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1.
Acta Diabetol ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775871

RESUMEN

AIMS: Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assess the trends of the visual impairment burden attributable to high FPG levels globally, regionally, nationally, and by income level. METHODS: We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. RESULTS: The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). CONCLUSIONS: The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.

2.
Epigenetics ; 19(1): 2348840, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38716769

RESUMEN

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- ß signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.


Asunto(s)
Adenosina , Síndrome de Exfoliación , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Femenino , Síndrome de Exfoliación/genética , Síndrome de Exfoliación/metabolismo , Masculino , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Anciano , Humor Acuoso/metabolismo , Redes Reguladoras de Genes , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metilación de ADN , Glaucoma de Ángulo Abierto/genética , Glaucoma de Ángulo Abierto/metabolismo
3.
Cell Death Dis ; 15(2): 128, 2024 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341429

RESUMEN

Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic hyperplasia (BPH) samples. We further investigate the function of PRL in prostate cancer (PCa) and explored its downstream effects. We found heterogeneous expression of the PRLR in clinical prostate samples. The VCaP and 22Rv1 cells exhibited PRLR expression. Among the downstream proteins, STAT5B was the dominant subtype in clinical samples and cell lines. Human recombinant PRL stimulation of PCa cells with PRLR expression resulted in increased phosphorylation of STAT5B(pSTAT5B) and progression of PCa in vitro and in vivo, and STAT5B knockdown can suppress the malignant behavior of PCa. To understand the mechanism further, we performed Bioinformatic analysis, ChIP qPCR, and luciferase reporter gene assay. The results revealed that ARRB2 was the transcription target gene of STAT5B, and higher expression of ARRB2 was related to higher aggression and poorer prognosis of PCa. Additionally, Gene set enrichment analysis indicated that higher expression of ARRB2 was significantly enriched in the MAPK signaling pathway. Immunohistochemistry (IHC) demonstrated elevated pSTAT5B, ARRB2, and pERK1/2 expression levels in CRPC tissues compared to HNPC and BPH. Mechanically, ARRB2 enhanced the activation of the MAPK pathway by binding to ERK1/2, thereby promoting the phosphorylation of ERK1/2 (pERK1/2). In conclusion, our study demonstrated that PRL stimulation can promote the progression of PCa through STAT5B/ARRB2 pathway and activation of MAPK signaling, which can be suppressed by intervention targeting STAT5B. Blockade of the STAT5B can be a potential therapeutic target for PCa.


Asunto(s)
Hiperplasia Prostática , Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Prolactina/genética , Prolactina/metabolismo , Hiperplasia Prostática/genética , Neoplasias de la Próstata/patología , Receptores de Prolactina/metabolismo , Fosforilación , Línea Celular Tumoral , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/metabolismo , Arrestina beta 2/metabolismo
4.
Br J Ophthalmol ; 108(3): 366-371, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-37236768

RESUMEN

AIMS: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects. METHODS: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression. RESULTS: A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement). CONCLUSION: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease. TRIAL REGISTRATION NUMBER: ISRCTN45213099.


Asunto(s)
Glaucoma de Ángulo Cerrado , Midriasis , Humanos , Presión Intraocular , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/prevención & control , Tomografía de Coherencia Óptica/métodos , Iris , Gonioscopía , Segmento Anterior del Ojo
5.
J Clin Invest ; 133(24)2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38099500

RESUMEN

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3ßHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3ßHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3ßHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3ßHSD1 inhibitors as early intervention.


Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/metabolismo , Próstata/patología , Deshidroepiandrosterona , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo
6.
Asia Pac J Ophthalmol (Phila) ; 12(4): 355-363, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37523426

