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1.
Res Sq ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38585965

RESUMEN

Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 is highly expressed and positively correlated with neuroendocrine markers in patients with NEPC. High PLXND1 expression is associated with poorer prognosis in prostate cancer patients. Additionally, PLXND1 was upregulated and negatively regulated by androgen receptor signaling in enzalutamide-resistant cells. Knockdown or knockout of PLXND1 inhibit neural lineage pathways, suppressing NEPC cell proliferation, PDX tumor organoid viability, and xenograft tumor growth. Mechanistically, the chaperone protein HSP70 regulates PLXND1 protein stability through degradation, and inhibition of HSP70 decreases PLXND1 expression and NEPC organoid growth. In summary, our findings suggest that PLXND1 could be a new therapeutic target and molecular indicator for NEPC.

2.
Aging Clin Exp Res ; 36(1): 71, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485798

RESUMEN

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.


Asunto(s)
Hiperplasia Prostática , Resección Transuretral de la Próstata , Obstrucción del Cuello de la Vejiga Urinaria , Masculino , Humanos , Hiperplasia Prostática/cirugía , Nomogramas , Estudios Retrospectivos , Obstrucción del Cuello de la Vejiga Urinaria/cirugía
3.
Biomed Pharmacother ; 173: 116312, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417288

RESUMEN

Bladder cancer (BC) is a common malignant tumor of urinary system, which can be divided into muscle-invasive BC (MIBC) and nonmuscle-invasive BC (NMIBC). The number of BC patients has been gradually increasing currently. At present, bladder tumours are diagnosed and followed-up using a combination of cystoscopic examination, cytology and histology. However, the detection of early grade tumors, which is much easier to treat effectively than advanced stage disease, is still insufficient. It frequently recurs and can progress when not expeditiously diagnosed and monitored following initial therapy for NMIBC. Treatment strategies are totally different for different stage diseases. Therefore, it is of great practical significance to study new biomarkers for diagnosis and prognosis. In this review, we summarize the current state of biomarker development in BC diagnosis and prognosis prediction. We retrospectively analyse eight diagnostic biomarkers and eight prognostic biomarkers, in which CK, P53, PPARγ, PTEN and ncRNA are emphasized for discussion. Eight molecular subtype systems are also identified. Clinical translation of biomarkers for diagnosis, prognosis, monitoring and treatment will hopefully improve outcomes for patients. These potential biomarkers provide an opportunity to diagnose tumors earlier and with greater accuracy, and help identify those patients most at risk of disease recurrence.


Asunto(s)
Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Biomarcadores de Tumor/genética , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria/patología
4.
Heliyon ; 10(2): e23203, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38312641

RESUMEN

Several clinical and preclinical studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, reduce the incidence of various cancer types. However, there is still a lack of literature evaluating the overall association between multiple cancer morbidities and NSAIDs. Thus, we conducted an umbrella review to evaluate the quality of evidence, validity, and biases of the existing systematic reviews and meta-analyses on the relationships between NSAIDS and multiple tumor incidence outcomes. We found that NSAIDs might be associated with a decreased risk of several cancers, including the central nervous system, breast, esophageal, gastric, head and neck, hepatocellular, cholangiocarcinoma, colorectal, endometrial, lung, ovary, prostate, and pancreatic cancers, but regular intake of any dose of non-aspirin NSAIDs (NA-NSAIDs) could increase the incidence of kidney cancer. However, most of included studies are evaluated as low quality according to our evidence assessment. Furthermore, due to the potential side effects, such as hemorrhage, digestive symptoms and peptic ulcer, it is still not recommend to use NSAIDs regularly to prevent cancers.

5.
Asian J Surg ; 47(1): 505-512, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37330300

RESUMEN

BACKGROUND: Primary urethral melanoma is extremely rare and malignant, and accounts for <1% of all melanoma cases. Here, we aimed to gain more insight into the pathological and follow-up outcomes of patients with this tumor type. METHODS: We conducted a retrospective analysis of nine patients who had undergone comprehensive treatment at West China Hospital since 2009. Furthermore, we also performed a questionnaire-based survey to determine the quality of life and health statuses of surviving patients. RESULTS: Most participants were women, and their ages ranged between 57 and 78 years (mean age: 64.9 years). Common clinical presentations included pigmentation, moles, and irregular neoplasms in the urethral meatus with or without bleeding. The final diagnosis was based on pathological and immunohistochemical examination results. All patients underwent regular follow-ups after receiving surgical or non-surgical therapy, such as chemotherapy or radiotherapy. DISCUSSION/CONCLUSION: Our study revealed that pathological and immunohistochemical tests are crucial for precise diagnosis, especially in asymptomatic patients. Primary malignant urethral melanoma generally has a poor prognosis; therefore, early and accurate diagnosis is imperative. Timely surgical intervention and immunotherapy can help improve patient prognosis. Moreover, an optimistic outlook and family support may augment the clinical management of this disease.


