Dry age-related macular degeneration classification from optical coherence tomography images based on ensemble deep learning architecture.

Background: Dry age-related macular degeneration (AMD) is a retinal disease, which has been the third leading cause of vision loss. But current AMD classification technologies did not focus on the classification of early stage. This study aimed to develop a deep learning architecture to improve the classification accuracy of dry AMD, through the analysis of optical coherence tomography (OCT) images. Methods: We put forward an ensemble deep learning architecture which integrated four different convolution neural networks including ResNet50, EfficientNetB4, MobileNetV3 and Xception. All networks were pre-trained and fine-tuned. Then diverse convolution neural networks were combined. To classify OCT images, the proposed architecture was trained on the dataset from Shenyang Aier Excellence Hospital. The number of original images was 4,096 from 1,310 patients. After rotation and flipping operations, the dataset consisting of 16,384 retinal OCT images could be established. Results: Evaluation and comparison obtained from three-fold cross-validation were used to show the advantage of the proposed architecture. Four metrics were applied to compare the performance of each base model. Moreover, different combination strategies were also compared to validate the merit of the proposed architecture. The results demonstrated that the proposed architecture could categorize various stages of AMD. Moreover, the proposed network could improve the classification performance of nascent geographic atrophy (nGA). Conclusion: In this article, an ensemble deep learning was proposed to classify dry AMD progression stages. The performance of the proposed architecture produced promising classification results which showed its advantage to provide global diagnosis for early AMD screening. The classification performance demonstrated its potential for individualized treatment plans for patients with AMD.

Nonlinear association between alanine aminotransferase to high-density lipoprotein cholesterol ratio and risk of gestational diabetes mellitus.

Previous studies have indicated a potential association between the alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) ratio and the risk of Type 2 Diabetes Mellitus, but its relation with gestational diabetes mellitus (GDM) remains uncertain. This study aims to investigate the correlation between the ALT/HDL-C ratio in early pregnancy and the risk of GDM. This study is a secondary analysis based on an open-source cohort study. A total of 590 single pregnant women attending two hospitals in Korea up to 14 weeks gestation were included between November 2014 and July 2016. Logistic regression analysis, subgroup analysis, and smooth curve fitting were employed to explore the association between the ALT/HDL-C ratio and GDM risk. The predictive capability of the ALT/HDL-C ratio for GDM was assessed using ROC curve analysis. The average age of participants was 32.06 ± 3.80 years, with a GDM incidence rate of 6.27%. Multifactorial logistic regression analysis revealed that the serum ALT/HDL-C ratio is an independent influencing factor for GDM (OR = 1.08, 95% CI: 1.02-1.16). Furthermore, a non-linear relationship between the ALT/HDL-C ratio and GDM risk was observed, with a turning point at 5.51. The effect size (OR) on the left and right sides of the turning point were 0.75 (95% CI: 0.37-1.59) and 1.55 (95% CI: 1.18-2.00), respectively. Additionally, when combined with age, pre-pregnancy body mass index, parity, and insulin resistance index in a prediction model for GDM, the ALT/HDL-C ratio demonstrated improved sensitivity of prediction by reaching up to 67.6%, specificity of prediction by reaching up to 87.3%, and an area under curve value of 0.819 (95%CI: 0.743-0.894). In early pregnancy, the serum ALT/HDL-C ratio shows a positive correlation with maternal risk in a nonlinear manner. The combination of ALT/HDL-C ratio with maternal characteristics and metabolic indicators provides good predictive value for GDM. This study may facilitate optimization of GDM prevention in pregnant women and enable timely and effective intervention to enhance their prognosis.

Acute effects of ambient nitrogen dioxide pollution on outpatient visits for neurological diseases in Xinxiang, China.

