From 2D to 3D: Automatic measurement of the Cobb angle in adolescent idiopathic scoliosis with the weight-bearing 3D imaging.

BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) necessitates accurate spinal curvature assessment for effective clinical management. Traditional two-dimensional (2D) Cobb angle measurements have been the standard, but the emergence of three-dimensional (3D) automatic measurement techniques, such as those using weight-bearing 3D imaging (WR3D), presents an opportunity to enhance the accuracy and comprehensiveness of AIS evaluation. PURPOSE: This study aimed to compare traditional 2D Cobb angle measurements with 3D automatic measurements utilizing the WR3D imaging technique in patients with AIS. STUDY DESIGN/SETTING: A cohort of 53 AIS patients was recruited, encompassing 88 spinal curves, for comparative analysis. PATIENT SAMPLE: The patient sample consisted of 53 individuals diagnosed with AIS. OUTCOME MEASURES: Cobb angles were calculated using the conventional 2D method and three different 3D methods: the Analytical Method (AM), the Plane Intersecting Method (PIM), and the Plane Projection Method (PPM). METHODS: The 2D cobb angle was manually measured by 3 experienced clinicians with 2D frontal whole-spine radiographs. For 3D cobb angle measurements, the spine and femoral heads were segmented from the WR3D images using a 3D-UNet deep-learning model, and the automatic calculations of the angles were performed with the 3D slicer software. RESULTS: AM and PIM estimates were found to be significantly larger than 2D measurements. Conversely, PPM results showed no statistical difference compared to the 2D method. These findings were consistent in a subgroup analysis based on 2D Cobb angles. CONCLUSION: Each 3D measurement method provides a unique assessment of spinal curvature, with PPM offering values closely resembling 2D measurements, while AM and PIM yield larger estimations. The utilization of WR3D technology alongside deep learning segmentation ensures accuracy and efficiency in comparative analyses. However, additional studies, particularly involving patients with severe curves, are required to validate and expand on these results. This study emphasizes the importance of selecting an appropriate measurement method considering the imaging modality and clinical context when assessing AIS, and it also underlines the need for continuous refinement of these techniques for optimal use in clinical decision-making and patient management.

Investigating the Synergistic Effects of Amitriptyline and H. Pylori Eradication on Depressive-like Behaviors and Inflammatory Cytokines in Mice.

BACKGROUND: Recent research has highlighted the potential role of Helicobacter pylori in the pathogenesis of psychiatric disorders. This study aimed to evaluate the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in a mouse model. METHODS: Male C57BL/6 mice were divided into four groups: control, H. pylori infection, antidepressant treatment, and combined treatment. H. pylori infection was induced by oral gavage with a clinically relevant strain, and the antidepressant drug was administered via intraperitoneal injections. Behavioral tests including the forced swim test, sucrose preference test, and open field test were conducted to assess depressive-like behaviors and locomotor activity. RESULTS: The study demonstrated that H. pylori infection induced depressive-like behaviors in mice, as evidenced by increased immobility time in the forced swim test and reduced sucrose preference. Antidepressant treatment alone partially ameliorated these behavioral changes. Strikingly, the combined treatment of the antidepressant drug and H. pylori eradication therapy led to a significantly greater reduction in depressive-like behaviors compared to either treatment alone. Furthermore, the combined treatment group exhibited increased locomotor activity in the open field test, suggesting a potential improvement in overall psychomotor functioning. ELISA assays revealed alterations in inflammatory cytokines in the H. pylori-infected mice, which were partially attenuated by the combined treatment. CONCLUSION: The study provides novel evidence for the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in alleviating depressive-like behaviors in a mouse model.

Elevated microRNA-214-3p level ameliorates neuroinflammation after spinal cord ischemia-reperfusion injury by inhibiting Nmb/Cav3.2 pathway.

