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The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx+ colitis-associated regenerative stem cell (CARSC) population that functionally contributes to mucosal repair in mouse models of colitis. Hopx+ CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known to facilitate regeneration. Importantly, we established a long-term, self-organizing two-dimensional (2D) epithelial monolayer system to model the regenerative properties and responses of Hopx+ CARSCs. This system can reenact the "homeostasis-injury-regeneration" cycles of epithelial alterations that occur in vivo. Using this system, we found that hypoxia and endoplasmic reticulum stress, insults commonly present in inflammatory bowel diseases, mediated the cyclic switch of cellular status in this process.
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Técnicas de Cultivo de Célula/métodos , Colon/patología , Células Madre/patología , Células 3T3 , Animales , Colitis/patología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Proteínas de Homeodominio/metabolismo , Ratones , Modelos Biológicos , Oxígeno/farmacología , Regeneración/efectos de los fármacos , Células Madre/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacosRESUMEN
Although chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, underlying causes for these disorders are poorly understood. We show that flavivirus infection of enteric neurons leads to acute neuronal injury and cell death, inflammation, bowel dilation, and slowing of intestinal transit in mice. Flavivirus-primed CD8+ T cells promote these phenotypes, as their absence diminished enteric neuron injury and intestinal transit delays, and their adoptive transfer reestablished dysmotility after flavivirus infection. Remarkably, mice surviving acute flavivirus infection developed chronic gastrointestinal dysmotility that was exacerbated by immunization with an unrelated alphavirus vaccine or exposure to a non-infectious inflammatory stimulus. This model of chronic post-infectious gastrointestinal dysmotility in mice suggests that viral infections with tropism for enteric neurons and the ensuing immune response might contribute to the development of bowel motility disorders in humans. These results suggest an opportunity for unique approaches to diagnosis and therapy of gastrointestinal dysmotility syndromes.
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Infecciones por Flavivirus/patología , Flavivirus/patogenicidad , Motilidad Gastrointestinal , Intestinos/patología , Animales , Linfocitos T CD8-positivos/inmunología , Flavivirus/genética , Infecciones por Flavivirus/inmunología , Infecciones por Flavivirus/virología , Intestinos/virología , Leucocitos/citología , Leucocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/patología , Neuronas/ultraestructura , ARN Viral/aislamiento & purificación , ARN Viral/metabolismo , SíndromeRESUMEN
The heart is an autoimmune-prone organ. It is crucial for the heart to keep injury-induced autoimmunity in check to avoid autoimmune-mediated inflammatory disease. However, little is known about how injury-induced autoimmunity is constrained in hearts. Here, we reveal an unknown intramyocardial immunosuppressive program driven by Tbx1, a DiGeorge syndrome disease gene that encodes a T-box transcription factor (TF). We found induced profound lymphangiogenic and immunomodulatory gene expression changes in lymphatic endothelial cells (LECs) after myocardial infarction (MI). The activated LECs penetrated the infarcted area and functioned as intramyocardial immune hubs to increase the numbers of tolerogenic dendritic cells (tDCs) and regulatory T (Treg) cells through the chemokine Ccl21 and integrin Icam1, thereby inhibiting the expansion of autoreactive CD8+ T cells and promoting reparative macrophage expansion to facilitate post-MI repair. Mimicking its timing and implementation may be an additional approach to treating autoimmunity-mediated cardiac diseases.
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The local microenvironment shapes macrophage differentiation in each tissue. We hypothesized that in the peritoneum, local factors in addition to retinoic acid can support GATA6-driven differentiation and function of peritoneal large cavity macrophages (LCMs). We found that soluble proteins produced by mesothelial cells lining the peritoneal cavity maintained GATA6 expression in cultured LCMs. Analysis of global gene expression of isolated mesothelial cells highlighted mesothelin (Msln) and its binding partner mucin 16 (Muc16) as candidate secreted ligands that potentially regulate GATA6 expression in peritoneal LCMs. Mice deficient for either of these molecules showed diminished GATA6 expression in peritoneal and pleural LCMs that was most prominent in aged mice. The more robust phenotype in older mice suggested that monocyte-derived macrophages were the target of Msln and Muc16. Cell transfer and bone marrow chimera experiments supported this hypothesis. We found that lethally irradiated Msln-/- and Muc16-/- mice reconstituted with wild-type bone marrow had lower levels of GATA6 expression in peritoneal and pleural LCMs. Similarly, during the resolution of zymosan-induced inflammation, repopulated peritoneal LCMs lacking expression of Msln or Muc16 expressed diminished GATA6. These data support a role for mesothelial cell-produced Msln and Muc16 in local macrophage differentiation within large cavity spaces such as the peritoneum. The effect appears to be most prominent on monocyte-derived macrophages that enter into this location as the host ages and also in response to infection.
