Dynamic changes in key factors of the blood-brain barrier in early diabetic mice.

Chronic hyperglycemia can result in damage to the hippocampus and dysfunction of the blood-brain barrier (BBB), potentially leading to neurological disorders. This study examined the histological structure of the hippocampus and the expression of critical genes associated with the BBB at 2 early stage time points in a streptozotocin-induced diabetes mellitus (DM) mouse model. Routine histology revealed vascular congestion and dilation of Virchow-Robin spaces in the hippocampal CA1 region of the DM group. Neuronal alterations included rounding and swelling and reduction in Nissl bodies and increased apoptosis. Compared to the control group, TJP1 mRNA expression in the DM group was significantly lower (P < .05 or P < .01), while mRNA levels of JAM3, TJP3, CLDN5, CLDN3, and OCLN initially increased and then decreased. At 7, 14, and 21 days, mRNA levels of the receptor for advanced glycation end products (AGER) were greater in the DM group than in the control group (P < .05 or P < .01). These findings indicate that early-stage diabetes may cause structural and functional impairments in hippocampal CA1 in mice. These abnormalities may parallel alterations in the expression of key BBB tight junction molecules and elevated AGER expression in early DM patients.

Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults: a Cross-sectional Study Based on the NHANES.

OBJECTIVE: Ferritin, initially acting as an iron-storage protein, was found to be associated with metabolic diseases. Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease (MAFLD) using data from the National Health and Nutrition Examination Survey (NHANES) of the United State of America. METHODS: A cross-sectional study was conducted, enrolling a total of 2145 participants from the NHANES in the 2017-2018 cycles. Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes. Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis. RESULTS: The analysis revealed that participants with higher serum ferritin levels (Q3 and Q4 groups) had a higher prevalence of MAFLD than those with the lowest serum ferritin levels [Q3 vs. Q1: OR=2.17 (1.33, 3.53), P<0.05 in fatty liver index (FLI); Q4 vs. Q1: OR=3.13 (1.91, 5.13), P<0.05 in FLI]. Additionally, participants with the highest serum ferritin levels (Q4 group) displayed a higher prevalence of liver fibrosis [Q4 vs. Q1: OR=2.59 (1.19, 5.62), P<0.05 in liver stiffness measurement; OR=5.06 (1.12, 22.94), P<0.05 in fibrosis-4 index], with significantly increased risk observed in participants with concomitant diabetes [OR=7.45 (1.55, 35.72), P=0.012]. CONCLUSION: Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients. Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.

Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum.

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Molecular properties, structure and chiral resolution of secondary metabolites from the leaves of Viburnum chingii.

A chemical investigation of leaves of Viburnum chingii afforded eleven compounds, including one undescribed lignan (1), a pair of known phenylpropanoid enantiomers (2a/2b), and eight known lignans (3-10). Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. The absolute configurations of compounds 1 was determined by comparing the experimental ECD data with the calculated values. The compounds 2a/2b were separated successfully by a chiral chromatographic column. In addition, the acetylcholinesterase (AChE) inhibitory activities of described compounds were evaluated.

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Two new iridoids and triterpenoid analogues from the leaves of Viburnum chingii and their anti-acetylcholinesterase activity.

Two undescribed split-ring iridoids (1-2) with six known triterpenes (3-8) and one steride (9) were isolated from the Viburnum chingii. Compound 2 possessed an unprecedented split-ring iridoid skeleton formed by electrocyclic reaction and split ring. The structures and absolute configurations of the new iridoids were established by NMR, HRESIMS, and ECD calculations. All the isolated compounds were tested for AChE inhibitory activity. Biologically, 1, 2, 3, 4, and 7 displayed significant AChE effects compared to the positive control donepezil, and have also been subjected to molecular docking studies.

Novel Bisamide Alkaloids Enantiomers from Pepper Roots (Piper nigrum L.) with Acetylcholinesterase Inhibitory and Anti-Neuroinflammatory Effects.

The roots of Piper nigrum L., a seasoning for cooking various types of broths, are renowned for their high nutritional content and potential medicinal benefits. In this study, nine pairs of novel cyclohexene-type bisamide alkaloids (1a/1b-9a/9b) were isolated from the pepper roots using molecular network analysis strategies. Their structures were determined by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and X-ray diffraction analyses. Using an intermolecular Diels-Alder reaction, a strategy for the synthesis of bisamide alkaloids from different monomeric amide alkaloids was developed. Furthermore, these compounds were chirally separated for the first time, and compounds 3a and 5a/5b showed significant anti-neuroinflammation effects in the models of lipopolysaccharide(LPS)-induced BV2 microglial cells. Meanwhile, compounds 6b and 7a displayed concentration-dependent inhibitory activities against acetylcholinesterase with IC50 values of 6.05 ± 1.10 and 3.81 ± 0.10 µM, respectively. These findings confirmed that these bisamide alkaloids could be applied in functional food formulations and pharmaceutical products as well as facilitate the further development and usage of pepper roots.

