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1.
Cell Rep ; 43(6): 114289, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38833371

RESUMO

Type I interferon (IFN-I) and IFN-γ foster antitumor immunity by facilitating T cell responses. Paradoxically, IFNs may promote T cell exhaustion by activating immune checkpoints. The downstream regulators of these disparate responses are incompletely understood. Here, we describe how interferon regulatory factor 1 (IRF1) orchestrates these opposing effects of IFNs. IRF1 expression in tumor cells blocks Toll-like receptor- and IFN-I-dependent host antitumor immunity by preventing interferon-stimulated gene (ISG) and effector programs in immune cells. In contrast, expression of IRF1 in the host is required for antitumor immunity. Mechanistically, IRF1 binds distinctly or together with STAT1 at promoters of immunosuppressive but not immunostimulatory ISGs in tumor cells. Overexpression of programmed cell death ligand 1 (PD-L1) in Irf1-/- tumors only partially restores tumor growth, suggesting multifactorial effects of IRF1 on antitumor immunity. Thus, we identify that IRF1 expression in tumor cells opposes host IFN-I- and IRF1-dependent antitumor immunity to facilitate immune escape and tumor growth.


Assuntos
Fator Regulador 1 de Interferon , Fator Regulador 1 de Interferon/metabolismo , Fator Regulador 1 de Interferon/genética , Animais , Camundongos , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/genética , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Fator de Transcrição STAT1/metabolismo , Antígeno B7-H1/metabolismo , Imunidade
2.
Int J Spine Surg ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744484

RESUMO

BACKGROUND: There is a lack of consensus on the use of postoperative bracing for lumbar degenerative conditions. Spine surgeons typically determine whether to apply postoperative braces based primarily on clinical experience rather than robust, evidence-based medical data. Thus, the present study sought to assess the impact of postoperative bracing on clinical outcomes, complications, and fusion rates following lumbar fusion surgery in patients with degenerative spinal conditions. METHODS: Only randomized controlled studies published between January 1990 and 20 October 2023 were included in this meta-analysis. The primary outcome measures consisted of pre- and postoperative assessments of the Oswestry Disability Index (ODI) and visual analog scale (VAS) scores. Improvements in VAS and ODI scores were analyzed in the early postoperative period (1 month after operation) and at final follow-up, respectively. The analysis also encompassed fusion rates and complications. RESULTS: Five studies with 362 patients were included in the present meta-analysis. In the early postoperative period, the brace group showed a relatively better improvement in ODI scores compared with the no-brace group (19.47 vs 18.18), although this difference was not statistically significant (P = 0.34). Similarly, during the late postoperative period, the brace group demonstrated a slightly greater improvement in VAS scores in comparison to the no-brace group (4.05 vs 3.84), but this difference did not reach statistical significance (P = 0.30). The complication rate was relatively lower in the brace group compared with the no-brace group (14.9% vs 17.4%), although there was no statistical difference between the 2 groups (P = 0.83). Importantly, there were no substantial differences in fusion rates between patients with or without braces. CONCLUSION: The present meta-analysis revealed that the implementation of a brace following lumbar fusion surgery did not yield substantial differences in terms of postoperative pain relief, functional recovery, complication rates, or fusion rates when compared with cases where no brace was employed. CLINICAL RELEVANCE: This meta-analysis provides valuable insights into the clinical impact of postoperative bracing following lumbar fusion surgery for degenerative spinal conditions.

3.
Cell Stem Cell ; 31(5): 754-771.e6, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38701759

RESUMO

Development of embryonic stem cells (ESCs) into neurons requires intricate regulation of transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) controls splicing of DPF2, a subunit of BRG1/BRM-associated factor (BAF) chromatin remodeling complexes. Dpf2 exon 7 splicing is inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss of PTBP1 allows exon 7 inclusion and DPF2-L expression. Different cellular phenotypes and gene expression programs were induced by these alternative DPF2 isoforms. We identified chromatin binding sites enriched for each DPF2 isoform, as well as sites bound by both. In ESC, DPF2-S preferential sites were bound by pluripotency factors. In neuronal progenitors, DPF2-S sites were bound by nuclear factor I (NFI), while DPF2-L sites were bound by CCCTC-binding factor (CTCF). DPF2-S sites exhibited enhancer modifications, while DPF2-L sites showed promoter modifications. Thus, alternative splicing redirects BAF complex targeting to impact chromatin organization during neuronal development.