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Macrófagos Peritoneales , Macrófagos , Ratones , Animales , Cavidad Peritoneal , Peritoneo , EpitelioRESUMEN
BACKGROUND: Sturge Weber syndrome (SWS), can cause extensive capillary malformations on the face, head, trunk, and other parts of the body, and the eyes can also suffer optic nerve injury. Secondary glaucoma can cause blindness, which has the characteristics of a relatively hidden onset and unclear pathogenesis. The treatment of SWS secondary glaucoma has always been difficult, and due to the characteristics of the disease, there is uncertainty about the long-term efficacy and safety of various treatment methods for such patients. METHODS: A total of 105 parents of children with SWS completed a self-designed general information questionnaire, a generalized anxiety questionnaire (GAD-7), a patient health questionnaire (PHQ-2), a stress perception scale (PSS-4), a simple coping scale (SCSQ) and a disease-uncertainty scale (PPUS). RESULTS: The total uncertainty score of parents of children with SWS was 79.07 ± 13.24, and the average item score was 2.82 ± 0.47. Multiple linear regression analysis revealed that anxiety and simple coping were the main influencing factors of disease uncertainty among parents of children with SWS (P < 0.05). CONCLUSIONS: Parents of children with SWS exhibit a high level of disease uncertainty. Medical staff should pay attention to the source of parents' disease uncertainty and provide targeted interventions, which are of great importance in reducing parents' disease uncertainty.
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Glaucoma , Síndrome de Sturge-Weber , Humanos , Niño , Síndrome de Sturge-Weber/complicaciones , Estudios Retrospectivos , Incertidumbre , Glaucoma/complicaciones , PadresRESUMEN
OBJECTIVE: This study aimed to investigate the relationship between anemia and restenosis in patients with femoropopliteal arterial disease following drug-coated balloon (DCB) angioplasty. METHODS: 194 patients treated with DCB for femoropopliteal lesions were retrospectively analyzed for up to 12 months of follow-up between January 2017 and September 2020. Baseline clinical and procedural characteristics were compared between the anemia and non-anemia patients, and predictors of restenosis were identified using logistic regression. RESULTS: 32.5% of the patients undergoing DCB angioplasty had anemia. Patients with anemia were significantly older, with higher rates of hypertension, coronary artery disease, chronic renal insufficiency, and diabetes, and with lower rates of smoking and male gender. In the multivariate analysis, anemia was independently and significantly associated with a higher risk of restenosis (OR, 3.872; 95% CI, 1.556-9.638; P = 0.004). CONCLUSION: Anemia is independently associated with restenosis in patients treated with DCB for femoropopliteal arterial disease. Patients with lower baseline hemoglobin might have more chances to develop restenosis at follow-up.
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Anemia , Angioplastia de Balón , Enfermedad Arterial Periférica , Humanos , Masculino , Arteria Poplítea , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Factores de Tiempo , Arteria Femoral , Angioplastia de Balón/efectos adversos , Factores de Riesgo , Constricción Patológica , Materiales Biocompatibles Revestidos , Anemia/complicaciones , Anemia/diagnóstico , Anemia/terapia , Grado de Desobstrucción VascularRESUMEN
OBJECTIVE: Fibrosis is a common feature of Crohn's disease (CD) which can involve the mesenteric fat. However, the molecular signature of this process remains unclear. Our goal was to define the transcriptional signature of mesenteric fibrosis in CD subjects and to model mesenteric fibrosis in mice to improve our understanding of CD pathogenesis. DESIGN: We performed histological and transcriptional analysis of fibrosis in CD samples. We modelled a CD-like fibrosis phenotype by performing repeated colonic biopsies in mice and analysed the model by histology, type I collagen-targeted positron emission tomography (PET) and global gene expression. We generated a gene set list of essential features of mesenteric fibrosis and compared it to mucosal biopsy datasets from inflammatory bowel disease patients to identify a refined gene set that correlated with clinical outcomes. RESULTS: Mesenteric fibrosis in CD was interconnected to areas of fibrosis in all layers of the intestine, defined as penetrating fibrosis. We found a transcriptional signature of differentially expressed genes enriched in areas of the mesenteric fat of CD subjects with high levels of fibrosis. Mice subjected to repeated colonic biopsies showed penetrating fibrosis as shown by histology, PET imaging and transcriptional analysis. Finally, we composed a composite 24-gene set list that was linked to inflammatory fibroblasts and correlated with treatment response. CONCLUSION: We linked histopathological and molecular features of CD penetrating fibrosis to a mouse model of repeated biopsy injuries. This experimental system provides an innovative approach for functional investigations of underlying profibrotic mechanisms and therapeutic concepts in CD.