RESUMEN

PURPOSE: Visual impairment from cataracts is closely associated with low income, but trial evidence regarding the impact of surgery on income is lacking. We investigated whether cataract surgery could increase personal income. DESIGN: A 2-arm, parallel-group, open-label, randomized controlled trial (ClinicalTrials.gov, NCT03020056). METHODS: Persons aged 50 years or older in rural Guangdong, China, with best-corrected visual acuity <6/19 in both eyes due to cataracts were randomly assigned (1:1) to receive surgery within 4 weeks (intervention group), or 1 year later (control group). All participants were interviewed at baseline and end-line regarding demographic characteristics, income, and quality of life. RESULTS: Among the 292 eligible persons (5.40%, mean age = 74.0 y, 61.0% women) randomly assigned to intervention (n = 146) or control (n = 146) groups, 12 participants (8.22%) in the intervention group and 1 (0.68%) in the control did not receive the allocated intervention. By study closeout, 18 participants (6.16%) were lost to follow-up. The mean 1-year income increase of the intervention group ($2469-$3588; change = $1119) was significantly larger than that of the controls ($2258-$2052; change = $-206), a between-group difference of $1325 (relative increase = 54.0%; 95% CI = $739 to $1911; P < 0.001). In multivariable modeling, intervention group membership was associated with greater income increase (ß = 1143.2; 95% CI = 582.0 to 1704.3; P < 0.001). Greater improvement in best-corrected visual acuity was associated with income increase in univariable modeling (ß = 1626.9; 95% CI = 1083.6 to 2170.1; P < 0.001). CONCLUSIONS: Cataract surgery substantially increases personal income in rural China, offering a strategy for poverty alleviation. The strong association between increased income and change in visual acuity enhances the biological plausibility of the result.


Asunto(s)
Extracción de Catarata , Catarata , Humanos , Femenino , Anciano , Masculino , Calidad de Vida , Catarata/complicaciones , Agudeza Visual , China/epidemiología
7.
Prostate ; 83(7): 619-627, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36842160

RESUMEN

BACKGROUND: Prostate cancer is addicted to androgens. The steroidogenic enzyme 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) recognizes pregnenolone, dehydroepiandrosterone (DHEA), and steroidal medicine abiraterone as substrates to accelerate disease progression. METHODS: References for this review were identified through searches of PubMed with the search terms "prostate cancer", "HSD3B1", and "3bHSD1" from 1990 until June, 2022. RESULTS: Genotype of 3ßHSD1 has been reported to correlate with tumor aggressiveness of advanced prostate cancer in multiple clinical scenarios. The ethnic differences and limitations of using 3ßHSD1 genotype as a prognostic biomarker have been discussed here. The activity of 3ßHSD1 increases in patients treated with abiraterone and enzalutamide, giving rise to treatment resistance. Further elucidation of 3ßHSD1 regulatory mechanisms will shed light on more approaches for disease intervention. We also review the recent advance on 3ßHSD1 inhibitors and targeting 3ßHSD1 for prostate cancer management. Novel 3ßHSD1 inhibitors will be needed to provide additional options for prostate cancer management. CONCLUSION: 3ßHSD1 is both a predictive biomarker and a promising therapeutic target for prostate cancer.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Medicina de Precisión , Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Andrógenos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Nitrilos/uso terapéutico
8.
Br J Ophthalmol ; 107(9): 1264-1268, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-35501120

RESUMEN

BACKGROUND/AIMS: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS. METHODS: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery. RESULTS: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59±5 years, 83% female). At 72 months, treated eyes had slightly higher average nuclear grades (p<0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2% in LPI vs 19.4% in control, p=0.401) or cataract surgery (1% for both). While LPI-treated eyes had a 10% higher risk of progression over 6 years (HR=1.10 (95% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43). CONCLUSION: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time. TRIAL REGISTRATION NUMBER: ISRCTN45213099.


Asunto(s)
Extracción de Catarata , Catarata , Glaucoma de Ángulo Cerrado , Terapia por Láser , Láseres de Estado Sólido , Humanos , Femenino , Persona de Mediana Edad , Masculino , Láseres de Estado Sólido/uso terapéutico , Glaucoma de Ángulo Cerrado/etiología , Glaucoma de Ángulo Cerrado/cirugía , Iris/cirugía , Catarata/etiología , Extracción de Catarata/efectos adversos , Terapia por Láser/métodos , Presión Intraocular , Iridectomía/métodos , Gonioscopía
9.
Oncogene ; 41(42): 4754-4767, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36109631

