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1.
Front Endocrinol (Lausanne) ; 15: 1399517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38982990

RESUMO

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Glândula Tireoide , Hepatopatia Gordurosa não Alcoólica/sangue , Humanos , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/sangue , Testes de Função Tireóidea , Tri-Iodotironina/sangue
2.
Inorg Chem ; 63(26): 12146-12155, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946339

RESUMO

The electrochemical conversion of nitrate pollutants into value-added ammonia (NH3) is an appealing alternative synthetic route for sustainable NH3 production. However, the development of the electrocatalytic nitrate-to-ammonia reduction reaction (NO3RR) has been hampered by unruly reactants and products at the interface and the accompanied sluggish kinetic rate. In this work, a built-in positive valence space is successfully constructed over FeCu nanocrystals to rationally regulate interfacial component concentrations and positively shift the chemical equilibrium. With positive valence Cu optimizing the active surface, the space between the stern and shear layers becomes positive, which is able to continuously attract the negatively charged NO3- reactant and repulse the positively charged NH4+ product even under high current density, thus significantly boosting the NO3RR kinetics. The system with a built-in positive valence space affords an ampere-level NO3RR performance with the highest NH3 yield rate of 150.27 mg h-1 mg-1 at -1.3 V versus RHE with an outstanding NH3 current density of 189.53 mA cm-2, as well as a superior Faradaic efficiency (FE) of 97.26% at -1.2 V versus RHE. The strategy proposed here underscores the importance of interfacial concentration regulation and can find wider applicability in other electrochemical syntheses suffering from sluggish kinetics.

3.
Theranostics ; 14(10): 3793-3809, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994031

RESUMO

Rationale: CD8+ T cells undergo a series of metabolic reprogramming processes during their activation and proliferation, including increased glycolysis, decreased aerobic oxidation of sugars, increased amino acid metabolism and increased protein synthesis. However, it is still unclear what factors regulate these metabolic reprogramming processes in CD8+ T cells in the tumor immune microenvironment. Methods: T cell chromobox protein 4 (CBX4) knock-out mice models were used to determine the role of CBX4 in CD8+ T cells on the tumor immune microenvironment and tumor progression. Flow cytometry, Cut-Tag qPCR, Chip-seq, immunoprecipitation, metabolite detection, lentivirus infection and adoptive T cells transfer were performed to explore the underlying mechanisms of CBX4 knock-out in promoting CD8+ T cell activation and inhibiting tumor growth. Results: We found that CBX4 expression was induced in tumor-infiltrating CD8+ T cells and inhibited CD8+ T cell function by regulating glucose metabolism in tumor tissue. Mechanistically, CBX4 increases the expression of the metabolism-associated molecule aldolase B (Aldob) through sumoylation of trans-acting transcription factor 1 (SP1) and Krüppel-like factor 3 (KLF3). In addition, Aldob inhibits glycolysis and ATP synthesis in T cells by reducing the phosphorylation of the serine/threonine protein kinase (Akt) and ultimately suppresses CD8+ T cell function. Significantly, knocking out CBX4 may improve the efficacy of anti-PD-1 therapy by enhancing the function of CD8+ T cells in the tumor microenvironment. Conclusion: CBX4 is involved in CD8+ T cell metabolic reprogramming and functional persistence in tumor tissues, and serves as an inhibitor in CD8+ T cells' glycolysis and effector function.


Assuntos
Linfócitos T CD8-Positivos , Glicólise , Camundongos Knockout , Microambiente Tumoral , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Frutose-Bifosfato Aldolase/metabolismo , Frutose-Bifosfato Aldolase/genética , Proteínas do Grupo Polycomb/metabolismo , Proteínas do Grupo Polycomb/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Humanos , Reprogramação Celular
4.
Orthop Surg ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887173

RESUMO

OBJECTIVE: The orthopedic surgical treatment strategies for patients with tumor-induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in-depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor-induced osteomalacia (TIO), whose causative tumors are located in the hip bones. METHODS: A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub-professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery-related data, perioperative changes in blood phosphorus levels, and postoperative follow-up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non-normally distributed data are shown as the means and 25th and 75th interquartile ranges. RESULTS: The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. CONCLUSION: In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.

