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Xi Ma,1,&ast; Yu-Rui Wang,2,&ast; Li-Yong Zhuo,1 Xiao-Ping Yin,1 Jia-Liang Ren,3 Cai-Ying Li,4 Li-Hong Xing,1 Tong-Tong Zheng4 1CT/MRI Room, Affiliated Hospital of Hebei University, Baoding, Hebei Province, 071000, People’s Republic of China; 2Department of Computed Tomography, Tangshan Gongren Hospital, Tangshan, Hebei Province, 063000, People’s Republic of China; 3GE Healthcare[Shanghai] Co Ltd, Shanghai, 210000, People’s Republic of China; 4Department of Radiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Ping YinCT/MRI Room, Affiliated Hospital of Hebei University, No. 212 Eastern Yuhua Road, Baoding City, Hebei Province, 071000, People’s Republic of ChinaTel +86 0312-5981699Email xpydr_sea123@163.comCai-Ying LiDepartment of Radiology, The Second Hospital of Hebei Medical University, 215 Eastern Heping Road, Shijiazhuang city, Hebei Province, 050000, People’s Republic of ChinaTel +86 0311-87046901Email lcy_dr06@126.comPurpose: To investigate the feasibility of enhanced computed tomography (CT) radiomics analysis to differentiate between pancreatic cancer (PC) and chronic pancreatitis.Methods and materials: The CT images of 151 PCs and 24 chronic pancreatitis were retrospectively analyzed in the three-dimensional regions of interest on arterial phase (AP) and venous phase (VP) and segmented by MITK software. A multivariable logistic regression model was established based on the selected radiomics features. The radiomics score was calculated, and the nomogram was established. The discrimination of each model was analyzed by the receiver operating characteristic curve (ROC). Decision curve analysis (DCA) was used to evaluate clinical utility. The precision recall curve (PRC) was used to evaluate whether the model is affected by data imbalance. The Delong test was adopted to compare the diagnostic efficiency of each model.Results: Significant differences were observed in the distribution of gender (P = 0.034), carbohydrate antigen 19-9 (P < 0.001), and carcinoembryonic antigen (P < 0.001) in patients with PC and chronic pancreatitis. The area under the ROC curve (AUC) value of AP multivariate regression model, VP multivariate regression model, AP combined with VP features model (Radiomics), clinical feature model, and radiomics combined with clinical feature model (COMB) was 0.905, 0.941, 0.941, 0.822, and 0.980, respectively. The sensitivity and specificity of the COMB model were 0.947 and 0.917, respectively. The results of DCA showed that the COMB model exhibited net clinical benefits and PRC shows that COMB model have good precision and recall (sensitivity).Conclusion: The COMB model could be a potential tool to distinguish PC from chronic pancreatitis and aid in clinical decisions.Keywords: pancreatic cancer, chronic pancreatitis, radiomics, computed tomography, differential diagnosis