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Enfermedad de Crohn , Animales , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/genética , Fibrosis , Humanos , Intestinos/patología , Mesenterio/patología , Ratones , Inhibidores del Factor de Necrosis TumoralRESUMEN
Aim: To investigate the role of LINC01160 in nasopharyngeal carcinoma (NPC). Materials & methods: Using NPC cells CNE-2 and HNE-2 in vitro, we performed quantitative PCR to determine mRNA expression and western blotting to determine protein expression. CCK-8, transwell, flow cytometry and wound healing assays were done to examine the function of LINC01160 and STAT1. Chromatin immunoprecipitation PCR (ChIP-PCR) confirmed that STAT1 combines with the LINC01160 promoter region. Xenograft experiments were used to verify the role of STAT1 and LINC01160 in vivo. Results: LINC01160 is upregulated in NPC and can promote a malignant cell phenotype. STAT1 is a transcription factor of LINC01160 and can promote a malignant cell phenotype through upregulating LINC01160 expression. Conclusion: STAT1 can promote a malignant cell phenotype by upregulating LINC01160.
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Regulación Neoplásica de la Expresión Génica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , ARN Largo no Codificante/genética , Factor de Transcripción STAT1/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Conjuntos de Datos como Asunto , Femenino , Humanos , Ratones , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica/genética , Regiones Promotoras Genéticas/genética , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Neurons in the auditory cortex are tuned to specific ranges of sound frequencies. Although the cellular and network mechanisms underlying neuronal sound frequency selectivity are well studied and reflect the interplay of thalamocortical and intracortical excitatory inputs and further refinement by cortical inhibition, the precise synaptic signaling mechanisms remain less understood. To gain further understanding on these mechanisms and their effects on sound-driven behavior, we used in vivo imaging as well as behavioral approaches in awake and behaving female and male mice. We discovered that synaptic zinc, a modulator of neurotransmission and responsiveness to sound, sharpened the sound frequency tuning of principal and parvalbumin-expressing neurons and widened the sound frequency tuning of somatostatin-expressing inhibitory neurons in layer 2/3 of the primary auditory cortex. In the absence of cortical synaptic zinc, mice exhibited reduced acuity for detecting changes in sound frequencies. Together, our results reveal that cell-type-specific effects of zinc contribute to cortical sound frequency tuning and enhance acuity for sound frequency discrimination.SIGNIFICANCE STATEMENT Neuronal tuning to specific features of sensory stimuli is a fundamental property of cortical sensory processing that advantageously supports behavior. Despite the established roles of synaptic thalamocortical and intracortical excitation and inhibition in cortical tuning, the precise synaptic signaling mechanisms remain unknown. Here, we investigated these mechanisms in the mouse auditory cortex. We discovered a previously unknown signaling mechanism linking synaptic zinc signaling with cell-specific cortical tuning and enhancement in sound frequency discrimination acuity. Given the abundance of synaptic zinc in all sensory cortices, this newly discovered interaction between synaptic zinc and cortical tuning can provide a general mechanism for modulating neuronal stimulus specificity and sensory-driven behavior.
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Corteza Auditiva/fisiología , Discriminación de la Altura Tonal/fisiología , Transducción de Señal/fisiología , Sinapsis/fisiología , Zinc/fisiología , Estimulación Acústica , Animales , Corteza Auditiva/diagnóstico por imagen , Proteínas de Transporte de Catión , Femenino , Masculino , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/fisiología , Ratones , Ratones Noqueados , Neuronas/fisiología , Parvalbúminas/metabolismo , Somatostatina/metabolismo , Transmisión Sináptica/fisiologíaRESUMEN
Organophosphorus-degrading enzymes show high hydrolysis efficiency and provide an environmentally friendly solution to the pollution of organophosphorus compound. However, poor enzyme stability and tedious purification process have limited practical applications. Spore-based display system can provide many advantages, such as safety, low cost, easy preparation and high resistance to harsh conditions. Recently, we have constituted the recombinant spore displaying organophosphorus hydrolase and organophosphorus acid anhydrolase. In the spore display systems, recombinant spores could be reliably produced and normal sporulation was not affected; the activities of recombinant spores were 15.81 and 10.67 U/mg spores (dry weight) respectively; furthermore, the recombinant spores exhibited significantly enhanced resistance to various harsh conditions compared to free-form enzymes. These results indicated that the spore display could contribute to the practical application of organophosphorus-degrading enzymes and provide a promising solution to bioremediation of organophosphorus compounds.
