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1.
Front Oncol ; 14: 1360956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737900

RESUMO

Advanced prostate cancer (PCa) is usually treated initially with androgen deprivation therapy (ADT). Although they experience a period of disease regression, most patients progress to metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC now have an unprecedented number of approved treatment options, including chemotherapies, hormone therapies, targeted therapies, etc. However, the improvement of overall survival (OS) in patients with mCRPC and its special subtype neuroendocrine prostate cancer (NEPC) is limited. In recent years, with the use of immune checkpoint inhibitors (ICIs), such as PD1/PDL1 and CTLA4 inhibitors, immunotherapy has once again become a promising treatment choice to stimulate antitumor immunity. However, the efficacy of NEPC receiving ICI has not been reported. Here, we describe a patient with mCRPC who developed primary resistance to current endocrine and chemotherapy regimens and progressed to mCRPC with NEPC as the main component, showing a significant and lasting response to PD1 monoclonal antibody combined with radiotherapy.

2.
Org Lett ; 26(17): 3557-3562, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38652078

RESUMO

A sequential dearomatization/rearrangement reaction between quinazoline-derived azomethine imines and crotonate sulfonium salts has been developed to provide a series of three-dimensional cage-like molecules. The reaction involves two dearomatizations, two cyclizations, and two C-C bond and three C-N bond formations in one step. The new transformation has a broad substrate scope, does not require any added reagents, and proceeds under room temperature in a short time. A mechanistic rationale for the sequential dearomatization/rearrangement is also presented. Furthermore, the synthetic compounds are evaluated for their glucose control effect. Compounds 3aa and 3aj were found to be hyperglycemic, which might be lead compounds for treating hypoglycemia.

3.
Int Neurourol J ; 28(1): 33-43, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38569618

RESUMO

PURPOSE: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. METHODS: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. RESULTS: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. CONCLUSION: This study aimed to improve clinicians' ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

4.
Cell Death Differ ; 31(5): 592-604, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514847

RESUMO

RB transcriptional corepressor 1 (RB) deletion is the most important genomic factor associated with the prognosis of castration-resistant prostate cancer (CRPC) patients receiving androgen receptor (AR) signaling inhibitor therapy. Loss of RB could support prostate cancer cell growth in a hormone-independent manner, but the underlying mechanism by which RB regulates tumor progression extends far beyond the cell cycle pathway. A previous study indicated that RB inactivates AKT signaling but has no effect on mTOR signaling in cancer cells. Here, we found that the S249/T252 site in RB is key to regulating the transcriptional activity of the tumor-promoting factor TRIM24 in CRPC, as identified through FXXXV mapping. The RB/TRIM24 complex functions through DUSP2, which serves as an intermediate bridge, to activate the mTOR pathway and promote prostate cancer progression. Accordingly, we designed RB-linker-proteolysis-targeting chimera (PROTAC) molecules, which decreased TRIM24 protein levels and inactivated the mTOR signaling pathway, thereby inhibiting prostate cancer. Therefore, this study not only elucidates the novel function of RB but also provides a theoretical basis for the development of new drugs for treating prostate cancer.


Assuntos
Transdução de Sinais , Serina-Treonina Quinases TOR , Masculino , Humanos , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Animais , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Proteína do Retinoblastoma/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Camundongos , Camundongos Nus , Proliferação de Células
5.
Nat Microbiol ; 9(4): 1075-1088, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553607

RESUMO

Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.4 nM and suggests that it dissociates about 12 times slower from Mpro compared with nirmatrelvir. The crystal structure of the SARS-CoV-2 Mpro:RAY1216 complex shows that RAY1216 covalently binds to the catalytic Cys145 through the α-ketoamide group. In vitro and using human ACE2 transgenic mouse models, RAY1216 shows antiviral activities against SARS-CoV-2 variants comparable to those of nirmatrelvir. It also shows improved pharmacokinetics in mice and rats, suggesting that RAY1216 could be used without ritonavir, which is co-administered with nirmatrelvir. RAY1216 has been approved as a single-component drug named 'leritrelvir' for COVID-19 treatment in China.


Assuntos
COVID-19 , Vacinas , Humanos , Animais , Camundongos , Ratos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Cinética , Lactamas , Nitrilas , Camundongos Transgênicos
6.
Emerg Infect Dis ; 30(4): 826-828, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38526372

RESUMO

In 2022, we assessed avian influenza A virus subtype H5N6 seroprevalence among the general population in Guangdong Province, China, amid rising numbers of human infections. Among the tested samples, we found 1 to be seropositive, suggesting that the virus poses a low but present risk to the general population.


