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1.
Adv Sci (Weinh) ; : e2407295, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39234809

RESUMO

Recently, solar-driven interfacial evaporation (SDIE) has been developed quickly for low-cost and sustainable seawater desalination, but addressing the conflict between a high evaporation rate and salt rejection during SDIE is still challenging. Here, a spatial confinement strategy is proposed to prepare the gel composite solar evaporator (SCE) by loading one thin hydrogel layer onto the skeleton of a carbon aerogel. The SCE retains the hierarchically porous structure of carbon aerogels with an optimized water supply induced by dual-driven forces (capillary effects and osmotic pressure) and takes advantage of both aerogels and hydrogels, which can gain energy from air and reduce water enthalpy. The SCE has a high evaporation rate (up to 4.23 kg m-2 h-1 under one sun) and excellent salt rejection performance and can maintain structural integrity after long-term evaporation even at high salinities. The SDIE behavior, including heat distribution, water transport, and salt ion distribution, is investigated by combining theoretical simulations and experimental results. This work provides new inspiration and a theoretical basis for the development of high-performance interfacial evaporators.

2.
Digit Health ; 10: 20552076241277713, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247098

RESUMO

Aim: To optimize gastric cancer screening score and reduce screening costs using machine learning models. Methods: This study included 228,634 patients from the Taizhou Gastric Cancer Screening Program. We used three machine learning models to optimize Li's gastric cancer screening score: Gradient Boosting Machine (GBM), Distributed Random Forest (DRF), and Deep Learning (DL). The performance of the binary classification models was evaluated using the area under the curve (AUC) and area under the precision-recall curve (AUCPR). Results: In the binary classification model used to distinguish low-risk and moderate- to high-risk patients, the AUC in the GBM, DRF, and DL full models were 0.9994, 0.9982, and 0.9974, respectively, and the AUCPR was 0.9982, 0.9949, and 0.9918, respectively. Excluding Helicobacter pylori IgG antibody, pepsinogen I, and pepsinogen II, the AUC in the GBM, DRF, and DL models were 0.9932, 0.9879, and 0.9900, respectively, and the AUCPR was 0.9835, 0.9716, and 0.9752, respectively. Remodel after removing variables IgG, PGI, PGII, and G-17, the AUC in GBM, DRF, and DL was 0.8524, 0.8482, 0.8477, and AUCPR was 0.6068, 0.6008, and 0.5890, respectively. When constructing a tri-classification model, we discovered that none of the three machine learning models could effectively distinguish between patients at intermediate and high risk for gastric cancer (F1 scores in the GBM model for the low, medium and high risk: 0.9750, 0.9193, 0.5334, respectively; F1 scores in the DRF model for low, medium, and high risks: 0.9888, 0.9479, 0.6694, respectively; F1 scores in the DL model for low, medium, and high risks: 0.9812, 0.9216, 0.6394, respectively). Conclusion: We concluded that gastric cancer screening indicators could be optimized when distinguishing low-risk and moderate to high-risk populations, and detecting gastrin-17 alone can achieve a good discriminative effect, thus saving huge expenditures.

3.
Life Sci ; 356: 123013, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39182568

RESUMO

AIMS: The RNA-binding protein LSM7 is essential for RNA splicing, acting as a key component of the spliceosome complex; however, its specific role in breast cancer (BC) has not been extensively investigated. MATERIALS AND METHODS: LSM7 expression in BC samples was evaluated through bioinformatics analysis and immunohistochemistry. The impact of LSM7 on promoting metastatic tumor characteristics was examined using transwell and wound healing assays, as well as an orthotopic xenograft model. Additionally, the involvement of LSM7 in alternative splicing of CD44 was explored via RNA immunoprecipitation and third-generation sequencing. The regulatory role of TCF3 in modulating LSM7 gene expression was further elucidated using luciferase reporter assays and chromatin immunoprecipitation. KEY FINDINGS: Our findings demonstrate that LSM7 was significantly overexpressed in metastatic BC tissues and was associated with poor prognostic outcomes in patients with BC. LSM7 overexpression markedly increased the migratory and invasive capabilities of BC cells in vitro and significantly promoted spontaneous lung metastasis in vivo. Furthermore, RIP-seq analysis revealed that LSM7 binded to CD44 RNA, enhancing the expression of its alternatively spliced isoform CD44s, thereby driving BC metastasis and invasion. Additionally, the transcription factor TCF3 was found to activate LSM7 transcription by directly binding to its promoter. SIGNIFICANCE: In summary, this study highlights the pivotal role of LSM7 in the production of the CD44s isoform and the promotion of breast cancer metastasis. Targeting the TCF3/LSM7/CD44s axis may offer a promising therapeutic strategy for breast cancer treatment.