RESUMEN

Strategies to degrade steroid receptors and their alternative splicing isoforms are critical for disease management. Here we report that celastrol recruited the ubiquitin ligase UBE3A and degraded androgen receptor (AR), AR-v7, and glucocorticoid receptor (GR) to suppress prostate cancer development. UBE3A was not an optimal endogenous AR ubiquitin ligase in mice and patients, but celastrol promoted the interaction between UBE3A and AR. Multiple domains of AR, including the DNA binding domain (DBD), were implicated into the UBE3A-AR interaction. Sharing a conserved DBD, GR, AR-v7, and other steroid receptors were recognized and degraded by UBE3A after celastrol treatment. Thus, celastrol suppressed prostate cancer cell proliferation more potently than enzalutamide. Modifying the carboxyl group of celastrol improved its anti-tumor activity. Together, our findings revealed that celastrol might be a potential molecular glue to enhance the interaction between UBE3A and steroid receptors to degrade multiple steroid receptors and splicing isoforms in prostate cancer, paving a way for further drug optimization and disease treatment.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Animales , ADN/metabolismo , Humanos , Ligasas , Masculino , Ratones , Triterpenos Pentacíclicos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/patología , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides , Ubiquitina-Proteína Ligasas/genética , Ubiquitinas
10.
Transl Androl Urol ; 11(8): 1169-1176, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36092845

RESUMEN

Background: The steroidal metabolism of abiraterone has been proposed to be involved in abiraterone resistance and limited approaches are available for abiraterone-resistant patients. Dutasteride regulates abiraterone metabolism in patients and might enhance the clinical efficacy of abiraterone. However, the function of dutasteride to overcome abiraterone resistance has not been investigated in clinic. Here we investigated the clinical efficacy and limitations of dutasteride in patients with abiraterone-resistant prostate cancer. Methods: Abiraterone-resistant patients with metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single-arm, open-label study, patients were treated with dutasteride (0.5 mg/day), abiraterone (1,000 mg/day), and prednisone (5 mg twice daily), prostate-specific antigen (PSA) was tested monthly. The primary objective was PSA response, and the secondary objectives were to assess symptom relief and safety. Kaplan-Meier analysis was used to assess the PSA progression free survival (PSA-PFS) of patients. Results: Twenty-two patients (median age: 75 years) were enrolled, and 19 patients completed the treatment. After a median treatment of 4.0 months, 7 (37%) patients showed a slight PSA reduction (-2% to -32%), and the median PSA-PFS was 2.0 months (1-7 months). No significant improvement was observed in Eastern Cooperative Oncology Group (ECOG) performance status. Bone pain was relieved in 6 patients after 1 month of treatment, but the improvement was not significant. No grade 3 or grade 4 adverse events were observed. Conclusions: The combination of dutasteride and abiraterone showed a mild effect in patients with abiraterone-resistant. The small sample size was the limitation of this study.

11.
Prostate ; 82(13): 1284-1292, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35747943

RESUMEN

BACKGROUND: To investigate the prognostic value and potential therapeutic target of the baseline serum hormones in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. METHODS: This retrospective study was performed in patients with mCRPC receiving abiraterone acetate (AA) from July 2016 to September 2020. Patients who had serum hormone tests within 2 weeks before AA treatment were included. Univariate analysis and Cox regression were performed to evaluate the correlation of sex hormones with progression-free survival (PFS) and overall survival (OS). Prolactin (PRL) expression in the clinical specimens was evaluated by immunohistochemistry. Bone metastases were quantified by automated Bone Scan Index (aBSI). RESULTS: The study included 61 patients with a median follow-up of 19.0 months. Patients with lower baseline PRL levels (median) responded better to AA than those with higher baseline PRL levels as indicated by prostate-specific antigen (PSA) reduction (PSA90, 66.7% vs. 25.8%, p = 0.001), PFS (19.6 vs. 7.9 months), and OS (52.8 vs. 19.2 months). Cox regression adjusted for clinical factors also confirmed that baseline PRL level was an independent predictive factor for PFS (hazard ratio = 1.096, p = 0.007). Prostatic PRL expression increased as the disease progressed. PRL expression was also detected in biopsy samples from bone metastasis but not in normal bone tissue, and the serum PRL levels were positively correlated with aBSIs (r = 0.28, p = 0.037). CONCLUSIONS: Serum PRL levels are predictive of response to AA in patients with mCRPC. Serum PRL levels are positively correlated with the volume of metastatic bone disease.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Acetato de Abiraterona/uso terapéutico , Androstenos/uso terapéutico , Humanos , Masculino , Prolactina/uso terapéutico , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Resultado del Tratamiento
12.
Cell Rep Med ; 3(3): 100561, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35492874