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Arildialquilfosfatasa/metabolismo , Biodegradación Ambiental , Compuestos Organofosforados/metabolismo , Esporas Bacterianas/enzimología , Arildialquilfosfatasa/análisis , Bacillus subtilis/enzimología , Técnicas de Visualización de Superficie Celular/métodos , Contaminantes Ambientales/metabolismo , Proteínas Recombinantes de FusiónRESUMEN
OBJECTIVES: Although diffusion-weighted imaging (DWI) is reported to be accurate in detecting bowel inflammation in Crohn's disease (CD), its ability to assess bowel fibrosis remains unclear. This study assessed the role of DWI in the characterization of bowel fibrosis using surgical histopathology as the reference standard. METHODS: Abdominal DWI was performed before elective surgery in 30 consecutive patients with CD. The apparent diffusion coefficients (ADCs) in pathologic bowel walls were calculated. Region-by-region correlations between DWI and the surgical specimens were performed to determine the histologic degrees of bowel fibrosis and inflammation. RESULTS: ADCs correlated negatively with bowel inflammation (r = - 0.499, p < 0.001) and fibrosis (r = - 0.464, p < 0.001) in 90 specimens; the ADCs in regions of nonfibrosis and mild fibrosis were significantly higher than those in regions of moderate-severe fibrosis (p = 0.008). However, there was a significant correlation between the ADCs and bowel fibrosis (r = - 0.641, p = 0.001) in mildly inflamed segments but not in moderately (r = - 0.274, p = 0.255) or severely (r = - 0.225, p = 0.120) inflamed segments. In the mildly inflamed segments, the ADCs had good accuracy with an area under the receiver-operating characteristic curve of 0.867 (p = 0.004) for distinguishing nonfibrosis and mild fibrosis from moderate-severe fibrosis. CONCLUSIONS: ADC can be used to assess bowel inflammation in patients with CD. However, it only enables the accurate detection of the degree of bowel fibrosis in mildly inflamed bowel walls. Therefore, caution is advised when using ADC to predict the degree of intestinal fibrosis. KEY POINTS: ⢠Diffusion-weighted imaging was used to assess bowel inflammation in patients with Crohn's disease. ⢠The ability of diffusion-weighted imaging to evaluate bowel fibrosis decreased with increasing bowel inflammation. ⢠Diffusion-weighted imaging enabled accurate detection of the degree of fibrosis only in mildly inflamed bowel walls.
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Enfermedad de Crohn/diagnóstico , Imagen de Difusión por Resonancia Magnética/métodos , Inflamación/diagnóstico por imagen , Intestinos/diagnóstico por imagen , Adulto , Femenino , Fibrosis/diagnóstico , Humanos , Masculino , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: The incidence of Ulcerative colitis (UC) in Asia is increasing but reports on its long-term course are few. The aim of this study was to identify risk factors predictive of extent progression in Asian patients with UC and to evaluate the clinical outcome by longitudinal follow-up. METHODS: We retrospectively analyzed 518 UC patients without ascending colon involvement at diagnosis who were regularly followed and underwent colonoscopy between 2003 and 2016 in an Asian tertiary referral center. Proximal disease extension and associated risk factors were analyzed. RESULTS: A total of 91 (17.6%) patients experienced proximal disease extension followed for a median period of 7.5 years. The median time for extent extension was 16.1 months (interquartile range (IQR) 8.3-42.2). The cumulative rate of disease extension was 9.9, 14.9, 19.6, 24.6 and 30.5% at 1,2,3,4 and 5 years after diagnosis. 43 (12.0%) patients with E1/E2 progressed to E3, and 40 (21.9%) with E1 progressed to E2. Of patients diagnosed with E3 involvement limited to the hepatic flexure distally, 8 (13.3%) progressed to pancolitis. Cox regression analysis found that disease extent at diagnosis was the sole predictor of disease extension (odds ratio (OR),1.74, 95% confidence interval (CI) 1.18-2.57, p = 0.01). Proximal disease extension was associated with disease relapse (p = 0.03) and increased use of steroids and immunosuppressive agents (p < 0.01). CONCLUSION: UC is a dynamic disease and that the disease extension in Asians was comparable to that in Caucasians. Proximal disease extension increased the risk of disease flare and treatment intensification.
