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BACKGROUND: Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD. METHODS: The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset. RESULTS: A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers. CONCLUSIONS: Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients. TRIAL REGISTRATION: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www. CLINICALTRIALS: gov .
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Biologia Computacional , Doença de Crohn , RNA Mensageiro , Ustekinumab , Adulto , Feminino , Humanos , Masculino , Análise por Conglomerados , Biologia Computacional/métodos , Doença de Crohn/genética , Doença de Crohn/tratamento farmacológico , Perfilação da Expressão Gênica , Ontologia Genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Estudos Prospectivos , Reprodutibilidade dos Testes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Transcriptoma/genética , Ustekinumab/uso terapêutico , Ustekinumab/farmacologiaRESUMO
Imaging through scattering media is a classical inverse issue in computational imaging. In recent years, deep learning(DL) methods have excelled in speckle reconstruction by extracting the correlation of speckle patterns. However, high-performance DL-based speckle reconstruction also costs huge hardware computation and energy consumption. Here, we develop an opto-electronic DL method with low computation complexity for imaging through scattering media. We design the "end-to-end" optronic structure for speckle reconstruction, namely optronic fully convolutional neural network (OP-FCNN). In OP-FCNN, we utilize lens groups and spatial light modulators to implement the convolution, down/up-sampling, and skip connection in optics, which significantly reduces the computational complexity by two orders of magnitude, compared with the digital CNN. Moreover, the reconfigurable and scalable structure supports the OP-FCNN to further improve imaging performance and accommodate object datasets of varying complexity. We utilize MNIST handwritten digits, EMNIST handwritten letters, fashion MNIST, and MIT-CBCL-face datasets to validate the OP-FCNN imaging performance through random diffusers. Our OP-FCNN reveals a good balance between computational complexity and imaging performance. The average imaging performance on four datasets achieves 0.84, 0.91, 0.79, and 16.3dB for JI, PCC, SSIM, and PSNR, respectively. The OP-FCNN paves the way for all-optical systems in imaging through scattering media.
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Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice. Despite the potential of rapamycin for OA disease alleviation, its clinical application is hindered by the challenge of achieving therapeutic concentrations, which necessitates multiple injections per week. To address this issue, rapamycin was loaded into poly(lactic-co-glycolic acid) nanoparticles (RNPs), which are nontoxic, have a high encapsulation efficiency and exhibit sustained release properties for OA treatment. The RNPs were found to promote chondrogenic differentiation of ATDC5 cells and prevent senescence caused by oxidative stress in primary mouse articular chondrocytes. Moreover, RNPs were capable to alleviate metabolism homeostatic imbalance of primary mouse articular chondrocytes in both monolayer and 3D cultures under inflammatory or oxidative stress. In the mouse destabilization of the medial meniscus (DMM) model, intra-articular injection of RNPs effectively mitigated joint cartilage destruction, osteophyte formation, chondrocytes hypertrophy, synovial inflammation, and pain. Our study demonstrates the feasibility of using RNPs as a potential clinically translational therapy to prevent the progression of post-traumatic OA.
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Cartilagem Articular , Nanopartículas , Osteoartrite , Camundongos , Animais , Sirolimo/farmacologia , Cartilagem Articular/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Primary failure of tooth eruption (PFE) is a rare autosome genetic disorder that causes open bite. This work aimed to report a small family of PFE(OMIM: # 125,350) with a novel PTH1R variant. One of the patients has a rare clinical phenotype of the anterior tooth involved only. CASE PRESENTATION: The proband was a 13-year-old young man with an incomplete eruption of the right upper anterior teeth, resulting in a significant open-bite. His left first molar partially erupted. Family history revealed that the proband's 12-year-old brother and father also had teeth eruption disorders. Genetic testing found a novel PTH1R variant (NM_000316.3 c.1325-1336del), which has never been reported before. The diagnosis of PFE was based on clinical and radiographic characteristics and the result of genetic testing. Bioinformatic analysis predicted this variant would result in the truncation of the G protein-coupled receptor encoded by the PTH1R, affecting its structure and function. CONCLUSION: A novel PTH1R variant identified through whole-exome sequencing further expands the mutation spectrum of PFE. Patients in this family have different phenotypes, which reflects the characteristics of variable phenotypic expression of PFE.