RESUMEN

Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens. In this study, mass-spectrometry-based screening of clinical specimens and a retrospective analysis on the clinical data of prostate cancer patients indicate the potential oncogenic effects of progesterone in patients. High doses of progesterone activate canonical and non-canonical androgen receptor (AR) target genes. Physiological levels of progesterone facilitate cell proliferation via GATA2. Inhibitors of 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) has been discovered and shown to suppress the generation of progesterone, eliminating its transient and accumulating oncogenic effects. An increase in progesterone is associated with poor clinical outcomes in patients and may be used as a predictive biomarker. Overall, we demonstrate that progesterone acts as an oncogenic hormone in prostate cancer, and strategies to eliminate its oncogenic effects may benefit prostate cancer patients.


Asunto(s)
Andrógenos , Neoplasias de la Próstata , Carcinogénesis , Humanos , Masculino , Progesterona/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/genética , Estudios Retrospectivos
13.
Cell Rep Med ; 3(5): 100608, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35584629

RESUMEN

Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3ßHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3ßHSD1, overcomes drug resistance. 3ßHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3ßHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3ßHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3ßHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3ßHSD1 inhibitor even after abiraterone and enzalutamide resistance.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Androstenos , Benzamidas , Resistencia a Antineoplásicos , Humanos , Masculino , Nitrilos/uso terapéutico , Feniltiohidantoína/farmacología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico
14.
Ophthalmol Glaucoma ; 5(6): 581-586, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35568336

RESUMEN

PURPOSE: Angle-closure glaucoma is a major cause of blindness worldwide that carries an excessive risk of severe, bilateral visual impairment. A common concern among clinicians is the precipitation of acute angle-closure (AAC) attacks because of mydriasis. We evaluated the risk of AAC after pharmacologic dilation in Chinese individuals classified as having bilateral primary angle-closure suspects (PACSs). DESIGN: Randomized, interventional, controlled trial. PARTICIPANTS: A total of 889 patients with bilateral PACSs, aged between 50 and 70 years, were identified through community screening in Guangzhou, China, and enrolled in the study. METHODS: In the Zhongshan Angle-Closure Prevention Trial, bilateral PACSs were treated with laser peripheral iridotomy (LPI) in 1 randomly selected eye, with the fellow eye serving as an untreated control. Over 72 months of follow-up, the participants had their pupils pharmacologically dilated 6 times with 5% phenylephrine and 0.5% tropicamide. MAIN OUTCOME MEASURES: Incidence and risk of post-mydriasis AAC in LPI-treated and untreated, control eyes classified as PACSs. RESULTS: One bilateral AAC attack occurred after mydriasis at the 2-week post-LPI visit. No other AAC events occurred in the LPI-treated eyes. In the untreated eyes, 4 additional attacks occurred: 2 occurred after dilation (1 at 54 months and 1 at 72 months of follow-up) and 2 occurred spontaneously. The risk of post-mydriasis AAC in the untreated eyes was 1 attack in 1587 dilations. The risk of spontaneous AAC in the untreated eyes was 0.44 per 1000 eye-years (95% confidence interval, 0.11-1.77 per 1000 eye-years). CONCLUSIONS: The risk of incident AAC attacks in PACSs was extremely low, even in a higher-risk group that underwent repeated pharmacologic pupillary dilation over 6 years of follow-up. Prophylactic LPI reduced this small but real risk. This trial was registered at ISRCTN.com as ISRCTN45213099.