Chemical constituents from Daphne giraldii and their cytotoxicities and inhibitory activities against acetylcholinesterase.

Seven triterpenoids (1-7), two prenylated coumarins (8 and 9), and one diphenylpropane (10), including five previously undescribed compounds (1-3, 8, and 10), were obtained from the stem and root barks of Daphne giraldii. The structures and absolute configurations of the new triterpenoids were established by NMR, HRESIMS, ECD calculations, and single-crystal X-ray diffraction analysis. All identified compounds were tested for cytotoxicities (human tumour cell line Hep3B) and inhibitory effects on AChE in vitro. Notably, prenylated coumarins (8 and 9) exhibited moderate cytotoxic activities and 3-hydroxy-substituted triterpenoids (2 and 4) showed mild inhibitory effects on AChE. Furthermore, compounds 2 and 4 have also been subjected to molecular docking studies to investigate the inhibitory mechanism.

Role of EtMIC4 EGF-like in regulating the apoptosis of Eimeria tenella host cells via the EGFR pathway.

This study aimed to explore the role and key point of EtMIC4 EGF-like recombinant protein in regulating the apoptosis of Eimeria tenella host cells via the epidermal growth factor receptor (EGFR) pathway. The cells were treated with EtMIC4 EGF-like protein, EGFR-specific siRNA, or both. Infection and apoptosis rates as well as dynamic changes in the key genes and proteins of the EGFR signaling pathway in the host cells were determined. Results showed that the E. tenella and EtMIC4 EGF-like group had the highest infection rate (P < 0.01). In cells treated with EtMIC4 EGF-like for 4 to 24 h, the apoptosis rate was significantly decreased (P < 0.01) and the relative mRNA expression and protein phosphorylation levels of EGFR, protein kinase B (AKT), and extracellular regulated protein kinases (ERK) were significantly increased (P < 0.01). In E. tenella sporozoites infected for 4 to 96 h, the rate of host cell apoptosis induced by E. tenella infection was significantly (P < 0.01) reduced by EtMIC4 EGF-like. The relative mRNA expression and protein phosphorylation levels of EGFR, AKT, and ERK in the host cells of E. tenella + EtMIC4 EGF-like group were significantly increased (P < 0.01). These results indicated that E. tenella could activate the EGFR pathway through EtMIC4 EGF-like and regulate the expression of key genes in the AKT and ERK signaling pathways, thereby inhibiting cell apoptosis.

Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Brain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer. Methods: Electronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models. Results: Fourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58-0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52-0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71-0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56-0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78-1.18; P = 0.72) and 0.97 (95% CI, 0.79-1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings. Conclusion: We demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).

Venous thromboembolism in patients with severe lung cancer: a narrative review.

OBJECTIVE: At present, there are several guidelines for cancer complicated with VTE, but there is no specific recommendation for the treatment of lung cancer complicated with VTE. Whether is necessary to explore treatment and prevention of VTE in lung cancer. BACKGROUND: Venous thromboembolism (VTE) is a common complication of severe lung cancer that can entail many adverse effects for patients. The incidence of VTE is higher in patients with lung cancer than in those with other kinds of solid tumors, and it is especially high among patients with lung adenocarcinoma, at advanced tumor-node-metastasis (TNM) stages, or with a history of central venous catheter (CVC) or chemotherapy. However, the clinical symptoms of VTE in patients with lung cancer are not typical and cannot be detected easily, and the clinical prevention rate is low. In the acute phase of VTE in lung cancer, the Eastern Cooperative Oncology Group (ECOG) performance status score of patients typically ranges from 2 to 4 points, leaving end-stage maintenance therapy as the only treatment option. METHODS: Here, we analyze the existing literature and discuss the current status (including epidemiology, clinical manifestations, and risk factors), risk assessment tools, and the treatment and prevention of VTE in severe lung cancer. We focus particularly on the use of low-molecular-weight heparin and new oral anticoagulants (including in the management of thrombocytopenia after antitumor therapy) in lung cancer patients with VTE. CONCLUSIONS: Large-scale prospective multicenter studies on the treatment and prevention of VTE in lung cancer are necessary.

