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1.
Cancer ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38798127

RESUMO

BACKGROUND: The objective of this study was to quantify disparities in cancer treatment delivery between minority-serving hospitals (MSHs) and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers from 2010 to 2019 and to estimate the impact of improving care at MSHs on national disparities. METHODS: Data from the National Cancer Database (2010-2019) identified patients who were eligible for definitive treatments for the specified cancers. Hospitals in the top decile by minority patient proportion were classified as MSHs. Multivariable logistic regression adjusted for patient and hospital characteristics compared the odds of receiving definitive treatment at MSHs versus non-MSHs. A simulation was used to estimate the increase in patients receiving definitive treatment if MSH care matched the levels of non-MSH care. RESULTS: Of 2,927,191 patients from 1330 hospitals, 9.3% were treated at MSHs. MSHs had significant lower odds of delivering definitive therapy across all cancer types (adjusted odds ratio: breast cancer, 0.83; prostate cancer, 0.69; nonsmall cell lung cancer, 0.73; colon cancer, 0.81). No site of care-race interaction was significant for any of the cancers (p > .05). Equalizing treatment rates at MSHs could result in 5719 additional patients receiving definitive treatment over 10 years. CONCLUSIONS: The current findings underscore systemic disparities in definitive cancer treatment delivery between MSHs and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers. Although targeted improvements at MSHs represent a critical step toward equity, this study highlights the need for integrated, system-wide efforts to address the multifaceted nature of racial and ethnic health disparities. Enhancing care at MSHs could serve as a pivotal strategy in a broader initiative to achieve health care equity for all.

2.
Microvasc Res ; 152: 104640, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38065353

RESUMO

The complexity of microvascular circulation has led to the development of advanced imaging techniques and biomimetic models. This study developed a multifaceted microfluidic-based microdevice as an in vitro model of microvasculature to replicate important geometric and functional features of in vivo perfusion in mice. The microfluidic device consisted of a microchannel for blood perfusion, mirroring the natural hierarchical branching vascular structures found in mice. Additionally, the device incorporated a steady gradient of oxygen (O2) which diffused through the polydimethylsiloxane (PDMS) layer, allowing for dynamic blood oxygenation. The assembled multi-layered microdevice was accompanied by a dual-modal imaging system that combined laser speckle contrast imaging (LSCI) and intrinsic signal optical imaging (ISOI) to visualize full-field blood flow distributions and blood O2 profiles. By closely reproducing in vivo blood perfusion and oxygenation conditions, this microvasculature model, in conjunction with numerical simulation results, can provide quantitative information on physiologically relevant hemodynamics and key O2 transport parameters that are not directly measurable in traditional animal studies.


Assuntos
Hemodinâmica , Microfluídica , Camundongos , Animais , Oxigênio , Microvasos
3.
World J Urol ; 42(1): 54, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38244128

RESUMO

PURPOSE: To evaluate how limited English proficiency (LEP) impacts the prevalence of prostate-specific antigen (PSA) screening in a contemporary, nationally representative cohort of men in the USA. METHODS: The Medical Expenditure Panel Survey was utilized to identify the prevalence of PSA screening between 2013 and 2016 among men ≥ 55. Men who speak a language other than English at home were stratified by self-reported levels of English proficiency (men who speak English very well, well, not well, or not at all). Survey weights were applied, and groups were compared using the adjusted Wald test. A multivariable logistic regression model was used to identify predictors of PSA screening adjusting for patient-level covariates. RESULTS: The cohort included 2,889 men, corresponding to a weighted estimate of 4,765,682 men. 79.6% of men who speak English very well reported receiving at least one lifetime PSA test versus 58.4% of men who do not speak English at all (p < 0.001). Men who reported not speaking English at all had significantly lower prevalence of PSA screening (aOR 0.56; 95% CI 0.35-0.91; p = 0.019). Other significant predictors of PSA screening included older age, income > 400% of the federal poverty level, insurance coverage, and healthcare utilization. CONCLUSIONS: Limited English proficiency is associated with significantly lower prevalence of PSA screening among men in the USA. Interventions to mitigate disparities in prostate cancer outcomes should account for limited English proficiency among the barriers to guideline-concordant care.