Asunto(s)
Glaucoma de Ángulo Cerrado , Terapia por Láser , Midriasis , Humanos , Persona de Mediana Edad , Anciano , Midriasis/inducido químicamente , Glaucoma de Ángulo Cerrado/diagnóstico , Fenilefrina , Procedimientos Quirúrgicos Oftalmológicos , Enfermedad Aguda
15.
BMC Ophthalmol ; 22(1): 167, 2022 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-35421948

RESUMEN

BACKGROUND: Phacoemulsification using phaco-chop technique has many challenging features in cataract patients with highly liquefied vitreous. This study aimed to compare the intraoperative parameters and safety between prechop technique and traditional phaco-chop in phacoemulsification for these patients. METHODS: A total of 54 eyes of 54 patients with high myopia-related or post-vitrectomy cataract that underwent phacoemulsification combined with intraocular lens implantation were included in this retrospective study. Of them, 25 eyes that received manual prechop were included in the prechop group, and 29 eyes with best match of age, axial length and nuclear opalescence (NO) that received standardized phaco-chop were included as the control group. The intraoperative complications and surgery parameters were compared between groups. RESULTS: No surgical complications were observed in the prechop group, while 2 eyes with posterior capsular rupture and 1 eye with a broken ciliary zonule (10.3%) were found in the control group. There was no significant difference in phaco time, average energy, and cumulative dissipated energy (CDE) between groups (all P > 0.05), but for hard nuclear cataracts with NO grading ≥ 5, prechop group required less phaco time (P = 0.008) and CDE (P = 0.029). There were significant correlations between phaco time vs. NO (r = 0.762 vs. 0.581, both P < 0.005) and CDE vs. NO (r = 0.717 vs. 0.668, both P < 0.001) in the prechop group and control group, respectively. CONCLUSIONS: The prechop technique which seemed to have less intraoperative complications, reduced phaco time and CDE compared to standardized phaco-chop might be a good alternative for cataract patients with highly liquefied or vitrectomized vitreous, especially those with hard nuclear cataracts.


Asunto(s)
Catarata , Facoemulsificación , Catarata/complicaciones , Humanos , Complicaciones Intraoperatorias , Facoemulsificación/métodos , Estudios Retrospectivos , Vitrectomía/métodos
16.
J Cancer Res Clin Oncol ; 148(7): 1627-1640, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35322299

RESUMEN

PURPOSE: Prostate cancer (PCa) is a leading cause of morbidity and mortality in males. Epigenetic modifier abnormalities are becoming a driving event in PCa. The specific role of KMT2C, a histone methyltransferase that is frequently aberrant in various tumors, is poorly understood in PCa. This study aimed to reveal the potential carcinogenic role of KMT2C in PCa. METHODS: We first examined the expression levels of KMT2C in prostate cancer tissues. Then, we assessed the function of KMT2C in prostate cancer cell proliferation, colony formation, and migration. To explore the mechanism of the biological consequences, RNA-seq and CHIP-qPCR were performed. We also analyzed the effects of overexpression of the KMT2C downstream genes CLDN8 and ITGAV to reverse the effects of KMT2C on prostate cancer cells. RESULTS: Herein, we first confirmed KMT2C overexpression in PCa at the transcript and protein levels. Knocking down KMT2C in VCaP and LNCaP cells inhibited cell viability, colony formation, and migration. Consistently, stable KMT2C depletion effectively decreased tumor growth by approximately 70% in vivo. Mechanistically, the results suggested that CLDN8 and ITGAV are two key downstream genes of KMT2C and further regulate the MAPK/ERK and EMT pathways. CONCLUSION: Our study suggests that KMT2C plays an oncogenic role in PCa. One of the mechanisms may be the epigenetic regulation of CLDN8 and ITGAV by KMT2C to modulate tumor-signaling pathways. Therefore, KMT2C may serve as a potential therapeutic target for PCa patients.