Evaluation of IGRT-Induced Imaging Doses and Secondary Cancer Risk for SBRT Early Lung Cancer Patients In Silico Study.

OBJECTIVES: This study performed dosimetry studies and secondary cancer risk assessments on using electronic portal imaging device (EPID) and cone beam computed tomography (CBCT) as image guided tools for the early lung cancer patients treated with SBRT. METHODS: The imaging doses from MV-EPID and kV-CBCT of the Edge accelerator were retrospectively added to sixty-one SBRT treatment plans of early lung cancer patients. The MV-EPID imaging dose (6MV Photon beam) was calculated in Pinnacle TPS, and the kV-CBCT imaging dose was simulated and calculated by modeling of the kV energy beam in TPS using Pinnacle automatic modeling program. Three types of plans, namely PlanEPID, PlanCBCT and Planorigin, were generated with incorporating doses of EPID, CBCT and no imaging, respectively, for analysis. The effects of imaging doses on dose-volume-histogram (DVH) and plan quality were analyzed, and the excess absolute risk (EAR) of secondary cancer for ipsilateral lung was evaluated. RESULTS: The regions that received less than 50 cGy were significantly impacted by the imaging doses, while the isodose lines greater than 1000 cGy were barely changed. The DVH values of ipsilateral lung increased the most in PlanEPID, followed by PlanCBCT. Compared to Planorigin on the average, the estimated EAR of ipsilateral lung in PlanEPID increased by 3.43%, while the corresponding EAR increase in PlanCBCT was much smaller (about 0.4%). Considering only the contribution of the imaging dose, the EAR values for the ipsilateral lung due to the MV-EPID dose in 5 years,10 years and 15 years were 1.49 cases, 2.09 cases and 2.88 cases per 104PY respectively, and those due to the kV-CBCT dose were about 9 times lower, correspondingly. CONCLUSIONS: The imaging doses produced by MV-EPID and kV-CBCT had little effects on the target dose coverage. The secondary cancer risk caused by MV-EPID dose is more than 8.5 times that of kV-CBCT.

Individualized Fraction Regimen of SBRT Patients With Non-Small Cell Lung Cancer Based on Uncomplicated and Cancer-Free Control Probability.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) currently adopts non-discriminative prescription regimen. This study attempts to investigate an individualized fraction regimen (IFR) method for SBRT patients with non-small cell lung cancer (NSCLC) based on Uncomplicated and Cancer-free Control Probability (UCFCP). METHODS: Twenty patients with NSCLC were retrospectively prescribed with 40 regimens, ranging from 8Gy×5f to 12Gy×5f in step of 0.1 Gy. Taking into consideration of the age and the BMI index of each patient as well, the tumor control probability (TCP), the normal tissue complication probability (NTCP) of the total lung, chest wall and rib, and the secondary cancer probability (SCP) of the total lung were calculated for each plan of the patients. For the 40 regimens, the UCFCP was calculated and the maximum value of UCFCP was the IFR of the specified patient. Besides, IFR of UCP approach which only took account of the TCP and NTCP was also derived and to be compared with the IFR based on the UCFCP method. RESULTS: For all the patients, the UCFCP value showed a bell-shaped trend with the change of prescription dose. Among the 20 patients, the IFRs of 16 patients were different from the original fixed regimen. Of the 16 patients, the IFR of 5 patients exhibited slight changes between UCP and UCFCP methods. CONCLUSION: The method based on the maximum value of UCFCP function may be helpful to provide IFR for specific SBRT patients with NSCLC, differentiating the patient specific characteristics such as anatomical structures and locations.

Association of menopausal status with COVID-19 outcomes: a propensity score matching analysis.

BACKGROUND: Despite the growing number of studies on the coronavirus disease-19 (COVID-19), little is known about the association of menopausal status with COVID-19 outcomes. MATERIALS AND METHODS: In this retrospective study, we included 336 COVID-19 inpatients between February 15, 2020 and April 30, 2020 at the Taikang Tongji Hospital (Wuhan), China. Electronic medical records including patient demographics, laboratory results, and chest computed tomography (CT) images were reviewed. RESULTS: In total, 300 patients with complete clinical outcomes were included for analysis. The mean age was 65.3 years, and most patients were women (n = 167, 55.7%). Over 50% of patients presented with comorbidities, with hypertension (63.5%) being the most common comorbidity. After propensity score matching, results showed that men had significantly higher odds than premenopausal women for developing severe disease type (23.7% vs. 0%, OR 17.12, 95% CI 1.00-293.60; p = 0.003) and bilateral lung infiltration (86.1% vs. 64.7%, OR 3.39, 95% CI 1.08-10.64; p = 0.04), but not for mortality (2.0% vs. 0%, OR 0.88, 95% CI 0.04-19.12, p = 1.00). However, non-significant difference was observed among men and postmenopausal women in the percentage of severe disease type (32.7% vs. 41.7%, OR 0.68, 95% CI 0.37-1.24, p = 0.21), bilateral lung infiltration (86.1% vs. 91.7%, OR 0.56, 95% CI 0.22-1.47, p = 0.24), and mortality (2.0% vs. 6.0%, OR 0.32, 95% CI 0.06-1.69, p = 0.25). CONCLUSIONS: Men had higher disease severity than premenopausal women, while the differences disappeared between postmenopausal women and men. These findings support aggressive treatment for the poor prognosis of postmenopausal women in clinical practice.

