl Med Mol Imaging ; 51(6): 1753-1762, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38212531

RESUMEN

PURPOSE: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. METHODS: The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. RESULTS: [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 µSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. CONCLUSIONS: We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.


Asunto(s)
Antígenos de Superficie , Glutamato Carboxipeptidasa II , Neoplasias de la Próstata , Radiometría , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Glutamato Carboxipeptidasa II/metabolismo , Persona de Mediana Edad , Antígenos de Superficie/metabolismo , Distribución Tisular , Radiofármacos/farmacocinética , Radiofármacos/química , Radioisótopos de Flúor/química , Anciano de 80 o más Años , Tomografía Computarizada por Tomografía de Emisión de Positrones
3.
Eur J Nucl Med Mol Imaging ; 51(7): 2124-2133, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38285206

RESUMEN

PURPOSE: This paper discusses the optimization of pharmacokinetic modelling and alternate simplified quantification method for [18F]AlF-P16-093, a novel tracer for in vivo imaging of prostate cancer. METHODS: Dynamic PET/CT scans were conducted on eight primary prostate cancer patients, followed by a whole-body scan at 60 min post-injection. Time-activity curves (TACs) were obtained by drawing volumes of interest for primary prostatic and metastatic lesions. Optimal kinetic modelling involved evaluating three compartmental models (1T2K, 2T3K, and 2T4K) accounting for fractional blood volume (Vb). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (Vt) obtained from the optimal pharmacokinetic analysis. RESULTS: In total, 17 intraprostatic lesions, 10 lymph nodes, and 36 osseous metastases were evaluated. Visually, the contrast of the tumor increased and showed the steepest incline within the first few minutes, whereas background activity decreased over time. Full pharmacokinetic analysis revealed that a reversible two-compartmental (2T4K) model is the preferred kinetic model for the given tracer. The kinetic parameters K1, k3, Vb, and Vt were all significantly higher in lesions when compared with normal tissue (P < 0.01). Several simplified protocols were tested for approximating comprehensive dynamic quantification in tumors, with image-based SURmean (the ratio of tumor SUVmean to blood SUVmean) within the 28-34 min window found to be sufficient for approximating the total distribution Vt values (R2 = 0.949, P < 0.01). Both Vt and SURmean correlated significantly with the total serum prostate-specific antigen (tPSA) levels (P < 0.01). CONCLUSIONS: This study introduced an optimized pharmacokinetic modelling approach and a simplified acquisition method for [18F]AlF-P16-093, a novel PSMA-targeted radioligand, highlighting the feasibility of utilizing one static PET imaging (between 30 and 60 min) for the diagnosis of prostate cancer. Note that the image-derived input function in this study may not reflect the true corrected plasma input function, therefore the interpretation of the associated kinetic parameter estimates should be done with caution.


Asunto(s)
Modelos Biológicos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Radiofármacos/farmacocinética , Cinética , Lisina/análogos & derivados , Urea/análogos & derivados
4.
World J Urol ; 42(1): 189, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38526675

RESUMEN

BACKGROUND: The stone burden based management strategy reported in the guidelines published by different associations is well known for a long time. Staghorn calculi, representing the largest burden and most complex stones, is one of the most challenging cases to practicing urologists in clinical practice. The International Alliance of Urolithiasis (IAU) has released a series of guidelines on the management of urolithiasis. PURPOSE: To develop a series of recommendations for the contemporary management management of staghorn calculi and to provide a clinical framework for urologists treating patients with these complex stones. METHODS: A comprehensive literature search for articles published in English between 01/01/1976 and 31/12/2022 in the PubMed, OVID, Embase and Medline database is performed. A series of recommendations are developed and individually graded following the review of literature and panel discussion. RESULTS: The definition, pathogenesis, pathophysiology, preoperative evaluation, intraoperative treatment strategies and procedural advice, early postoperative management, follow up and prevention of stone recurrence are summarized in the present document. CONCLUSION: A series of recommendations regarding the management of staghorn calculi, along with related commentary and supporting documentation offered in the present guideline is intended to provide a clinical framework for the practicing urologists in the management of staghorn calculi.