5.
Eur J Radiol ; 176: 111533, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38833770

RESUMO

PURPOSE: To develop and validate an end-to-end model for automatically predicting hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH) using a novel deep learning framework. METHODS: This multicenter retrospective study collected cranial noncontrast computed tomography (NCCT) images of 490 patients with sICH at admission for model training (n = 236), internal testing (n = 60), and external testing (n = 194). A HE-Mind model was designed to predict HE, which consists of a densely connected U-net for segmentation process, a multi-instance learning strategy for resolving label ambiguity and a Siamese network for classification process. Two radiomics models based on support vector machine or logistic regression and two deep learning models based on residual network or Swin transformer were developed for performance comparison. Reader experiments including physician diagnosis mode and artificial intelligence mode were conducted for efficiency comparison. RESULTS: The HE-Mind model showed better performance compared to the comparative models in predicting HE, with areas under the curve of 0.849 and 0.809 in the internal and external test sets respectively. With the assistance of the HE-Mind model, the predictive accuracy and work efficiency of the emergency physician, junior radiologist, and senior radiologist were significantly improved, with accuracies of 0.768, 0.789, and 0.809 respectively, and reporting times of 7.26 s, 5.08 s, and 3.99 s respectively. CONCLUSIONS: The HE-Mind model could rapidly and automatically process the NCCT data and predict HE after sICH within three seconds, indicating its potential to assist physicians in the clinical diagnosis workflow of HE.


Assuntos
Hemorragia Cerebral , Hematoma , Tomografia Computadorizada por Raios X , Humanos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Masculino , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Hematoma/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Idoso , Aprendizado Profundo , Máquina de Vetores de Suporte , Progressão da Doença , Valor Preditivo dos Testes
6.
Opt Express ; 32(8): 13277-13292, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859302

RESUMO

Phase microscopy that records the bandlimited image and its Fourier image simultaneously (BIFT) is a phase retrieval method with unique and rapid convergence. In this paper, we present a single-exposure quantitative differential interference contrast (DIC) microscopy based on BIFT method. The contrasts of the recorded DIC image and its Fourier image, analyzed by simulation and experiment, can be largely improved by the initial phase difference between two sheared lights (bias), however their trends with biases are opposite. By adding the optimized bias with the compromise of the contrasts in image and Fourier space, the phase sensitivity can be improved than BIFT method only. We have experimentally demonstrated that a sample of 25 nm height can be successfully recovered from a single exposure. The presented single-exposure quantitative DIC microscopy provides a promising technique for real-time phase imaging.

7.
JAMA Oncol ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869885

RESUMO

Importance: Patients with acute myeloid leukemia (AML) recognize days spent at home (home time) vs in a hospital or nursing facility as an important factor in treatment decision making. No study has adequately described home time among older adults with AML. Objective: To describe home time among older adults with AML (aged ≥66 years) and compare home time between 2 common treatments: anthracycline-based chemotherapy and hypomethylating agents (HMAs). Design, Setting, and Participants: A cohort of adults aged 66 years or older with a new diagnosis of AML from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in 2004 to 2016 was identified. Individuals were stratified into anthracycline-based therapy, HMAs, or chemotherapy, not otherwise specified (NOS) using claims. Main Outcomes and Measures: The primary outcome was home time, quantified by subtracting the total number of person-days spent in hospitals and nursing facilities from the number of person-days survived and dividing by total person-days. A weighted multinomial regression model with stabilized inverse probability of treatment weighting to estimate adjusted home time was used. Results: The cohort included 7946 patients with AML: 2824 (35.5%) received anthracyclines, 2542 (32.0%) HMAs, and 2580 (32.5%) were classified as chemotherapy, NOS. Median (IQR) survival was 11.0 (5.0-27.0) months for those receiving anthracyclines and 8.0 (3.0-17.0) months for those receiving HMAs. Adjusted home time for all patients in the first year was 52.4%. Home time was highest among patients receiving HMAs (60.8%) followed by those receiving anthracyclines (51.9%). Despite having a shorter median survival, patients receiving HMAs had more total days at home and 33 more days at home in the first year on average than patients receiving anthracyclines (222 vs 189). Conclusions and Relevance: This retrospective study of older adults with AML using SEER-Medicare data and propensity score weighting suggests that the additional survival afforded by receiving anthracycline-based therapy was entirely offset by admission to the hospital or to nursing facilities.

