Development and validation of a CT algorithm for the identification of nonperforated duodenal bulb ulcer.

PURPOSE: To assess the value of multiplanar computed tomography (CT) in the diagnosis of nonperforated duodenal bulb ulcer (NPDBU). METHOD: We retrospectively analyzed data from 135 patients with NPDBU (ulcer group) and 150 patients with a normal duodenal bulb (control group) who underwent contrast-enhanced abdominal CT and were diagnosed via upper endoscopy from January 2018 to February 2022. The clinical and CT features were compared between the two groups. Independent prognostic factors for diagnosing NPDBU were determined using binary logistic regression analysis. An external validation cohort to determine the model's efficiency comprised 80 patients from another center. RESULTS: Gastrointestinal bleeding was more frequent in patients with NPDBU than in those without (p < 0.001). No significant differences in age and sex were observed between the groups (all p > 0.05). The duodenal bulbar wall was significantly thicker in the ulcer group than in the control group, as determined using CT (p < 0.001). Irregular mucosal surface, layered enhancement, and blurred fat space around the duodenal bulb were more common in the ulcer group than in the control group (all p < 0.001). Binary logistic regression analysis revealed that gastrointestinal bleeding, wall thickness of ≥ 4.85 mm, irregular mucosal surface, and blurred peripheral fat space were the most significant variations associated with NPDBU, with an area under the curve (AUC) of 0.974. The external validation cohort had an AUC of 0.916. CONCLUSIONS: Careful multiplanar CT interpretation suggests the underlying presence of NPDBU and allows timely endoscopic verification and appropriate treatment.

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.

Using combined CT-clinical radiomics models to identify epidermal growth factor receptor mutation subtypes in lung adenocarcinoma.

Background: To investigate the value of computed tomography (CT)-based radiomics signatures in combination with clinical and CT morphological features to identify epidermal growth factor receptor (EGFR)-mutation subtypes in lung adenocarcinoma (LADC). Methods: From February 2012 to October 2019, 608 patients were confirmed with LADC and underwent chest CT scans. Among them, 307 (50.5%) patients had a positive EGFR-mutation and 301 (49.5%) had a negative EGFR-mutation. Of the EGFR-mutant patients, 114 (37.1%) had a 19del -mutation, 155 (50.5%) had a L858R-mutation, and 38 (12.4%) had other rare mutations. Three combined models were generated by incorporating radiomics signatures, clinical, and CT morphological features to predict EGFR-mutation status. Patients were randomly split into training and testing cohorts, 80% and 20%, respectively. Model 1 was used to predict positive and negative EGFR-mutation, model 2 was used to predict 19del and non-19del mutations, and model 3 was used to predict L858R and non-L858R mutations. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate their performance. Results: For the three models, model 1 had AUC values of 0.969 and 0.886 in the training and validation cohorts, respectively. Model 2 had AUC values of 0.999 and 0.847 in the training and validation cohorts, respectively. Model 3 had AUC values of 0.984 and 0.806 in the training and validation cohorts, respectively. Conclusion: Combined models that incorporate radiomics signature, clinical, and CT morphological features may serve as an auxiliary tool to predict EGFR-mutation subtypes and contribute to individualized treatment for patients with LADC.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

Differential diagnosis of localized pneumonic-type lung adenocarcinoma and pulmonary inflammatory lesion.

BACKGROUND: In clinical practice, a number of delayed diagnoses of localized pneumonic-type lung adenocarcinoma (L-PLADC) mimicking pneumonia have been identified due to the lack of knowledge regarding the radiological findings associated with this condition. Here, we defined L-PLADC as a special type of lung adenocarcinoma that presents as a focal consolidation involving < 50% of the area of a lobe and aimed to investigate the differential clinical and imaging features between L-PLADC and localized pulmonary inflammatory lesion (L-PIL). RESULTS: The data of 120 patients with L-PLADC and 125 patients with L-PIL who underwent contrast-enhanced chest computed tomography (CT) scan were retrospectively analyzed. For clinical characteristics, older age, women, nonsmokers, and no symptom were more common in L-PLADC (all p < 0.001). With regard to CT features, air bronchogram, irregular air bronchogram, ground-glass opacity (GGO) component, and pleural retraction were more frequently observed in L-PLADC, while necrosis, satellite lesions, halo sign, bronchial wall thickening, interlobular septa thickening, pleural attachment, and pleural thickening were more commonly seen in L-PIL (all p < 0.001). Multivariate analysis showed age ≥ 58 years, female sex, GGO component, irregular air bronchogram, pleural retraction, and the absence of necrosis and pleural attachment were the most effective variations associated with L-PLADC with an AUC of 0.979. Furthermore, an external validation cohort containing 62 patients obtained an AUC of 0.929. CONCLUSIONS: L-PLADC and L-PIL have different clinical and imaging characteristics. An adequate understanding of these differential features can contribute to the early diagnosis of L-PLADC and the subsequent therapeutic strategy.