Li-Yong Zhuo,&ast; Li-Hong Xing,&ast; Xi Ma, Yu Zhang, Ze-Peng Ma, Xiao-Ping Yin, Jia-Ning Wang Department of CT-MRI Diagnostic, Affiliated Hospital of Hebei University, Baoding, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Ping Yin; Jia-Ning WangDepartment of CT-MRI Diagnostic, Affiliated Hospital of Hebei University, 212 Eastern Yuhua Road, Baoding City, Hebei Province, 071000, People’s Republic of ChinaTel +8613103128133; +8618233289724Email xiaoping_yin@outlook.com; jianingwang06@outlook.comObjective: To identify diffusion-weighted imaging (DWI) patterns and conspicuity discrepancies on hepatobiliary phase imaging (HBPI) to distinguish atypical hepatic abscesses from hepatic metastases.Materials and Methods: This retrospective study recruited 31 patients with 43 atypical hepatic abscesses and 32 patients with 35 hepatic metastases who underwent gadobenate dimeglumine-enhanced magnetic resonance imaging. All lesions were confirmed by pathological or clinical diagnosis. For the qualitative and quantitative analyses, the signal intensity, DWI pattern, apparent diffusion coefficient, degree of perilesional edema, perilesional hyperemia, perilesional signal on HBPI, conspicuity, size discrepancy between sequences, contrast-to-noise ratio, signal-to-noise ratio, and relative enhancement ratio on dynamic phases were independently assessed by two radiologists. Significant findings for differentiating the two groups were identified via univariate and multivariate analyses with a nomogram for predicting atypical hepatic abscesses. The interobserver agreement was also analyzed for each variable.Results: The multivariate analysis revealed that the conspicuity discrepancy (odds ratio [OR] 34.78, 95% confidence interval [CI] 2.09– 579.47, p = 0.013) and non-peripheral high signal intensity (SI) rim on DWI (OR 67.46, 95% CI 2.64, 1723.20, p = 0.011) were significant independent factors for predicting atypical hepatic abscesses. They were also shown to be high predictor points on the nomogram. When any of the set criteria were satisfied, 97.7% of atypical hepatic abscesses were correctly identified, with a specificity of 65.7%. When both criteria were combined, the specificity was up to 100%, with a sensitivity of 44.9%.Conclusion: Conspicuity discrepancy and a non-peripheral high SI rim on DWI are reliable and meaningful features that can distinguish atypical hepatic abscesses from hepatic metastases.Keywords: liver, MRI, abscess, metastasis, hepatocyte-specific contrast

Is the radiomic approach, utilizing diffusion-weighted imaging (DWI), capable of predicting the various pathological grades of intrahepatic mass-forming cholangiocarcinoma (IMCC)? Furthermore, which model demonstrates superior performance among the diverse algorithms currently available? The objective of our study is to develop DWI radiomic models based on different machine learning algorithms and identify the optimal prediction model. We undertook a retrospective analysis of the DWI data of 77 patients with IMCC confirmed by pathological testing. Fifty-seven patients initially included in the study were randomly assigned to either the training set or the validation set in a ratio of 7:3. We established four different classifier models, namely random forest (RF), support vector machines (SVM), logistic regression (LR), and gradient boosting decision tree (GBDT), by manually contouring the region of interest and extracting prominent radiomic features. An external validation of the model was performed with the DWI data of 20 patients with IMCC who were subsequently included in the study. The area under the receiver operating curve (AUC), accuracy (ACC), precision (PRE), sensitivity (REC), and F1 score were used to evaluate the diagnostic performance of the model. Following the process of feature selection, a total of nine features were retained, with skewness being the most crucial radiomic feature demonstrating the highest diagnostic performance, followed by Gray Level Co-occurrence Matrix lmc1 (glcm-lmc1) and kurtosis, whose diagnostic performances were slightly inferior to skewness. Skewness and kurtosis showed a negative correlation with the pathological grading of IMCC, while glcm-lmc1 exhibited a positive correlation with the IMCC pathological grade. Compared with the other three models, the SVM radiomic model had the best diagnostic performance with an AUC of 0.957, an accuracy of 88.2%, a sensitivity of 85.7%, a precision of 85.7%, and an F1 score of 85.7% in the training set, as well as an AUC of 0.829, an accuracy of 76.5%, a sensitivity of 71.4%, a precision of 71.4%, and an F1 score of 71.4% in the external validation set. The DWI-based radiomic model proved to be efficacious in predicting the pathological grade of IMCC. The model with the SVM classifier algorithm had the best prediction efficiency and robustness. Consequently, this SVM-based model can be further explored as an option for a non-invasive preoperative prediction method in clinical practice., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense , and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Deng, Zhao, Cai, Zhang, Ma, Lv, Jiang, Peng, Wang, Xing and Yu.)