BACKGROUND: Accumulating evidence suggests that exposure to air pollution acts as a potential trigger for neurological diseases (NDs), yet the current knowledge regarding the impact of ambient nitrogen dioxide (NO2) on the patients with NDs remains limited. In this study, we conducted a time-series study to evaluate the association between short-term exposure to NO2 and hospital visits for NDs in Xinxiang, China. METHODS: An over-dispersed Poisson generalized additive model was used to analyze the association between ambient NO2 concentrations and daily outpatient visits for NDs from January 1, 2015 to December 31, 2017. The model adjusted for meteorological factors, temporal trends, day of the week, and public holidays. The concentrations of air pollutants were collected from four air quality stations in Xinxiang. RESULTS: A total of 38, 865 outpatient visits for NDs were retrieved during the study period. 86.5% of the patients were below the age of 65 years. It was revealed that a 10 µg/m3 increase in NO2 at lag 0 was associated with a significant rise of 1.50% (95% CI: 0.45-2.56%) in outpatient visits for NDs, which was stronger during the cold season. However, the overall results from stratified analyses did not reach statistical significance. CONCLUSIONS: Short-term exposure to NO2 is associated with increased outpatient visits for NDs. These findings underscore the need for implementing mitigating measures to reduce the neurological health effects of air pollutants.

Leg Attachment Devices of Tiger Beetles (Coleoptera, Cicindelidae) and Their Relationship to Their Habitat Preferences.

The ability of many insects to adhere vertically or even upside down to smooth substrates is closely related to the morphology and distribution of the adhesive structures on their legs. During locomotion, the legs are in direct contact with different substrates, and it is hypothesized that the adhesive structures have been evolved as an adaption to smooth substrates in specific environments. To investigate whether there is a relationship between the presence of adhesive structures and the combined effects of different environments and mating behavior, we compared five species of tiger beetles belonging to two tribes living in arboreal and non-arboreal environments, respectively. In three non-arboreal species, we found a specific type of adhesive structure consisting of elongated spoon-like setae present on the protarsi of males but absent on the male meso- and metatarsi and on females. In Tricondyla pulchripes, an arboreal species living on stems, we found three types of adhesive setae on male protarsi, while only two types of setae were found on male meso- and metatarsi and on females. In Neocollyris linearis, an arboreal species living on leaves, we found three types of adhesive setae on male pro-, meso- and meta-tarsi but only two types of adhesive setae on females. The adaptive evolution of these adhesive structures was probably driven by the selective pressures of both mating behavior and the presence of smooth substrates in the respective environments. It is discussed that the adhesive structures in tiger beetles may be an adaptive evolutionary response to the plant surfaces and may play an important role in species differentiation.

Quantifying Bevacizumab Efficacy in Recurrent Respiratory Papillomatosis.

OBJECTIVES: To develop and validate a novel method for quantifying the efficacy of Bevacizumab (Bev) in treating Recurrent Respiratory Papillomatosis (RRP), and to evaluate the clinical outcomes of a three-dose Bev induction therapy followed by surgical intervention. METHODS: Twenty-one RRP patients treated with a three-dose Bev regimen were included. A novel efficacy evaluation method using ImageJ software was developed to calculate the standardized lesion volume from laryngoscopic images. This was compared with the Derkay score. Clinical outcomes, including reduction rate, cumulative reduction rate, efficacy grading, recurrence, and adverse reactions, were analyzed. RESULTS: In the study cohort, the reduction rate was significantly higher after the first treatment compared with subsequent treatments. The overall response rate increased from 75% after the first treatment to 100% after the third. Among patients with localized lesions who underwent surgery, 76% experienced recurrence with a mean recurrence time of 114.23 days. Most recurrent lesions were smaller than at baseline. Adverse reactions included increased blood pressure in seven patients, which resolved without intervention. The new method showed a significant positive correlation with the Derkay score. CONCLUSION: In conclusion, based on the above findings, systemic Bev treatment for RRP is a safe and effective therapeutic approach, though further research is needed. Moreover, the new efficacy evaluation method we developed can significantly aid in studying the effectiveness of Bev treatment for RRP. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.