Asunto(s)
Cálculos Renales , Cálculos Coraliformes , Urolitiasis , Humanos , Cálculos Coraliformes/cirugía , Cálculos Renales/cirugía , Urolitiasis/terapia
5.
Mol Cancer ; 22(1): 117, 2023 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-37481520

RESUMEN

BACKGROUND: The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive. METHODS: The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay. RESULTS: We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo. CONCLUSIONS: The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Carcinoma de Células Renales , Vesículas Extracelulares , Neoplasias Renales , Humanos , Fibroblastos
6.
Mol Pharm ; 19(7): 2335-2342, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35604773

RESUMEN

Alcoholic liver disease (ALD) has a significant impact on human health and is one of the leading causes of liver disease mortality. The early and exact diagnosis of ALD is very important since the early stage of disease progression can be reversible. Although ALD can be evaluated by ultrasound, CT, or MRI, there is still no imaging technique sufficient in the diagnosis of early-stage ALD. Of the current studies, epigenetic modulation plays a significant role in the development and progression of ALD. In this work, we evaluate whether BRDs play a vital role in the early-stage ALD using our new PET imaging probe of BET proteins, [11C]CW22. PET/CT imaging of [11C]CW22 and [18F]FDG was used to identify early-stage lesions of livers and brains in the mice model. We found that the average uptake values of livers and brains in early-stage ALD were significantly increased for [11C]CW22 PET/CT imaging but only slightly changed in [18F]FDG PET/CT imaging. Consistently, we also found that BRD 3, 4 protein expression levels were significantly higher in the liver and brain tissues of early-stage ALD. Furthermore, through Pmod software, we found that [11C]CW22 PET/CT uptakes in the brain stem, cerebellum, and midbrain were significantly up-regulated in the early-stage ALD. In conclusion, BRDs were important mediators of damage in early-stage ALD. [11C]CW22 PET/CT imaging can detect the early-phase alcohol-induced damage of livers and brains, which will likely lead to human trials in the future.


Asunto(s)
Fluorodesoxiglucosa F18 , Hepatopatías Alcohólicas , Animales , Encéfalo/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Hepatopatías Alcohólicas/diagnóstico por imagen , Hepatopatías Alcohólicas/patología , Ratones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones/métodos
7.
Cell Mol Biol Lett ; 27(1): 41, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35596159

RESUMEN

BACKGROUND: The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N6-methyladenosine (m6A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. METHODS: The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. RESULTS: METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m6A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. CONCLUSIONS: This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment.


Asunto(s)
Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Metiltransferasas , MicroARNs , ARN Largo no Codificante , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Metiltransferasas/genética , Metiltransferasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
8.
BMC Urol ; 22(1): 209, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36544109

RESUMEN

BACKGROUND: Day-surgery percutaneous nephrolithotomy (PCNL) is being developed quickly but some potential factors are affecting the recovery process. This study is aim to analyze the reasons and risk factors for delayed discharge after day-surgery PCNL. METHODS: The data of 205 patients who accepted day-surgery PCNL in our institution between January 2018 and February 2020 were analyzed, retrospectively. Univariate and multivariate logistic regression analysis were used to analyze the risk factors for delayed discharge. Besides, the nomogram prediction model was established by the multivariable logistic regression analysis. RESULTS: The rate of delayed discharge was 14.6%. Independent risk factors for delayed discharge were larger stone burden (odds ratio [OR] = 3.814, P = 0.046), positive urine nitrite (OR = 1.001, P = 0.030), longer duration of surgery (OR = 1.020, P = 0.044), multiple nephrostomy tubes (OR = 4.282, P = 0.008). The five main reasons that caused delayed discharge included psychological reasons, pain, bleeding, urosepsis, and urine leakage. CONCLUSIONS: This study identified some independent risk factors for a hospital length of stay longer than 24 h. Patients with larger renal stones or positive urine nitrite may be at increased risk of delayed discharge after day-surgery PCNL. Reducing surgery time and nephrostomy tubes will help to facilitate recovery.


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Humanos , Nefrolitotomía Percutánea/efectos adversos , Estudios Retrospectivos , Nitritos , Alta del Paciente , Nefrostomía Percutánea/efectos adversos , Cálculos Renales/cirugía , Cálculos Renales/etiología , Factores de Riesgo
9.
Br J Cancer ; 125(6): 865-876, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34274945