Radiological classification, gene-mutation status, and surgical prognosis of synchronous multiple primary lung cancer.

OBJECTIVE: To investigate the radiological classification, gene-mutation status, and surgical prognosis of synchronous multiple primary lung cancer (sMPLC). METHODS: From January 2013 to October 2019, 192 consecutive patients with sMPLC were investigated. The clinical, CT, molecular, and pathological features of all patients were analyzed. Furthermore, the prognosis of 89 patients who only underwent surgical resection was evaluated. RESULTS: Among 192 patients, all lesions pathologically confirmed or highly suspected as tumors based on radiological findings were retrospectively analyzed, and the CT findings of sMPLC were classified into three types: (I) all lesions manifested as solid nodules/masses (14.06%, 27/192), (II) all lesions manifested as subsolid nodules/masses (43.23%, 83/192), and (III) tumor lesions manifested as a combination of ≥ 2 of the following patterns: solid nodules/masses, subsolid nodules/masses, cystic airspace, and focal consolidation (42.71%, 82/192). For 252 tumors undergoing epidermal growth factor receptor (EGFR)-mutation testing, the EGFR-mutation rate was higher in subsolid tumors than that in solid tumors (p < 0.05). Among 19 patients with all tumors undergoing surgery and driver-gene testing, genetic heterogeneity was prevalent among the multiple tumors (63.16%,12/19). The highest clinical stage of non-I, ipsilateral distribution of tumors, and CT classification of I indicated a poor prognosis for patients with sMPLC (all p < 0.05). CONCLUSION: Subsolid lesions are the most common presentation of sMPLC. Genetic heterogeneity in driver mutations among sMPLC may be present. Prognosis in patients with sMPLC is determined by the highest clinical TNM stage, distribution, and radiological classification among the multiple tumors. KEY POINTS: • Synchronous multiple primary lung cancer (sMPLC) has three types of CT findings. • Genetic heterogeneity may be prevalent among the multiple tumors. • Prognosis in patients with sMPLC is associated with the highest clinical TNM stage, distribution, and radiological classification among the multiple tumors.

MiR-196a promotes the proliferation and migration of esophageal cancer via the UHRF2/TET2 axis.

The aim of this study was to investigate the functions and molecular mechanism of miR-196a in esophageal cancer (EC). miR-196a as well as UHRF2 and TET2 mRNA and protein levels in EC tissues and cells were detected using quantitative real-time PCR or western blot, respectively. Cell proliferation was evaluated via MTT assay. Transwell assays were used to detect cell migration. In addition, the targeted relationship between miR-196a and UHRF2 was assessed through a dual luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the levels of the cytosine intermediates 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). We found increased miR-196a expression in EC tissues and cells but decreased UHRF2 and TET2 expression. Next, functional experiments showed that knockdown of miR-196a or UHRF2 overexpression suppress EC cell proliferation and migration. miR-196a negatively regulates TET2 expression by directly targeting UHRF2. UHRF2 overexpression decreased 5mC levels but increased 5hmC levels. Furthermore, TET2 downregulation reversed the functions of miR-196a inhibition on EC cell proliferation and migration. Collectively, our study suggested that miR-196a was closely related to the progression of EC possibly by regulating the UHRF2/TET2 axis. Thus, miR-196a represents a potential new EC therapeutic target.

Pneumonic-type lung adenocarcinoma with different ranges exhibiting different clinical, imaging, and pathological characteristics.