Assuntos
Processamento Alternativo , Neoplasias da Mama , Receptores de Hialuronatos , Proteínas de Ligação a RNA , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Processamento Alternativo/genética , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/genética , Animais , Camundongos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Camundongos Nus , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Movimento Celular/genética , Prognóstico
4.
Sensors (Basel) ; 24(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39205132

RESUMO

The surge in image data has significantly increased the pressure on storage and transmission, posing new challenges for image compression technology. The structural texture of an image implies its statistical characteristics, which is effective for image encoding and decoding. Consequently, content-adaptive compression methods based on learning can better capture the content attributes of images, thereby enhancing encoding performance. However, learned image compression methods do not comprehensively account for both the global and local correlations among the pixels within an image. Moreover, they are constrained by rate-distortion optimization, which prevents the attainment of a compact representation of image attributes. To address these issues, we propose a syntax-guided content-adaptive transform framework that efficiently captures image attributes and enhances encoding efficiency. Firstly, we propose a syntax-refined side information module that fully leverages syntax and side information to guide the adaptive transformation of image attributes. Moreover, to more thoroughly exploit the global and local correlations in image space, we designed global-local modules, local-global modules, and upsampling/downsampling modules in codecs, further eliminating local and global redundancies. The experimental findings indicate that our proposed syntax-guided content-adaptive image compression model successfully adapts to the diverse complexities of different images, which enhances the efficiency of image compression. Concurrently, the method proposed has demonstrated outstanding performance across three benchmark datasets.

5.
Genet Test Mol Biomarkers ; 28(7): 267-274, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39034913

RESUMO

Background: A high-altitude environment has inhibitory effects on obesity. Tibetans are not a high-risk population for obesity, but there are still obese individuals within that population. Obesity has become a worldwide health problem, and previous studies have found that obesity is closely associated with hereditary factors. Few studies have investigated obesity in Tibetans, and the association between gene polymorphisms and obesity in Tibetans remains unclear. Methods: Our study investigated the fat mass of 140 native Tibetan individuals (70 men and 70 women) from Lhasa and analyzed the associations between polymorphisms of melanocortin 4 receptor (MC4R), Src homology 2B adapter protein 1 (SH2B1), and neuronal growth regulator 1 (NEGR1) and obesity. Result: Among Tibetan individuals, there were differences in genotype and allele frequencies between those in the obesity group and those in the healthy group at MC4R (rs17782313) and SH2B1 (rs7359397). The polymorphisms of MC4R (rs17782313) were associated with fat mass and obesity in Tibetan men and women, and there was an association between SH2B1 (rs7359397) polymorphisms and fat mass and obesity in Tibetan men. However, polymorphisms of NEGR1 (rs3101336) were not associated with fat mass or obesity in Tibetan individuals. Conclusion: Among Tibetan individuals, polymorphisms of MC4R (rs17782313) and SH2B1 (rs7359397) were associated with obesity, but NEGR1 (rs3101336) polymorphisms were not associated with obesity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Moléculas de Adesão Celular Neuronais , Obesidade , Receptor Tipo 4 de Melanocortina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/genética , Alelos , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/genética , População do Leste Asiático/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Proteínas Ligadas por GPI , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética , Tibet
6.
World J Clin Cases ; 12(19): 3866-3872, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994274

RESUMO

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

7.
Phys Rev Lett ; 132(26): 266602, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996328

RESUMO

Twisted moiré materials, a new class of layered structures with different twist angles for neighboring layers, are attracting great attention because of the rich intriguing physical phenomena associated with them. Of particular interest are the topological network modes, first proposed in the small angle twisted bilayer graphene under interlayer bias. Here we report the observations of such topological network modes in twisted moiré phononic crystals without requiring the external bias fields. Acoustic topological network modes that can be constructed in a wide range of twist angles are both observed in the domain walls with and without reconstructions, which serve as the analogy of the lattice relaxations in electronic moiré materials. Topological robustness of the topological network modes is observed by introducing valley-preserved defects to the network channel. Furthermore, the network can be reconfigured into two-dimensional patterns with any desired connectivity, offering a unique prototype platform for acoustic applications.

8.
Cell Death Dis ; 15(6): 437, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902257

RESUMO

TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20-CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.


Assuntos
Quimiocina CCL20 , Neoplasias Colorretais , Células-Tronco Neoplásicas , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Receptores CCR6 , Transdução de Sinais , Linfócitos T Reguladores , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Ligante RANK/metabolismo , Receptores CCR6/metabolismo , Receptores CCR6/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Masculino , Camundongos , Feminino , Metástase Neoplásica , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Camundongos Nus , Movimento Celular
9.
Adv Sci (Weinh) ; 11(30): e2309471, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38889269

RESUMO

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.


