Machine learning models to predict submucosal invasion in early gastric cancer based on endoscopy features and standardized color metrics.

Conventional endoscopy is widely used in the diagnosis of early gastric cancers (EGCs), but the graphical features were loosely defined and dependent on endoscopists' experience. We aim to establish a more accurate predictive model for infiltration depth of early gastric cancer including a standardized colorimetric system, which demonstrates promising clinical implication. A retrospective study of 718 EGC cases was performed. Clinical and pathological characteristics were included, and Commission Internationale de l'Eclariage (CIE) standard colorimetric system was used to evaluate the chromaticity of lesions. The predicting models were established in the derivation set using multivariate backward stepwise logistic regression, decision tree model, and random forest model. Logistic regression shows location, macroscopic type, length, marked margin elevation, WLI color difference and histological type are factors significantly independently associated with infiltration depth. In the decision tree model, margin elevation, lesion located in the lower 1/3 part, WLI a*color value, b*color value, and abnormal thickness in enhanced CT were selected, which achieved an AUROC of 0.810. A random forest model was established presenting the importance of each feature with an accuracy of 0.80, and an AUROC of 0.844. Quantified color metrics can improve the diagnostic precision in the invasion depth of EGC. We have developed a nomogram model using logistic regression and machine learning algorithms were also explored, which turned out to be helpful in decision-making progress.

Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing.

BACKGROUND: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. METHODS: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. RESULTS: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. CONCLUSIONS: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment.

The protective effect of puerarin-loaded mesoporous silicon nanoparticles on alcoholic hepatitis through mTOR-mediated autophagy pathway.

Puerarin, a bioactive flavone compound isolated from Pueraria (Wild.), provides hepatoprotection by anti-inflammatory, anti-alcoholism, and regulating mechanistic target of rapamycin (mTOR). Building evidence suggests that the activation of mTOR reduces liver injuries associated with alcohol consumption and metabolism. However, the poor water solubility, low bioavailability, and short half-life of puerarin hinder its clinical application. The utility of mesoporous silicon nanoparticles (MSNs) can improve traditional Chinese medicine limitations. Stober methods were used to fabricate MSNs@Pue, and the size, zeta potentials and drug encapsulation efficiency were characterized by a series of analytical methods. IVIS Imaging System demonstrated liver-targeted bio-distribution, and then high-throughput sequencing, immunoproteomics and ultrastructure methods indicated autophagy related protective mechanism, followed by curative effect evaluation for the treatment efficacy. An acute-on chronic ethanol-drinking according to Gao-binge model induced alcoholic hepatitis (AH) pathology and resulted in hepatic hyper-autophagy, which was improved with MSNs@Pue administration (puerarin: 30 mM, 42 mg/kg; intravenously [i.v.]). Ethanol-fed mice were found to have increased expression of autophagy-related proteins (Atg3, Atg7, LC3 and p62). In contrast, MSNs@Pue administration significantly decreased the expression of these proteins and alleviated fatty droplets infiltration in damaged liver. Furthermore, acute-on-chronic ethanol feeding also resulted in the activiation of ERK activation and mTOR expression, which were reversed with MSNs@Pue administration and better than the usage of puerarin alone. Results point to MSNs@Pue mediated ERK/mTOR signaling pathway activation as a possible protective strategy to improve AH, which provides a strategy and evidence for treating liver disease using an MSN delivery system.

The mitophagosome, a novel ultrastructure of mitophagy in the alcoholic steatohepatitis mouse model: a transmission electron microscope study.

Acute alcohol feeding can activate autophagy and promotes the selection of autophagic vacuoles in the mitochondria, which is a key process regulating the occurrence and progression of alcohol steatohepatitis (ASH). In this study, ASH mice expressed more autophagy-associated proteins than healthy controls, as revealed by immunohistochemistry. In addition, transmission electron microscopy (TEM) detected a unique autophagy ultrastructure in ASH mouse liver cells, consisting of a large vesicle fused directly with mitochondria, which differed from the classical pattern. This novel type of mitophagy may provide a new avenue for a protective mechanism targeting mitophagy, which would benefit patients with ASH.Abbreviations: ASH: alcoholic steatohepatitis; ALD: Alcoholic liver disease; ALT: alanine aminotransferase; AST: aspartate aminotransferase; HE: hematoxylin and eosin; TEM: transmission electron microscope; LC3: microtubule-associated protein 1 light chain 3; SQSTM1/p62: sequestosome 1; UQCRC2: ubiquinol-cytochrome c reductase core protein 2; PINK1: PTEN induced kinase 1; AMPK: AMP-activated protein kinase.