RESUMEN

BACKGROUND: Many molecular alterations are shared by embryonic liver development and hepatocellular carcinoma (HCC). Identifying the common molecular events would provide a novel prognostic biomarker and therapeutic target for HCC. METHODS: Expression levels and clinical relevancies of SLC38A4 and HMGCS2 were investigated by qRT-PCR, western blot, TCGA and GEO datasets. The biological roles of SLC38A4 were investigated by functional assays. The downstream signalling pathway of SLC38A4 was investigated by qRT-PCR, western blot, immunofluorescence, luciferase reporter assay, TCGA and GEO datasets. RESULTS: SLC38A4 silencing was identified as an oncofetal molecular event. DNA hypermethylation contributed to the downregulations of Slc38a4/SLC38A4 in the foetal liver and HCC. Low expression of SLC38A4 was associated with poor prognosis of HCC patients. Functional assays demonstrated that SLC38A4 depletion promoted HCC cellular proliferation, stemness and migration, and inhibited HCC cellular apoptosis in vitro, and further repressed HCC tumorigenesis in vivo. HMGCS2 was identified as a critical downstream target of SLC38A4. SLC38A4 increased HMGCS2 expression via upregulating AXIN1 and repressing Wnt/ß-catenin/MYC axis. Functional rescue assays showed that HMGCS2 overexpression reversed the oncogenic roles of SLC38A4 depletion in HCC. CONCLUSIONS: SLC38A4 downregulation was identified as a novel oncofetal event, and SLC38A4 was identified as a novel tumour suppressor in HCC.


Asunto(s)
Sistema de Transporte de Aminoácidos A/genética , Sistema de Transporte de Aminoácidos A/metabolismo , Carcinoma Hepatocelular/patología , Regulación hacia Abajo , Hidroximetilglutaril-CoA Sintasa/metabolismo , Neoplasias Hepáticas/patología , Hígado/embriología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Hígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Trasplante de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-myc/metabolismo , Vía de Señalización Wnt
10.
Cancer Immunol Immunother ; 70(12): 3587-3602, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33934205

RESUMEN

Accumulating evidences indicates that the immune landscape signature dramatically correlates with tumorigenesis and prognosis of prostate cancer (PCa). Here, we identified a novel immune-related gene-based prognostic signature (IRGPS) to predict biochemical recurrence (BCR) after radical prostatectomy. We also explored the correlation between IRGPS and tumor microenvironment. We identified an IRGPS consisting of seven immune-related genes (PPARGC1A, AKR1C2, COMP, EEF1A2, IRF5, NTM, and TPX2) that were related to the BCR-free survival of PCa patients. The high-risk patients exhibited a higher fraction of regulatory T cells and M2 macrophages than the low-risk BCR patients (P < 0.05) as well as a lower fraction of resting memory CD4 T cells and resting mast cells. These high-risk patients also had higher expression levels of CTLA4, TIGIT, PDCD1, LAG3, and TIM3. Finally, a strong correlation was detected between IRGPS and specific clinicopathological features, including Gleason scores and tumor stage. In conclusion, our study reveals the clinical significance and potential functions of the IRGPS, provides more data for predicting outcomes, and suggests more effective immunotherapeutic target strategies for PCa.


Asunto(s)
Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Linfocitos T CD4-Positivos/inmunología , Bases de Datos Genéticas , Humanos , Macrófagos/inmunología , Masculino , Mastocitos/inmunología , Clasificación del Tumor/métodos , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Prostatectomía/métodos , Neoplasias de la Próstata/inmunología , Estudios Retrospectivos , Factores de Riesgo , Linfocitos T Reguladores/inmunología , Microambiente Tumoral/inmunología
11.
World J Urol ; 39(1): 239-246, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32198565

RESUMEN

OBJECTIVE: Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is one of the most frightening multidrug-resistant bacteria that usually causes sepsis. Herein we explored the benefits of nephrostomy drainage prior to percutaneous nephrolithotomy (PCNL) on infection outcomes in patients with ESBL-EC. PATIENTS AND METHODS: Between June 2016 and April 2019, 43 consecutive patients with ESBL-EC who received nephrostomy drainage for > 24 h prior to PCNL were retrospectively evaluated as group 1. 86 patients were randomly selected from patients with ESBL-EC who received concurrent percutaneous access during PCNL as group 2. The postoperative infection complications were compared. RESULTS: Although the total infection complications were not statistically different (11.6% vs. 25.6%, p = 0.066), the severity seemed to be worse among group 2 subjects. Severe infections, including urosepsis (4.7% vs.13.9%) and septic shock (2.3% vs 4.6%), were observed at twice or greater rates in group 2. Blood transfusions were also more frequent (2.3% vs. 13.9%, p = 0.039). Multivariate analysis demonstrated that preoperative drainage was an independent risk factor for postoperative infection events (OR 2.31 CI 1.14-3.48, p = 0.017). Subgroup analyses indicated that preoperative drainage may largely reduce the incidence of urosepsis in patients with hydronephrosis or without receiving preoperative carbapenem therapy. CONCLUSION: Because of the high rate of severe infection after PCNL in patients with ESBL­positive E. coli, preoperative nephrostomy drainage for > 24 h is an effective measure to reduce the risk of severe infection complications, especially in patients with hydronephrosis or those without preoperative carbapenem therapy.