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Pueblo Asiatico , Colitis Ulcerosa/etnología , Colitis Ulcerosa/patología , Progresión de la Enfermedad , Corticoesteroides/uso terapéutico , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Colonoscopía , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Neoplasias de la Mama/patología , Moléculas de Adhesión Celular/metabolismo , Tolerancia Inmunológica/genética , Células Supresoras de Origen Mieloide/patología , Metástasis de la Neoplasia/patología , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Moléculas de Adhesión Celular/genética , Ratones , Ratones Noqueados , Células Supresoras de Origen Mieloide/metabolismo , Metástasis de la Neoplasia/genética , Transducción de Señal/fisiologíaRESUMEN
PURPOSE: Behçet's disease (BD) is a complex disorder affecting multiple systems and organs, and gastrointestinal BD is poorly understood. We aimed to identify factors influencing the long-term outcomes of patients with gastrointestinal BD. METHODS: Consecutive patients with gastrointestinal BD were analyzed retrospectively. Data on the following clinical characteristics were collected: sex, age at diagnosis, symptoms, endoscopic findings, medical treatments, and surgery. Mucosal healing and surgical rates at 1, 2, and 5 years were evaluated. Log-rank test and Cox proportional hazards regression models were used to evaluate the factors affecting long-term outcomes. FINDINGS: Baseline data of 175 patients with gastrointestinal BD were included. The mean (SD) age at diagnosis was 38.3 (12.9) years. The typical clinical symptoms were oral ulcer (72.6%), abdominal pain (71.4%), and weight loss (41.1%). The most commonly involved location was the ileocecum; isolated oval ulcer was the most common ulcer type. Seventeen patients (9.7%) underwent 18 surgeries after inclusion. The cumulative surgical rates were 8.6% (n/N = 15/175), 8.6% (n/N = 15/175), and 9.1% (n/N = 16/175) in 1, 2, and 5 years, respectively. Data from 101 patients who underwent at least 2 endoscopies were included in the analysis for mucosal healing. Kaplan-Meier curve showed that the cumulative mucosal healing rates at 1, 2, and 5 years were 34.7% (n/N = 35/101), 41.6% (n/N = 42/101), and 61.4% (n/N = 62/101), respectively. We compared cumulative mucosal healing rates between 4 treatment groups, including 5-aminosalicylic acid (3% [n/N = 3/101]), mono-immunosuppressant (31.7% [n/N = 32/101]), combined therapy (36.6% [n/N = 37/101]), and escalation therapy (28.7% [n/N = 29/101]), and found that mono-immunosuppressant achieved earlier mucosal healing than combined therapy (P = 0.0008) and escalation therapy (P = 0.0008). The univariate analysis showed that moderate to severe disease activity (P = 0.013, P = 0.004), diameter of the maximal ulcer >4 cm (P = 0.002), and nonsimple esophageal involvement (P < 0.001) were risk factors, and number of ulcers between 2 and 5 was the protective factor of mucosal healing (P = 0.001). Multivariate regression analysis indicated that nonsimple esophageal involvement (P < 0.001) and the maximal ulcer >4 cm (P = 0.041) were independent risk factors of mucosal healing. IMPLICATIONS: Most patients with gastrointestinal BD need long-term treatment to achieve mucosal healing. The location and size of ulcers have a significant impact on the mucosal healing of gastrointestinal BD.