Vibration pattern recognition using a compressed histogram of oriented gradients for snoring source analysis.

BACKGROUND: Snoring source analysis is essential for an appropriate surgical decision for both simple snorers and obstructive sleep apnea/hypopnea syndrome (OSAHS) patients. OBJECTIVE: As snoring sounds carry significant information about tissue vibrations within the upper airway, a new feature entitled compressed histogram of oriented gradients (CHOG) is proposed to recognize vibration patterns of the snoring source acoustically by compressing histogram of oriented gradients (HOG) descriptors via the multilinear principal component analysis (MPCA) algorithm. METHODS: Each vibration pattern corresponds to a sole or combinatorial vibration among the four upper airway soft tissues of soft palate, lateral pharyngeal wall, tongue base, and epiglottis. 1037 snoring events from noncontact sound recordings of 76 simple snorers or OSAHS patients during drug-induced sleep endoscopy (DISE) were evaluated. RESULTS: With a support vector machine (SVM) as the classifier, the proposed CHOG achieved a recognition accuracy of 89.8% for the seven observable vibration patterns of the snoring source categorized in our most recent work. CONCLUSION: The CHOG outperforms other single features widely used for acoustic analysis of sole vibration site.

[46,XY DSD induced by a novel mutation c.458T>C (p.Leu153Pro) of the LHCGR gene: A case report and review of the literature].

OBJECTIVE: To investigate the clinical characteristics and pathogenic basis of a case of 46, XY disorders of sex development (DSD) and analyze the relationship of the missense mutation with the phenotype of the LHCGR gene. METHODS: We analyzed the causative gene mutation by next-generation high-throughput sequencing (HTS) and confirmed it by Sanger sequencing. We detected the effect of the mutation on the splicing function by minigene assay, evaluated its pathogenicity using the ANNOVAR mutation annotation software, and analyzed the relationship of the missense mutation and the phenotype of the LHCGR gene via literature review and data mining. RESULTS: A homozygous mutation of C.458T>C (p.Leu153Pro) was detected in the last base of exon5 of the LHCGR gene in the 46,XY DSD patient, which was a new mutation not reported previously. The mother of the patient was a heterozygous carrier of the mutation. Minigene assay indicated that c.458T>C (p.Leu153Pro) did not affect the splicing function. The mutation was shown to be pathogenic by ANNOVAR software analysis and presumed inactive, possibly affecting its binding with the ligand and leading to type-I Leydig cell hypoplasia (LCH). Literature review and data mining showed that only 19 missense mutations could cause LCH, which scattered in the LHCGR gene. CONCLUSIONS: The new mutation c.458T> C (p.Leu153Pro) of the LHCGR gene found in the 46, XY DSD patient may cause LCH by interfering with the binding function of the ligand, which has enriched the LHCGR gene mutation database and provided some reference for the studies on the LCH genotype, its phenotypic correlation and gene functions.

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury.

Six pairs of alkaloid enantiomers including 11 new alkaloids (1A: /1B: -5A: /5B, 6A: ) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5A/5B: and 6A/6B: exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.

Comparison of the host cells apoptosis induced by precocious strains and virulent strains of Eimeria tenella.