Asunto(s)
Melanoma , Neoplasias Uretrales , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Melanoma/diagnóstico , Melanoma/terapia , Melanoma/patología , Uretra , Estudios Retrospectivos , Calidad de Vida , Neoplasias Uretrales/diagnóstico , Neoplasias Uretrales/terapia , Neoplasias Uretrales/patología
6.
Chin Med J (Engl) ; 137(2): 209-221, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-37390491

RESUMEN

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.


Asunto(s)
Cadenas beta de Integrinas , Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Vejiga Urinaria , Animales , Ratones , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Actinas/metabolismo , Recurrencia Local de Neoplasia , Serina-Treonina Quinasas TOR/metabolismo , Glucólisis , Línea Celular Tumoral , Proliferación Celular , Mamíferos/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo
7.
Front Nutr ; 10: 1263853, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781125

RESUMEN

Selenium is an essential trace metalloid element that is associated with fundamental importance to human health. Our umbrella review aimed to evaluate the quality of evidence, validity, and biases in the relationship between selenium intake and health-related outcomes according to published systematic reviews with pooled data and meta-analyses. Selenium intake is associated with a decreased risk of digestive system cancers, all-cause mortality, depression, and Keshan disease, when in children reduce the risk of Kashin-Beck disease. Additionally, selenium supplementation can improve sperm quality, polycystic ovary syndrome, autoimmune thyroid disease, cardiovascular disease, and infective outcomes. Selenium supplementation also has relationship with a decreased concentration of serum lipids including total cholesterol and very low-density lipoprotein cholesterol. However, no evidence has shown that selenium is associated with better outcomes among patients in intensive care units. Furthermore, selenium intake may be related with a higher risk of type 2 diabetes and non-melanoma skin cancers. Moreover, most of included studies are evaluated as low quality according to our evidence assessment. Based on our study findings and the limited advantages of selenium intake, it is not recommended to receive extra supplementary selenium for general populations, and selenium supplementation should not be continued in patients whose selenium-deficient status has been corrected.

8.
Asian J Androl ; 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37594295

RESUMEN

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

9.
Apoptosis ; 28(7-8): 1198-1215, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37184582

RESUMEN

Cell death constitutes an indispensable part of the organismal balance in the human body. Generally, cell death includes regulated cell death (RCD) and accidental cell death (ACD), reflecting the intricately molecule-dependent process and the uncontrolled response, respectively. Furthermore, diverse RCD pathways correlate with multiple diseases, such as tumors and neurodegenerative diseases. Meanwhile, with the development of precision medicine, novel nano-based materials have gradually been applied in the clinical diagnosis and treatment of tumor patients. As the carrier, organic, inorganic, and biomimetic nanomaterials could facilitate the distribution, improve solubility and bioavailability, enhance biocompatibility and decrease the toxicity of drugs in the body, therefore, benefiting tumor patients with better survival outcomes and quality of life. In terms of the most studied cell death pathways, such as apoptosis, necroptosis, and pyroptosis, plenty of studies have explored specific types of nanomaterials targeting the molecules and signals in these pathways. However, no attempt was made to display diverse nanomaterials targeting different RCD pathways comprehensively. In this review, we elaborate on the potential mechanisms of RCD, including intrinsic and extrinsic apoptosis, necroptosis, ferroptosis, pyroptosis, autophagy-dependent cell death, and other cell death pathways together with corresponding nanomaterials. The thorough presentation of RCD pathways and diverse nano-based materials may provide a wider cellular and molecular landscape of tumor diagnosis and treatments.


Asunto(s)
Neoplasias , Muerte Celular Regulada , Humanos , Apoptosis , Calidad de Vida , Muerte Celular , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico
10.
BMJ ; 381: e071609, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-37019448