Asunto(s)
Drenaje , Infecciones por Escherichia coli/prevención & control , Nefrolitotomía Percutánea/métodos , Nefrotomía , Infecciones Urinarias/prevención & control , Adulto , Anciano , Escherichia coli/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Estudios Retrospectivos , beta-Lactamasas
12.
World J Urol ; 39(3): 921-927, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32447440

RESUMEN

PURPOSE: The purpose of this study was to evaluate the safety and efficiency of multiple-tract percutaneous nephrolithotomy (PCNL) as a day surgery for the treatment of complex renal stones. PATIENTS AND METHODS: A mature protocol for day surgery was implemented. Forty-six patients who underwent planned day-surgery PCNL via multiple tracts for the treatment of complex renal stones were retrospectively reviewed. All procedures were performed by an experienced surgeon. The outcomes were recorded. RESULTS: The mean stone size and burden were 4.8 cm and 990.2 mm2, respectively. There were 26 (56.5%) and 20 (43.5%) patients with staghorn stones and multiple stones, respectively. Totals of two, three, and more than three tracts (with up to 7 tracts) were established in 22, 11, and 13 patients, respectively. The tract sizes ranged from 14 to 24 Fr. One to four nephrostomy tubes were placed in most patients, and a tubeless process was accomplished in only 3 (6.5%) patients. The mean surgery time was 116 min with a hemoglobin drop of 22.1 ± 16.8 g/L. Eight (17.4%) patients developed postoperative complications, with severe complications (Clavien grades III-IV) in two cases (4.4%). 39 (84.8%) patients were discharged within 24 h after surgery, and 7 (15.2%) patients were fully admitted. Only 1 (2.2%) patient required readmission. The stone clearance rate was 84.8%. CONCLUSIONS: Day-surgery PCNL can be safely performed via multiple percutaneous tracts by experienced surgeons and is an efficient strategy for the treatment of complex renal stones.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Cálculos Renales/cirugía , Nefrolitotomía Percutánea/métodos , Adulto , Anciano , Femenino , Humanos , Cálculos Renales/patología , Masculino , Persona de Mediana Edad , Nefrolitotomía Percutánea/efectos adversos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
13.
World J Urol ; 38(5): 1323-1328, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31522237

RESUMEN

PURPOSE: Percutaneous nephrolithotomy (PCNL) is traditionally performed on an inpatient basis. We determine the safety and outcome of day-surgery PCNL by experienced surgeon hands. PATIENTS AND METHODS: A protocol for day-surgery PCNL was undertaken. A retrospective analysis of all 86 cases of planned day-surgery PCNL accomplished by an experienced surgeon who followed this protocol between May 2017 and March 2019 was performed. Patient demographics, operative data, complications, and readmission rates were recorded. Day-surgery PCNL was defined as discharge of patients either the same day or within 24 h after surgery. RESULTS: The average stone burden was 361.1 mm2 and 70 (81.4%) of patients had multiple stones or staghorn stones. 82 (95.4%) patients achieved same-day discharge or received overnight observation prior to discharge, and 4 patients (4.6%) required full admission (longer than 24 h). The readmission rate was 2.3% (2 patients). The postoperative complications occurred in 10 (11.6%) patients, including 7, 2, 2 of grade I, II, III complications. The average operation time was 64 min and the hemoglobin drop was 15.7 ± 16.9 g/L. The established tracts size ranged from 16 to 22Fr. The stone clearance rate was 90.7%. The tubeless without nephrostomy tube was performed in 60.5%. Eight cases were performed by multiple-tracts PCNL with 2-4 tracts, with only two case required full admission. CONCLUSION: Experienced surgeons who performed day-surgery PCNL experience excellent patient outcomes in appropriately selected patients. Most complications can be treated conservatively and only a few required intervention or readmission.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Cálculos Renales/cirugía , Nefrolitotomía Percutánea , Adulto , Femenino , Hospitales de Alto Volumen , Humanos , Masculino , Persona de Mediana Edad , Nefrolitotomía Percutánea/efectos adversos , Nefrolitotomía Percutánea/métodos , Estudios Retrospectivos , Resultado del Tratamiento
14.
Biochem Biophys Res Commun ; 520(1): 1-7, 2019 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-31554600