The current role of dendritic cells in the progression and treatment of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses. As a crucial component of the immune system, DCs have a pivotal role in the pathogenesis and clinical treatment of CRC. DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response. However, the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment. This review systematically elucidates the specific characteristics and functions of different DC subsets, as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment. Moreover, how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed, which will provide new perspectives and approaches for immunotherapy in patients with CRC.

Identifying polyamine related biomarkers in diagnosis and treatment of ulcerative colitis by integrating bulk and single-cell sequencing data.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.

Adverse events related to neuromuscular blocking agents: a disproportionality analysis of the FDA adverse event reporting system.

Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in "cardiac disorders," "immune system disorders," "respiratory, thoracic and mediastinal disorders" and "vascular disorders." At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study.

Effectiveness of surgery combined with photodynamic therapy for recurrent respiratory papillomatosis.

OBJECTIVE: This study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). METHODS: Review the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. RESULTS: A total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. CONCLUSION: In conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).

Genetic switch selectively kills hepatocellular carcinoma cell based on microRNA and tissue-specific promoter.

The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.

miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and Western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin, and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

Effects of Cr Addition on the Microstructure and Mechanical Properties of an Al-Si-Cu-Mg Alloy.

The effects of chromium (Cr) addition ranging 0.1-0.3 wt.% on the microstructure and mechanical properties of Al-7Si-4Cu-0.25Mg (wt.%) alloy have been investigated. The cast Cr-free alloy consisted of α-Al, eutectic Si, Q-Al5Mg8Cu2Si6 and θ-Al2Cu phases. Doping of Cr resulted in the appearance of a polyhedron-shaped α-Al13Cr4Si4 phase with a cubic structure. The Al13Cr4Si4 particles were found to embed with Al2Cu blocks and bring about size reduction for the Al2Cu blocks. The area fraction of Al13Cr4Si4 monotonously increased with Cr content. After T6 treatment, the Al2Cu blocks almost fully dissolved and transformed to θ'-Al2Cu precipitates in the Cr-containing alloys. TEM observation revealed relatively large-sized θ' precipitates attached to Al13Cr4Si4 dispersoids. The Cr-containing alloys showed impressive mechanical properties, with the peak strength up to 452 MPa at room temperature. The ductility exhibited an increasing trend with Cr content, but the strength dropped dramatically when the Cr content reached 0.3 wt.%. It is suggested that the strength contribution from the Al13Cr4Si4 phase is limited, especially at an elevated temperature.

Roles of alcohol dehydrogenase 1 in the biological activities of Candida albicans.

Candida albicans stands as the foremost prevalent human commensal pathogen and a significant contributor to nosocomial fungal infections. In the metabolism of C. albicans, alcohol dehydrogenase 1 (Adh1) is one of the important enzymes that converts acetaldehyde produced by pyruvate decarboxylation into ethanol at the end of glycolysis. Leveraging the foundational processes of alcoholic fermentation, Adh1 plays an active role in multiple biological phenomena, including biofilm formation, interactions between different species, the development of drug resistance, and the potential initiation of gastrointestinal cancer. Additionally, Adh1 within C. albicans has demonstrated associations with regulating the cell cycle, stress responses, and various intracellular states. Furthermore, Adh1 is extracellularly localized on the cell wall surface, where it plays roles in processes such as tissue invasion and host immune responses. Drawing from an analysis of ADH1 gene structure, expression patterns, and fundamental functions, this review elucidates the intricate connections between Adh1 and various biological processes within C. albicans, underscoring its potential implications for the prevention, diagnosis, and treatment of candidiasis.

Both intra- and peri-tumoral radiomics signatures can be used to predict lymphatic vascular space invasion and lymphatic metastasis positive status from endometrial cancer MR imaging.