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Biologia Computacional , Erupção Dentária , Humanos , Masculino , Dente Molar , Mutação , Fenótipo , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Erupção Dentária/genética , Criança , AdolescenteRESUMO
The development of optical neural networks greatly slows the urgent demand of searching for fast computing approaches to solve big data processing. However, most optical neural networks following electronic training and optical inferencing do not really take full advantage of optical computing to reduce computational burden. Take the extensively used optronic convolutional neural networks (OPCNN) as an example, the convolutional operations still require vast computational operations in training stages on the computer. To address this issue, this study proposes the in-situ training algorithm to train the networks directly in optics. We derive the backpropagation algorithms of OPCNN hence the complicated gradient calculation in backward propagating processes can be obtained through optical computing. Both forward propagation and backward propagation are all executed on the same optical system. Furthermore, we successfully realize the introduction of optical nonlinearity in networks through utilizing photorefractive crystal SBN:60 and we also derive the corresponding backpropagation algorithm. The numerical simulation results of classification performance on several datasets validates the feasibility of the proposed algorithms. Through in-situ training, the reduction in performance resulting from the inconsistency of the plantform between training and inferencing stages can be eliminated completely. For example, we demonstrate that by using the optical training approach, OPCNN is capable of gaining a strong robustness under several misalignmed situations, which enhances the practicability of OPCNN and greatly expands its application range.
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Optical coherence tomography angiography (OCTA) images suffer from inevitable micromotion (breathing, heartbeat, and blinking) noise. These image artifacts can severely disturb the visibility of results and reduce accuracy of vessel morphological and functional metrics quantization. Herein, we propose a multiple wavelet-FFT algorithm (MW-FFTA) comprising multiple integrated processes combined with wavelet-FFT and minimum reconstruction that can be used to effectively attenuate motion artifacts and significantly improve the precision of quantitative information. We verified the fidelity of image information and reliability of MW-FFTA by the image quality evaluation. The efficiency and robustness of MW-FFTA was validated by the vessel parameters on multi-scene in vivo OCTA imaging. Compared with previous algorithms, our method provides better visual and quantitative results. Therefore, the MW-FFTA possesses the potential capacity to improve the diagnosis of clinical diseases with OCTA.
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Artefatos , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Reprodutibilidade dos Testes , Algoritmos , Angiografia/métodosRESUMO
Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron-chelating agent with BSA, thus leading to biocompatible and stable Cro-Fe@BSA nanoparticles (NPs). The Cro-Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature-dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat-induced formation of heat shock proteins and thus the self-protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro-Fe@BSA NPs also enabled safe and reliable cancer theranostics.
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Ferroptose , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fototerapia , Medicina de Precisão , Nanomedicina TeranósticaRESUMO
BACKGROUND AND AIMS: Serum infliximab trough level(S-IFX) and antibody were documented to correlate with clinical response. The aim of this study was to identify the relationship between early S-IFX, early mucosal healing (MH) and one-year outcome in a cohort on maintenance IFX therapy in Crohn's disease (CD). METHODS: The study group comprised of retrospectively enrolled patients diagnosed for Crohn's disease (n = 108). Patients received scheduled maintenance therapy after response to IFX induction, and had undergone the early S-IFX test and endoscopic examination at week 14. Clinical outcomes were evaluated during maintenance therapy until week 52. RESULTS: Early S-IFX was 4.78 ± 6.16 ug/ml in all the patients and 19% (21/108) of them developed antibodies, and 52 patients reached early MH. During 52 weeks' follow-up. Twenty-eight percent (30/108) of patients showed loss of response to IFX. Patients who lost response had lower early S-IFX than those who had sustained response (3.01 ± 3.66 vs. 5.47 ± 6.79 ug/ml, p = .02; 48 vs. 23%, p = .02). At week 52, 73 patients had repeated endoscopy and 42% of them reached MH. Early S-IFX had a predictive value on MH at week 52. When early S-IFX > 2.5 ug/ml, the sensitivity for predicting MH at week 52 was 87%, and the specificity were 61% (AUC = 0.73, p < .01). The combined predictive value of early S-IFX and early MH became stronger. Only 6% (1/18) of those patients who had low early S-IFX and had not reached early MH could reach MH at week 52. CONCLUSIONS: Early S-IFX and early MH could predict one-year response after initiating IFX therapy in Crohn's disease.
