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1.
J Pharm Biomed Anal ; 245: 116161, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38714135

RESUMO

In this study, Fe3O4@ZnCr-layered double hydroxide/zeolitic imidazolate frameworks-8 (MLDH/ZIF-8) magnetically functionalized composites were synthesized by co-precipitation and in situ growth based on the advantages of LDHs and ZIF-8 using Fe3O4 nanoparticles as a magnetic substrate to obtain adsorbents with excellent performance. Moreover, the composite was used for the efficient enrichment of flavonoids in Chinese herbal medicines. The internal structures and surface properties were characterized by SEM, Fourier transform infrared spectroscopy, X-ray diffraction and so on. MLDH/ZIF-8 exhibited a large specific surface area and good paramagnetic properties. The MLDH/ZIF-8 magnetic composite was used as a magnetic solid-phase extraction (MSPE) adsorbent, and a MLDH/ZIF-8 MSPE-pressurized capillary electrochromatography coupling method was developed for the separation and detection of flavonoids (luteolin, kaempferol and apigenin) in a sample of the Chinese herb Ohwia caudata (Thunberg) H. Ohashi. The relevant parameters affecting the extraction efficiency were optimized to determine the ideal conditions for MSPE. 5 mg of adsorbent in sample solution at pH 6, vortex extraction for 5 min, elution with 1.5 mL of ethyl acetate for 15 min. The method showed good linearity in the concentration range of 3-50 µg mL-1 with correlation coefficients of 0.9934-0.9981, and displayed a relatively LODs of 0.07-0.09 µg mL-1. The spiked recoveries of all analytes ranged from 84.5% to 122.0% with RSDs (n=3) between 4.5% and 7.7%. This method is straightforward and efficient, with promising potential in the separation and analysis of active ingredients in various Chinese herbal medicines.

2.
Cell Rep ; 43(5): 114180, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38733581

RESUMO

Macrophage activation is a hallmark of atherosclerosis, accompanied by a switch in core metabolism from oxidative phosphorylation to glycolysis. The crosstalk between metabolic rewiring and histone modifications in macrophages is worthy of further investigation. Here, we find that lactate efflux-associated monocarboxylate transporter 4 (MCT4)-mediated histone lactylation is closely related to atherosclerosis. Histone H3 lysine 18 lactylation dependent on MCT4 deficiency activated the transcription of anti-inflammatory genes and tricarboxylic acid cycle genes, resulting in the initiation of local repair and homeostasis. Strikingly, histone lactylation is characteristically involved in the stage-specific local repair process during M1 to M2 transformation, whereas histone methylation and acetylation are not. Gene manipulation and protein hydrolysis-targeted chimerism technology are used to confirm that MCT4 deficiency favors ameliorating atherosclerosis. Therefore, our study shows that macrophage MCT4 deficiency, which links metabolic rewiring and histone modifications, plays a key role in training macrophages to become repair and homeostasis phenotypes.

3.
Minerva Urol Nephrol ; 76(2): 241-246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742557

RESUMO

BACKGROUND: To evaluate the feasibility and safety of dual-console telesurgery with the new KangDuo system in an animal experiment and clinical study. METHODS: Six canine models were performed radical prostatectomy with dual-console KanDuo surgical robot-1500 (KD-SR-1500-RARP). The perioperative outcomes, physical and mental workload of the surgeon were collected. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with NASA-TLX. After conducting animal experiments to verify safety of dual-console KD-SR-1500-RARP, we conducted the clinical trial using 5G and wired networks. RESULTS: In the animal experiment, all surgeries were performed successfully. The operative time was 80.2±32.1 min. The docking time was 2.4±0.5 min. The console time was 49.7±25.3 min. There were no perioperative complications or equipment related adverse events. All dogs can micturate after catheter removal at one week postoperatively. The mental workload was at a low level (a scale ranging from 0 to 60), which scored 15.7±6.9. Among the eight recorded muscles, the fatigue degree of the right radial flexor and left biceps was the highest two (iEMG, resection, 299.8±344 uV, 109.9±16.9 uV; suture, 849.4±1252.5 uV, 423.1±621.3 uV, respectively). In the clinical study, the console time was 136 min. The mean latency time was ≤200 ms. The data pocket loss was <1%. The operation was successfully completed without malfunctions occurring throughout the entire process. CONCLUSIONS: Dual-console telesurgery with the KD-SR-1500 system was shown to be feasible and safe in radical prostatectomy using 5G and wired networks.