Assuntos
Influenza Aviária , Influenza Humana , Animais , Humanos , Influenza Aviária/epidemiologia , Estudos Soroepidemiológicos , Influenza Humana/epidemiologia , China/epidemiologia , Aves
7.
J Immunother Cancer ; 12(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355278

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic renal cell carcinoma (RCC); however, most patients develop de novo or acquired resistance to ICIs. Oxidative phosphorylation (OXPHOS) has been rarely explored as a potential target for correcting ICI resistance. METHODS: We systematically analyzed RNA sequencing and clinical data from CheckMate, JAVELIN Renal 101, and NCT01358721 clinical trials, and clinicopathological data of 25 patients from Tongji Hospital to investigate the relationship between OXPHOS and ICI resistance. The Ndufb8-knockdown Renca cell line was derived to determine the effect of OXPHOS on RCC immunotherapy in vivo. RESULTS: An analysis of the CheckMate series data revealed that high OXPHOS levels are risk factors for ICI in patients with RCC, but are affected by thevon Hippel-Lindau protein (VHL) and hypoxia-inducible factor-1α status. This result is consistent with correlation between clinicopathological characteristics and prognostic observations at our institute. Knockdown of the mitochondrial complex I subunit Ndufb8 of the Renca cell line had no effect on cell growth and migration in vitro, but slowed down cell growth in vivo. Among anti-programmed death ligand 1 (PD-L1)-treated BALB/c mice, shNdufb8 Renca tumors grew slower than shControl Renca tumors and the corresponding mice survived longer. Flow cytometry revealed that CD8+ T cells in shNdufb8 Renca tumors, which were exposed to a lower degree of hypoxia and expressed less programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3), secreted more interferon-γ after stimulation. Immunofluorescence demonstrated that the shNdufb8 Renca tumors had a higher proportion of CD8+ T cells and the proportion of these cells was lower in the hypoxic area. CONCLUSIONS: OXPHOS is a reliable predictor of immunotherapy response in RCC and is more pronounced in metastatic lesions. RCC cells generate a hypoxic tumor microenvironment and inhibit T-cell function through oxidative metabolism, thereby leading to immunotherapy resistance.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Animais , Camundongos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Linfócitos T CD8-Positivos , Fosforilação Oxidativa , Linhagem Celular Tumoral , Microambiente Tumoral
8.
Environ Sci Pollut Res Int ; 31(12): 18842-18855, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351355

RESUMO

Copper-containing stainless steel (SS) has been reported to mitigate biofilms in industrial and clinical environments. However, the impact of copper released from copper-containing SS in natural seawater on biofilms and corrosion is still unclear. In this study, three kinds of 316L SS were immersed in natural seawater for 6 months, and the pitting depth decreased in the order: 316L-Cu SS (annealed) > 316L SS > 316L-Cu SS (aged). The biofilm thickness and number of sessile cells on the surface of 316L-Cu SS (annealed) and 316L SS were similar but notably greater than those of 316L-Cu SS (aged). Furthermore, the results of the community analysis indicated that the addition of copper in 316L-Cu SS (aged) reduced the diversity and richness of the microbial community, resulting in a significant reduction in the number of genera constituting the biofilms. Copper ions exhibit a broad-spectrum bactericidal effect, effectively reducing the abundance of dominant populations and microbial genera in the biofilms, thereby mitigating pitting corrosion induced by microorganisms. In addition, the PCoA scatter plot showed that time also played an important role in the regulation of microbial community structure.


Assuntos
Cobre , Aço Inoxidável , Cobre/química , Aço Inoxidável/química , Corrosão , Biofilmes , Água do Mar
9.
Urol Oncol ; 42(5): 158.e17-158.e27, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38388243