RESUMEN

Serine palmitoyltransferase long chain-1 (SPTLC1), which is the rate-limiting enzyme for sphingolipid biosynthesis, has been indicated to be essential for carcinoma cell survival and proliferation in recent, but its role in the regulation of renal cell carcinoma (RCC) remains unknown. In the present study, we found that SPTLC1 expression was significantly decreased in RCC tissues compared to non-tumor tissues, and low SPTLC1 expression was associated with poor overall survival of RCC patients. In addition, our results revealed that forced expression of SPTLC1 could significantly inhibit cell growth in vitro and in vivo via, at least in part, modulating Akt/FOXO1 signaling pathway, thus representing a novel role of SPTLC1 in the regulation of tumor growth in RCC for the first time.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Proteína Forkhead Box O1/metabolismo , Neoplasias Renales/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina C-Palmitoiltransferasa/metabolismo , Animales , Carcinoma de Células Renales/patología , Proliferación Celular , Humanos , Neoplasias Renales/patología , Masculino , Ratones , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Serina C-Palmitoiltransferasa/biosíntesis , Células Tumorales Cultivadas
15.
BJU Int ; 124(3): 496-503, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31136070

RESUMEN

OBJECTIVE: To study the incidence of postoperative systemic inflammatory response syndrome (SIRS) following different antibiotic prophylaxis (ABP) regimens in retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Single-centre, randomised, controlled trial (August 2014-September 2017) including 426 patients with renal stones with preoperative sterile urine managed by RIRS (ClinicalTrials.gov NCT02304822). Different ciprofloxacin-based ABP regimens were used and included a zero dose, single dose (30 min before surgery) or two doses (first dose at 30 min before RIRS and additional dose within 6 h after RIRS). The incidence of SIRS was compared using intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: Each group enrolled 142 patients. In the ITT analysis, a zero dose of ABP was statistically similar to the two ABP regimes for the incidence of SIRS (9.9% vs single dose 4.9%, P = 0.112; vs two doses 4.2%, P = 0.062). There were also no relevant differences across groups in the PP analysis; no urosepsis was recorded. In subgroup analysis with stratification by stone area, the three regimens all had a low and similar incidence of SIRS for stones of ≤200 mm2 in the ITT analysis with a sufficient power value (5.4% vs 6.2% vs 3.6%, P = 0.945 vs single dose and P = 0.553 vs two doses). However, there was a greater chance of SIRS in patients who received no ABP with stones of >200 mm2 (18% vs single dose 4.3%, P = 0.036; vs two doses 5.5%, P = 0.044). Similar trends were seen in the PP analysis. CONCLUSIONS: For patients with preoperative sterile urine, ABP is not strongly recommended in patients with stones of ≤200 mm2 , but for stones >200 mm2 single-dose ABP is still required.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Cálculos Renales/cirugía , Complicaciones Posoperatorias/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Adulto , Antibacterianos/administración & dosificación , Femenino , Humanos , Incidencia , Riñón/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control
16.
BJU Int ; 124(3): 395-400, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30993821

RESUMEN

OBJECTIVES: To investigate the prevalence and associated factors of urolithiasis amongst Uyghur children. SUBJECTS AND METHODS: A cross-sectional survey was conducted of Uyghur children (aged ≤14 years) in the Kashgar Region of China, from July to December 2016. Children were selected by a two-stage random clustered sampling method, evaluated by urinary tract ultrasonography, low-dose computed tomography (CT) examination, blood and urine analysis, and a questionnaire. The prevalence by CT, the prevalence by self-report in the questionnaires, and the lifetime prevalence were evaluated. Binary logistic regression was used to estimate the associated factors. RESULTS: A total of 5605 children were selected and invited to participate in the study. In all, 4813 Uyghur children (2471 boys and 2342 girls), with an mean (SD; range) age of 75.79 (43.81; 2-177) months, were included in the final analysis, with a response rate of 85.9%. The prevalence of paediatric urolithiasis was 1.8% (95% confidence interval [CI] 1.5-2.2) by CT, 2.3% (95% CI 1.9-2.7) by self-report, and 3.6% (95% CI 3.0-4.1) for the overall life-time. The age-sex adjusted prevalence was 2.0% (95% CI 1.6-2.4) by CT. Binary logistic regression analysis showed that body mass index, urinary tract infection, a family history of urolithiasis, and excessive sweating could increase the risk of stone formation, whilst breast feeding and drinking water at midnight could decrease the risk. CONCLUSIONS: Urolithiasis is a major public health problem amongst Uyghur children, and strategies aimed at the prevention of urolithiasis are needed.