BACKGROUND: Neuromedin B (Nmb) plays a pivotal role in the transmission of neuroinflammation, particularly during spinal cord ischemia-reperfusion injury (SCII). However, the detailed molecular mechanisms underlying this process remain elusive. METHODS: The SCII model was established by clamping the abdominal aorta of male Sprague-Dawley (SD) rats for 60 min. The protein expression levels of Nmb, Cav3.2, and IL-1ß were detected by Western blotting, while miR-214-3p expression was quantified by qRT-PCR. The targeted regulation between miR-214-3p and Nmb was investigated using a dual-luciferase reporter gene assay. The cellular localization of Nmb and Cav3.2 with cell-specific markers was visualized by immunofluorescence staining. The specific roles of miR-214-3p on the Nmb/Cav3.2 interactions in SCII-injured rats were explored by intrathecal injection of Cav3.2-siRNA, PD168368 (a specific NmbR inhibitor) and synthetic miR-214-3p agomir and antagomir in separate experiments. Additionally, hind-limb motor function was evaluated using the modified Tarlov scores. RESULTS: Compared to the Sham group, the protein expression levels of Nmb, Cav3.2, and the proinflammatory factor Interleukin(IL)-1ß were significantly elevated at 24 h post-SCII. Intrathecal injection of PD168368 and Cav3.2-siRNA significantly suppressed the expression of Cav3.2 and IL-1ß compared to the SCII group. The miRDB database and dual-luciferase reporter gene assay identified Nmb as a direct target of miR-214-3p. As expected, in vivo overexpression of miR-214-3p by agomir-214-3p pretreatment significantly inhibited the increases in Nmb, Cav3.2 and IL-1ß expression and improved lower limb motor function in SCII-injured rats, while antagomiR-214-3p pretreatment reversed these effects. CONCLUSIONS: Nmb protein levels positively correlated with Cav3.2 expression in SCII rats. Upregulating miR-214-3p ameliorated hind-limb motor function and protected against neuroinflammation via inhibiting the aberrant Nmb/Cav3.2 interactions and downstream IL-1ß release. These findings provide novel therapeutic targets for clinical prevention and treatment of SCII.

The association between atherogenic index of plasma and metabolic dysfunction-associated fatty liver disease as detected by FibroScan / Asociación entre el índice aterogénico del plasma y la enfermedad hepática grasa asociadaa disfunción metabólica detectada por FibroScan

Objectives: this study aimed to explore the potential of the atherogenic index of plasma (AIP) as a predictor of metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: a cross-sectional study, including data from 4473 participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2018, was performed. A control attenuation parameter (CAP) ≥ 285 dB/m was used to confirm hepatic steatosis. Degrees of liver stiffness were confirmed according to liver stiffness measurement (LSM). Weighted multivariate logistic regression models were used to assess the association between AIP and the risk for MAFLD and liver fibrosis. Finally, receiver operating characteristic (ROC) curve analysis was used to test the accuracy of AIP in predicting MAFLD. Results: the association between AIP and the prevalence of MAFLD was positive in all three multivariate logistic regression models (model 1, odds ratio (OR), 18.2 (95 % confidence interval (CI), 14.4-23.1); model 2, OR, 17.0 (95 % CI, 13.3-21.8); model 3, OR, 5.2 (95 % CI, 3.9-7.0)). Moreover, this positive relationship was found to be significant in patients of different sexes and whether they had diabetes. However, no significant differences were observed between AIP and significant fibrosis or cirrhosis as assessed by different liver fibrosis indices. Finally, ROC curve analysis demonstrated that the AIP index also demonstrated positive diagnostic utility (area under the ROC curve, 0.733 (95 % CI, 0.718-0.747); p < 0.001). Conclusion: This study revealed a positive association between AIP and MAFLD among American adults. Furthermore, this association persisted in different sexes and whether they had diabetes.(AU)

Objetivos: este estudio tuvo como objetivo explorar el potencial del índice aterogénico del plasma (AIP) como predictor de enfermedad hepática grasa asociada a disfunción metabólica (MAFLD). Métodos: se realizó un estudio transversal que incluyó datos de 4473 participantes de la encuesta nacional de exémenes de salud y nutrición (NHANES) 2017-2018. Se utilizó un parámetro de atenuación de control (CAP) ≥ 285 dB/m para confirmar la esteatosis hepática. Los grados de rigidez hepática se confirmaron de acuerdo con la medición de rigidez hepática (LSM). Se utilizaron modelos de regresión logística multiva-riponderponderados para evaluar la asociación entre AIP y el riesgo de MAFLD y fibrosis hepática. Por último, se utilizó el análisis de la curva ROC para probar la precisión de la AIP en la predicción de la MAFLD.Resultados: la asociación entre AIP y prevalencia de MAFLD fue positiva en los tres modelos de regresión logística multivariable (modelo 1, odds ratio (OR): 18,2 (intervalo de confianza (IC) del 95 %: 14,4-23,1); Modelo 2, OR: 17,0 (IC del 95 %: 13,3-21,8); Modelo 3, OR: 5,2 (IC del 95 %: 3,9-7,0)). Además, esta relación positiva se encontró significativa en pacientes de diferentes sexos ya tuvieran o no diabetes. Sin embargo, no se observaron diferencias significativas entre la AIP y la fibrosis o cirrosis significativa evaluada por diferentes índices de fibrosis hepática. Finalmente, el análisis de la curva ROC demostró que el índice AIP también demostró utilidad diagnóstica positiva (área bajo la curva ROC = 0,733 (IC del 95 %: 0,718-0,747); p < 0,001). Conclusión: este estudio reveló una asociación positiva entre AIP y MAFLD en los adultos estadounidenses. Además, esta asociación persistióen los diferentes sexos ya tuvieran o no diabetes.(AU)