Assessment of clinical activity and severity using serum ANCA and ASCA antibodies in patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) with unknown etiology. The lack of specific clinical manifestations, standard diagnostic criteria, objective and accurate indicators to the severity of the disease and the efficacy of the treatment, often results in difficulties in diagnosis and timely treatment of UC. Therefore, there is a need to develop a clinically suitable serum biomarker assay with high specificity and sensitivity. OBJECTIVE AND METHODS: To explore the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-saccharomyces cerevisiae antibodies (ASCA) in the diagnosis, differential diagnosis and treatment assessment in patients with ulcerative colitis (UC). Serum levels of ANCA-IgG, ASCA-IgA and ASCA-IgG were measured by an enzyme-linked immunosorbent assay (ELISA) in 105 UC patients, 52 non-UC patients and 100 healthy controls. RESULTS: (1) Both the ANCA-IgG level and its positive rate in UC patients were significantly higher than those in non-UC controls and healthy controls (p < 0.01). However, the levels of ASCA-IgA, ASCA-IgG and the positive rates in UC patients had no statistical differences when compared with those in non-UC controls or healthy controls (p > 0.05). (2) The sensitivity of ANCA+ and ANCA+/ASCA- in detecting UC patients was 61.90% and 55.24%, respectively, whereas the specificity was 91.45% and 94.08%, respectively. The sensitivity of ASCA+ and ASCA+/ANCA- in non-UC disease controls was 5.33% and 3.85%, respectively, and specificity was 83.9% and 88.78%, respectively. (3) When UC patients were grouped into mild, moderate or severe subtypes, the ANCA-IgG levels were correlated with the severity of UC, and the differences of the ANCA-IgG levels were statistically different among the three subtypes (p < 0.05). There was no correlation between the levels of ANCA-IgG and the disease locations of UC. CONCLUSIONS: (1) Serum levels of ANCA may be useful in the diagnosis of UC. (2) Dynamic quantitation of ANCA-IgG levels may be helpful in determining the severity of UC and therefore, may guide treatment of UC.

Histopathological changes in the infrapatellar fat pad in an experimental rabbit model of early patellofemoral osteoarthritis.

BACKGROUND: The purpose of this study was to characterise the histopathological changes in the infrapatellar fat pad (IPFP) in the early stage of patellofemoral osteoarthritis (PFOA). METHODS: Sixty-four New Zealand white rabbits were randomly divided into experimental (n = 24), sham (n = 16), and control groups (n = 24). In the experimental group, denoted as the patellar ligament uneven shortening group (US group), the patellar ligament (PL) was folded eight millimetres and sutured. After eight weeks, all animals were euthanised, and magnetic resonance imaging (MRI) evaluation, wet IPFP weight measurement, and histopathological and immunohistochemistry analysis were performed to analyse the histopathological changes in the IPFPs. RESULTS: The maximum cross-sectional area (CSA) of the IPFPs in the sagittal position of MRI in the control group, sham group, and US group were 45.50 ±â€¯7.19 mm2, 45.88 ±â€¯6.60 mm2 (vs. control group, P = 0.907), and 53.83 ±â€¯8.24 mm2 (vs. control group, P = 0.015; vs. sham group, P = 0.035), respectively. The MRI intensity of the IPFPs in the control group, sham group, and US group were 115.53 ±â€¯28.85, 108.53 ±â€¯26.73 (vs. control group, P = 0.589), and 154.52 ±â€¯18.48 (vs. control group, P = 0.002; vs. sham group, P = 0.002), respectively. The wet weight of the IPFPs in the control group, sham group, and US group were 0.32 ±â€¯0.05 g, 0.32 ±â€¯0.04 g (vs. control group, P = 0.895), and 0.38 ±â€¯0.06 g (vs. control group, P = 0.017; vs. sham group, P = 0.033), respectively. The Osteoarthritis Research Society International (OARSI) scores of the IPFPs in the US group were 6.00 ±â€¯1.91, which was higher than the scores of 2.50 ±â€¯2.02 (P < 0.001) in the control group and of 2.75 ±â€¯1.67 (P = 0.001) in the sham group. CONCLUSIONS: The histopathological changes of the IPFPs as determined via MRI and microscopic structure appeared to occur much earlier than cartilage damage in PFOA. Furthermore, detecting and treating the IPFP changes may offer aid in the diagnosis and treatment of PFOA.