Asunto(s)
Etnicidad/estadística & datos numéricos , Urolitiasis/epidemiología , Adolescente , Niño , Preescolar , China/epidemiología , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Prevalencia
17.
Cell Physiol Biochem ; 48(6): 2549-2562, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30121668

RESUMEN

BACKGROUND/AIMS: Kidney renal clear cell carcinoma (KIRC) is one of the most fatal malignancies due to late diagnosis and poor treatment. To improve its prognosis, a screening for molecular biomarkers of KIRC is urgently needed. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and prognosis of cancers. However, it is not clear whether lncRNAs can be used as molecular biomarkers in predicting the survival of KIRC patients. METHODS: In this study, our aim was to identify lncRNAs/mRNAs signatures and their prognostic values in KIRC. The aberrant expression profile of mRNAs and lncRNAs in 529 KIRC tissues and 72 adjacent non-tumor pancreatic tissues were obtained from the Cancer Genome Atlas (TCGA). A weighted gene co-expression network analysis (WGCNA) of two key lncRNAs was constructed. We constructed an aberrant lncRNA-mRNA-miRNA ceRNA network in CESC. In addition, Gene Ontology (GO) and KEGG pathway analysis were performed. RESULTS: Using lncRNA/mRNA expression profiling data, the overall analysis revealed that two novel lncRNA signatures (DNM1P35 and MIR155HG) and several mRNAs were found to be significantly correlated with KIRC patient's overall analysis. Based on the target gene of the two lncRNA in co-expression network, the GO and KEGG analysis were also performed. A dysregulated lncRNA-related ceRNA network was also observed. CONCLUSION: These results suggested that the two novel lncRNAs signatures may act as independent prognostic biomarkers for predicting the survival of KIRC patient.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , ARN Largo no Codificante/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , ARN Largo no Codificante/genética , ARN Mensajero/metabolismo
18.
World J Urol ; 36(6): 955-961, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29387932

RESUMEN

PURPOSE: To compare the efficacy and safety of Super-mini percutaneous nephrolithotomy (SMP, F12-F14) and Miniperc (F18) in the treatment of renal stones of 2-4 cm in size. METHODS: A prospective comparative analysis of outcomes of patients who underwent SMP and Miniperc for treatment of 2-4 cm renal stones was conducted between July 2014 and January 2017. Demographic data, stone criteria, operative technique, complications, blood transfusion, hemoglobin decrease, stone-free rate (SFR) and length of hospital stay were compared between the two groups. Propensity score-matching (PSM) analysis was performed to further compare the outcomes between the two groups. RESULTS: 79 and 257 patients underwent SMP and Miniperc, respectively. After matching, 73 patients in each group were included. The stone burden was comparable for both groups (3.0 ± 1.1 vs 3.2 ± 0.7 cm, p = 0.577). Mean operation time was not significant different between two groups (p = 0.115), while the hospital stay of SMP was much shorter than Miniperc (2.6 ± 1.4 vs 5.2 ± 1.8, p < 0.0001). Both groups had similar SFRs in postoperative 1 day and at 1 month follow-up (p = 0.326, p = 0.153), while SMP achieved a markedly higher tubeless rate than Miniperc (84.9 vs 47.9%, p < 0.0001). The total complication rate was significantly lower in SMP (16.4 vs 41.1%, p = 0.0001), and the SIRS rate was markedly lower in SMP group (1.4 vs 12.3%, p = 0.009). CONCLUSIONS: SMP is equally effective as Miniperc in the treatment of moderate renal calculi, and has the significant advantage in hospital duration and tubeless rate.