Assuntos
Processamento Alternativo , Diferenciação Celular , Cromatina , Ribonucleoproteínas Nucleares Heterogêneas , Neurônios , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Fatores de Transcrição , Processamento Alternativo/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Animais , Diferenciação Celular/genética , Cromatina/metabolismo , Camundongos , Neurônios/metabolismo , Neurônios/citologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Transcrição Gênica , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/citologia , Éxons/genética , Humanos , Autorrenovação Celular/genética
4.
BMC Musculoskelet Disord ; 25(1): 322, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654321

RESUMO

OBJECTIVE: This study aimed to assess the impact of full endoscopic transforaminal discectomy (FETD) on clinical outcomes and complications in both obese and non-obese patients presenting with lumbar disc herniation (LDH). METHODS: A systematic search of relevant literature was conducted across various primary databases until November 18, 2023. Operative time and hospitalization were evaluated. Clinical outcomes included preoperative and postoperative assessments of the Oswestry Disability Index (ODI) and visual analogue scale (VAS) scores, conducted to delineate improvements at 3 months postoperatively and during the final follow-up, respectively. Complications were also documented. RESULTS: Four retrospective studies meeting inclusion criteria provided a collective cohort of 258 patients. Obese patients undergoing FETD experienced significantly longer operative times compared to non-obese counterparts (P = 0.0003). Conversely, no statistically significant differences (P > 0.05) were observed in hospitalization duration, improvement of VAS for back and leg pain scores at 3 months postoperatively and final follow-up, improvement of ODI at 3 months postoperatively and final follow-up. Furthermore, the overall rate of postoperative complications was higher in the obese group (P = 0.02). The obese group demonstrated a total incidence of complications of 17.17%, notably higher than the lower rate of 9.43% observed in the non-obese group. CONCLUSION: The utilization of FETD for managing LDH in individuals with obesity is associated with prolonged operative times and a higher total complication rate compared to their non-obese counterparts. Nevertheless, it remains a safe and effective surgical intervention for treating herniated lumbar discs in the context of obesity.


Assuntos
Discotomia , Endoscopia , Deslocamento do Disco Intervertebral , Vértebras Lombares , Obesidade , Complicações Pós-Operatórias , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Obesidade/cirurgia , Obesidade/complicações , Vértebras Lombares/cirurgia , Resultado do Tratamento , Endoscopia/métodos , Endoscopia/efeitos adversos , Discotomia/efeitos adversos , Discotomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Duração da Cirurgia , Medição da Dor , Avaliação da Deficiência , Estudos Retrospectivos
5.
Immunity ; 57(3): 462-477.e9, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38430908

RESUMO

Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Nucleossomos , Transdução de Sinais , Regulação da Expressão Gênica , Fator de Transcrição RelA/metabolismo
6.
Nanoscale ; 16(9): 4628-4636, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38357835

RESUMO

Hydrogel-based solar vapour generators (SVGs) are promising for wastewater treatment and desalination. The performance of SVG systems is governed by solar thermal conversion and water management. Progress has been made in achieving high energy conversion efficiency, but the water evaporation rates are still unsatisfactory under 1 sun irradiation. This study introduced novel two-dimensional (2D) boron nanosheets as additives into hydrogel-based SVGs. The resulting SVGs exhibit an outstanding evaporation rate of 4.03 kg m-2 h-1 under 1 sun irradiation. This significant improvement is attributed to the 2D boron nanosheets, which leads to the formation of a higher content of intermediate water and reduced water evaporation enthalpy to 845.11 kJ kg-1. The SVGs into which boron nanosheets were incorporated also showed high salt resistance and durability, demonstrating their great potential for desalination applications.