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Doença de Crohn , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Early gastric cancer is associated with a much better prognosis than advanced disease, and strategies to improve prognosis is strictly dependent on earlier detection and accurate diagnosis. Therefore, a label-free, non-invasive imaging technique that allows the precise identification of morphologic changes in early gastric cancer would be of considerable clinical interest. METHODS: In this study, multiphoton microscopy (MPM) using two-photon excited fluorescence combined with second-harmonic generation was used for the identification of early gastric cancer. RESULTS: This microscope was able to directly reveal improved cellular detail and stromal changes during the development of early gastric cancer. Furthermore, two features were quantified from MPM images to assess the cell change in size and stromal collagen change as gastric lesion developed from normal to early cancer. CONCLUSIONS: These results clearly show that multiphoton microscopy can be used to examine early gastric cancer at the cellular level without the need for exogenous contrast agents. This study would be helpful for early diagnosis and treatment of gastric cancer, and may provide the groundwork for further exploration into the application of multiphoton microscopy in clinical practice.
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Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Detecção Precoce de Câncer , HumanosRESUMO
BACKGROUND: In dogs with heart failure (HF) induced by overload pressure, the role of renal sympathetic denervation (RSD) on heart failure and in the renal artery is unclear. Therefore, we investigated the efficacy and safety of RSD in dogs with pressure overload-induced heart failure. METHODS: Twenty mongrel dogs were divided into a sham-operated group, an HF group and an HF + RSD group. In the sham-operated group, the abdominal aorta was located but was not constricted, in the HF group, the abdominal aorta was constricted without RSD, and the HF+RSD group underwent RSD with constriction of the abdominal aorta after 10 weeks. Blood sampling assays, echocardiography, intravascular ultrasound (IVUS) measurement and histopathological examination were performed. RESULTS: Renal sympathetic denervation caused a significant reduction in the levels of noradrenaline (166.62±6.84 vs. 183.48±13.66 pg/ml, P<0.05), plasma renin activity (1.93±0.12 vs. 2.10±0.13 ng/mlh, P<0.05) and B-type natriuretic peptide (71.14±3.86 vs. 83.15±5.73 pg/ml, P<0.05) at eight weeks after RSD in the HF+RSD group. Compared with the HF group at eight weeks, the left ventricular internal dimension at end-diastole and end-systole were lower and the left ventricular ejection fraction was higher (all P<0.05) at eight weeks after RSD in the HF+RSD group. Intravenous ultrasound images showed no changes in the renal artery lumen, and intimal hyperplasia and vascular lumen stenosis were not observed after RSD. CONCLUSIONS: Renal sympathetic denervation could improve cardiac function in dogs with HF induced by pressure overload; RSD had no adverse influence on the renal artery.