8.
Pestic Biochem Physiol ; 202: 105914, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879295

RESUMO

Indoor cases of Tetranychus cinnabarinus displaying resistance have been documented, but the resistance level in field populations remains unexplored in China. This study delves into the resistance dynamics of T. cinnabarinus to fenpropathrin in various field populations across China, a pressing concern in contemporary agricultural pest control. The conventional bioassay and amplicon sequencing reveal a notable absence of significant fenpropathrin resistance in field populations, contrasting with known resistance in indoor cases. Current study highlights the limitations of traditional bioassays in detecting early-stage resistance and underscores the nuanced capabilities and constraints of amplicon sequencing in resistance gene frequency analysis. By employing an integrated approach, we combined dose-response bioassays, amplicon sequencing, and statistical modeling to assess resistance levels and investigate underlying genetic factors. The model with empirical data indicates that a 5% mutation frequency represents the threshold before resistance emerges. However, the detection of the kdr mutation in certain populations ranging from 0 to 1.2%, signals an early looming threat of future resistance emergence. Additionally, we further assessed a specific dsRNA targeting VGSC genes at two concentrations (10 ng/µL and 100 ng/µL), both inducing substantial mortality by silencing target genes effectively. The exploration of RNA interference (RNAi) as a novel, more environmentally friendly pest control measure opens new avenues, despite the ongoing challenge of resistance evolution. Overall, this study underscores the necessity for evolving pest management strategies, integrating advanced biotechnological approaches with traditional methods, to effectively counter pesticide resistance and ensure sustainable agricultural productivity.


Assuntos
Resistência a Inseticidas , Piretrinas , Interferência de RNA , Tetranychidae , Animais , Tetranychidae/genética , Tetranychidae/efeitos dos fármacos , Piretrinas/farmacologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia
9.
Biochem Biophys Rep ; 38: 101722, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38711549

RESUMO

Background: The tumor microenvironment (TME) plays an important role in cancer development; however, its implications in lung squamous cell carcinoma (LUSC) and pan-cancer have been poorly understood. Methods: In this study, The Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissue using Expression Data (ESTIMATE) datasets were applied to identify differentially expressed genes. Additionally, online public databases were utilized for in-depth bioinformatics analysis of pan-cancer datasets to investigate the prognostic implications of TME-related genes further. Results: Our study demonstrated a significant association between stromal scores, immune scores, and specific clinical characteristics in LUSC patients. C3AR1, CSF1R, CCL2, CCR1, and CD14 were identified as prognostic genes related to the TME. All TME-related prognostic genes demonstrated varying degrees of correlation with immune infiltration subtypes and tumor cell stemness. Moreover, our study revealed that TME-related prognostic genes, particularly C3AR1 and CCR1, might contribute to drug resistance in cancer cells. Conclusions: The identified TME-related prognostic genes, particularly C3AR1 and CCR1, have potential implications for understanding and targeting drug resistance mechanisms in cancer cells.