Assuntos
Proficiência Limitada em Inglês , Neoplasias da Próstata , Masculino , Humanos , Estados Unidos , Antígeno Prostático Específico , Idioma , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/prevenção & controle , Renda
4.
Curr Opin Urol ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38881293

RESUMO

PURPOSE OF REVIEW: Natural disasters are on the rise, driven by shifts in climatic patterns largely attributed to human-induced climate change. This relentless march of climate change intensifies the frequency and severity of these disasters, heightening the vulnerability of communities and causing significant harm to both lives and socio-economic systems. Healthcare services are particularly strained during extreme weather events, with impacts felt not only on infrastructure but also on patient care. RECENT FINDINGS: This narrative review explored the overarching impact of natural disasters on healthcare infrastructure. We delved into how these disasters impact diverse health conditions, the healthcare systems of low and middle-income countries (LMICs), the psychological toll on both clinicians and survivors, and the ramifications for end-of-life care. SUMMARY: Natural disasters significantly impact healthcare, especially in LMICs due to their limited resources. Patients with cancer or chronic diseases struggle to access care following a natural disaster. Those in need for palliative care experience delay due to shortages in medical resources. Psychological consequences like posttraumatic stress disorder on disaster survivors and healthcare providers highlight the need for mental health support. Addressing challenges requires proactive disaster preparedness policies and urgent public policy initiatives are needed for optimal disaster response.

5.
Mol Cell ; 64(5): 859-874, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27867011

RESUMO

Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is "hijacked" to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers. The resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity, leading to increased PDC flux and oxidative phosphorylation with attenuated cancer cell proliferation and tumor growth. These findings provide a mechanistic understanding of how oncogenic events signal through distinct acetyltransferases to regulate cancer metabolism and suggest ACAT1 as an anti-cancer target.


Assuntos
Acetil-CoA C-Acetiltransferase/metabolismo , Mitocôndrias/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Acetil-CoA C-Acetiltransferase/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Fator de Crescimento Epidérmico/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Células NIH 3T3 , Neoplasias/enzimologia , Neoplasias/patologia , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo
6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 167-172, 2024 Mar 30.
Artigo em Zh | MEDLINE | ID: mdl-38605616

RESUMO

A pulse and respiration synchronous detection system is designed to explore the changes of physiological signals in different situations. The system obtains the corresponding signal through STM32 control pulse and respiratory acquisition circuit, calculates and displays real-time parameters such as heart rate and respiratory rate, and transmits the data to the upper computer for storage in the database. The experimental test results show that the system can monitor pulse and respiratory waveform in different situations, and the waveform is in good condition. Compared with medical pulse oximeter, the error of measured heart rate and blood oxygen concentration is less than 3%, and the error of respiratory rate is less than 5% compared with the actual value, which verifies the accuracy of system signal acquisition. The system is small in size, low in cost, and comfortable to wear, and can be applied in experimental research related to pulse and respiratory signals.


Assuntos
Oximetria , Processamento de Sinais Assistido por Computador , Frequência Cardíaca/fisiologia , Taxa Respiratória , Gasometria
7.
Anticancer Drugs ; 34(9): 1046-1057, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578814

RESUMO

Cisplatin-based chemotherapy plays a vital role in the management of muscle-invasive bladder cancer (MIBC); however, off-tumor toxicity and resistance often lead to cancer recurrence and eventual treatment failure. The loss of function of the nucleotide excision repair gene excision repair cross-complementing rodent repair deficiency gene 2 ( ERCC2 ) in cancer cells correlates with sensitivity to cisplatin, while its overexpression causes cisplatin resistance. Small interfering RNA (siRNA) knockdown of ERCC2 combined with cisplatin treatment may improve therapeutic outcomes in patients with bladder cancer. Here, we aimed to develop macrophage-derived mimetic nanovesicles (MNVs) as a nanoplatform for the simultaneous delivery of cisplatin and ERCC2 siRNA for enhancing the efficacy of bladder cancer chemotherapy. The cellular uptake, gene down-regulation, tumor inhibition effects, and biosafety of the synthesized nanodrugs (MNV-Co) as a synergistic therapeutic strategy for MIBC were evaluated in vitro and in vivo . The results indicated high efficacy of MNV-Co against MIBC and low off-tumor toxicity. Furthermore, by down-regulating ERCC2 mRNA and protein levels, MNV-Co improved chemosensitivity, promoted cancer cell apoptosis, and effectively suppressed tumor growth. This study presents a potential approach for delivering cisplatin and ERCC2 siRNA concurrently to treat bladder cancer using a biomimetic nanosystem.