Assuntos
Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Disbiose/metabolismo , Disbiose/microbiologia , Disbiose/imunologia , Humanos , Camundongos , Masculino , Feminino , Animais , Doença de Depósito de Glicogênio Tipo I/metabolismo , Doença de Depósito de Glicogênio Tipo I/genética , Doença de Depósito de Glicogênio Tipo I/complicações , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia
10.
Sci Bull (Beijing) ; 69(11): 1660-1666, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38653684

RESUMO

Bound states in the continuum (BICs) are spatially localized states with energy embedded in the continuum spectrum of extended states. The combination of BICs physics and nontrivial band topology theory givs rise to topological BICs, which are robust against disorders and meanwhile, the merit of conventional BICs is attracting wide attention recently. Here, we report valley edge states as topological BICs, which appear at the domain wall between two distinct valley topological phases. The robustness of such BICs is demonstrated. The simulations and experiments show great agreement. Our findings of valley related topological BICs shed light on both BICs and valley physics, and may foster innovative applications of topological acoustic devices.

11.
J Cardiothorac Surg ; 19(1): 248, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632604

RESUMO

BACKGROUND: The occurrence of massive retroperitoneal hematoma caused by intercostal artery bleeding is exceedingly uncommon. CASE PRESENTATION: A middle-aged male presented to the hospital after a fall. Computed tomography scan revealed a massive retroperitoneal hematoma without any evidence of organ or major vessel rupture. The angiogram revealed extravasation from a branch of the twelfth intercostal artery, and successful transcatheter arterial embolization was performed on this specific artery. CONCLUSIONS: The possibility of intercostal artery rupture should be considered in cases of retroperitoneal hematomas, and accurate diagnosis can be achieved through imaging studies. Transcatheter arterial embolization represents an effective treatment modality.


Assuntos
Embolização Terapêutica , Ferimentos não Penetrantes , Pessoa de Meia-Idade , Masculino , Humanos , Hematoma/etiologia , Artérias , Angiografia , Embolização Terapêutica/métodos , Hemorragia Gastrointestinal , Ferimentos não Penetrantes/complicações
12.
Sci Transl Med ; 16(743): eadk5395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630847

RESUMO

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.


Assuntos
Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Pessoa de Meia-Idade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Lesões Pré-Cancerosas/patologia
13.
Adv Sci (Weinh) ; 11(22): e2309668, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537163

RESUMO

Tin-based perovskite solar cells (PSCs) are promising environmentally friendly alternatives to their lead-based counterparts, yet they currently suffer from much lower device performance. Due to variations in the chemical properties of lead (II) and tin (II) ions, similar treatments may yield distinct effects resulting from differences in underlying mechanisms. In this work, a surface treatment on tin-based perovskite is conducted with a commonly employed ligand, iso-butylammonium iodide (iso-BAI). Unlike the passivation effects previously observed in lead-based perovskites, such treatment leads to the recrystallization of the surface, driven by the higher solubility of tin-based perovskite in common solvents. By carefully designing the solvent composition, the perovskite surface is effectively modified while preserving the integrity of the bulk. The treatment led to enhanced surface crystallinity, reduced surface strain and defects, and improved charge transport. Consequently, the best-performing power conversion efficiency of FASnI3 PSCs increases from 11.8% to 14.2%. This work not only distinguishes the mechanism of surface treatments in tin-based perovskites from that of lead-based counterparts, but also underscores the critical role in designing tailor-made strategies for fabricating efficient tin-based PSCs.

14.
Haematologica ; 109(9): 2955-2968, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38385251

RESUMO

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1's target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function, and the role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.


Assuntos
Fator de Transcrição GATA1 , Mutação em Linhagem Germinativa , Ligação Proteica , Proteína-Arginina N-Metiltransferases , Humanos , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Diferenciação Celular/genética , Eritropoese/genética , Masculino , Feminino , Anemia/genética
15.
Phys Rev Lett ; 132(6): 066601, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394560

RESUMO

Higher-order topological insulators and semimetals, which generalize the conventional bulk-boundary correspondence, have attracted extensive research interest. Among them, higher-order Weyl semimetals feature twofold linear crossing points in three-dimensional momentum space, 2D Fermi-arc surface states, and 1D hinge states. Higher-order nodal-point semimetals possessing Weyl points or Dirac points have been implemented. However, higher-order nodal-line or nodal-surface semimetals remain to be further explored in experiments in spite of many previous theoretical efforts. In this work, we realize a second-order nodal-line semimetal in 3D phononic crystals. The bulk nodal lines, 2D drumhead surface states guaranteed by Zak phases, and 1D flat hinge states attributed to k_{z}-dependent quadrupole moments are observed in simulations and experiments. Our findings of nondispersive surface and hinge states may promote applications in acoustic sensing and energy harvesting.