7.
Cell Death Discov ; 10(1): 102, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413558

RESUMO

Substantial evidence attests to the pivotal role of cancer stem cells (CSC) in both tumorigenesis and drug resistance. A member of the forkhead box (FOX) family, FOXC1, assumes significance in embryonic development and organogenesis. Furthermore, FOXC1 functions as an overexpressed transcription factor in various tumors, fostering proliferation, enhancing migratory capabilities, and promoting drug resistance, while maintaining stem-cell-like properties. Despite these implications, scant attention has been devoted to its role in esophageal squamous cell carcinoma. Our investigation revealed a pronounced upregulation of FOXC1 expression in ESCC, correlating with a poor prognosis. The downregulation of FOXC1 demonstrated inhibitory effects on ESCC tumorigenesis, proliferation, and tolerance to chemotherapeutic agents, concurrently reducing the levels of stemness-related markers CD133 and CD44. Further studies validated that FOXC1 induces ESCC stemness by transactivating CBX7 and IGF-1R. Additionally, IGF-1 activated the PI3K/AKT/NF-κB and MEK/ERK/NF-κB pathways through its binding to IGF-1R, thereby augmenting FOXC1 expression. Conversely, suppressing FOXC1 impeded ESCC stemness induced by IGF-1. The presence of a positive feedback loop, denoted by IGF-1-FOXC1-IGF-1R, suggests the potential of FOXC1 as a prognostic biomarker for ESCC. Taken together, targeting the IGF-1-FOXC1-IGF-1R axis emerges as a promising approach for anti-CSC therapy in ESCC.

8.
J Clin Invest ; 134(4)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175723

RESUMO

Aster proteins mediate the nonvesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). However, the importance of nonvesicular sterol movement for physiology and pathophysiology in various tissues is incompletely understood. Here we show that loss of Aster-B leads to diet-induced obesity in female but not in male mice, and that this sex difference is abolished by ovariectomy. We further demonstrate that Aster-B deficiency impairs nonvesicular cholesterol transport from the PM to the ER in ovaries in vivo, leading to hypogonadism and reduced estradiol synthesis. Female Aster-B-deficient mice exhibit reduced locomotor activity and energy expenditure, consistent with established effects of estrogens on systemic metabolism. Administration of exogenous estradiol ameliorates the diet-induced obesity phenotype of Aster-B-deficient female mice. These findings highlight the key role of Aster-B-dependent nonvesicular cholesterol transport in regulating estradiol production and protecting females from obesity.


Assuntos
Colesterol , Estradiol , Feminino , Camundongos , Masculino , Animais , Estradiol/metabolismo , Membrana Celular/metabolismo , Colesterol/metabolismo , Obesidade/genética , Obesidade/metabolismo , Dieta
9.
ChemSusChem ; 17(11): e202301905, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38268017

RESUMO

Atmospheric water harvesting (AWH) is considered one of the promising technologies to alleviate the uneven-distribution of water resources and water scarcity in arid regions of the world. Hydrogel-based AWH materials are currently attracting increasing attention due to their low cost, high energy efficiency and simple preparation. However, there is a knowledge gap in the screening of hydrogel-based AWH materials in terms of structure-property relationships, which may increase the cost of trial and error in research and fabrication. In this study, we synthesised a variety of hydrogel-based AWH materials, characterized their physochemcial properties visualized the electrostatic potential of polymer chains, and ultimately established the structure-property-application relationships of polymeric AWH materials. Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) hydrogel is able to achieve an excellent water adsorption capacity of 0.62 g g-1 and a high water desorption efficiency of more than 90 % in relatively low-moderate humidity environments, which is regarded as one of the polymer materials with potential for future AWH applications.

10.
Eur J Radiol ; 170: 111266, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38185027

RESUMO

PURPOSE: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). METHOD: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. RESULTS: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). CONCLUSIONS: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Abscesso Hepático , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Doxorrubicina , Quimioembolização Terapêutica/efeitos adversos , Abscesso Hepático/etiologia , Resultado do Tratamento
11.
Am J Cancer Res ; 13(11): 5719-5732, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058819