Assuntos
Antineoplásicos , Neoplasias da Bexiga Urinária , Proteína Grupo D do Xeroderma Pigmentoso , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomimética , Linhagem Celular Tumoral , Cisplatino , Resistencia a Medicamentos Antineoplásicos , RNA Interferente Pequeno/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Proteína Grupo D do Xeroderma Pigmentoso/genética
8.
J Nat Prod ; 86(6): 1449-1462, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37243616

RESUMO

Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (-)-N-hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1-TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo. This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias Colorretais , Animais , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , NF-kappa B/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Dig Dis Sci ; 68(5): 1780-1790, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600118

RESUMO

INTRODUCTION: Colorectal cancer screening continuously decreased its mortality and incidence. In 2010, the Affordable Care Act extended Medicaid eligibility to low-income and childless adults. Some states elected to adopt Medicaid at different times while others chose not to. Past studies on the effects of Medicaid expansion on colorectal cancer screening showed equivocal results based on short-term data following expansion. AIMS: To examine the long-term impact of Medicaid expansion on colorectal cancer screening among its targeted population at its decade mark. METHODS: Behavioral Risk Factor Surveillance System data were extracted for childless adults below 138% federal poverty level in states with different Medicaid expansion statuses from 2012 to 2020. States were stratified into very early expansion states, early expansion states, late expansion states, and non-expansion states. Colorectal cancer screening prevalence was determined for eligible respondents. Difference-in-differences analyses were used to examine the effect of Medicaid expansion on colorectal cancer screening in states with different expansion statuses. RESULTS: Colorectal cancer screening prevalence in very early, early, late, and non-expansion states all increased during the study period (40.45% vs. 48.14%, 47.52% vs 61.06%, 46.06% vs 58.92%, and 43.44% vs 56.70%). Difference-in-differences analysis showed significantly increased CRC screening prevalence in very early expansion states during 2016 compared to non-expansion states (Crude difference-in-differences + 16.45%, p = 0.02, Adjusted difference-in-differences + 15.9%, p = 0.03). No statistical significance was observed among other years and groups. CONCLUSIONS: Colorectal cancer screening increased between 2012 and 2020 in all states regardless of expansion status. However, Medicaid expansion is not associated with long-term increased colorectal cancer screening prevalence.


Assuntos
Neoplasias Colorretais , Medicaid , Adulto , Estados Unidos/epidemiologia , Humanos , Patient Protection and Affordable Care Act , Detecção Precoce de Câncer , Pobreza , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Cobertura do Seguro , Acessibilidade aos Serviços de Saúde
10.
Can J Urol ; 30(6): 11714-11723, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38104328

RESUMO

INTRODUCTION: Robot-assisted laparoscopic prostatectomy (RALP) and transurethral resection of bladder tumor (TURBT) are two common surgeries for prostate and bladder cancer. We aim to assess the trends in the site of care for RALP and TURBT before and after the COVID outbreak. MATERIALS AND METHODS: We identified adults who underwent RALP and TURBT within the California Healthcare Cost and Utilization Project State Inpatient Database and the State Ambulatory Surgery Database between 2018 and 2020. Multivariable analysis and spline analysis with a knot at COVID outbreak were performed to investigate the time trend and factors associated with ambulatory RALP and TURBT. RESULTS: Among 17,386 RALPs, 6,774 (39.0%) were ambulatory. Among 25,070 TURBTs, 21,573 (86.0%) were ambulatory. Pre-COVID, 33.5% of RALP and 85.3% and TURBT were ambulatory, which increased to 53.8% and 88.0% post-COVID (both p < 0.001). In multivariable model, RALP and TURBT performed after outbreak in March 2020 were more likely ambulatory (OR 2.31, p < 0.0001; OR 1.25, p < 0.0001). There was an overall increasing trend in use of ambulatory RALP both pre- and post-COVID, with no significant change of trend at the time of outbreak (p = 0.642). TURBT exhibited an increased shift towards ambulatory sites post-COVID (p < 0.0001). CONCLUSIONS: We found a shift towards ambulatory RALP and TURBT following COVID outbreak. There was a large increase in ambulatory RALP post-COVID, but the trend of change was not significantly different pre- and post-COVID - possibly due to a pre-existing trend towards ambulatory RALP which predated the pandemic.