The present study aims to investigate the similarities and differences between the host cells apoptosis induced by virulent line of Eimeria tenella (Tsx) and precocious line (PTsx), which can provide a theoretical basis for the study of drugs and vaccines against coccidiosis. HE staining, Hoechst 33342/AnnexinV-FITC/PI composite staining, and ELISA were used to detect the infection rate, apoptosis rate, and Caspase-3 enzyme activity of host cells infected by PTsx or Tsx, respectively. The apoptotic rates and Caspase-3 absorbance of the inoculation groups were lower (P < 0.05 or P < 0.01) than those of the control group at 4 h, whereas the apoptotic rates and Caspase-3 absorbance of the inoculation groups were higher (P < 0.05 or P < 0.01) than those of the control groups at 24 to 120 h. At the same inoculation dose, there was no significant difference in the infection rate, apoptosis rate or Caspase-3 absorbance between Tsx groups and PTsx groups after E. tenella inoculation for 4 to 72 h (P > 0.05). However, these indicators of PTsx groups were lower (P < 0.01) than those of the same dose inoculated Tsx groups at 120 h. The apoptosis rates of cecal and glandular epithelial cells in the inoculated groups were higher (P < 0.01) than those in the control group after inoculated E. tenella 5 D in vivo, and the apoptosis rates of cecal and glandular epithelial cells in PTsx group was lower (P < 0.01) than that in the same dose inoculated Tsx group. These observations indicate that both Tsx and PTsx inhibit host cell apoptosis in the early development of E. tenella, induce host cell apoptosis in the middle and late stages, and the apoptosis-inducing effect on host cells increases with increasing dose. However, when the same dose of oocysts was inoculated, the amount of apoptosis induced by PTsx in late development was less than Tsx.

Differential expression of pro-inflammatory and anti-inflammatory genes of layer chicken bursa after experimental infection with infectious bursal disease virus.

Infectious bursal disease (IBD) is one of the most prevalent infectious diseases caused by IBD virus (IBDV), which results in bursal necrosis and immunosuppression that cause severe damage to the immune system in chickens. Cytokines are important mediators and regulators of both types of host responses. In the present study, layer chickens were artificially challenged with IBDV, and the differential expression of inflammatory genes was explored by using quantitative real-time PCR, which offered basic data for further study of IBDV pathogenesis. Data showed that after IBDV infection, the virus load in the bursa of Fabricius (BF) peaked at 96 h and then gradually decreased. Compared with those of the negative-infected group, the mRNA expression levels of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-7, IL-8, tumor necrosis factor [TNF]-α, transforming growth factor [TGF]-ß) and anti-inflammatory cytokine IL-10 in the infected group increased to varying degrees at 12 to 192 h, respectively. Furthermore, the IL-1ß mRNA expression peaked at 48 h; the mRNA transcript levels of IL-6, IL-8, and IL-10 were the highest at 96 h; TNF-α mRNA expression peaked at 120 h; the IL-7 mRNA expression peaked at 144 h; and the TGF-ß mRNA transcript level was the highest at 192 h. Taken together, these observations indicated that along with the change pattern of IBDV proliferation in BF, the mRNA expression of cytokines (IL-1ß, IL-6, IL-7, IL-8, IL-10, TNF-α, TGF-ß) obviously increased, and the kinetics of each of these cytokines was different. The kinetics of IL-6/IL-10 mRNA expression ratio was significantly positively correlated with that of the virus load. These results suggest that IBDV infection seriously interferes with the natural immune response mediated by inflammatory cytokines in chickens.

Identifying EGFR mutations in lung adenocarcinoma by noninvasive imaging using radiomics features and random forest modeling.

OBJECTIVES: The tyrosine kinase inhibitor (TKI)-sensitive mutations of the epidermal growth factor receptor (EGFR) gene is essential in the treatment of lung adenocarcinoma. To overcome the difficulty of EGFR gene test in situations where surgery and biopsy samples are too risky to obtain, we tried a noninvasive imaging method using radiomics features and random forest models. METHODS: Five hundred three lung adenocarcinoma patients who received surgery-based treatment were included in this study. The diagnosis and EGFR gene test were based on resections. TKI-sensitive mutations were found in 60.8% of the patients. CT scans before any invasive operation were gathered and analyzed to extract quantitative radiomics features and build random forest classifiers to identify EGFR mutants from wild types. Clinical features (sex and smoking history) were added to the image-based model. The model was trained on a set of 345 patients and validated on an independent test group (n = 158) using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: The performance of the random forest model with 94 radiomics features reached an AUC of 0.802. Its AUC was further improved to 0.828 by adding sex and smoking history. The sensitivity and specificity are 60.6% and 85.1% at the best diagnostic decision point. CONCLUSION: Our results showed that radiomics could not only reflect the genetic differences among tumors but also have diagnostic value and the potential to be a diagnostic tool. KEY POINTS: • Radiomics provides a potential noninvasive method for the prediction of EGFR mutation status. • In situations where surgeries and biopsy are not available, CT image-based radiomics models could help to make treatment decisions. • The accuracy, sensitivity, and specificity still need to be improved before the image-based EGFR identifier could be used in clinics.