10.
Br J Radiol ; 97(1159): 1261-1267, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38724228

RESUMO

OBJECTIVE: To methodically analyse the swirl sign and construct a scoring system to predict the risk of hematoma expansion (HE) after spontaneous intracerebral haemorrhage (sICH). METHODS: We analysed 231 of 683 sICH patients with swirl signs on baseline noncontrast CT (NCCT) images. The characteristics of the swirl sign were analysed, including the number, maximum diameter, shape, boundary, minimum CT value of the swirl sign, and the minimum distance from the swirl sign to the edge of the hematoma. In the development cohort, univariate and multivariate analyses were used to identify independent predictors of HE, and logistic regression analysis was used to construct the swirl sign score system. The swirl sign score system was verified in the validation cohort. RESULTS: The number and the minimum CT value of the swirl sign were independent predictors of HE. The swirl sign score system was constructed (2 points for the number of swirl signs >1 and 1 point for the minimum CT value ≤41 Hounsfield units). The area under the curve of the swirl sign score system in predicting HE was 0.773 and 0.770 in the development and validation groups, respectively. CONCLUSIONS: The swirl sign score system is an easy-to-use radiological grading scale that requires only baseline NCCT images to effectively identify subjects at high risk of HE. ADVANCES IN KNOWLEDGE: Our newly developed semiquantitative swirl sign score system greatly improves the ability of swirl sign to predict HE.


Assuntos
Hemorragia Cerebral , Hematoma , Tomografia Computadorizada por Raios X , Humanos , Masculino , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hematoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Medição de Risco/métodos , Idoso de 80 Anos ou mais , Valor Preditivo dos Testes
11.
J Environ Manage ; 361: 121239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815422

RESUMO

The roles of plateau pika (Ochotona coronae) in the Tibetan Plateau are often controversial, because it is often regarded as a destructive pest or an ecosystem engineer. Here a meta-analysis using 72 paired observations was conducted to examine whether the impacts of plateau pika on environmental quality (i.e., plant and soil properties) depend on population density in the Tibetan Plateau. Pika population density was used as a proxy for disturbance intensity. The pika disturbance intensity was divided into five groups based on the number of burrows, including low disturbance intensity (LD) (9-30 burrows per ha), medium disturbance intensity (MD) (31-100 burrows per ha), high disturbance intensity (HD) (101-170 burrows per ha), extreme disturbance intensity (ED) (171-240 burrows per ha) and uncontrolled (or excessive) disturbance intensity (UD) (>241 burrows per ha). Given that sample sizes in some of the groups are small (especially for the HD), we further pooled the disturbance groups including the LD-MD and HD-UD. Overall, relative to control (i.e., no disturbing), there was a great increase (80.3%) in aboveground biomass under the LD-MD, whereas a decrease of 41.1% occurred under the HD-UD. At the same time, plant coverage, species richness, height, and belowground biomass greatly decreased only in the HD-UD. Furthermore, the effect size of plant coverage, species richness, and aboveground biomass also declined with pika burrow density significantly. With regard to soil properties, there was a significant increase in soil organic carbon, ammonium nitrogen, and soil organic carbon stock under the LD-MD, whereas a decrease under the HD-UD. In addition, soil total nitrogen, total potassium, and nitrate nitrogen increased at the LD-MD and HD-UD. Nevertheless, the effect size of these soil properties (with >20 observations) was not related to pika burrow density. In summary, there is an implication that the low and moderate disturbance of pikas is beneficial to maintain and promote ecosystem functioning in the Tibetan grasslands. In the future pikas' eradication policy should be reconsidered in alpine grassland management.


Assuntos
Ecossistema , Lagomorpha , Tibet , Animais , Biomassa , Solo/química , Densidade Demográfica
12.
Phytomedicine ; 129: 155680, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728923