Assuntos
COVID-19 , Laparoscopia , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Masculino , Adulto , Humanos , Pandemias , Prostatectomia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Procedimentos Cirúrgicos Ambulatórios , COVID-19/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia
11.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 54-60, 2023 Jan 30.
Artigo em Zh | MEDLINE | ID: mdl-36752007

RESUMO

In this study, a surface electromyography (sEMG) and blood oxygen signal real-time monitoring system is designed to explore the changes of physiological signals during muscle fatigue, so as to detect muscle fatigue. The analysis method of sEMG and the principle of blood oxygen detection are respectively introduced, and the system scheme is expounded. The hardware part of the system takes STM32 as the core. Conditioning module composition; blood oxygen signal acquisition is based on near infrared spectroscopy (NIRS), specifically including light source, light source driving, photoelectric conversion, signal conditioning and other modules. The system software part is based on the real-time uC/OS-III software system. The characteristic parameters of sEMG were extracted by isometric contraction local muscle fatigue experiment; the relative changes of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) were calculated in the forearm blocking experiment, thereby verifying that the system collects two signals effectiveness.


Assuntos
Músculo Esquelético , Oxigênio , Eletromiografia , Fadiga Muscular/fisiologia , Computadores
12.
World J Urol ; 40(11): 2649-2656, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36125504

RESUMO

PURPOSE: To assess whether the 5-item Frailty Index (5i-FI) predicts surgical complications of endoscopic surgery for benign prostatic obstruction (BPO) and examine the rates of these complications across BPO surgical modalities adjusting for patient frailty. METHODS: The ACS-NSQIP registry was queried for patients who underwent transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), and laser enucleation of the prostate (LEP) between 2009 and 2019. Patients' frailties were estimated using the 5i-FI. We assessed the association between 5i-FI and the following endpoints: all complications, major complications (Clavien-Dindo ≥ 3), length of stay (LOS) ≥ 2 days, and 30-day postoperative readmission. Inverse probability of treatment weighting (IPTW) was used to account for selection bias in treatment allocation. IPTW-adjusted rates for 30-day complications were compared between surgical modalities. RESULTS: The cohort included 38,399 (62.6%) TURP, 19,121 (31.2%) PVP, and 3797 (6.2%) LEP. Men with 5i-FI score ≥ 2 were more likely to receive TURP (22.7%) and PVP (22.5%) than LEP (18.8%). 5i-FI ≥ 2 was associated with higher odds of all complications (OR 1.50), major complications (OR 1.63), LOS ≥ 2 (OR 1.31), and readmission (OR 1.65). After IPTW, LEP had the lowest rates for all complications (6.29%; 95%CI 5.48-7.20), major complications (2.30%; 95%CI 1.83-2.89), and readmission (3.80%; 95%CI 3.18-4.53). CONCLUSION: The 5i-FI score is an independent predictor of 30-day postoperative surgical complications after endoscopic BPO surgery. After IPTW, LEP and PVP were associated with lower rates of complications than TURP. However, frail patients were less likely to undergo PVP and LEP. Preoperative frailty assessment could improve risk stratification before BPO surgery.