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Insuficiência Cardíaca , Artéria Renal , Simpatectomia , Animais , Modelos Animais de Doenças , Cães , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/fisiopatologia , Rim/irrigação sanguínea , Rim/inervação , Rim/fisiopatologia , Norepinefrina/sangue , Artéria Renal/inervação , Artéria Renal/fisiopatologia , Volume SistólicoRESUMO
BACKGROUND: Ambiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring. METHODS: We conducted (1)H nuclear magnetic resonance (NMR)-based metabolic analysis on cell lines (CHG5, SHG44, U87, U118, U251) developed from gliomas of different malignant grades (WHO II and WHO IV). Several methods were applied to analyze the (1)H-NMR spectral data of polar extracts of cell lines and to identify characteristic metabolites, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), fuzzy c-means clustering (FCM) analysis and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). The expression analyses of glial fibrillary acidic protein (GFAP) and matrix metal proteinases (MMP-9) were used to assess malignant behaviors of cell lines. GeneGo pathway analysis was used to associate characteristic metabolites with malignant behavior protein markers GFAP and MMP-9. RESULTS: Stable and distinct metabolic profiles of the five cell lines were obtained. The metabolic profiles of the low malignancy grade group (CHG5, SHG44) were clearly distinguished from those of the high malignancy grade group (U87, U118, U251). Seventeen characteristic metabolites were identified that could distinguish the metabolic profiles of the two groups, nine of which were mapped to processes related to GFAP and MMP-9. Furthermore, the results from both quantitative comparison and metabolic correlation analysis indicated that the significantly altered metabolites were primarily involved in perturbation of metabolic pathways of tricarboxylic acid (TCA) cycle anaplerotic flux, amino acid metabolism, anti-oxidant mechanism and choline metabolism, which could be correlated with the changes in the glioma cells' malignant behaviors. CONCLUSIONS: Our results reveal the metabolic heterogeneity of glioma cell lines with different degrees of malignancy. The obtained metabolic profiles and characteristic metabolites are closely associated with the malignant features of glioma cells, which may lay the basis for both determining the molecular mechanisms underlying glioma malignant transformation and exploiting non-invasive biomarkers for prognosis monitoring.
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Biomarcadores Tumorais/metabolismo , Glioma/metabolismo , Glioma/patologia , Espectroscopia de Prótons por Ressonância Magnética/métodos , Linhagem Celular Tumoral , Humanos , Metaboloma , Metabolômica/métodos , Análise de Componente PrincipalRESUMO
CuS/Bi2O3 composite photocatalyst was prepared by calcination and in situ precipitation, and peroxymonosulfate (PMS) was applied to the degradation of tetracycline (TC) wastewater under visible light. The microscopic morphology, chemical composition, and optical properties of the composites were investigated by characterization means of XRD, FTIR, SEM, XPS, and UV-Vis DRS. The results showed that the introduction of CuS increased the specific surface area of Bi2O3 and increased the visible absorption boundary of Bi2O3 from 455 to 524 nm, which effectively inhibited the complexation of photogenerated electron-hole pairs. The experimental results showed that the introduction of PMS strengthened the removal of TC from the composites, and 95% of TC could be removed under visible light irradiation, and the reaction rate was 8.22 times higher than that of the unspiked PMS, indicating that the BC-15+vis/PMS catalytic system could degrade the pollutants efficiently. The radical capture experiments showed that several radicals, including ·OH, SO4·-, ·O2-, h+, and 1O2, were present in the catalytic system as the main active species to degrade TC, and the mechanism of photocatalytic activation of PMS by Z-type heterostructures of CuS/Bi2O3 composites was proposed. The present study showed that BC-15 has excellent degradation performance and stability, which provides new ideas for the treatment of antibiotic wastewater.