Assuntos
Estudos de Viabilidade , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Animais , Cães , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Masculino , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Humanos , Pessoa de Meia-Idade , Desenho de Equipamento , Duração da Cirurgia , Idoso , Eletromiografia , Telemedicina/métodos
4.
EBioMedicine ; 104: 105152, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38728838

RESUMO

BACKGROUND: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. METHODS: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. FINDINGS: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046-1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139-1.569, P < 0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. INTERPRETATION: The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. FUNDING: This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

5.
Brain Res ; 1838: 148977, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705556

RESUMO

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

6.
Small ; : e2310678, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708801

RESUMO

The quality requirements of graphene depend on the applications. Some have a high tolerance for graphene quality and even require some defects, while others require graphene as perfect as possible to achieve good performance. So far, synthesis of large-area graphene films by chemical vapor deposition of carbon precursors on metal substrates, especially on Cu, remains the main way to produce high-quality graphene, which has been significantly developed in the past 15 years. However, although many prototypes are demonstrated, their performance is still more or less far from the theoretical property limit of graphene. This review focuses on how to make super graphene, namely graphene with a perfect structure and free of contaminations. More specially, this study focuses on graphene synthesis on Cu substrates. Typical defects in graphene are first discussed together with the formation mechanisms and how they are characterized normally, followed with a brief review of graphene properties and the effects of defects. Then, the synthesis progress of super graphene from the aspects of substrate, grain size, wrinkles, contamination, adlayers, and point defects are reviewed. Graphene transfer is briefly discussed as well. Finally, the challenges to make super graphene are discussed and a strategy is proposed.

7.
Schizophr Res ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704344

RESUMO

BACKGROUND: Previous investigations have revealed substantial differences in neuroimaging characteristics between healthy controls (HCs) and individuals diagnosed with schizophrenia (SCZ). However, we are not entirely sure how brain activity links to symptoms in schizophrenia, and there is a need for reliable brain imaging markers for treatment prediction. METHODS: In this longitudinal study, we examined 56 individuals diagnosed with 56 SCZ and 51 HCs. The SCZ patients underwent a three-month course of antipsychotic treatment. We employed resting-state functional magnetic resonance imaging (fMRI) along with fractional Amplitude of Low Frequency Fluctuations (fALFF) and support vector regression (SVR) methods for data acquisition and subsequent analysis. RESULTS: In this study, we initially noted lower fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, coupled with higher fALFF values in the left hippocampus and right putamen in SCZ patients compared to the HCs at baseline. However, when comparing fALFF values in brain regions with abnormal baseline fALFF values for SCZ patients who completed the follow-up, no significant differences in fALFF values were observed after 3 months of treatment compared to baseline data. The fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, and the left postcentral gyrus were useful in predicting treatment effects. CONCLUSION: Our findings suggest that reduced fALFF values in the sensory-motor networks and increased fALFF values in the limbic system may constitute distinctive neurobiological features in SCZ patients. These findings may serve as potential neuroimaging markers for the prognosis of SCZ patients.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124339, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38696995

RESUMO

The FDA (Food and Drug Administration, (USA)) lists ZnO as a material that is widely acknowledged to be safe. ZnO NPs with a range of tiny particle sizes were made using the precipitation process. ZnO nanoparticles' surface is embellished with a tripodal sensor containing naphthol units. The assembly with the same receptor decorated on ZnO NPs is contrasted with the cation detection capabilities of the purified tripodal receptor. The UV-visible spectrophotometric analysis was conducted to study the state transitions of the receptor and the decorated ZnO receptor. A positive selectivity to Al3+ cations is determined by the fluorescence study under ideal circumstances. The particle size and surface morphologies are determined by DLS and SEM analysis for the same receptor - TP1 and embellished with a tripodal receptor TP2. Using a fluorescence switch-on Photoinduced Electron Transfer (PET) mechanism, the receptor coated on ZnO detects the presence of Al3+ ions with specificity. The binding constant value was determined using the B-H plot equation. Binding stoichiometry for [TP1-Al3+, TP2-Al3+] showed a 1:1 ratio. The fluorescence switches ON-OFF process of the ZnO surface adorned - TP2 with Tripodal receptor- TP1 was used to create molecular logic gates, which can function as a module for sensors and molecular switches. The addition of Na2EDTA in the solution of the [TP1; TP2 - Al3+] complex resulted in a noticeable reduction in the emission of fluorescence. This finding offers compelling support for the reversibility of the chemosensor. To enable the practical application of this sensor, we have developed a cassette containing receptors TP1 and TP2. Successfully, it can detect Al3+ metal ions. We performed a comprehensive assessment of the dependability and appropriateness of our approach in measuring the concentration of Al3+ ions in wastewater produced by important industrial procedures.