Conservative versus stent treatment for spontaneous isolated superior mesenteric artery dissection after the failure of initial 3 days' conservative treatment: A 10-year follow-up study.

OBJECTIVES: To compare the safety and effectiveness of conservative and stent treatment for spontaneous isolated superior mesenteric artery dissection (SISMAD) patients after the failure of initial 3 days' conservative treatment. METHODS: All newly diagnosed SISMAD patients between 2013 and 2017 were retrospectively reviewed. After the failure of 3 days' conservative treatment, all patients were recommended for stent treatment, but some patients refused to choose it. Their demographic, radiologic, and clinical data were compared. RESULTS: 57 patients were not improved after initial 3 days' conservative treatment. Among them, 19 patients were chose to receive stent placement and 38 patients were continually treated with conservative treatment. The median follow-up time was 92.0 (range 62.7-120.4) months. There were no bowel ischemia and arterial rupture. No significant difference was observed in clinical complete recovery (Conservative 31/38 vs Stent 12/19, p =.19) and hospitalization time (Conservative 8.3 ± 1.7 days vs Stent 7.2 ± 1.5 days, p =.59) between conservative and stent treatment groups. Significant statistical differences were found in radiological complete remodeling (6/38 vs 16/19, p < .01) and hospitalization expense (8662 ± 2886 China Yuan vs 32,935 ± 11,767 China Yuan, p < .01) between these two groups. CONCLUSIONS: Although undergoing the failure of initial 3 days' conservative treatment, continue conservative treatment still is safe and effective for SISMAD patients. Stent placement could be chosen as an alternative treatment, especially for patients potentially with bowel ischemia or arterial rupture.

Progress and challenges in the clinical evaluation of immune responses to respiratory mucosal vaccines.

INTRODUCTION: Following the coronavirus disease pandemic, respiratory mucosal vaccines that elicit both mucosal and systemic immune responses have garnered increasing attention. However, human physiological characteristics pose significant challenges in the evaluation of mucosal immunity, which directly impedes the development and application of respiratory mucosal vaccines. AREAS COVERED: This study summarizes the characteristics of immune responses in the respiratory mucosa and reviews the current status and challenges in evaluating immune response to respiratory mucosal vaccines. EXPERT OPINION: Secretory Immunoglobulin A (S-IgA) is a major effector molecule at mucosal sites and a commonly used indicator for evaluating respiratory mucosal vaccines. However, the unique physiological structure of the respiratory tract pose significant challenges for the clinical collection and detection of S-IgA. Therefore, it is imperative to develop a sampling method with high collection efficiency and acceptance, a sensitive detection method, reference materials for mucosal antibodies, and to establish a threshold for S-IgA that correlates with clinical protection. Sample collection is even more challenging when evaluating mucosal cell immunity. Therefore, a mucosal cell sampling method with high operability and high tolerance should be established. Targets of the circulatory system capable of reflecting mucosal cellular immunity should also be explored.

Hg16O12(NO3)6F2(H2O): A Mercury-Rich Nitrate Oxyfluoride with Diverse Triple-Coordinated Mercury-Based Units That Exhibits an Unparalleled [(Hg16O12F2(H2O))6+]∞ Cationic Framework and a Large Birefringence.

Designing new compounds based on anion regulation has been widely favored due to the production of diverse crystal structures and excellent optical properties. Here, a new nitrate oxyfluoride, Hg16O12(NO3)6F2(H2O), has been obtained through a hydrothermal reaction. It crystallizes in the centric Ibca space group and shows a novel three-dimensional [(Hg16O12F2(H2O))6+]∞ cationic framework composed of interconnected HgO2F, HgO3, and HgO2(H2O) units, with isolated NO3- groups as balanced anions to build the whole structure. Notably, the HgO2F and HgO2(H2O) units are first presented here among mercury (Hg)-based compounds. Additionally, Hg16O12(NO3)6F2(H2O) exhibits a large birefringence of 0.17 at 546 nm. This work enriches the multiformity of Hg-based compounds and provides a route for developing promising birefringent materials.