Assuntos
Fragilidade , Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução Uretral , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Fragilidade/complicações , Resultado do Tratamento , Terapia a Laser/efeitos adversos , Obstrução Uretral/etiologia , Complicações Pós-Operatórias/etiologia
13.
Biomed Eng Online ; 21(1): 79, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414958

RESUMO

The pathological features of cerebral edema are complicated. The intracranial pressure (ICP) is regarded as the most important indicator for monitoring cerebral edema. Recently, multi-parameter has been used to explore the types and pathogenesis of cerebral edema and design effective treatment strategies. This research focused on investigating the characteristic of the cerebral edema induced by lipopolysaccharide (LPS) in rats by using simultaneous electrophysical and hemodynamic parameters. The results showed that neurophysiologic parameters (firing rate (FR) and the power spectrum of local field potential (LFP power)) and hemodynamic parameters (relative concentration of oxygenated hemoglobin (ΔCHbO2), relative concentration of deoxyhemoglobin ΔCHbR) and relative cerebral blood flow (rCBF)) were linearly correlated, and the Pearson's correlation coefficient was changed by pathological progression of cerebral edema induced by LPS. Furtherly, the treatment after two agents were observed successfully through these multi-parameters. Our findings revealed the relationship between neural activity and hemodynamic response during the progression of cerebral edema and provided a multi-parameter solution for cerebral edema functional monitoring and anti-edema drug efficacy evaluation.


Assuntos
Edema Encefálico , Ratos , Animais , Lipopolissacarídeos , Hemodinâmica , Circulação Cerebrovascular , Pressão Intracraniana
14.
Int J Hyperthermia ; 39(1): 868-879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35858640

RESUMO

PURPOSE: The charring tissue formation in the ablated lesion during the microwave ablation (MWA) of tumors would induce various unwanted inflammatory responses. This paper aimed to deliver appropriate thermal dose for effective ablations while preventing tissue carbonization by optimizing the treatment protocol during MWA with the set combinations of temperature control and pulsed microwave energy delivery. MATERIAL AND METHODS: The thermal phase transition of ex vivo porcine liver tissues were recorded by differential scanning calorimetry (DSC) to determine the temperature threshold during microwave output control. MWA was performed by an in-house built system with the ease of microwave output parameter adjustment and real-time temperature monitoring. The effects of continuous and pulsed microwave deliveries as well as various intermittent time-set of MWA were evaluated by measuring the dimensions of the coagulation zone and the carbonization zone. RESULTS: The DSC scans demonstrated that the ex vivo porcine liver tissues have been in a state of endothermic heat during the heating process, where the maximum absorbed heat occurred at the temperature of 105 °C ± 5 °C. The temperature control during MWA resulted in effective coagulative necrosis while preventing tissue carbonization, after setting 100 °C as the upper threshold temperature and 60 °C as the lower threshold. Both the numerical simulation and ex vivo experiments have shown that, upon the optimization of the time-set parameters in the periodic intermittent pulsed microwave output, the tissue carbonization was significantly diminished. CONCLUSION: This study developed a straight-forward anti-carbonization strategy in MWA by modulating the pulsing mode and intermittent time. The programmed protocols of intermittent pulsing MWA have demonstrated its potentials toward future expansion of MWA technology in clinical application.


Assuntos
Técnicas de Ablação , Ablação por Cateter , Ablação por Radiofrequência , Técnicas de Ablação/métodos , Animais , Ablação por Cateter/métodos , Fígado/cirurgia , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/métodos , Suínos , Temperatura
15.
Microvasc Res ; 133: 104092, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007315

RESUMO

The in vitro reconstruction of the microvascular network model provides a reproducible platform for hemodynamic study with great biological relevance. In the present study, microvascular models with different parametric features were designed under the guidance of Murray's law and derived from representative natural vascular network topography in vivo. Computational fluid dynamics (CFD) was used to numerically simulate blood velocity distributions inside of the designed microvasculature models. Full-field blood flow in the vascular network was visualized in vivo using a laser speckle contrast imaging (LSCI) system, from which the measured relative velocity was compared with CFD computed flow distribution. The results have shown that, in comparison with the simplified flow patterns obtained from idealized geometries, the irregular vascular topography is expected to lead to nonuniform and poor regional blood velocity distribution. The velocity distribution acquired by in vivo LSCI experiment is in good agreement with that of numerical simulation, indicating the technical feasibility of using biomimetic microchannels as a reasonable approximation of the microcirculatory flow conditions. This study provides a new paradigm that can be well suited to the study of microvascular blood flow properties and can further expand to mimic other in-vivo scenarios for accurately recapitulating the physical and hemodynamic environment of the microcirculation.