9.
Biochem Biophys Res Commun ; 715: 149979, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38678779

RESUMO

Endothelial dysfunction is an initiating factor in atherosclerosis. Endothelial cells (ECs) are constantly subject to blood flow shear stress, and atherosclerotic plaques tend to occur in aortic bends or bifurcations impaired by low oscillatory shear stress (OSS). However, the mechanism that how OSS affects the initiation and progression of atherosclerosis remains to be explored. Here, we first reported that OSS can promote endothelial dysfunction and atherogenesis in vivo and in vitro by activating STING pathway. Mechanistically, at atherosclerosis-prone areas, OSS caused mitochondria damage in ECs, leading to the leakage of mitochondrial DNA (mtDNA) into the cytoplasm. The cytoplasmic mtDNA was recognized by cGAS to produce cGAMP, activating the STING pathway and leading to endothelial senescence, which resulted in endothelial dysfunction and atherosclerosis. We found that STING was activated in plaques of atherosclerotic patients and in aortic arch ECs of high-fat diet (HFD)-fed ApoeKO mice, as well as in ECs exposed to OSS. STING-specific deficiency in ECs attenuates endothelial senescence and resulted in a significant reduction in aortic arch plaque area in HFD-fed ApoeKO mice. Consistently, specific deficiency or pharmacological inhibition of STING attenuated OSS-induced senescence and endothelial dysfunction. Pharmacological depletion of mtDNA ameliorated OSS-induced senescence and endothelial dysfunction. Taken together, our study linked hemodynamics and endothelial senescence, and revealed a novel mechanism by which OSS leads to endothelial dysfunction. Our study provided new insights into the development of therapeutic strategies for endothelial senescence and atherosclerosis.


Assuntos
Aterosclerose , Senescência Celular , DNA Mitocondrial , Células Endoteliais , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Estresse Mecânico , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/genética , Animais , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Humanos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Masculino , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Dieta Hiperlipídica , Células Cultivadas
11.
Cancer Invest ; : 1-19, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644691

RESUMO

This study aims to develop a prognostic signature based on m6A-related lncRNAs for clear cell renal cell carcinoma (ccRCC). Differential expression analysis and Pearson correlation analysis were used to identify m6A-related lncRNAs associated with patient outcomes in The Cancer Genome Atlas (TCGA) database. Our approach led to the development of an m6A-related lncRNA risk score (MRLrisk), formulated using six identified lncRNAs: NFE4, AL008729.2, AL139123.1, LINC02154, AC124854.1 and ARHGAP31-AS1. Higher MRLrisk was identified as a risk factor for patients' prognosis in ccRCC. Furthermore, an MRLrisk-based nomogram was developed and demonstrated as a reliable tool for prognosis prediction in ccRCC. Enrichment analysis and tumor mutation signature studies were conducted to investigate MRLrisk-related biological phenotypes. The tumor immune dysfunction and exclusion (TIDE) score was employed to infer patients' response to immunotherapy, indicating a negative correlation between high MRLrisk and immunotherapy response. Our focus then shifted to LINC02154 for deeper exploration. We assessed LINC02154 expression in 28 ccRCC/normal tissue pairs and 3 ccRCC cell lines through quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments, including EdU incorporation, flow cytometry and transwell assays, were performed to assess the role of LINC02154 in ccRCC cell functions, discovering that its downregulation hinders cancer cell proliferation and migration. Furthermore, the influence of LINC02154 on ccRCC cells' sensitivity to Sunitinib was explored using CCK-8 assays, demonstrating that decreased LINC02154 expression increases Sunitinib sensitivity. In summary, this study successfully developed an MRLrisk model with significant prognostic value for ccRCC and established LINC02154 as a critical biomarker and prospective therapeutic target in ccRCC management.

12.
Magn Reson Imaging ; 110: 86-95, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631533

RESUMO

Segmentation of cerebral vasculature on MR vascular images is of great significance for clinical application and research. However, the existing cerebrovascular segmentation approaches are limited due to insufficient image contrast and complicated algorithms. This study aims to explore the potential of the emerging four-dimensional arterial spin labeling magnetic resonance angiography (4D ASL-MRA) technique for fast and accurate cerebrovascular segmentation with a simple machine-learning approach. Nine temporal features were extracted from the intensity-time signal of each voxel, and eight spatial features from the neighboring voxels. Then, the unsupervised outlier detection algorithm, i.e. Isolation Forest, is used for segmentation of the vascular voxels based on the extracted features. The total length of the centerlines of the intracranial arterial vasculature, the dice similarity coefficient (DSC), and the average Hausdorff Distance (AVGHD) on the cross-sections of small- to large-sized vessels were calculated to evaluate the performance of the segmentation approach on 4D ASL-MRA of 18 subjects. Experiments show that the temporal information on 4D ASL-MRA can largely improve the segmentation performance. In addition, the proposed segmentation approach outperforms the traditional methods that were performed on the 3D image (i.e. the temporal average intensity projection of 4D ASL-MRA) and the previously proposed frame-wise approach. In conclusion, this study demonstrates that accurate and robust segmentation of cerebral vasculature is achievable on 4D ASL-MRA by using a simple machine-learning approach with appropriate features.