RESUMO

BACKGROUND: The Prostate Imaging Reporting and Data System (PI-RADS) is an established reporting scheme for multiparametric magnetic resonance imaging (mpMRI) to distinguish clinically significant prostate cancer (csPCa). Deep learning (DL) holds great potential for automating csPCa classification on mpMRI. METHOD: To compare the performance between a DL algorithm and PI-RADS categorization in PCa detection and csPCa classification, we included 1,729 consecutive patients who underwent radical prostatectomy or biopsy in Tongji hospital. We developed DL models by integrating individual mpMRI sequences and employing an ensemble approach for distinguishing between csPCa and CiSPCa (specifically defined as PCa with a Gleason group 1 or benign prostate disease, training cohort: 1,285 patients vs. external testing cohort: 315 patients). RESULTS: DL-based models exhibited higher csPCa detection rates than PI-RADS categorization (area under the curve [AUC]: 0.902; sensitivity: 0.728; specificity: 0.906 vs. AUC: 0.759; sensitivity: 0.761; specificity: 0.756) (P < 0.001) Notably, DL networks exhibited significant strength in the prostate-specific antigen (PSA) arm < 10 ng/ml compared with PI-RADS assessment (AUC: 0.788; sensitivity: 0.588; specificity: 0.883 vs. AUC: 0.618; sensitivity: 0.379; specificity: 0.763) (P = 0.041). CONCLUSIONS: We developed DL-based mpMRI ensemble models for csPCa classification with improved sensitivity, specificity, and accuracy compared with clinical PI-RADS assessment. In the PSA-stratified condition, the DL ensemble model performed better than PI-RADS in the detection of csPCa in both the high PSA group and the low PSA group.


Assuntos
Aprendizado Profundo , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos
10.
Circulation ; 149(20): 1578-1597, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38258575

RESUMO

BACKGROUND: Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA; AVCAPIR) that increases valvular calcification and promotes CAVD progression. METHODS: Using piRNA sequencing, we identified piRNAs contributing to the pathogenesis of CAVD that we termed AVCAPIRs. High-cholesterol diet-fed ApoE-/- mice with AVCAPIR knockout were used to examine the role of AVCAPIR in aortic valve calcification (AVC). Gain- and loss-of-function assays were conducted to determine the role of AVCAPIR in the induced osteogenic differentiation of human valvular interstitial cells. To dissect the mechanisms underlying AVCAPIR-elicited procalcific effects, we performed various analyses, including an RNA pulldown assay followed by liquid chromatography-tandem mass spectrometry, methylated RNA immunoprecipitation sequencing, and RNA sequencing. RNA pulldown and RNA immunoprecipitation assays were used to study piRNA interactions with proteins. RESULTS: We found that AVCAPIR was significantly upregulated during AVC and exhibited potential diagnostic value for CAVD. AVCAPIR deletion markedly ameliorated AVC in high-cholesterol diet-fed ApoE-/- mice, as shown by reduced thickness and calcium deposition in the aortic valve leaflets, improved echocardiographic parameters (decreased peak transvalvular jet velocity and mean transvalvular pressure gradient, as well as increased aortic valve area), and diminished levels of osteogenic markers (Runx2 and Osterix) in aortic valves. These results were confirmed in osteogenic medium-induced human valvular interstitial cells. Using unbiased protein-RNA screening and molecular validation, we found that AVCAPIR directly interacts with FTO (fat mass and obesity-associated protein), subsequently blocking its N6-methyladenosine demethylase activity. Further transcriptomic and N6-methyladenosine modification epitranscriptomic screening followed by molecular validation confirmed that AVCAPIR hindered FTO-mediated demethylation of CD36 mRNA transcripts, thus enhancing CD36 mRNA stability through the N6-methyladenosine reader IGF2BP1 (insulin-like growth factor 2 mRNA binding protein 1). In turn, the AVCAPIR-dependent increase in CD36 stabilizes its binding partner PCSK9 (proprotein convertase subtilisin/kexin type 9), a procalcific gene, at the protein level, which accelerates the progression of AVC. CONCLUSIONS: We identified a novel piRNA that induced AVC through an RNA epigenetic mechanism and provide novel insights into piRNA-directed theranostics in CAVD.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Calcinose , RNA Interferente Pequeno , Animais , Calcinose/metabolismo , Calcinose/genética , Calcinose/patologia , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Valva Aórtica/anormalidades , Humanos , Camundongos , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/patologia , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/genética , Masculino , Osteogênese , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais de Doenças , Valvopatia Aórtica/metabolismo , Valvopatia Aórtica/genética , Valvopatia Aórtica/patologia , RNA de Interação com Piwi
11.
Med ; 5(1): 32-41.e5, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38070511

RESUMO

BACKGROUND: Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. METHODS: Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. FINDINGS: All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. CONCLUSIONS: For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness. FUNDING: This work was funded by the National Natural Science Foundation of China (81761128014).