RESUMO

Gene expression signatures provide valuable information to guide postoperative treatment in breast cancer (BC) patients. However, genetic tests are prohibitively expensive for the majority of BC patients. Immunohistochemical staining (IHC) subtype classification system has been widely used for treatment guideline and is affordable to most BC patients. We aimed to revise immunohistochemical staining (IHC) subtyping to better match gene expression-based Prediction Analysis of Microarray 50 (PAM50) subtyping. Real world data of 372 BC patients were recruited in the Tri-Service General Hospital between Jan 2019 and Dec 2021. Clinical pathological information, blood, twelve pathological tissue slide samples, and fresh surgical tumor specimens were collected to examine IHC and PAM50. Current IHC subtyping (cIHC) tends to misclassify PAM50-based luminal A (lum A) to luminal B (lum B) by 35.81%, PAM50-lum B to PAM50-lum A by 9.09%, PAM50-Her2-enriched to lum B by 61.11%, PAM50-based Her2-enriched to lum B by 61.11%, and PAM50-based basal-like to lum B by 33.33%. We used random forest to identify estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), and Ki-67 status as the best indicators for revised IHC subtyping (rIHC4) and revised the classification rules by stratified analysis and prediction efficacy. rIHC4 increased the concordance rate for PAM50 subtypes from 68.3% to 74.7%. Both sensitivity and precision increased in most rIHC4 subtypes. Sensitivity increased from 33.3% to 87.4% in the Her2-enriched subtype; precision increased more evidently in the basal-like and lum B subtypes, from 71.4% to 83.3% and 57% to 65.1%, respectively. Our rIHC4 subtyping improved consistency with the PAM50 subtype, which could improve clinical management of BC patients without increasing medical expense.

12.
J Sports Sci ; 41(12): 1179-1186, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37732628

RESUMO

The impact of mitral valve prolapse (MVP) and mitral regurgitation (MR) on physical performance has not been examined. Of 1,808 physically fit Asian military males, we compared the physical fitness between 62 subjects with MVP (MVP(+)) and 1,311 age- and anthropometrics-matched controls from the 1,746 participants without MVP (MVP(-)). MVP and MR grade were defined based on the American Society of Echocardiography criteria. Aerobic endurance capacity was evaluated by a 3000-m run and muscular endurance capacity was separately evaluated by 2-min sit-ups and 2-min push-ups. Analysis of covariance was used to determine the difference between groups. As compared to the MVP(-), the MVP(+) completed the 3000-m run test faster (839.2 ± 65.3 sec vs. 866.6 ± 86.8 sec, p = 0.019), but did fewer push-ups (41.3 ± 3.92 vs. 48.0 ± 10.1, p = 0.02) and similar sit-ups within 2 min. Of the MVP(+), those with any MR (trivial, mild or moderate) completed the 3000-m run test faster than those without MR (830.6 ± 61.7 sec vs. 877.2 ± 61.7 sec, p = 0.02). Our findings suggest that in physically active Asian military males, the MVP(+) may have greater aerobic endurance capacity but lower muscular endurance capacity than the MVP(-). The presence of MR may play a role for the MVP(+) to have greater aerobic endurance capacity.

13.
Wideochir Inne Tech Maloinwazyjne ; 18(2): 254-263, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37680729

RESUMO

Introduction: Hilar cholangiocarcinoma (HC) is the leading cause of hilar biliary obstruction. Radioactive stent insertion has been utilized extensively for inoperable HC patients. Aim: To assess the relative clinical outcomes of inoperable HC patients who underwent either normal or radioactive stent insertion. Material and methods: This single-center, prospective, randomized, open-label study enrolled 90 inoperable HC patients from April 2021 to March 2022 and randomly assigned them to normal or radioactive stent groups (n = 45/group), with clinical data then being compared between these groups. Results: Technical success rates in the normal and radioactive stent insertion groups were 93.3% and 97.9%, respectively (p = 1.000), and clinical success rates were similarly consistent in both groups (95.3% vs. 97.7%, p = 0.983). Individuals in the radioactive stent group exhibited significantly longer median stent patency as compared to the normal stent group (195 days vs. 115 days, p < 0.001), and median overall survival (OS) was also significantly increased in the normal stent group (242 days vs. 125 days, p = 0.002). In the normal stent insertion group, 6 (14.3%) and 5 (11.9%) patients experienced early and late postoperative complications, respectively. Additionally, early and late postoperative complications impacted 7 (16.3%) and 8 (18.6%) patients in the radioactive stent insertion group, respectively. Complication rates were comparable in these 2 patient groups. Conclusions: Radioactive stent insertion represents a safe and effective strategy for patients with inoperable HC, potentially contributing to prolonged stent patency and OS relative to normal stent insertion.