Asunto(s)
Cálculos Renales/cirugía , Nefrostomía Percutánea/estadística & datos numéricos , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Cálculos Renales/patología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Nefrostomía Percutánea/métodos , Ensayos Clínicos Controlados no Aleatorios como Asunto , Tempo Operativo , Puntaje de Propensión , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
19.
Clin Chem Lab Med ; 56(4): 642-648, 2018 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-29095693

RESUMEN

BACKGROUND: The aim of the study was to establish reference intervals for 24-h urinary stone risk factors in the healthy Chinese Han population. METHODS: From May 2013 to July 2014, we collected and analyzed 24-h urine samples from healthy adult Han population during a cross-sectional study across China. The protocol for analysis of 24-h urine included volume, pH, oxalate, citrate, sodium, potassium, chloride, calcium, phosphorous, creatinine, urate, magnesium, the ion activity products of calcium oxalate (AP(CaOx) indexs) and calcium phosphate (AP(CaP) indexs). We calculated the reference intervals according to the Clinical and Laboratory Standards Institute (CLSI) 2008 guidelines and compared them with those recorded in other studies. RESULTS: A total of 132 male and 123 female healthy subjects with a mean (SD, range) age of 52.4 (15.2, 19-89) years were eligible in the final analysis. Men had higher 24-h excretion of creatinine, calcium, urate and phosphorus and lower levels of citrate, magnesium, chloride, sodium and potassium than women. AP(CaOx) indexs and AP(CaP) indexs were significantly higher among men than women. When urinary findings were compared with the reference intervals, most of our data showed a high abnormality rate, especially for creatinine, calcium, citrate, magnesium, chloride, sodium and potassium. CONCLUSIONS: The present study revealed the normal metabolic status for stone risk factors of the Chinese Han population. It is therefore necessary for each country or region to define their own reference intervals for comparison of stone risk factors between patients and healthy subjects.


Asunto(s)
Pueblo Asiatico , Etnicidad , Cálculos Urinarios/orina , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Factores de Tiempo , Adulto Joven
20.
BJU Int ; 119(4): 612-618, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27862806

RESUMEN

OBJECTIVE: To compare the safety and efficacy of fluoroscopic guidance (FG), total ultrasonographic guidance (USG), and combined ultrasonographic and fluoroscopic guidance (CG) for percutaneous renal access in mini-percutaneous nephrolithotomy (mini-PCNL). PATIENTS AND METHODS: The present study was conducted between July 2014 and May 2015 as a prospective randomised trial at the First Affiliated Hospital of Guangzhou Medical University. In all, 450 consecutive patients with renal stones of >2 cm were randomised to undergo FG, USG, or CG mini-PCNL (150 patients for each group). The primary endpoints were the stone-free rate (SFR) and blood loss (haemoglobin decrease during the operation and transfusion rate). Secondary endpoints included access failure rate, operating time, and complications. S.T.O.N.E. score was used to document the complexity of the renal stones. The study was registered at http://clinicaltrials.gov/ (NCT02266381). RESULTS: The three groups had similar baseline characteristics. With S.T.O.N.E. scores of 5-6 or 9-13, the SFRs were comparable between the three groups. For S.T.O.N.E. scores of 7-8, FG and CG achieved significantly better SFRs than USG (one-session SFR 85.1% vs 88.5% vs 66.7%, P = 0.006; overall SFR at 3 months postoperatively 89.4% vs 90.2% vs 69.8%, P = 0.002). Multiple-tracts mini-PCNL was used more frequently in the FG and CG groups than in the USG group (20.7% vs 17.1% vs 9.5%, P = 0.028). The mean total radiation exposure time was significantly greater for FG than for CG (47.5 vs 17.9 s, P < 0.001). The USG had zero radiation exposure. There was no significant difference in the haemoglobin decrease, transfusion rate, access failure rate, operating time, nephrostomy drainage time, and hospital stay among the groups. The overall operative complication rates using the Clavien-Dindo grading system were similar between the groups. CONCLUSIONS: Mini-PCNL under USG is as safe and effective as FG or CG in the treatment of simple kidney stones (S.T.O.N.E. scores 5-6) but with no radiation exposure. FG or CG is more effective for patients with S.T.O.N.E. scores of 7-8, where multiple percutaneous tracts may be necessary.


Asunto(s)
Fluoroscopía/métodos , Cálculos Renales/cirugía , Litotricia , Procedimientos Quirúrgicos Mínimamente Invasivos , Nefrostomía Percutánea , Ultrasonografía/métodos , Analgésicos/uso terapéutico , Femenino , Humanos , Cálculos Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
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