Assuntos
Dibenzotiepinas , Vírus da Influenza A , Influenza Aviária , Influenza Humana , Morfolinas , Piridonas , Síndrome do Desconforto Respiratório , Sepse , Triazinas , Animais , Humanos , Influenza Aviária/tratamento farmacológico , Influenza Aviária/epidemiologia , Oseltamivir/uso terapêutico , Virus da Influenza A Subtipo H5N6 , Interleucina-18/uso terapêutico , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Sepse/tratamento farmacológico
12.
Environ Sci Pollut Res Int ; 31(1): 1644-1653, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38038922

RESUMO

Harmful algal blooms, particularly those of Microcystis aeruginosa, present significant ecological and health risks. To address this issue, this study utilized a custom static algal growth assessment apparatus to investigate the anti-algal performance of a copper-alloyed 316L stainless steel (SS), named 316L-Cu SS. This material was compared with traditional 316L SS, which is widely utilized in freshwater systems for its corrosion resistance. Algal growth dynamics were monitored through optical density (OD) and chlorophyll A concentration measurements. Notably, 316L-Cu SS exhibited superior inhibitory effects on Microcystis aeruginosa growth compared to 316L SS and control groups. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the copper ion release from 316L-Cu SS played a critical role in this algal suppression, which interfered with photosynthesis, induced oxidative stress, and damaged algal cell membranes. In contrast, other metal ions (Ni, Cr, Fe) had a negligible impact on algal growth. The study highlights 316L-Cu SS as a promising material for mitigating harmful algal blooms, thereby offering potential benefits for both aquatic ecosystem conservation and public health protection.


Assuntos
Cianobactérias , Microcystis , Cobre/química , Aço Inoxidável/química , Clorofila A , Ecossistema
13.
Adv Sci (Weinh) ; 10(36): e2302368, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37949681

RESUMO

The development of castration-resistant prostate cancer (CRPC) is a significant factor that reduces life expectancy among patients with prostate cancer. Previously, it is reported that CDK4/6 inhibitors can overcome the resistance of CRPC to BET inhibitors by destabilizing BRD4, suggesting that the combination of CDK4/6 inhibitors and BET inhibitors is a promising approach for treating CRPC. In this study, candidates that affect the combined antitumor effect of CDK4/6 inhibitors and BET inhibitors on CRPC is aimed to examine. The data demonstrates that CBX3 is abnormally upregulated in CDK4/6 inhibitors-resistant cells. CBX3 is almost positively correlated with the cell cycle in multiple malignancies and is downregulated by BET inhibitors. Mechanistically, it is showed that CBX3 is transcriptionally upregulated by BRD4 in CRPC cells. Moreover, it is demonstrated that CBX3 modulated the sensitivity of CRPC to CDK4/6 inhibitors by binding with RB1 to release E2F1. Furthermore, it is revealed that PLK1 phosphorylated CBX3 to enhance the interaction between RB1 and CBX3, and desensitize CRPC cells to CDK4/6 inhibitors. Given that BRD4 regulates CBX3 expression and PLK1 affects the binding between RB1 and CBX3, it is proposed that a dual BRD4/PLK1 inhibitor can increase the sensitivity of CRPC cells to CDK4/6 inhibitors partially through CBX3.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Fatores de Transcrição/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/metabolismo , Antineoplásicos/uso terapêutico , Proteínas que Contêm Bromodomínio , Quinase 4 Dependente de Ciclina/uso terapêutico , Proteínas Cromossômicas não Histona/uso terapêutico
14.
Bladder (San Franc) ; 10: e21200006, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936585