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Síndrome de Behçet , Enfermedades Gastrointestinales , Humanos , Adulto , Úlcera/etiología , Úlcera/cirugía , Úlcera/diagnóstico , Estudios Retrospectivos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Behçet/cirugía , Enfermedades Gastrointestinales/etiología , China/epidemiologíaRESUMEN
Background: Transmural healing (TH) has emerged as a potential treatment goal for Crohn's disease (CD). However, further research is needed to confirm its benefits and risk factors associated with TH remain unclear. Objectives: We aimed to assess the value of TH based on magnetic resonance enterography (MRE) in Chinese CD patients regarding the long-term outcomes and its associated factors. Design: Retrospective, observational cohort study. Methods: Patients with CD diagnosed by colonoscopy and MRE examination between 2015 and 2022 were included. All patients were evaluated with endoscopy together with MRE within 6-12 months after baseline and followed up for at least 6 months after evaluation. The primary endpoint was the occurrence of major outcomes during the follow-up, including drug escalation, hospitalization, and surgery. The cumulative probabilities of major outcomes were calculated using Kaplan-Meier survival curves. Logistic regression analyses were used to predict TH within 6-12 months after baseline. Results: A total of 175 patients were included in the study. Of these, 69 (39.4%) patients achieved mucosal healing (MH), but only 34 (19.4%) of them achieved TH. The median follow-up duration was 17.4 months (interquartile range, 11.6-25.5), and major outcomes occurred in 58.3% of patients. A lower occurrence rate of major outcomes was noted in patients who achieved TH than in those who achieved MH only (p = 0.012). The baseline lymphocyte/C-reactive protein ratio (LCR) [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.50; p = 0.039] and bowel wall thickness (BWT) (OR, 0.72; 95% CI, 0.59-0.90; p = 0.003) were independent predictors associated with TH. According to multivariate Cox regression analysis, low LCR [hazard ratio (HR), 2.34; 95% CI, 1.51-3.64; p < 0.001], and no healing (HR, 5.45; 95% CI, 2.28-13.00; p < 0.001) were associated with an increased risk of major outcomes. Conclusion: Patients with CD who achieved TH showed improved prognosis compared to those who achieved MH only. Baseline LCR and BWT might predict TH.
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INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.
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Enfermedad de Crohn , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/fisiopatología , Enfermedad de Crohn/diagnóstico , Diagnóstico por Imagen de Elasticidad/métodos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Adulto Joven , Persona de Mediana Edad , Nomogramas , Adolescente , Intestinos/diagnóstico por imagen , Intestinos/fisiopatología , Valor Predictivo de las PruebasRESUMEN
Crohn's disease (CD) is a chronic inflammatory disease that leads to intestinal stricture in nearly 35% of cases within 10 years of initial diagnosis. The unknown pathogenesis, lack of universally accepted criteria, and absence of an effective management approach remain unconquered challenges in structuring CD. The pathogenesis of stricturing CD involves intricate interactions between factors such as immune cell dysbiosis, fibroblast activation, and microecology imbalance. New techniques such as single-cell sequencing provide a fresh perspective. Non-invasive diagnostic tools such as serum biomarkers and novel cross-sectional imaging techniques offer a precise understanding of intestinal fibrostenosis. Here, we provide a timely and comprehensive review of the worthy advancements in intestinal strictures in 2023, aiming to dispense cutting-edge information regarding fibrosis and to build a cornerstone for researchers and clinicians to make greater progress in the field of intestinal strictures.
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Enfermedad de Crohn , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Humanos , Constricción Patológica/etiología , Obstrucción Intestinal/etiología , Fibrosis , Intestinos/patología , Biomarcadores/sangre , Disbiosis/inmunología , Disbiosis/complicacionesRESUMEN
Purpose: To construct a risk assessment model for forecasting the likelihood of myopia in elementary school students. Design: A cross-sectional study. Methods: This study utilized convenient sampling and questionnaire survey to collect data from eligible elementary students and their parents during the coronavirus disease 2019 (COVID-19) pandemic period from March to December 2020. The data were divided into training and testing sets in a 7:3 ratio. Lasso regression was employed to screen variables for inclusion in the model to establish a generalized linear model, with a nomogram model as the final result. Results: The study included 1139 elementary students, comprising 54.5 % male and 45.5 % female participants. A total of 37 variables were obtained, which were analyzed using lasso regression. Cross-validation revealed that the best lambda value was 0.04201788. Five variables affecting myopia were identified: three risk and two protective factors. The three risk factors were student age (OR = 1.32), family location (urban vs. rural, OR = 2.33), and parents' occupation (compared with farmer: worker, OR = 2.03; teacher, OR = 1.62; medical worker, OR = 5.64; self-employed, OR = 1.78; civil servant, OR = 1.65; company employee, OR = 1.45; service industries, OR = 3.38; and others, OR = 3.20). The two protective factors were eye distance score (OR = 0.83) and eye health exercise score (OR = 0.95). The model was verified and showed good accuracy with an AUC of 0.778 and Brier score of 0.122 in addition to satisfactory clinical effects. Conclusions: The model effectively predicted the risk of myopia in elementary school students during the COVID-19 pandemic. Using this model, high-risk groups can be identified to provide a foundation for early intervention and follow-up, thereby reducing the incidence of myopia in this population.