14.
Nutrients ; 15(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37432206

RESUMO

Breast cancer is a significant public health problem globally and prevention strategies have become of great interest as its incidence rises. Exploring the connection between dietary patterns and the reduction of breast cancer risk is considered a promising approach. High levels of fiber, phytochemicals, a good antioxidant profile, and a composition of advantageous fatty acids are characteristics of healthy dietary programs such as the Mediterranean diet. This review summarized and discussed the active compounds that are considered important in preventing breast cancer, including dietary components from recent related reports. These include polyunsaturated fatty acids, fiber, phytochemicals, and alcohol. Although the exact mechanism for preventing breast cancer using these dietary factors is not well understood, the combination of all the elements in a healthy diet plays a role in reducing breast cancer risk. Considering the elevated probability of breast cancer relapse and mortality, it is crucial to investigate the correlation between a nutritious dietary pattern and breast cancer, while identifying bioactive components that have the potential to mitigate the risk of breast cancer incidence.


Assuntos
Dieta Mediterrânea , Neoplasias , Pesquisa , Antioxidantes , Dieta Saudável , Etanol
15.
J Clin Oncol ; 41(22): 3772-3781, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37499357

RESUMO

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P < .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P < .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

16.
ChemSusChem ; 16(14): e202300137, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37019848

RESUMO

Atmospheric water harvesting (AWH) has been recognized as a next-generation technology to alleviate water shortages in arid areas. However, the current AWH materials suffer from insufficient water adsorption capacity and high-water retention, which hinder the practical application of AWH materials. In this study, we developed a novel dual-layered hydrogel (DLH) composed of a light-to-heat conversion layer (LHL) containing novel polydopamine-manganese nanoparticles (PDA-Mn NPs) and a water adsorption layer (WAL) made of 2-(acryloyloxyethyl) trimethylammonium chloride (AEtMA). The WAL has a strong ability to adsorb water molecules in the air and has a high-water storage capacity, and the PDA-Mn NPs embedded in the LHL have excellent photothermal conversion efficiency, leading to light-induced autonomous water release. As a result, the DLH displays a high-water adsorption capacity of 7.73 g g-1 under optimal conditions and could near-quantitatively release captured water within 4 h sunlight exposure. Coupled with its low cost, we believed that the DLH will be one of the promising AWH materials for practical applications.

17.
Health Econ ; 32(6): 1205-1219, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36879473

RESUMO

This study investigates how exposure to riskier environments influences risky road behaviors, using the COVID-19 pandemic as a natural experiment. Utilizing administrative individual traffic violation records from Taipei, where neither mandatory lockdown nor mobility restrictions were imposed, we find that pandemic-induced risk decreased speeding violations and that the effect was transitory. However, no significant changes were observed concerning violations with a minimal risk of casualties, such as illegal parking. These findings suggest that experiencing a higher level of life-threatening risk discourages risky behaviors concerning human life but has little spillover effect on those concerning only financial costs.


Assuntos
Condução de Veículo , COVID-19 , Humanos , Acidentes de Trânsito , Pandemias , Saúde Pública , Controle de Doenças Transmissíveis , Assunção de Riscos
18.
Genes Dev ; 36(21-24): 1129-1144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36522129

RESUMO

GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism. Knocking out GATA4 in the adult liver (Gata4LKO) decreased transcriptional activity at GATA4 binding sites, especially during feeding. Gata4LKO mice have reduced plasma HDL cholesterol and increased liver triglyceride levels. The expression of a panel of GATA4 binding genes involved in hepatic cholesterol export and triglyceride hydrolysis was down-regulated in Gata4LKO mice. We further demonstrate that GATA4 collaborates with LXR nuclear receptors in the liver. GATA4 and LXRs share a number of binding sites, and GATA4 was required for the full transcriptional response to LXR activation. Collectively, these results show that hepatic GATA4 contributes to the transcriptional control of hepatic and systemic lipid homeostasis.