BACKGROUND: Pneumonic-type lung adenocarcinoma (PLADC) with different ranges might exhibit different imaging and clinicopathological features. This study divided PLADC into localized PLADC (L-PLADC) and diffuse PLADC (D-PLADC) based on imaging and aimed to clarify the differences in clinical, imaging, and pathologic characteristics between the two new subtypes. RESULTS: The data of 131 patients with L-PLADC and 117 patients with D-PLADC who were pathologically confirmed and underwent chest computed tomography (CT) at our institute from December 2014 to December 2020 were retrospectively collected. Patients with L-PLADC were predominantly female, non-smokers, and without respiratory symptoms and elevated white blood cell count and C-reactive protein level, whereas those with D-PLADC were predominantly male, smokers, and had respiratory symptoms and elevated white blood cell count and C-reactive protein level (all p < 0.05). Pleural retraction was more common in L-PLADC, whereas interlobular fissure bulging, hypodense sign, air space, CT angiogram sign, coexisting nodules, pleural effusion, and lymphadenopathy were more frequent in D-PLADC (all p < 0.001). Among the 129 patients with surgically resected PLADC, the most common histological subtype of L-PLADC was acinar-predominant growth pattern (76.7%, 79/103), whereas that of D-PLADC was invasive mucinous adenocarcinoma (80.8%, 21/26). Among the 136 patients with EGFR mutation status, L-PLADC had a significantly higher EGFR mutation rate than D-PLADC (p < 0.001). CONCLUSIONS: L-PLADC and D-PLADC have different clinical, imaging, and pathological characteristics. This new imaging-based classification may help improve our understanding of PLADC and develop personalized treatment plans, with concomitant implications for patient outcomes.

Clinicopathological and computed tomographic features associated with occult lymph node metastasis in patients with peripheral solid non-small cell lung cancer.

OBJECTIVES: To investigate the value of combining clinicopathological characteristics with computed tomographic (CT) features of tumours for predicting occult lymph node metastasis (OLNM) in peripheral solid non-small cell lung cancer (PS-NSCLC). METHODS: The study included 478 NSCLC clinically N0 (cN0) patients who underwent lobectomy and systemic lymph node dissection from January 2014 to August 2019. Patients were classified into OLNM and negative lymph node metastasis (NLNM) groups. The CT features of non-metastatic and metastatic lymph nodes with a largest short-diameter > 5 mm were compared in the OLNM group. Thereafter, the clinicopathological characteristics and CT morphological features of tumours were compared between both groups. Multivariable logistic regression analysis and receiver-operating characteristic curve were developed. RESULTS: CT images detected 103 metastatic and 705 non-metastatic lymph nodes, and no significant differences in CT features of lymph nodes were found in all 161 OLNM patients (P > 0.05). For both groups, sex, carcinoembryonic antigen and pathological type differed significantly (all P < 0.05), while tumour size, necrosis, calcification, vascular convergence, pleural involvement, and the shortest interval of tumour-pleura differed significantly on CT images (all P < 0.05). Multivariable logistic regression analysis showed that carcinoembryonic antigen > 5.00 ng/ml, adenocarcinoma, absence of vascular convergence, and pleural involvement of Type II (one linear or cord-like pleural tag or tumour abut to the pleura with a broad base observed on both lung and mediastinal window images) were independent predicting factors of OLNM. CONCLUSIONS: CT findings of lymph nodes can provide limited value and integrating clinicopathological characteristics with the CT morphological features of tumours is helpful in predicting OLNM in patients with PS-NSCLC.

Computed Tomography Morphological Classification of Lung Adenocarcinoma and Its Correlation with Epidermal Growth Factor Receptor Mutation Status: A Report of 1075 Cases.