RESUMO

OBJECTIVE: Influenza, a viral respiratory illness, leads to seasonal epidemics and occasional pandemics. Given the rising resistance and adverse reactions associated with anti-influenza drugs, Traditional Chinese Medicine (TCM) emerges as a promising approach to counteract the influenza virus. Specifically, Haoqin Qingdan Tang (HQQDT), a TCM formula, has been employed as an adjuvant treatment for influenza in China. However, the active compounds and underlying mechanisms of HQQDT remain unknown. AIM: The aim of this study was to investigate HQQDT's antiviral and anti-inflammatory activities in both in vivo and in vitro, and further reveal its active ingredients and mechanism. METHODS: In vivo and in vitro experiments were conducted to verify the antiviral and anti-inflammatory activities of HQQDT. Subsequently, the active ingredients and mechanism of HQQDT were explored through combining high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS) analysis and network pharmacology. Finally, the examinations of cell cytokines and signaling pathways aimed to elucidate the predicted mechanisms. RESULTS: The results indicated that HQQDT exhibited inhibitory effects on influenza viruses A/PR/8/34 (H1N1), A/HK/1/68 (H3N2), and A/California/4/2009 (H1N1) in vitro. Furthermore, HQQDT enhanced the survival rate of influenza-infected mice, reduced the lung index and lung virus titer, and mitigated lung tissue damage in vivo. The proinflammatory cytokine expression levels upon influenza virus infection in PR8-induced A549 cells or mice were suppressed by HQQDT, including IL-6, IL-1ß, CCL2, CCL4, IP-10, interferon ß1 (IFN-ß1), the interferon regulatory factor 3 (IRF3), and hemagglutinin (HA). Twenty-two active components of HQQDT against influenza were identified using HPLC-Q-TOF-MS analysis. Based on network pharmacological predictions, the JAK/STAT signaling pathway is considered the most relevant for HQQDT's action against influenza. Finally, western blot assays revealed that HQQDT regulated the protein level of the JAK/STAT signaling pathway in PR8-infected A549 cells and lung tissue. CONCLUSION: These findings verified the antiviral and anti-inflammatory effects of HQQDT through JAK-STAT signaling pathway in influenza infections, laying the foundation for its further development.


Assuntos
Antivirais , Medicamentos de Ervas Chinesas , Vírus da Influenza A , Janus Quinases , Infecções por Orthomyxoviridae , Transdução de Sinais , Animais , Cães , Feminino , Humanos , Camundongos , Células A549 , Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Janus Quinases/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/virologia , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Farmacologia em Rede , Infecções por Orthomyxoviridae/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo
13.
Virol Sin ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734183

RESUMO

The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA in vivo. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38760283

RESUMO

INTRODUCTION: The therapeutic landscape in relapsed/refractory multiple myeloma (RRMM) has changed rapidly, with twenty-two drug approvals since 2012. We characterized population-level trends in RRMM therapy selection, survival and cost outcomes associated with RRMM treatment over time. MATERIALS AND METHODS: Our cohort included adults diagnosed with multiple myeloma (MM) in the SEER-Medicare database from 2007-2017 who received at least one antimyeloma agent. MM-directed therapies and lines of therapy were identified. Changes in 2LT regimens over time were described. Trends in overall survival from 2LT initiation over time were analyzed using a Cox proportional hazards model adjusting for factors associated with survival in MM. Trends in mean inflation-adjusted cost per 12 months of 2LT were analyzed using JoinPoint analysis. RESULTS: A total of 9,822 patients met eligibility criteria, of whom 5,866 (59.7%) received 2LT. By 2018, 46% of 2LT regimens contained at least one agent approved in 2012 or later. Year of 2LT initiation was associated with improved overall survival (HR 0.78 per 5 years, 95% CI 0.74-0.84) after adjustment. Costs associated with 2LT increased over the study period, and the rate of cost increase increased significantly after 2012 (0.89%/year vs. 9.9%/year, P < .001), with higher total costs for regimens containing newer novel agents (mean $224,193 vs. $189,381, P < .001) CONCLUSION: Overall survival after initiation of 2LT has improved, however this has been accompanied by significant increases in costs of RRMM treatment, particularly for patients receiving newer novel agents. These findings provide useful context for existing and future drug approvals in RRMM.

15.
World J Surg ; 48(5): 1149-1156, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38558414

RESUMO

BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS. METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging. RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1). CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.


Assuntos
Neoplasias da Mama , Conduta Expectante , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Idoso , Adulto , Biópsia com Agulha de Grande Calibre , Hiperplasia/cirurgia , Hiperplasia/patologia , Progressão da Doença , Resultado do Tratamento
16.
ACS Biomater Sci Eng ; 10(5): 3057-3068, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38641433

RESUMO

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.