RESUMEN

OBJECTIVE: To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary sugar consumption and health outcomes. DESIGN: Umbrella review of existing meta-analyses. DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of reference lists. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomised controlled trials, cohort studies, case-control studies, or cross sectional studies that evaluated the effect of dietary sugar consumption on any health outcomes in humans free from acute or chronic diseases. RESULTS: The search identified 73 meta-analyses and 83 health outcomes from 8601 unique articles, including 74 unique outcomes in meta-analyses of observational studies and nine unique outcomes in meta-analyses of randomised controlled trials. Significant harmful associations between dietary sugar consumption and 18 endocrine/metabolic outcomes, 10 cardiovascular outcomes, seven cancer outcomes, and 10 other outcomes (neuropsychiatric, dental, hepatic, osteal, and allergic) were detected. Moderate quality evidence suggested that the highest versus lowest dietary sugar consumption was associated with increased body weight (sugar sweetened beverages) (class IV evidence) and ectopic fatty accumulation (added sugars) (class IV evidence). Low quality evidence indicated that each serving/week increment of sugar sweetened beverage consumption was associated with a 4% higher risk of gout (class III evidence) and each 250 mL/day increment of sugar sweetened beverage consumption was associated with a 17% and 4% higher risk of coronary heart disease (class II evidence) and all cause mortality (class III evidence), respectively. In addition, low quality evidence suggested that every 25 g/day increment of fructose consumption was associated with a 22% higher risk of pancreatic cancer (class III evidence). CONCLUSIONS: High dietary sugar consumption is generally more harmful than beneficial for health, especially in cardiometabolic disease. Reducing the consumption of free sugars or added sugars to below 25 g/day (approximately 6 teaspoons/day) and limiting the consumption of sugar sweetened beverages to less than one serving/week (approximately 200-355 mL/week) are recommended to reduce the adverse effect of sugars on health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022300982.


Asunto(s)
Azúcares de la Dieta , Aumento de Peso , Humanos , Azúcares de la Dieta/efectos adversos , Estudios Transversales , Revisiones Sistemáticas como Asunto , Azúcares , Bebidas/efectos adversos
11.
Int Urol Nephrol ; 55(11): 2829-2844, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37017820

RESUMEN

BACKGROUND: Intravenous fluid therapy is important for pediatric and adult patients in intensive care units (ICUs). However, medical professionals continue to struggle to determine the most appropriate fluids to obtain the best possible outcomes for each patient. OBJECTIVE: We conducted a meta-analysis involving cohort studies and randomized controlled trials (RCTs) to compare the influence of balanced crystalloid solutions and normal saline among patients in ICUs. PATIENTS AND METHODS: Studies that compared balanced crystalloid solutions and saline in ICU patients from databases including PubMed, Embase, Web of Science, and Cochrane Library were systematically searched up to July 25, 2022. The primary outcomes were mortality and renal-related outcomes, which included major adverse kidney events within 30 days (MAKE30), acute kidney injury (AKI), new receipt of renal replacement therapy (RRT), maximum creatinine increasing, maximum creatinine level, and final creatinine level ≥ 200% of baseline. Service utilization including length of hospital stay, ICU stay, ICU-free days and ventilator-free days were also reported. RESULTS: A total of 13 studies (10 RCTs and 3 cohort studies) involving 38,798 patients in ICUs met the selection criteria. Our analysis revealed that each subgroup had no significant difference in mortality outcomes among ICU patients between balanced crystalloid solutions and normal saline. A significant difference was detected between the adult groups (odds ratio [OR], 0.92; 95% confidence interval [CI], [0.86, 1.00]; p = 0.04) indicating that the AKI in the balanced crystalloid solutions group was lower than that in the normal saline group. Other renal-related outcomes, such as MAKE30, RRT, maximum creatinine increasing, maximum creatinine level, and final creatinine level ≥ 200% of baseline showed no significant difference between the two groups. Regarding secondary outcomes, the balanced crystalloid solution group had a longer ICU stay time (WMD, 0.02; 95% CI, [0.01, 0.03]; p = 0.0004 and I2 = 0%; p = 0.96) than the normal saline group among adult patients. Furthermore, children treated with balanced crystalloid solution had a shorter hospital stay time (WMD, - 1.10; 95% CI, [- 2.10, - 0.10]; p = 0.03 and I2 = 17%; p = 0.30) than those treated with saline. CONCLUSIONS: Compared with saline, balanced crystalloid solutions could not reduce the risk of mortality and renal-related outcomes, including MAKE30, RRT, maximum creatinine increasing, maximum creatinine level, and final creatinine level ≥ 200% of baseline, but the solutions may reduce total AKI incidence among adult patients in ICUs. For service utilization outcomes, balanced crystalloid solutions were associated with a longer length of ICU stay in the adult group and shorter length of hospital stay in the pediatric group.