17.
Int J Med Sci ; 21(1): 61-69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164345

RESUMO

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.


Assuntos
Cirrose Hepática Biliar , Humanos , Prognóstico , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Estudos Retrospectivos , Cirrose Hepática/tratamento farmacológico
18.
J Clin Gastroenterol ; 58(1): 53-56, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36507929

RESUMO

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.


Assuntos
Endoscopia Gastrointestinal , Lesões Pré-Cancerosas , Humanos , Pronase/uso terapêutico , Estudos Prospectivos , Pré-Medicação
19.
Front Genet ; 14: 1221388, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034496

RESUMO

Introduction: The Qinghai-Tibet Plateau is one of the last terrestrial environments conquered by modern humans. Tibetans are among the few high-altitude settlers in the world, and understanding the genetic profile of Tibetans plays a pivotal role in studies of anthropology, genetics, and archaeology. Methods: In this study, we investigated the maternal genetic landscape of Tibetans based on the whole mitochondrial genome collected from 145 unrelated native Lhasa Tibetans. Molecular diversity indices, haplotype diversity (HD), Tajima's D and Fu's Fs were calculated and the Bayesian Skyline Plot was obtained to determining the genetic profile and population fluctuation of Lhasa Tibetans. To further explore the genetic structure of Lhasa Tibetans, we collected 107 East Asian reference populations to perform principal component analysis (PCA), multidimensional scaling (MDS), calculated Fst values and constructed phylogenetic tree. Results: The maternal genetic landscape of Tibetans showed obvious East Asian characteristics, M9a (28.28%), R (11.03%), F1 (12.41%), D4 (9.66%), N (6.21%), and M62 (4.14%) were the dominant haplogroups. The results of PCA, MDS, Fst and phylogenetic tree were consistent: Lhasa Tibetans clustered with other highland Tibeto-Burman speakers, there was obvious genetic homogeneity of Tibetans in Xizang, and genetic similarity between Tibetans and northern Han people and geographically adjacent populations was found. In addition, specific maternal lineages of Tibetans also be determined in this study. Discussion: In general, this study further shed light on long-time matrilineal continuity on the Tibetan Plateau and the genetic connection between Tibetans and millet famers in the Yellow River Basin, and further revealed that multiple waves of population interaction and admixture during different historical periods between lowland and highland populations shaped the maternal genetic profile of Tibetans.

20.
Front Immunol ; 14: 1270411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022496

RESUMO

Background: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder affecting millions worldwide. Due to the complexity of its pathogenesis, the treatment options for IBD are limited. This study focuses on ELF4, a member of the ETS transcription factor family, as a target to elucidate its role in IBD and investigate its mechanism of action in alleviating IBD symptoms by activating IL1RN transcription to suppress the activity of inflammatory TH17 cells. Methods: Using the GEO database, this study examined LPS-induced intestinal inflammatory genes and their regulation mechanisms. We examined the colon length of LPS-treated mice and derived the Disease Activity Index (DAI). H&E staining, ELISA, and flow cytometry were used to detect mice colon tissue damage, inflammatory factor levels in mouse serum, mouse macrophage types and inflammatory TH17 cell activity. RT-qPCR and Western blot detected ELF4, IL1RN, M1, and M2 polarization markers. In Vitro, using dual-luciferase and ChIP assays, we tested mouse bone marrow-derived macrophages (BMDMs) and mouse intestinal epithelial cells for IL1RN promoter activity and ELF4 enrichment. Results: Bioinformatics showed that LPS-induced colitis animals have reduced ELF4 expression in their colon tissue. In vivo tests confirmed reduced ELF4 expression in mice with LPS-induced colitis. ELF4 overexpression reduced mouse intestinal inflammation. ELF4 activated IL1RN transcription in bioinformatics and in vitro tests. ELF4 promoted IL1RN transcription and macrophage M2 polarization to limit intestinal epithelial cell death and inflammation and reduce mouse intestinal inflammation in vitro. ELF4 also reduced the Th17/Treg ratio by increasing IL1RN transcription. Conclusion: ELF4 activates IL1RN transcription, suppresses inflammatory TH17 cells, and induces macrophage M2 polarization to treat IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Diferenciação Celular/genética , Colite/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Lipopolissacarídeos/efeitos adversos , Macrófagos/metabolismo , Células Th17 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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