The mechanism of anthracene degradation by tryptophan -2,3-dioxygenase (T23D) in Comamonas testosteroni.

It is well known that anthracene is a persistent organic pollutant. Among the four natural polycyclic aromatic hydrocarbons (PAHs) degrading strains, Comamonas testosterone (CT1) was selected as the strain with the highest degradation efficiency. In the present study, prokaryotic transcriptome analysis of CT1 revealed an increase in a gene that encodes tryptophane-2,3-dioxygenase (T23D) in the anthracene and erythromycin groups compared to CK. Compared to the wild-type CT1 strain, anthracene degradation by the CtT23D knockout mutant (CT-M1) was significantly reduced. Compared to Escherichia coli (DH5α), CtT23D transformed DH5α (EC-M1) had a higher degradation efficiency for anthracene. The recombinant protein rT23D oxidized tryptophan at pH 7.0 and 37 °C with an enzyme activity of 2.42 ± 0.06 µmol min-1·mg-1 protein. In addition, gas chromatography-mass (GC-MS) analysis of anthracene degradation by EC-M1 and the purified rT23D revealed that 2-methyl-1-benzofuran-3-carbaldehyde is an anthracene metabolite, suggesting that it is a new pathway.

Differential Disruption of Glucose and Lipid Metabolism Induced by Phthalates in Human Hepatocytes and White Adipocytes.

Phthalic acid esters (PAEs), commonly used as plasticizers, are pervasive in the environment, leading to widespread human exposure. The association between phthalate exposure and metabolic disorders has been increasingly recognized, yet the precise biological mechanisms are not well-defined. In this study, we explored the effects of monoethylhexyl phthalate (MEHP) and monocyclohexyl phthalate (MCHP) on glucose and lipid metabolism in human hepatocytes and adipocytes. In hepatocytes, MEHP and MCHP were observed to enhance lipid uptake and accumulation in a dose-responsive manner, along with upregulating genes involved in lipid biosynthesis. Transcriptomic analysis indicated a broader impact of MEHP on hepatic gene expression relative to MCHP, but MCHP particularly promoted the expression of the gluconeogenesis key enzymes G6PC and FBP1. In adipocytes, MEHP and MCHP both increased lipid droplet formation, mimicking the effects of the Peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi). Transcriptomic analysis revealed that MEHP predominantly altered fatty acid metabolism pathways in mature adipocytes (MA), whereas MCHP exhibited less impact. Metabolic perturbations from MEHP and MCHP demonstrate shared activation of the PPARs pathway in hepatocytes and adipocytes, but the cell-type discrepancy might be attributed to the differential expression of PPARγ. Our results indicate that MEHP and MCHP disrupt glucose and lipid homeostasis in human liver and adipose through mechanisms that involve the PPAR and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways, highlighting the nuanced cellular responses to these environmental contaminants.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation.

OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study).

BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.

Dielectric Liquid Microlens Array with Tunable Focal Length Based on Microdroplet Array Created via Dip-Coating Method.

A dielectric liquid microlens array (LMA) with a tunable focal length was fabricated by using a microdroplet array generated through the dip-coating method. The process began with treating the octadecyltrichlorosilane (OTS) layer with selective UV/O3 irradiation for 20 min to establish a hydrophilic-hydrophobic patterning surface. The substrate was subsequently immersed in glycerol and then withdrawn at a constant rate to create a microdroplet array. Upon filling the cell with matching oil (SL5267) and placing it within a square array of a 200 µm diameter glycerol microdroplet array, the LMA was produced. The focal length ranged from approximately -0.96 to -0.3 mm within a voltage range of 0 to 60 Vrms. The glycerol microdroplets, characterized by their shapes, sizes, curvatures, and filling factors, can be precisely controlled by designing an OTS patterning or adjusting the dip-coating speed. This approach offers a rapid and high-throughput method for preparation. Our approach to fabricating tunable LMA offers several advantages, including simplicity of fabrication, uniform structural properties, cost-effectiveness, polarization independence, and excellent optical performance. These focus-tunable LMAs hold significant potential for applications in image processing, 3D displays, medical endoscopy, and military technologies.