Asunto(s)
Proteínas de Unión al ADN , Histona Metiltransferasas , Hiperplasia Prostática , Neoplasias de la Próstata , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Histona Metiltransferasas/genética , Humanos , Masculino , Oncogenes , Hiperplasia Prostática/genética , Neoplasias de la Próstata/patología
17.
Photoacoustics ; 25: 100327, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34987958

RESUMEN

Pathology is currently the gold standard for grading prostate cancer (PCa). However, pathology takes considerable time to provide a final result and is significantly dependent on subjective judgment. In this study, wavelet transform-based photoacoustic power spectrum analysis (WT-PASA) was used for grading PCa with different Gleason scores (GSs). The tumor region was accurately identified via wavelet transform time-frequency analysis. Then, a linear fitting was conducted on the photoacoustic power spectrum curve of the tumor region to obtain the quantified spectral parameter slope. The results showed that high GSs have small glandular cavity structures and higher heterogeneity, and consequently, the slopes at both 1210 nm and 1310 nm were high (p < 0.01). The classification accuracy of the PA time frequency spectrum (PA-TFS) of tumor region using ResNet-18 was 89% at 1210 nm and 92.7% at 1310 nm. Further, the testing time was less than 7 mins. The results demonstrated that identification of PCa can be rapidly and objectively realized using WT-PASA.

18.
Photodiagnosis Photodyn Ther ; 37: 102689, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34933166

RESUMEN

Keratitis and conjunctivitis are the most common ocular diseases, their symptoms are similar and easy to confuse, however infectious conjunctivitis is highly contagious. If misdiagnosed, it may worsen the disease and pose a threat to public health.This is a preclinical study to propose a method for rapid and accurate screening of keratitis and conjunctivitis by combining tear Raman spectroscopy with deep learning models that may be applied to clinical applications in the future.The tears of 16 cases of keratitis patients, 13 cases of conjunctivitis patients and 46 cases of healthy subjects were collected, and their Raman spectra were compared and analyzed. By adding different decibels of Gaussian white noise to expand the data, the performance of the tear Raman spectra with a large sample size in the deep learning model was discussed. Principal component analysis (PCA), partial least squares (PLS) and maximum correlation minimum redundancy (mRMR) were used for feature extraction. The processed data were imported into convolutional neural network (CNN) and recurrent neural network (RNN) depth models for classification. After the data were enhanced and processed by PLS, the highest classification accuracy of healthy subjects and keratitis patients, healthy subjects and conjunctivitis patients, and keratitis and conjunctivitis patients reached 94.8%, 95.4%, and 92.7%, respectively. The results of this study show that the use of large sample tear Raman spectra data combined with PLS feature extraction and depth learning algorithms may have great potential in clinical screening of keratitis and conjunctivitis.


Asunto(s)
Conjuntivitis , Queratitis , Fotoquimioterapia , Humanos , Queratitis/diagnóstico , Análisis de los Mínimos Cuadrados , Fotoquimioterapia/métodos , Espectrometría Raman
19.
BMC Ophthalmol ; 21(1): 439, 2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34930170

RESUMEN

PURPOSE: To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification. DESIGN: Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China. SUBJECTS: Patients who underwent cataract surgery at UCSF 03/2014-03/2019 and at ZOC 10/2018-05/2019. METHODS: Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month. OUTCOME MEASURES: CDE, postoperative BCVA. RESULTS: In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20-0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12-0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34-0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13-0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL). CONCLUSIONS: Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.


Asunto(s)
Catarata , Anciano , Anciano de 80 o más Años , Catarata/epidemiología , China/epidemiología , Humanos , Agudeza Visual
20.
Photoacoustics ; 23: 100280, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34168956

RESUMEN

Photoacoustic spectroscopy can generate abundant chemical and physical information about biological tissues. However, this abundance of information makes it difficult to compare these tissues directly. Data mining methods can circumvent this problem. We describe the application of machine-learning methods (including unsupervised hierarchical clustering and supervised classification) to the diagnosis of prostate cancer by photoacoustic spectrum analysis. We focus on the content and distribution of hemoglobin, collagen, and lipids, because these molecules change during the development of prostate cancer. A higher correlation among the ultrasonic power spectra of these chemical components is observed in cancerous than in normal tissues, indicating that the microstructural distributions in cancerous tissues are more consistent. Different classifiers applied in cancer-tissue diagnoses achieved an accuracy of 82 % (better than that of standard clinical methods). The technique thus exhibits great potential for painless early diagnosis of aggressive prostate cancer.

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