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Antibacterianos , Peróxidos , Águas Residuárias , Tetraciclina/química , LuzRESUMO
AIMS: Acute kidney injury (AKI) has been associated with a variety of neurological problems, while the neurobiological mechanism remains unclear. In the present study, we utilized resting-state functional magnetic resonance imaging (rs-fMRI) to detect brain injury at an early stage and investigated the impact of microglia on the neuropathological mechanism of AKI. METHODS: Rs-fMRI data were collected from AKI rats and the control group with a 9.4-Tesla scanner at 24, 48, and 72 h post administration of contrast medium or saline. The amplitude of low-frequency fluctuations (ALFF) was then compared across the groups at each time course. Additionally, flow cytometry and SMART-seq2 were employed to evaluate microglia. Furthermore, pathological staining and Western blot were used to analyze the samples. RESULTS: MRI results revealed that AKI led to a decreased ALFF in the hippocampus, particularly in the 48 h and 72 h groups. Additionally, western blot suggested that AKI-induced the neuronal apoptosis at 48 h and 72 h. Flow cytometry and confocal microscopy images demonstrated that AKI activated the aggregation of microglia into neurons at 24 h, with a strong upregulation of M1 polarization at 48 h and peaking at 72 h, accompanying with the release of proinflammatory cytokines. The ALFF value was strongly correlated with the proportion of microglia (|r| > 0.80, p < 0.001). CONCLUSIONS: Our study demonstrated that microglia aggregation and inflammatory factor upregulation are significant mechanisms of AKI-induced neuronal apoptosis. We used fMRI to detect the alterations in hippocampal function, which may provide a noninvasive method for the early detection of brain injury after AKI.
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Injúria Renal Aguda , Lesões Encefálicas , Ratos , Animais , Microglia , Hipocampo/diagnóstico por imagem , Apoptose , Injúria Renal Aguda/diagnóstico por imagemRESUMO
BACKGROUND/AIMS: Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. METHODS: This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively. RESULTS: Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. CONCLUSIONS: In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.
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Background: Small bowel involvement is related to poor prognosis in Crohn's disease (CD), which may be a potential marker to stratify patients with a high risk of progression. This study aimed to establish a novel location classification system for CD and to develop a predictive model for disease progression. Methods: Consecutive patients with non-stricturing/non-penetrating CD were retrospectively included in the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou, P. R. China) between January 2012 and January 2018. Patients were classified into two groups according to disease location: small bowel involvement group and isolated colon group. The primary outcome was disease progression to stricturing or penetrating phenotypes. Progression-free survival was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Results: A total of 463 patients were analysed, with a median follow-up time of 55.3 months. Patients with small bowel involvement had a higher risk of disease progression than those with isolated colon disease (hazard ratio = 1.998, P = 0.007), while no differences were found between Montreal location classification and disease progression. Median progression-free survival was higher in the isolated colon group than in the small bowel involvement group (84.5 vs 77.3 months, P = 0.006). Four independent factors associated with disease progression were identified: small bowel involvement, duration of onset of >1 year, deep mucosal ulcer, and C-reactive protein levels of ≥10 mg/L (all P < 0.05). The nomogram model based on these factors showed good performance in predicting disease progression, with a C-index of 0.746 (95% confidence interval, 0.707-0.785). Conclusions: Classifying CD based on small bowel involvement and isolated colon was superior to the Montreal location classification for predicting disease progression.
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Objective: The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. Subjects and methods: In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. Results: The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). Conclusion: Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.
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Pancreatite , Humanos , Doença Aguda , China/epidemiologia , Genótipo , Lipase Lipoproteica/genética , Pancreatite/diagnóstico , Pancreatite/genética , TriglicerídeosRESUMO
BACKGROUND: Achieving long-term clinical remission in Crohn's disease (CD) with antitumor necrosis factor α (anti-TNF-α) agents remains challenging. AIMS: This study aims to establish a prediction model based on patients' clinical characteristics using a machine-learning approach to predict the long-term efficacy of infliximab (IFX). METHODS: Three cohorts comprising 746 patients with CD were included from 3 inflammatory bowel disease (IBD) centers between June 2013 and January 2022. Clinical records were collected from baseline, 14-, 30-, and 52-week post-IFX treatment. Three machine-learning approaches were employed to develop predictive models based on 23 baseline predictors. The SHapley Additive exPlanations (SHAP) algorithm was used to dissect underlying predictors, and latent class mixed model (LCMM) was applied for trajectory analysis of the longitudinal change of blood routine tests along with long-term IFX therapy. RESULTS: The XGBoost model exhibited the best discrimination between long-term responders and nonresponders. In the internal training and testing set, the model achieved an AUC of 0.91 (95% CI, 0.86-0.95) and 0.71 (95% CI, 0.66-0.87), respectively. Moreover, it achieved a moderate predictive performance in the independent external cohort, with an AUC of 0.68 (95% CI, 0.59-0.77). The SHAP algorithm revealed disease-relevant laboratory measurements, notably hemoglobin (HB), white blood cells (WBC), erythrocyte sedimentation rate (ESR), albumin (ALB), and platelets (PLT), alongside age at diagnosis and the Montreal classification, as the most influential predictors. Furthermore, 2 distinct patient clusters based on dynamic laboratory tests were identified for monitoring the long-term remission. CONCLUSIONS: The established prediction model demonstrated remarkable discriminatory power in distinguishing long-term responders from nonresponders to IFX therapy. The identification of distinct patient clusters further emphasizes the need for tailored therapeutic approaches in CD management.