The association between atherogenic index of plasma and metabolic dysfunction-associated fatty liver disease as detected by FibroScan.

Introduction: Objectives: this study aimed to explore the potential of the atherogenic index of plasma (AIP) as a predictor of metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: a cross-sectional study, including data from 4473 participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2018, was performed. A control attenuation parameter (CAP) ≥ 285 dB/m was used to confirm hepatic steatosis. Degrees of liver stiffness were confirmed according to liver stiffness measurement (LSM). Weighted multivariate logistic regression models were used to assess the association between AIP and the risk for MAFLD and liver fibrosis. Finally, receiver operating characteristic (ROC) curve analysis was used to test the accuracy of AIP in predicting MAFLD. Results: the association between AIP and the prevalence of MAFLD was positive in all three multivariate logistic regression models (model 1, odds ratio (OR), 18.2 (95 % confidence interval (CI), 14.4-23.1); model 2, OR, 17.0 (95 % CI, 13.3-21.8); model 3, OR, 5.2 (95 % CI, 3.9-7.0)). Moreover, this positive relationship was found to be significant in patients of different sexes and whether they had diabetes. However, no significant differences were observed between AIP and significant fibrosis or cirrhosis as assessed by different liver fibrosis indices. Finally, ROC curve analysis demonstrated that the AIP index also demonstrated positive diagnostic utility (area under the ROC curve, 0.733 (95 % CI, 0.718-0.747); p < 0.001). Conclusion: This study revealed a positive association between AIP and MAFLD among American adults. Furthermore, this association persisted in different sexes and whether they had diabetes.

Introducción: Objetivos: este estudio tuvo como objetivo explorar el potencial del índice aterogénico del plasma (AIP) como predictor de enfermedad hepática grasa asociada a disfunción metabólica (MAFLD). Métodos: se realizó un estudio transversal que incluyó datos de 4473 participantes de la encuesta nacional de exémenes de salud y nutrición (NHANES) 2017-2018. Se utilizó un parámetro de atenuación de control (CAP) ≥ 285 dB/m para confirmar la esteatosis hepática. Los grados de rigidez hepática se confirmaron de acuerdo con la medición de rigidez hepática (LSM). Se utilizaron modelos de regresión logística multivariponderponderados para evaluar la asociación entre AIP y el riesgo de MAFLD y fibrosis hepática. Por último, se utilizó el análisis de la curva ROC para probar la precisión de la AIP en la predicción de la MAFLD. Resultados: la asociación entre AIP y prevalencia de MAFLD fue positiva en los tres modelos de regresión logística multivariable (modelo 1, odds ratio (OR): 18,2 (intervalo de confianza (IC) del 95 %: 14,4-23,1); Modelo 2, OR: 17,0 (IC del 95 %: 13,3-21,8); Modelo 3, OR: 5,2 (IC del 95 %: 3,9-7,0)). Además, esta relación positiva se encontró significativa en pacientes de diferentes sexos ya tuvieran o no diabetes. Sin embargo, no se observaron diferencias significativas entre la AIP y la fibrosis o cirrosis significativa evaluada por diferentes índices de fibrosis hepática. Finalmente, el análisis de la curva ROC demostró que el índice AIP también demostró utilidad diagnóstica positiva (área bajo la curva ROC = 0,733 (IC del 95 %: 0,718-0,747); p < 0,001). Conclusión: este estudio reveló una asociación positiva entre AIP y MAFLD en los adultos estadounidenses. Además, esta asociación persistió en los diferentes sexos ya tuvieran o no diabetes.

Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis.

Objective: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis. Methods: We collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis. Results: The cytokine response in peripheral CD4+ T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified. Conclusion: We comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells' function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.

OGG1 prevents atherosclerosis-induced vascular endothelial cell injury through mediating DNA damage repair.