Assuntos
Catéteres , Materiais Revestidos Biocompatíveis , Heparina , Polifenóis , Taninos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Catéteres/microbiologia , Polifenóis/química , Polifenóis/farmacologia , Heparina/química , Heparina/farmacologia , Taninos/química , Taninos/farmacologia , Silanos/química , Silanos/farmacologia , Anticoagulantes/química , Anticoagulantes/farmacologia , Propilaminas/química , Aminas/química , Aminas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Polilisina/química , Polilisina/farmacologia , Propriedades de Superfície , Interações Hidrofóbicas e Hidrofílicas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Elastômeros de Silicone/química , Adsorção , Escherichia coli/efeitos dos fármacos
18.
QJM ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38603614
19.
Sci Rep ; 14(1): 8854, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632291

RESUMO

Ongoing rapid urbanization has triggered significant changes in land use, rendering landscape patterns adversely impacted and certain habitat patches degraded. Ecological networks have consequently contracted overall. As such, an investigation into how land-use landscape patterns and ecological networks change over time and space is of major significance for ecological restoration and regional sustainability. Taking Xuzhou Planning Area as a case study, we examined spatiotemporal changes and features of the landscape pattern by employing the land-use change degree, the land-use transition matrix, and quantified landscape pattern indices. An ecological network analysis, which studies the changes in network connectivity and robustness, as well as their causes and contributors, was undertaken to probe into the features and trends of spatiotemporal changes in the land-use landscape pattern and ecological network amid expeditious urbanization. Analysis results unveiled the following: (1) From 1985 to 2020, there was a decline in the area of farmland, forest, and grassland, accompanied by an increase in land for construction, water bodies, and unused land. The southwestern research area witnessed farmland substantially give way to land for construction for this period, and the most dramatic change in land use occurred between 2000 and 2010. (2) The area of dominant patches in the research area shrank, along with more fragmented, complex landscapes. The land for construction was emerging as the dominant landscape by area, whereas patches of farmland, forest, grassland, and water bodies became less connected. (3) The ecological network was densely linked in the northeast, with sparser connections in the southwest. Spatial shrinkage was observed in the research area's southwestern and central ecological corridors. Overall, the number of ecological sources and corridors rose and subsequently dropped before a rebound. (4) The ecological network grew more connected and robust from 1985 through 1990, as portions of farmland were converted into water bodies, which led to an increase in ecological sources. Given a reduction in ecological sources and corridors in the southwestern and central regions between 1990 and 2010, network connectivity and robustness declined, which was reversed from 2010 onward with the addition of two ecological sources-Pan'an Lake and Dugong Lake. With an optimal ecological network in 1990, however, it deteriorated significantly by 2010. The research area saw the minimum value of its network connectivity indices of network stability index (α), evenness index (ß), and connectivity index (γ), in 2010, when its ecological network was highly fragmented and vulnerable, attributing to a strong contrast between the maximal connected subgraph's relative size and connectivity robustness. The research findings can lay scientific groundwork for addressing ecological issues, restoring landscape patterns, and developing ecological networks amid urbanization.

20.
J Bone Oncol ; 45: 100600, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577550

RESUMO

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is very rare, with about 1000 reported cases globally. Removing most TIO culprit tumors requires the evaluation and intervention of orthopedic doctors. However, orthopedic doctors often have a poor understanding of the optical treatment of TIO due to its rarity. In addition, most TIO patients lack specific clinical manifestations. Also, the clinical localization and qualitative diagnosis of TIO are difficult and thus can easily be misdiagnosed and mistreated. Furthermore, the true incidence rate of TIO may be underestimated. Although many breakthroughs have been made in exploring the pathogenesis, clinical diagnosis, and treatment of TIO, rational and standardized orthopedic surgical treatment experience summary and sorting for TIO patients are lacking. In this article, the recent experience and progress in the field of orthopedic surgical treatment for TIO globally have been summarized, providing a theoretical basis and new clinical practice guidance for the rational treatment of TIO patients.

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