Asunto(s)
Lesión Renal Aguda , Solución Salina , Adulto , Humanos , Niño , Solución Salina/uso terapéutico , Soluciones Cristaloides/uso terapéutico , Creatinina , Fluidoterapia , Unidades de Cuidados Intensivos , Lesión Renal Aguda/etiología
12.
J Clin Med ; 12(5)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36902608

RESUMEN

Benign prostatic hyperplasia (BPH) is a common male condition that impacts many men's quality of life by generating lower urinary tract symptoms (LUTS). In recent years, inflammation has become very common in the prostate, and BPH with inflammation has a higher International Prostate Symptom Score (IPSS) score and an enlarged prostate. Chronic inflammation leads to tissue damage and the release of pro-inflammatory cytokines, which play an important role in the pathogenesis of BPH. We will focus on current advancements in pro-inflammatory cytokines in BPH, as well as the future of pro-inflammatory cytokine research.

13.
Int J Surg ; 109(4): 982-994, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36974696

RESUMEN

BACKGROUND: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains controversial. In addition, several unanswered questions regarding the use of CN remain: Can CN provide survival benefits for patients with mRCC? Where do we place CN in the treatment sequence paradigm among patients with mRCC? How do we best stratify patients with mRCC for CN therapy? MATERIALS AND METHODS: A search strategy was conducted in the PubMed, Embase, and Web of Science databases. Studies were included only in the English language. The risk of bias assessment was made by using ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) and RoB 2 (Risk of Bias 2) tools. The expected outcomes were analyzed by meta-analyses with the fixed-effects model or random effects model, including overall survival (OS) and progression-free survival (PFS). The measure of effect was the hazard ratio (HR) with a 95% CI, and sensitivity analysis was conducted to assess the reliability of the final results. RESULTS: A total of 30 studies were included in the qualitative analysis. The HR for OS was 0.55 (95% CI, 0.50-0.61), and PFS was 0.72 (95% CI, 0.66-0.80), favoring CN compared with no CN. The upfront CN plus targeted therapy (TT) group had superior OS (HR, 0.57; 95% CI, 0.51-0.64) compared with the TT alone group. Furthermore, upfront CN plus systemic therapy (ST) was associated with numerically inferior OS compared with ST plus deferred CN in patients with mRCC (HR, 1.31; 95% CI, 0.98-1.74). Finally, the leave-one-out test of sensitivity analysis indicated that the results of this meta-analysis were stable and reliable in the overall HR estimates for these survival outcomes. CONCLUSIONS: First, CN was associated with better survival than no CN in patients with mRCC. Second, the combination of upfront CN and TT may lead to superior survival outcomes compared to TT alone in patients with mRCC. Survival outcomes were similar between the upfront CN+ST group and the ST+deferred CN group in patients with mRCC. Exact patient selection based on baseline prognostic factors is needed to promise maximal survival for patients with mRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción , Reproducibilidad de los Resultados , Nefrectomía/métodos , Estudios Retrospectivos
14.
Lasers Med Sci ; 38(1): 73, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36800022

RESUMEN

Holmium laser lithotripsy is currently the optimum standard for surgical treatment of upper urinary calculi. This study aims to evaluate the clinical efficacy and safety of Moses compared with conventional holmium laser lithotripsy for the treatment of patients with upper urinary calculi. We conducted a systematic search using multiple databases (PubMed/Medline, Scopus, Web of Science, and ClinicalTrials.gov) until June 2022. Clinical trials comparing Moses and conventional holmium laser lithotripsy were included. Analysis was performed using RevMan version 5.4.4 software. Four studies with 892 patients were included. There were no significant differences regarding stone-free rate (mean difference [MD] 1.19, 95% CI 0.54, 2.64, p = 0.66), operative time (MD - 9.31, 95% CI - 21.11, 2.48, p = 0.12), fragmentation time (MD - 1.71, 95% CI - 11.81, 8.38, p = 0.74), total energy used (MD 1.23, 95% CI - 0.44, 2.90, p = 0.15), auxiliary procedures (MD 0.38, 95% CI 0.08, 1.90, p = 0.24), and overall complications (odds ratio [OR] 0.70, 95% CI 0.30, 1.66, p = 0.42) between the groups. However, the laser working time (MD - 0.94, 95% CI - 1.20, - 0.67, p < 0.001) of Moses technology was shorter than that of conventional technology. Moses technology has similar outcomes to regular technology in terms of safety and efficacy. Given the higher operating costs of the Moses technology, further study is required to determine whether there are benefits to this new technology.