OBJECTIVE: This study was designed to investigate the role of 8-oxoguanine DNA glycosylase 1 (OGG1) in preventing atherosclerosis-induced vascular EC injury, thereby providing a theoretical basis for the exploration of drug targets and treatment methods for atherosclerosis. METHODS: Human umbilical vein cell line (EA.hy926) was treated with ox-LDL to construct an in vitro atherosclerotic cell model. pcDNA3.1-OGG1 was transfected into EA.hy926 cells to overexpress OGG1. qRT-PCR, CCK-8 assay, flow cytometry, oil red O staining, ELISA, comet assay and western blot were used to evaluate the OGG1 expression, viability, apoptosis level, lipid droplet content, 8-OHdG level and DNA damage of cells in each group. RESULTS: Compared with the Control group, ox-LDL stimulation of endothelial cells significantly decreased cell viability, promoted apoptosis and DNA damage, and increased intracellular levels of 8-OHdG and γH2AX, while decreasing protein levels of PPARγ, FASN, FABP4, RAD51 and POLB. However, overexpression of OGG1 can significantly inhibit ox-LDL damage to endothelial cells, promote lipid metabolism, decrease lipid droplet content, and improve DNA repair function. CONCLUSION: Over-expression of OGG1 improves DNA repair. Briefly, OGG1 over-expression enhances the DNA damage repair of ECs by regulating the expression levels of γH2AX, RAD51 and POLB, thereby enhancing cell viability and reducing apoptosis.

SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury.

BACKGROUND: Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a rat model of chronic constriction injury (CCI). METHODS: Sprague-Dawley rats were randomly grouped to establish CCI models. We examined the effects of SPOCK2 on pain hpersensitivity and spinal astrocyte activation after CCI-induced NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to reflects the pain behavioral degree. Molecular mechanisms involved in SPOCK2-mediated NP in vivo were examined by western blot analysis, immunofluorescence, immunohistochemistry, and co-immunoprecipitation. In addition, we examined the SPOCK2-mediated potential protein-protein interaction (PPI) in vitro coimmunoprecipitation (Co-IP) experiments. RESULTS: We founded the expression level of SPOCK2 in rat spinal cord was markedly increased after CCI-induced NP, while SPOCK2 downregulation could partially relieve pain caused by CCI. Our research showed that SPOCK2 expressed significantly increase in spinal astrocytes when CCI-induced NP. In addition, SPOCK2 could act as an upstream signaling molecule to regulate the activation of matrix metalloproteinase-2 (MMP-2), thus affecting astrocytic ERK1/2 activation and interleukin (IL)-1ß production in the development of NP. Moreover, in vitro coimmunoprecipitation (Co-IP) experiments showed that SPOCK2 could interact with membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14) to regulate MMP-2 activation by the SPARC extracellular (SPARC_EC) domain. CONCLUSIONS: Research shows that SPOCK2 can interact with MT1-MMP to regulate MMP-2 activation, thus affecting astrocytic ERK1/2 activation and IL-1ß production to achieve positive promotion of NP.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

Neuroprotective effects of a novel peptide through the Rho-integrin-Tie2 and PI3K/Akt pathways in experimental autoimmune encephalomyelitis model.

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvß3 and α5ß1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model. Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE. Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvß3, and α5ß1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16. Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.

Unveiling the role of KRAS in tumor immune microenvironment.

Kirsten rats sarcoma viral oncogene (KRAS), the first discovered human oncogene, has long been recognized as "undruggable". KRAS mutations frequently occur in multiple human cancers including non-small cell lung cancer(NSCLC), colorectal cancer(CRC) and pancreatic ductal adenocarcinoma(PDAC), functioning as a "molecule switch" determining the activation of various oncogenic signaling pathways. Except for its intrinsic pro-tumorigenic role, KRAS alteration also exhibits an unique immune signature characterized by elevated PD-L1 level and high tumor mutational burden(TMB). KRAS mutation shape an immune suppressive microenvironment by impeding effective T cells infiltration and recruiting suppressive immune cells including myeloid-derived suppressor cells(MDSCs), regulatory T cells(Tregs), cancer associated fibroblasts(CAFs). In immune checkpoint inhibitor(ICI) era, NSCLC patients with mutated KRAS tend to be more responsive to ICI than patients with intact KRAS. The hallmark for KRAS mutation is the existence of multiple kinds of co-mutations. Different types of co-alterations have distinct tumor microenvironment(TME) signatures and responses to ICI. TP53 co-mutation possess a "hot" TME and achieve higher response to immunotherapy while other loss of function mutation correlated with a "colder" TME and a poor outcome to ICI-based therapy. The groundbreaking discovery of KRAS G12C inhibitors significantly improved outcomes for this KRAS subtype even though efficacy was limited to NSCLC patients. KRAS G12C inhibitors also restore the suppressive TME, creating an opportunity for combinations with ICI. However, an inevitable challenge to KRAS inhibitors is drug resistance. Promising combination strategies such as combination with SHP2 is an approach deserve further exploration because of their immune modulatory effect.