13.
J Endourol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623792

RESUMO

PURPOSE: To investigate the feasibility, safety, and efficacy of the KangDuo Surgical Robot-01 (KD-SR-01) system for robot-assisted radical nephroureterectomy (UTUC). MATERIALS AND METHODS: This prospective, single-center, single-arm clinical study of patients with UTUC was conducted from August 2022 to July 2023 using the KD-SR-01 system. The perioperative and follow-up data were prospectively recorded. The National Aeronautics and Space Administration Task Load Index was calculated to present ergonomics. The technique was described in detail. RESULTS: A total of 13 patients underwent RARNU. None of the cases conversed to laparoscopic surgery or open surgery. The median docking time and console time were 524 (range, 139-963) seconds and 102.2 (range, 55.3-249.3) minutes, respectively. The median estimated blood loss was 40 (range, 10-100) ml. None of the patients required intraoperative blood transfusion. The median postoperative hospital stay was 4 (range, 2-7) days. Intraoperative or postoperative complications (Clavien-Dindo grade I) occurred in 9 patients. The surgeon Task Load Index global score achieved 1.05±1.86. Three patients received the single-docking technique, demonstrating similar perioperative results compared to patients with re-docking. CONCLUSIONS: The KD-SR-01 system was feasible, safe, and effective for robot-assisted radical nephroureterectomy.

14.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38610537

RESUMO

Conventional spherical nucleic acid enzymes (SNAzymes), made with gold nanoparticle (AuNPs) cores and DNA shells, are widely applied in bioanalysis owing to their excellent physicochemical properties. Albeit important, the crowded catalytic units (such as G-quadruplex, G4) on the limited AuNPs surface inevitably influence their catalytic activities. Herin, a hybridization chain reaction (HCR) is employed as a means to expand the quantity and spaces of G4 enzymes for their catalytic ability enhancement. Through systematic investigations, we found that when an incomplete G4 sequence was linked at the sticky ends of the hairpins with split modes (3:1 and 2:2), this would significantly decrease the HCR hybridization capability due to increased steric hindrance. In contrast, the HCR hybridization capability was remarkably enhanced after the complete G4 sequence was directly modified at the non-sticky end of the hairpins, ascribed to the steric hindrance avoided. Accordingly, the improved SNAzymes using HCR were applied for the determination of AFB1 in food samples as a proof-of-concept, which exhibited outstanding performance (detection limit, 0.08 ng/mL). Importantly, our strategy provided a new insight for the catalytic activity improvement in SNAzymes using G4 as a signaling molecule.


Assuntos
Nanopartículas Metálicas , Ácidos Nucleicos , Aflatoxina B1 , Ouro , Hibridização de Ácido Nucleico
17.
Urol Int ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38513631

RESUMO

INTRODUCTION: To present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253±51.4 min and 238.9±196.9 ml, with a mean postoperative follow-up time of 13.0±5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (P=0.006 and P=0.024). The postoperative 3-month and 1-year eGFR values were significantly increased comapred with those before operation (P=0.0002 and P=0.018). The separation value of left renal pelvis collection system after operation were significantly reduced compared with preoperative evaluation (P=0.023 at 3 month and P=0.042 at 1 year) and so was the right side (P=0.019 and P=0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

18.
Pharmacol Res ; 203: 107162, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554788

RESUMO

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.


Assuntos
Autofagia , Ferroptose , Neoplasias da Próstata , Humanos , Ferroptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo
19.
Ann Lab Med ; 44(4): 343-353, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38433572

RESUMO

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.


Assuntos
Hipotireoidismo Congênito , Humanos , China , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , AMP Cíclico , Oxidases Duais/genética , Mutação , Fenótipo , Receptores da Tireotropina/genética , Tireotropina
20.
Curr Urol ; 18(1): 71-74, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505162

RESUMO

Continuous cutaneous urinary diversion is challenging when the appendix is physically unavailable. The Yang-Monti channel is an alternative to the tunneled appendix for urinary diversion. We present a case involving a 49-year-old man who underwent total urethrectomy and cystostomy 10 months previously. No tumor recurrence was observed; however, the patient experienced severe catheter-related bladder irritation after the procedure. The patient was readmitted to the authors' hospital and underwent laparoscopic continent cutaneous urinary diversion using extracorporeal construction of a modified Yang-Monti channel. The operation lasted 232 minutes, with an estimated blood loss of 10 mL. The patient was discharged from hospital 6 days after surgery and removal of the cystostomy tube. After this, clean intermittent catheterization was performed every 3 hours for 4 weeks. Five years after the procedure, the modified Yang-Monti channel was still used for clean intermittent catheterization without any stomal stenosis being observed. The patient was satisfied with his postoperative quality of life.

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