RESUMO

OBJECTIVE: To investigate the utility of fluorescence in situ hybridization (FISH) in secondary electroresection of bladder cancer. METHODS: From January 2016 to April 2022, bladder cancer patients who had undergone secondary electroresection in Tongji Hospital and had preoperative urine FISH were recruited, and the positive rate, accuracy, sensitivity, specificity, genetic material changes and predictive power on malignancy degree of FISH in the secondary electroresection of bladder cancer were examined. RESULTS: Twenty-six patients with bladder cancer were included in this study, and 8 were confirmed by secondary electroresection, including 6 cases positive for FISH positive and 2 negative for FISH. Besides, among the subjects, 18 were without tumor recurrence, including 1 case with positive FISH results and 17 with negative FISH results. Tumor recurrence was diagnosed in 85.71% (6/7) of FISH-positive patients in secondary electroresection while only 10.53% (2/19) of FISH-negative patients were found to develop tumor recurrence in the secondary electroresection. The sensitivity of FISH for the detection of bladder cancer before secondary electroresection was 75%, with a specificity of 94.44%, and an accuracy of 88.46%. A 6-month follow-up revealed that 2 of the 8 recurrent patients underwent radical resection of bladder cancer, and the remaining 6 patients had no recurrence, as confirmed by regular bladder perfusion and microscopy. In the 18 non-recurrent patients during secondary electroresection, no recurrence developed. CONCLUSIONS: Urine FISH can achieve a high detection rate and specificity for secondary electroresection of bladder cancer. If a bladder cancer patient who are indicated for secondary electroresection is negative for urine FISH, the recurrence rate after secondary electroresection will be low, and the cystoscopy can be performed before deciding whether to perform secondary electroresection.

15.
Front Mol Biosci ; 10: 1250442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37867556

RESUMO

Background: Positive UroVysion™ fluorescence in situ hybridization (FISH) is generally considered as urothelial carcinoma (UC). We clarify if UroVysion™ FISH can be positive in carcinoma of non-urothelial lineages (CNUL), and verify the consistency of urine FISH and histological FISH in CNUL. Methods: All CNUL subjects detected by urine FISH assay due to haematuria from Tongji Hospital were screened. Meanwhile, 2 glandular cystitis and 2 urothelial carcinoma were served as negative or positive control. Paraffin-embedded tissue sections of all subjects were sent to the pathology department for histological FISH detection. Results: A total of 27 patients were included in this study, including 9 with adenocarcinomas, 11 with squamous cell carcinomas, and 7 with other tumour types. The overall positive rate in urine FISH was 64.00% (16/25) in patients with CNUL, 77.78% (7/9) in those with adenocarcinoma and 54.55% (6/11) in those with squamous carcinoma. There was a significant difference in the GLP p16 gene deletion rate between UC and CNUL (100% vs. 8.00%, p = 0.017). Histological FISH results showed that the histological results of 19 patients were consistent with their urine FISH results, and only one patient with stage Ⅲa urachal carcinoma had inconsistent histological FISH results (positive) and urine FISH (negative) results. Conclusion: We demonstrated for the first time the application value of FISH in CNUL on urine samples. Positive urine FISH tests indicate not only UC, but also CNUL. UroVysion™ FISH possibly has a high positive rate in CNUL. CNUL and UC have different genetic changes shown by FISH.

16.
J Transl Med ; 21(1): 465, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438820

RESUMO

BACKGROUND: Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa. METHODS: We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm. RESULTS: 197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573-0.853), specificity of 0.869 (95% CI 0.764-0.974), F1 of 0.699 (95% CI 0.557-0.841), and AUC of 0.864 (95% CI 0.794-0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved. CONCLUSION: Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients.


Assuntos
Nomogramas , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico , Linfócitos , Aprendizado de Máquina , Medição de Risco
17.
Heliyon ; 9(4): e15157, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37123934

RESUMO

Purpose: Platinum-based regimens are regarded as the preferred alternative for neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC) patients. However, some patients cannot tolerate platinum-based regimens. We report an MIBC case with severe renal insufficiency treated by neoadjuvant therapy with gemcitabine and Disitamab Vedotin. Materials and Methods: A 68-year-old man with severe renal insufficiency was admitted to our department and diagnosed with cT3N0M0 MIBC. Immunohistochemical staining of the biopsy tissues showed human epidermal growth factor receptor 2 expression (1+). This patient received neoadjuvant therapy with gemcitabine 1600 mg and DV 120 mg intravenously every three weeks 3 times. We compared the imaging results of the patient before and after neoadjuvant therapy. In addition, the white blood cell count, alanine aminotransferase, aspartate aminotransferase, and serum creatinine were followed up during neoadjuvant therapy. Abnormal symptoms such as hair loss, fatigue, and hypoesthesia were also recorded. Results: According to the imaging examinations, the lesions were significantly reduced after receiving neoadjuvant therapy. Significant adverse side effects did not occur during neoadjuvant therapy. Conclusions: In this T3N0M0 cisplatin-ineligible patient, gemcitabine combined with DV as neoadjuvant therapy achieved radiological partial response, and no significant adverse events were observed during neoadjuvant therapy.