The study developed a machine-learning model using clinical data to predict long-term efficacy of IFX in Crohn's disease. The XGBoost model demonstrated strong discriminatory power, revealing influential predictors and distinct patient clusters, emphasizing the importance of tailored therapeutic approaches in CD management.
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Laser speckle contrast imaging (LSCI) is widely used for in vivo real-time detection and analysis of local blood flow microcirculation due to its non-invasive ability and excellent spatial and temporal resolution. However, vascular segmentation of LSCI images still faces a lot of difficulties due to numerous specific noises caused by the complexity of blood microcirculation's structure and irregular vascular aberrations in diseased regions. In addition, the difficulties of LSCI image data annotation have hindered the application of deep learning methods based on supervised learning in the field of LSCI image vascular segmentation. To tackle these difficulties, we propose a robust weakly supervised learning method, which selects the threshold combinations and processing flows instead of labor-intensive annotation work to construct the ground truth of the dataset, and design a deep neural network, FURNet, based on UNet++ and ResNeXt. The model obtained from training achieves high-quality vascular segmentation and captures multi-scene vascular features on both constructed and unknown datasets with good generalization. Furthermore, we intravital verified the availability of this method on a tumor before and after embolization treatment. This work provides a new approach for realizing LSCI vascular segmentation and also makes a new application-level advance in the field of artificial intelligence-assisted disease diagnosis.
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Inteligência Artificial , Redes Neurais de Computação , Lasers , Microcirculação/fisiologia , Aprendizado de Máquina Supervisionado , Processamento de Imagem Assistida por Computador/métodosRESUMO
Non-obese nonalcoholic fatty liver disease (NAFLD) is characterized by metabolic disorders and related complications. This study aimed to provide an integrated description of clinical, metabolic, and influencing factors for a specific category of patients with non-obese NAFLD. A total of 36 participants with body mass index (BMI) < 28 kg/m2 and visceral adipose tissue < 100 cm2 were classified into 2 groups: the non-obese, non-centrally obese control group (n = 17) and non-obese, non-centrally obese NAFLD group (n = 19). Hypertriglyceridemia, impaired fasting glucose, low high-density lipoprotein cholesterol levels, and hypertension were used to determine whether participants were metabolically abnormal. Based on a logistic regression model, odds ratios for the factors influencing NAFLD with 95% confidence intervals were calculated. Insulin resistance (IR) and fasting plasma glucose (FPG) levels were higher in the NAFLD group than in the control group (P < .05). The NAFLD group had a higher metabolic abnormality rate than the healthy control group (36.84% vs 5.88%, P = .044). Correlation analysis showed that IR was positively correlated with FPG and triglyceride (P < .05). BMI was the main influencing factor of NAFLD (regression coefficient ß = 0.631; odds ratio = 1.879; 95% confidence interval, 1.233-2.863). NAFLD patients with a BMI < 28 kg/m2 and visceral adipose tissue < 100 cm2 had more apparent IR, higher FPG, and a higher metabolic abnormality rate. IR may be affected by FPG and triglyceride. Even in non-obese and non-centrally obese individuals, BMI should be controlled to avoid NAFLD.