BACKGROUND: Many delayed diagnoses of lung adenocarcinoma (LADC) are identified due to poor understanding of protean imaging findings. Moreover, clarifying the relationship between computed tomography (CT) morphological classification and epidermal growth factor receptor (EGFR) mutations of LADC might inform therapeutic decision-making while obtaining pathological specimens is difficult. Here, we retrospectively analyzed CT manifestations of LADC and investigated the morphological classification of tumors in relation to EGFR mutation status. METHODS: We included 1075 LADC patients undergoing chest CT and EGFR genotype examinations from January 2013 to January 2019. CT morphological characteristics of tumors were carefully evaluated and their correlation with EGFR mutation status was analyzed using the chi-squared test. RESULTS: Tumors were divided into eight types: I (peripheral solid nodule/mass; 526/1075, 48.93%), II (central solid nodule/mass; 220/1075, 20.47%), III (subsolid nodule/mass; 92/1075, 8.56%), IV (focal consolidation; 32/1075, 2.98%), V (cystic airspace; 14/1075, 1.30%), VI (multiple lesions with similar appearances to I-V; 85/1075, 7.91%), VII (diffuse consolidation; 53/1075, 4.93%), VIII (occult lesion usually obscured by nonobstructive atelectasis; 53/1075, 4.93%). Type III and IV tumors were more frequent in patients with EGFR mutation, whereas type II and VII tumors were more common in patients without EGFR mutation (all P < 0.05). However, we did not identify any significant associations between other tumor types and EGFR mutation status (all P > 0.05). Among patients with type VI tumors, EGFR mutation status was closely related to tumor density (all P < 0.05). Furthermore, type VII tumors were associated with 19 deletion mutation positive and non-L858R mutation positive (all P < 0.05). CONCLUSION: LADC can be categorized into eight types based on CT imaging. Improving our understanding of the morphological classification and correlation with EGFR mutation status may contribute to the accurate diagnosis of LADC, while suggesting the presence of underlying EGFR genetic mutations.

EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis.

Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.

ATF6 aggravates acinar cell apoptosis and injury by regulating p53/AIFM2 transcription in Severe Acute Pancreatitis.

Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.

Spectral CT in Lung Cancer: Usefulness of Iodine Concentration for Evaluation of Tumor Angiogenesis and Prognosis.

OBJECTIVE. The purpose of this study was to investigate the correlation between iodine concentration (IC) derived from spectral CT and angiogenesis and the relationships between IC and clinical-pathologic features associated with lung cancer prognosis. SUBJECTS AND METHODS. Sixty patients with lung cancer were enrolled and underwent spectral CT. The IC, IC difference (ICD), and normalized IC (NIC) of tumors were measured in the arterial phase, venous phase (VP), and delayed phase. The microvessel densities (MVDs) of CD34-stained specimens were evaluated. Correlation analysis was performed for IC and MVD. The relationships between the IC index showing the best correlations with MVD and clinical-pathologic findings of pathologic types, histologic differentiation, tumor size, lymph node status, pathologic TNM stage, and intratumoral necrosis were investigated. RESULTS. The mean (± IQR) MVD of all tumors was 42.00 ± 27.50 vessels per field at ×400 magnification, with two MVD distribution types. The MVD of lung cancer correlated positively with the IC, ICD, and NIC on three-phase contrast-enhanced scanning (r range, 0.581-0.800; all p < 0.001), and the IC in the VP showed the strongest correlation with MVD (r = 0.800; p < 0.001). The correlations between IC and MVD, ICD and MVD, and NIC and MVD varied depending on whether the same scanning phase or same IC index was used. The IC in the VP showed statistically significant differences in the pathologic types of adenocarcinoma and squamous cell carcinoma, histologic differentiation, tumor size, and status of intratumoral necrosis of lung cancer (p < 0.05), but was not associated with nodal metastasis and pathologic TNM stages (p > 0.05). CONCLUSION. IC indexes derived from spectral CT, especially the IC in the VP, were useful indicators for evaluating tumor angiogenesis and prognosis.

The effect of Salvia miltiorrhiza in a mouse model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum

Background and aims: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). Methods: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-alfa), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. Results: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-alfa, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. Conclusions: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS

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The effect of Salvia miltiorrhiza in a mouse model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum.

BACKGROUND AND AIMS: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). METHODS: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-α), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-α, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. CONCLUSIONS: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS.

Histone deacetylase 6 is overexpressed and promotes tumor growth of colon cancer through regulation of the MAPK/ERK signal pathway.