OBJECTIVES: To identify lymphatic vascular space invasion (LVSI) and lymphatic node metastasis (LNM) status of endometrial cancer (EC) patients, using radiomics based on MRI images. METHODS: Five hundred and ninety-eight EC patients between January 2015 and September 2020 from two institutions were retrospectively included. Tumoral regions on DWI, T1CE, and T2W images were manually outlined. Radiomics features were extracted from tumor region and peri-tumor region of different thicknesses. We established sub-models to select features from each smaller category. Using this method, we separately constructed radiomic signatures for intra-tumoral and peri-tumoral images using different sequences. We constructed intra-tumoral and peri-tumoral models by combining their features, and a multi-sequence model by combining logits. Models were trained with 397 patients and validated with 170 internal and 31 external patients. RESULTS: For LVSI positive/LNM positive status identification, the multi-parameter MRI radiomics model achieved the area under curve (AUC) values of 0.771 (95%CI: [0.692-0.849])/0.801 (95%CI: [0.704, 0.898]) and 0.864 (95%CI: [0.728-1.000])/0.976 (95%CI: [0.919, 1.000]) in internal and external test cohorts, respectively. CONCLUSIONS: Intra-tumoral and peri-tumoral radiomics signatures based on mpMRI can both be used to identify LVSI or LNM status in EC patients non-invasively. Further studies on LVSI and LNM should pay attention to both of them.

Evolutionary radiation strategy revealed in the Scarabaeidae with evidence of continuous spatiotemporal morphology and phylogenesis.

Evolutionary biology faces the important challenge of determining how to interpret the relationship between selection pressures and evolutionary radiation. The lack of morphological evidence on cross-species research adds to difficulty of this challenge. We proposed a new paradigm for evaluating the evolution of branches through changes in characters on continuous spatiotemporal scales, for better interpreting the impact of biotic/abiotic drivers on the evolutionary radiation. It reveals a causal link between morphological changes and selective pressures: consistent deformation signals for all tested characters on timeline, which provided strong support for the evolutionary hypothesis of relationship between scarabs and biotic/abiotic drivers; the evolutionary strategies under niche differentiation, which were manifested in the responsiveness degree of functional morphological characters with different selection pressure. This morphological information-driven integrative approach sheds light on the mechanism of macroevolution under different selection pressures and is applicable to more biodiversity research.

Associations between renal function, hippocampal volume, and cognitive impairment in 544 outpatients.

Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants.

Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2 (ERBB2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase (ALK/ROS1), neurotrophic receptor tyrosine kinases (NTRKs), ret proto-oncogene (RET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

A novel lncRNA associated with the prognosis of patients with colorectal cancer resists apoptosis through the LYN/BCL-2 pathway.

PURPOSE: We found a novel lncRNA named lncAC138150.2 related to the overall survival and staging of patients with colorectal cancer (CRC) by bioinformatic analysis using data from the Cancer Genome Atlas (TCGA), and the study aimed to elucidate the function of lncAC138150.2 and underlying mechanisms. METHODS: Target molecules were knocked down by transfection with antisense oligonucleotides (ASOs), siRNAs, or lentiviruses and overexpressed by transfection with plasmids. The function of lncAC138150.2 was determined using histological, cytological, and molecular biology methods. The underlying mechanism of lncAC138150.2 function was investigated using RNA-seq, bioinformatics analysis, and molecular biology methods. RESULTS: The expression of lncAC138150.2 was increased in colorectal tissues compared with paired normal tissues. The lncAC138150.2 knockdown increased apoptosis but did not change the cell proliferation, cell cycle distribution, or cell migration ability of CRC cells, while lncAC138150.2 overexpression decreased CRC apoptosis. lncAC138150.2 was mainly located in the cell nucleus, and each lncAC138150.2 transcript knockdown increased CRC apoptosis. BCL-2 pathway was significantly altered in apoptosis induced by lncAC138150.2 knockdown, which was alleviated by BAX knockdown. The expression of LYN was significantly decreased with lncAC138150.2 knockdown, LYN knockdown increased CRC apoptosis, and its overexpression completely alleviated CRC apoptosis induced by lncAC138150.2 knockdown. CONCLUSION: lncAC138150.2 significantly inhibited CRC apoptosis and affected the prognosis of patients with CRC, through the LYN/BCL-2 pathway.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Background: Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. Methods: All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. Results: A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Conclusion: Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.