Assuntos
Orelha Externa/irrigação sanguínea , Imagem de Contraste de Manchas a Laser , Microcirculação , Microvasos/diagnóstico por imagem , Microvasos/fisiologia , Modelos Cardiovasculares , Animais , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Hidrodinâmica , Camundongos Endogâmicos ICR
16.
Cancer Invest ; 39(6-7): 571-581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34148483

RESUMO

We aimed to explore whether chronic psychological stress affects the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy in bladder cancer. The chronic unpredictable mild stress (CUMS) process was applied during the administration of anti-PD-L1 for subcutaneous tumors in mice. Tumor regression was obviously shown in anti-PD-L1 therapy groups, while this effect was notably attenuated by CUMS. Additionally, increased infiltration of regulatory T-cells, decreased amount of CD8+ lymphocytes, and reduced levels of tumor-associated cytokines in tumor sites were observed in mice treated with anti-PD-L1 under CUMS. Therefore, chronic psychological stress could weaken the potency of anti-PD-L1 immunotherapy for bladder cancer.


Assuntos
Antígeno B7-H1/metabolismo , Inibidores de Checkpoint Imunológico/administração & dosagem , Estresse Psicológico/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunocompetência , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Camundongos , Estresse Psicológico/etiologia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/psicologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Am J Med Genet A ; 185(9): 2782-2788, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34050715

RESUMO

Ovotesticular differences of sexual development (OT-DSD) are rare genetic variances defined by the coexistence of both testicular and ovarian tissues. Various molecular etiologies including SRY translocation or SOX9 pathogenic variants with different modes of inheritance have been associated with 46,XX OT-DSD. Here we describe a child diagnosed with SRY-negative 46,XX OT-DSD after completing a series of complex clinical genetic analyses, including chromosomal microarray, DSD gene panel (sequencing and deletion/duplication analysis), whole exome sequencing, and whole genome sequencing. Of these, only whole genome sequencing reported a pathogenic duplication in a non-coding region that contains the RevSex regulatory element, which modifies SOX9 expression and is associated with 46,XX OT-DSD and complete sex reversal. This is the first clinical RevSex duplication detected by clinical whole genome sequencing. We highlight the utility of whole genome sequencing in shortening the diagnostic odyssey and the importance of optimal counseling through a team-based multi-specialty approach for patients with DSDs.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/patologia , Duplicação Gênica , Transtornos Ovotesticulares do Desenvolvimento Sexual/patologia , Fatores de Transcrição SOX9/genética , Sequenciamento Completo do Genoma/métodos , Transtornos 46, XX do Desenvolvimento Sexual/genética , Humanos , Recém-Nascido , Masculino , Transtornos Ovotesticulares do Desenvolvimento Sexual/genética , Prognóstico
18.
Mol Pharm ; 18(11): 4015-4028, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648293

RESUMO

Combination immunotherapy is a promising strategy to remove the inhibitory effect of the tumor microenvironment on immune effector cells, improving the efficacy of immune checkpoint inhibitor treatment in bladder cancer. However, it is challenging to deliver multiple drugs to the tumor tissue effectively and simultaneously to ensure optimal therapeutic effects. Macrophage-derived exosome-mimetic nanovesicles (EMVs) were designed and validated as a nanoplatform for coloading and delivery of the CD73 inhibitor (AB680) and the monoclonal antibody to programmed cell death ligand 1 (aPDL1). The tumor-targeting, biosafety, and therapeutic effects of these nanocomplexes (AB680@EMVs-aPDL1), as a combined immunotherapy strategy for bladder cancer, were assessed in vitro and in vivo. Our results indicate that the nanodrug system was highly stable, provided adequate biosafety, and enhanced tumor targeting in a mouse model of bladder cancer. Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted the activation and infiltration of cytotoxic T-lymphocytes, which helped to optimally suppress tumor growth and extend median survival in vivo. Therefore, using EMVs to deliver a combination of aPDL1 and the CD73 inhibitor may be a useful combined immunotherapy strategy for treating bladder cancer.