Purpose: To investigate the expression of histone deacetylase 6 (HDAC6) in colon cancer and its role in colon cancer cell growth and migration. Materials and methods: We detected the expression of HDAC6 in a colon cancer tissue chip using immunochemical staining, and analyzed the difference in HDAC6 expression between cancer and adjacent noncancerous tissues. Then, we explored the relationship between HDAC6 expression and patients' clinicopathological characteristics and prognoses. In adidition, the role of HDAC6 in colon cancer cell growth and migration, as well as its potential related signal pathway, through HDAC6 knockdown was explored. Results: The immunochemical score of HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (4.54 vs 3.08, P<0.005); similarly, as well as the rate of high HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (71.1% vs 40.9%, P<0.001). Patients showing high HDAC6 expression had a shorter overall survival time. Additionally, Cox regression analysis showed that high HDAC6 expression was an independent risk factor for poor prognosis. HDAC6 knockdown decreased cell viability, colony formation, and number of migrated colon cancer cells (HCT116 and HT29); the expression of p-MEK, p-ERK, and p-AKT was also decreased, but had no influence on MEK, ERK, and AKT expression. Conclusion: HDAC6 is highly expressed in colon cancer and associated with a poor prognosis. HDAC6 knockdown inhibits colon cancer cell growth and migration, partly through the MAPK/ERK pathway.

Altered metabolites in guinea pigs with allergic asthma after acupoint sticking therapy: New insights from a metabolomics approach.

BACKGROUND: Clinical evidence gathered in Chinese communities suggested that acupoint sticking therapy could be an alternative treatment for asthma-related diseases. However, its underlying mechanism is still poorly understood. AIM/HYPOTHESIS: In this study, we aimed to investigate the mechanism of the anti-inflammatory effect of acupoint sticking application with 'Treatment of Winter Disease in Summer' (TWDS) prescription by using metabolomics. METHODS: Allergic asthma in guinea pig was sensitized and challenged by ovalbumin (OVA). Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The levels of Th2 cytokine and IgE level in serum were measured using enzyme-linked immunoassay (ELISA). The mRNA expression levels of IL-4, IL-5, IL-13 and orosomucoid-like 3 (ORMDL3) were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Proteins of NF-κB signaling pathway were measured using western blot. The serum metabolomics profiles were obtained by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS). RESULTS: The overall results confirmed that AST with TWDS prescription had a significant protective effect against OVA-induced allergic asthma in guinea pig. This treatment not only attenuated airway inflammation and collagen deposition in the airway, but also decreased the levels of IL-4, IL-5, IL-13 and IgE in serum. In addition, metabolomics results indicated that metabolisms of phospholipid, sphingolipid, purine, amino acid and level of epinephrine were restored back to the normal control level. Moreover, results of the gene expression of ORMDL3 in lung tissues indicated that AST using TWDS could alter the sphingolipid metabolism. Further western blotting analysis also showed that its anti-inflammatory mechanism was by decreasing the phosphorylation of p65 and IκB. CONCLUSION: The study demonstrated that metabolomics provides a better understanding of the actions of TWDS acupoint sticking therapy on OVA-induced allergic asthma.

Orientation-dependent structural and photocatalytic properties of LaCoO3 epitaxial nano-thin films.

LaCoO3 epitaxial films were grown on (100), (110) and (111) oriented LaAlO3 substrates by the polymer-assisted deposition method. Crystal structure measurement and cross-section observation indicate that all the LaCoO3 films are epitaxially grown in accordance with the orientation of LaAlO3 substrates, with biaxial compressive strain in the ab plane. Owing to the different strain directions of CoO6 octahedron, the mean Co-O bond length increases by different amounts in (100), (110) and (111) oriented films compared with that of bulk LaCoO3, and the (100) oriented LaCoO3 has the largest increase. Photocatalytic degradation of methyl orange indicates that the order of photocatalytic activity of the three oriented films is (100) > (111) > (110). Combined with analysis of electronic nature and band structure for LaCoO3 films, it is found that the change of the photocatalytic activity is closely related to the crystal field splitting energy of Co3+ and Co-O binding energy. The increase in the mean Co-O bond length will decrease the crystal field splitting energy of Co3+ and Co-O binding energy and further reduce the value of band gap energy, thus improving the photocatalytic activity. This may also provide a clue for expanding the visible-light-induced photocatalytic application of LaCoO3.