18.
Materials (Basel) ; 16(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37109867

RESUMO

Food contamination caused by microorganisms is a significant issue in the food field that not only affects the shelf life of food, but also threatens human health, causing huge economic losses. Considering that the materials in direct or indirect contact with food are important carriers and vectors of microorganisms, the development of antibacterial food contact materials is an important coping strategy. However, different antibacterial agents, manufacturing methods, and material characteristics have brought great challenges to the antibacterial effectiveness, durability, and component migration associated with the use security of materials. Therefore, this review focused on the most widely used metal-type food contact materials and comprehensively presents the research progress regarding antibacterial food contact materials, hoping to provide references for exploring novel antibacterial food contact materials.

19.
Transl Cancer Res ; 12(2): 301-309, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36915574

RESUMO

Background: To compare the effectiveness of cytoreductive partial nephrectomy (CPN) and cytoreductive radical nephrectomy (CRN) in the treatment of metastatic T1-T2 renal cell carcinoma (RCC). Methods: We obtained the clinical and pathological data of patients with metastatic T1-T2 RCC who underwent CPN or CRN from the Surveillance, Epidemiology, and End Results (SEER) database (https://seer.cancer.gov). Propensity score matching (PSM) was used to balance differences in characteristics between CPN and CRN cases. Kaplan-Meier survival analysis and univariate and multivariate Cox regression were used to assess the effect of partial nephrectomy (PN) versus radical nephrectomy (RN) on overall survival (OS) and cancer-specific survival (CSS). Results: After screening, 866 eligible cases were obtained. During the 1-107 months of follow-up, 500 patients died, 453 (90.6%) of whom died of RCC. The tumor size in the CRN group was significantly greater than that in the CPN group. Kaplan-Meier survival analysis showed that there was no significant difference in OS and CSS between the CPN group and the CRN group before and after matching. Univariate and multivariate Cox regression analysis found that the risk factors for OS were older age at diagnosis [hazard ratio (HR) =1.02, P=0.008], non-clear cell renal cell carcinoma (ccRCC) pathological type (HR =1.69, P=0.002), number of metastases ≥2 (HR =2.13, P<0.001), and regional lymph node involvement (HR =2.22, P=0.004), while the risk factors for CSS were non-ccRCC pathological type (HR =1.51, P=0.021) and the number of metastases ≥2 (HR =2.24, P <0.001). Conclusions: CPN can provide similar oncologic outcomes as can CRN in T1-2M1 cases, and tumor metastatic burden is a major risk factor for survival in these patients with metastatic renal cell carcinoma (mRCC).

20.
Urol Oncol ; 41(7): 327.e1-327.e8, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36966065

RESUMO

PURPOSE: To compare the oncologic outcomes of bladder cancer (BCa) patients after partial cystectomy (PC) or radical cystectomy (RC) combined with lymph node dissection (LND). METHODS: Relevant data from BCa patients who had >3 lymph nodes (LNs) removed were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Different thresholds of LN count in LND were tested to eliminate potential selection bias, and the optimal threshold was applied to screen patients who underwent adequate LND. After propensity score matching, the oncologic outcomes after PC or RC were compared in patients who underwent adequate LND. RESULTS: After preliminary screening, 6,785 BCa cases diagnosed between 2004 and 2015 with removal of > 3 LNs were enrolled in the analysis, including 633 (9.3%) PC cases and 6,152 (90.7%) RC cases. The PC and RC groups presented entirely different profiles in clinical parameters such as sex, T stage, number of lymph nodes (LNs) removed, and adjuvant therapy. In particular, the LN-positive rate and count were higher in the RC group, even after adjusting for other confounding factors. After comparison using different thresholds, the LN positive rate and count were similar when the LN count in LND was restricted to > 12. In patients who had > 12 LNs removed, after propensity score matching, PC and RC presented similar oncologic outcomes. Further exploration found that the prognosis of patients was associated with age, T stage, and the number of positive LNs. CONCLUSION: PC and RC could provide equivalent oncologic outcomes in BCa when combined with adequate LND. The conclusion needs further validation in future studies.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Resultado do Tratamento , Excisão de Linfonodo/métodos , Neoplasias da Bexiga Urinária/patologia , Linfonodos/cirurgia , Linfonodos/patologia
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