Asunto(s)
Láseres de Estado Sólido , Litotripsia por Láser , Litotricia , Cálculos Urinarios , Humanos , Litotripsia por Láser/métodos , Holmio , Cálculos Urinarios/terapia , Láseres de Estado Sólido/uso terapéutico , Tecnología
15.
Pharmacol Res ; 189: 106692, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36773708

RESUMEN

Ubiquitin proteasome activity is suppressed in enzalutamide resistant prostate cancer cells, and the heat shock protein 70/STIP1 homology and U-box-containing protein 1 (HSP70/STUB1) machinery are involved in androgen receptor (AR) and AR variant protein stabilization. Targeting HSP70 could be a viable strategy to overcome resistance to androgen receptor signaling inhibitor (ARSI) in advanced prostate cancer. Here, we showed that a novel HSP70 allosteric inhibitor, JG98, significantly suppressed drug-resistant C4-2B MDVR and CWR22Rv1 cell growth, and enhanced enzalutamide treatment. JG98 also suppressed cell growth in conditional reprogramed cell cultures (CRCs) and organoids derived from advanced prostate cancer patient samples. Mechanistically, JG98 degraded AR/AR-V7 expression in resistant cells and promoted STUB1 nuclear translocation to bind AR-V7. Knockdown of the E3 ligase STUB1 significantly diminished the anticancer effects and partially restored AR-V7 inhibitory effects of JG98. JG231, a more potent analog developed from JG98, effectively suppressed the growth of the drug-resistant prostate cancer cells, CRCs, and organoids. Notably, the combination of JG231 and enzalutamide synergistically inhibited AR/AR-V7 expression and suppressed CWR22Rv1 xenograft tumor growth. Inhibition of HSP70 using novel small-molecule inhibitors coordinates with STUB1 to regulate AR/AR-V7 protein stabilization and ARSI resistance.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Receptores Androgénicos/metabolismo , Antagonistas de Andrógenos , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Línea Celular Tumoral , Nitrilos/farmacología , Antagonistas de Receptores Androgénicos , Andrógenos/farmacología , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/farmacología , Resistencia a Antineoplásicos , Ubiquitina-Proteína Ligasas
16.
Front Pharmacol ; 14: 1033492, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36814496

RESUMEN

Background: To investigate the function of sildenafil on diseases other than urogenital system, an umbrella review was conducted. Methods: Meta-analysis and systematic reviews on this topic were comprehensively evaluated in this umbrella review. Quality of evidence was evaluated through AMSTAR and the Grading of Recommendations, Assessment, Development and Evaluation system to generate a reliable and valid conclusion. Results: 77 out of 1164 meta-analysis were enrolled. 33 significant outcomes and 41 non-significant outcomes were extracted from all eligible articles. We found sildenafil did significant help in reducing arterial systolic pressure, mean pulmonary arterial pressure, pulmonary arterial pressure, systolic pulmonary arterial pressure in patients with pulmonary and cardiovascular diseases. Besides, sildenafil also improved exercise capacity or performance in patients with pulmonary and cardiovascular diseases. Other than these patients, this drug contributed great help in pregnant women with fetal growth restriction and preeclampsia by increasing the weight of newborns and lowering uterine and umbilical pulsatility indices. Additionally, it was reported that utilization of sildenafil has brought increased risk of melanoma. Conclusion: We can conclude from our study that sildenafil played an important role in many fields, especially in vascular protection. This finding provides a strong evidence for further expansion of sildenafil utilization in other diseases.

17.
Asian J Androl ; 25(3): 356-360, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36254889

RESUMEN

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Hiperplasia Prostática , Resección Transuretral de la Próstata , Masculino , Humanos , Hiperplasia Prostática/complicaciones , Calidad de Vida , Resección Transuretral de la Próstata/efectos adversos , Resultado del Tratamiento
18.
Crit Rev Food Sci Nutr ; 63(16): 2910-2927, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34583608

RESUMEN

Iron is an essential trace element, while excess iron can lead to different levels of physical abnormalities or diseases. This umbrella review aimed to conduct a systematic evaluation of the possible relationships between iron intake and various health outcomes. We retrieved PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews from inception through May 2021. A total of 34 meta-analyses with 46 unique health outcomes were identified. Heme iron intake was positively associated with nine outcomes, including colorectal cancer, type 2 diabetes mellitus, and cardiovascular disease mortality, while dietary total iron intake could decrease the risk of colorectal adenoma, esophageal cancer, coronary heart disease, and depression. Iron supplementation was a protective factor against eight outcomes. However, it was associated with decreased length and weight gain. The quality of evidence for most outcomes was "low" or "very low" with the remaining eleven as "high" or "moderate". All outcomes were categorized as class III, IV, or NS based on evidence classification. Although high iron intake has been identified to be significantly associated with a range of outcomes, firm universal conclusions about its beneficial or negative effects cannot be drawn given the low quality of evidence for most outcomes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/prevención & control , Dieta , Hierro , Estado Nutricional , Revisiones Sistemáticas como Asunto
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