Assuntos
Fígado , Receptores Nucleares Órfãos , Camundongos , Animais , Receptores Nucleares Órfãos/metabolismo , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Fígado/metabolismo , Homeostase/genética , Colesterol , Triglicerídeos/metabolismo , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo
19.
Front Cell Infect Microbiol ; 12: 994175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225233

RESUMO

Objectives: The metagenomic next-generation sequencing (mNGS) test is useful for rapid and accurate detection and identification of pathogenic microorganisms. The aim of the present study was to investigate the factors associated with in-hospital mortality in pneumocystis pneumonia (PCP) patients with mNGS-assisted diagnosis. Methods: Our study enrolled 154 patients with mNGS-positive PCP from August 2018 to February 2022 at the First Affiliated Hospital of Zhengzhou University respectively. Patients were divided into the survivor group (n=98) and the death group (n=56) according to whether in-hospital death occurred. Baseline characteristics, patients' pre-hospital symptoms and patients' CT imaging performance during hospitalization were carefully compared between the two groups. Risk factors for the occurrence of in-hospital death were sought by selecting indicators that were significantly different between the two groups for modelling and performing multiple logistic regression analysis. Results: Compared with the in-hospital death patients, the survivors were younger and had higher levels of albumin (ALB) (age: 50.29 ± 14.63 years vs 59.39 ± 12.27 years, p<0.001; ALB: 32.24 ± 5.62 g/L vs 29.34 ± 5.42g/L, p=0.002; respectively), while the levels of lactate dehydrogenase (LDH) and C-reactive protein CRP were lower (LDH: 574.67 ± 421.24 U/L vs 960.80 ± 714.94 U/L, p=0.001; CRP: 54.97 ± 55.92 mg/L vs80.45 ± 73.26 mg/L, p=0.018; respectively). Multiple logistic regression analysis revealed that age, the baseline LDH and CRP levels were all positively associated with high in-hospital mortality [age: OR(95%CI): 1.115 (1.062-1.172), p<0.001; LDH: OR(95%CI): 1.002 (1.001-1.003), p<0.001; CRP: OR(95%CI): 1.008 (1.000-1.017), p=0.045; respectively] while the platelet counts was negatively associated with it [OR(95%CI): 0.986 (0.979-0.992), p<0.001]. Conclusions: Old age, high baseline levels of LDH and CRP and low platelet counts were risk factors of the in-hospital mortality in mNGS positive PCP patients.


Assuntos
Pneumonia por Pneumocystis , Adulto , Albuminas , Proteína C-Reativa , Sequenciamento de Nucleotídeos em Larga Escala , Mortalidade Hospitalar , Humanos , L-Lactato Desidrogenase , Metagenômica , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/diagnóstico , Estudos Retrospectivos , Fatores de Risco
20.
BMC Oral Health ; 22(1): 404, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115999

RESUMO

BACKGROUND: Prior studies have shown an association between generalized periodontitis and anemia in older or undernourished adults. The aim of the study was to examine the associations of erythrocyte indices with localized periodontitis in robust young adults, which has never been reported before. METHODS: The study included 1286 military participants, aged 19-40 years, with regular exercise training in Hualien, Taiwan. Localized periodontitis was grouped to healthy/stage I and stage II/III (n = 803 and 325) in men and (n = 130 and 28) in women according to the 2017 criteria of the world workshop. Systemic inflammation was evaluated by leukocyte counts. Multiple logistic regression analysis with adjustment for age, tobacco smoking status, betel nut chewing status, body mass index and leucocyte counts were used to determine the associations. RESULTS: Greater mean corpuscular volume in young men [odds ratio (OR) and 95% confidence intervals 1.03 (1.01-1.06)], and greater hematocrit and hemoglobin levels in young women were associated with a higher risk of localized stage II/III periodontitis [OR: 1.17 (1.02-1.34) and 1.60 (1.06-2.41), respectively]. However, there were no associations for erythrocyte counts. CONCLUSIONS: The localized stage II/III periodontitis risk increased with greater erythrocyte indices in robust young adults. This finding could be explained in part by that localized periodontitis may promote physical stress, possibly resulting in an increase of erythrocyte indices. On the other side, greater physical fitness associated with a lower risk of periodontitis may consume iron storage in the body, leading to exercise-induced anemia or smaller erythrocyte volume.


Assuntos
Anemia , Índices de Eritrócitos , Militares , Periodontite , Anemia/sangue , Estudos Transversais , Feminino , Hemoglobinas , Humanos , Ferro , Masculino , Saúde Bucal , Periodontite/sangue , Periodontite/classificação , Adulto Jovem
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