Assuntos
Exossomos/química , Inibidores de Checkpoint Imunológico/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas , Linfócitos T Citotóxicos/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/imunologia , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/imunologia , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/citologia , Masculino , Camundongos , Linfócitos T Citotóxicos/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
19.
J Nanobiotechnology ; 19(1): 434, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930285

RESUMO

BACKGROUND: As an efficient tumor immunotherapy, PD-1 antibody has been gradually used in clinical tumor treatment, but the low response rate and excessive immune response limit its extensive application. RESULTS: Herein, a therapeutic regime for the reinvigoration and activation of the tumor immune microenvironment is introduced to improve the anti-tumor effect of the PD-1 antibody. To comprehensively improve the effect of the immunotherapy and reduce excessive immune response, a biomimetic cascade targeting nanosystem, siRNA@PLOV, which was fused by photothermal sensitive liposomes (PTSLs) and attenuated Salmonella outer membrane vesicles (OMVs), was administered in the tumor therapy for targeting of tumor tissues and T cells within tumor respectively. The fused PLOVs which not only retained the biological character of the OMVs, but also enhanced the drug loading ability. The results demonstrated that the immunogenicity of OMVs and photothermal effects can obviously increase the infiltration of T cells and the silencing of CD38 can effectively improve the T cell cytotoxicity, especially combining with PD-1 antibody. CONCLUSIONS: Interesting, this study revealed that anti-PD-1 administration on the 5th day after siRNA@PLOV treatment had the best performance in killing tumors compared with other groups. In addition, this new therapeutic regime also presents a novel strategy for inducing "vaccine effects", conclusively highlighting its potential in preventing tumor recurrence and improving prognosis.


Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Vesículas Secretórias/química , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/genética , ADP-Ribosil Ciclase 1/metabolismo , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Membrana Externa Bacteriana/metabolismo , Linhagem Celular Tumoral , Humanos , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/uso terapêutico , Salmonella/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Heterólogo
20.
Minim Invasive Ther Allied Technol ; 30(6): 347-355, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32459544

RESUMO

BACKGROUND AND OBJECTIVE: In the clinical treatment of tumors using microwave ablation (MWA), although temperature can be used as an important reference index for evaluating the curative effect of ablation, it cannot fully reflect the biological activity status of tumor tissue during thermal ablation. Finding multi-parameter comprehensive evaluation factors to achieve real-time evaluation of therapeutic effects has become the key for precise ablation. More and more scholars use the reduced scattering coefficient (µs') and Young's modulus (E) to evaluate the treatment outcomes of MWA. However, the intrinsic relationship between these parameters is unclear. This paper aims to investigate the specific relationship between µs' and E during MWA. MATERIAL AND METHODS: The MWA experiment was conducted on porcine liver in vitro, the two-parameter simultaneous acquisition system was designed to obtain the reduced scattering coefficient and Young's modulus of the liver tissue during MWA. The relationship between reduced scattering coefficient and Young's modulus was investigated. RESULTS: It is found that the trend of change of µs' is very similar to E in the process of MWA, i.e. first increasing and then reaching a steady state, and in some experiments there are synchronous changes. Based on this, the quantitative relationship between E-µs'  is established, enabling the quantitative estimation of Young's modulus of liver tissue based on reduced scattering coefficient. The maximum absolute error is 29.37 kPa and the minimum absolute error is 0.88 kPa. CONCLUSION: This study contributes to the further establishment of a multi-parameter MWA effectiveness evaluation model. It is also valuable for clinically evaluating the ablation outcomes of tumor in real time.


Assuntos
Neoplasias , Ablação por Radiofrequência , Animais , Módulo de Elasticidade , Fígado/diagnóstico por imagem , Fígado/cirurgia , Micro-Ondas , Suínos
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