Objective: To establish a machine learning-based radiomics model to differentiate between glioma and solitary brain metastasis from lung cancer and its subtypes, thereby achieving accurate preoperative classification., Materials and Methods: A retrospective analysis was conducted on MRI T1WI-enhanced images of 105 patients with glioma and 172 patients with solitary brain metastasis from lung cancer, which were confirmed pathologically. The patients were divided into the training group and validation group in an 8:2 ratio for image segmentation, extraction, and filtering; multiple layer perceptron (MLP), support vector machine (SVM), random forest (RF), and logistic regression (LR) were used for modeling; fivefold cross-validation was used to train the model; the validation group was used to evaluate and assess the predictive performance of the model, ROC curve was used to calculate the accuracy, sensitivity, and specificity of the model, and the area under curve (AUC) was used to assess the predictive performance of the model., Results: The accuracy and AUC of the MLP differentiation model for high-grade glioma and solitary brain metastasis in the validation group was 0.992, 1.000, respectively, while the sensitivity and specificity were 1.000, 0.968, respectively. The accuracy and AUC for the MLP and SVM differentiation model for high-grade glioma and small cell lung cancer brain metastasis in the validation group was 0.966, 1.000, respectively, while the sensitivity and specificity were 1.000, 0.929, respectively. The accuracy and AUC for the MLP differentiation model for high-grade glioma and non-small cell lung cancer brain metastasis in the validation group was 0.982, 0.999, respectively, while the sensitivity and specificity were 0.958, 1.000, respectively., Conclusion: The application of machine learning-based radiomics has a certain clinical value in differentiating glioma from solitary brain metastasis from lung cancer and its subtypes. In the HGG/SBM and HGG/NSCLC SBM validation groups, the MLP model had the best diagnostic performance, while in the HGG/SCLC SBM validation group, the MLP and SVM models had the best diagnostic performance., (© 2023. The Author(s).)

Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium , and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection.

Clostridium perfringens (C. perfringens) is an important Gram-positive anaerobic spore-forming pathogen that provokes life-threatening gas gangrene and acute enterotoxaemia, although it colonizes as a component of the symbiotic bacteria in humans and animals. However, the mechanisms by which C. perfringens is cleared from the host remains poorly understood, thereby impeding the development of novel strategies for control this infection. Here, we uncover a beneficial effect of extracellular traps (ETs) formation on bacterial killing and clearance by phagocytes. C. perfringens strain ATCC13124, and wild-type isolates CP1 and CP3 markedly trigger ETs formation in macrophages and neutrophils. As expected, visualization of DNA decorated with histone, myeloperoxidase (MPO) and neutrophils elastase (NE) in C. perfringens-triggered classical ETs structures. Notably, the bacteria-induced ETs formation is an ERK1/2-, P38 MAPK-, store-operated calcium entry (SOCE)-, NADPH oxidase-, histone-, NE-, and MPO-dependent process, and is independent of LDH activity. Meanwhile, the defect of bactericidal activity is mediated by impairing ETs formation in phagocytes. Moreover, In vivo studies indicated that degradation of ETs by DNase I administration leads to a defect in the protection against experimental gas gangrene, with higher mortality rates, exacerbated tissue damage, and more bacterial colonization. Together, these results suggest that phagocyte ETs formation is essential for the host defense against C. perfringens infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The clinical and imaging features of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 and symptomatic COVID-19 patients., Methods: The clinical and chest computed tomography imaging data of 47 asymptomatic carriers and 36 symptomatic COVID-19 patients were derived. All patients underwent 4-6 CT scans over a period of 2-5 days., Results: The bulk of asymptomatic carriers who developed symptoms and most of the COVID-19 patients were older than 18 years of age with a decreased lymphocyte count, abnormal hepatic and renal function, and increased D-dimer and C-reactive protein. In the early stage, the pulmonary lesion involved mostly 1-2 lobes at the peripheral area in asymptomatic carriers but more than three lobes at both the central and peripheral areas in COVID-19 patients. In the progression stage, the lesion of asymptomatic carriers extended from the peripheral to the central area, and no significant difference was found in the lesion range compared with the symptomatic control group. In early improvement stage, the lesion was rapidly absorbed, and lesions were located primarily at the peripheral area in asymptomatic carriers; contrastingly, lesions were primarily located at both the central and peripheral areas in symptomatic patients. Asymptomatic carriers reflected a significantly shorter duration from disease onset to peak progression stage compared with the symptomatic., Conclusions: Asymptomatic carriers are a potential source of transmission and may become symptomatic COVID-19 patients despite indicating less severe pulmonary damage, earlier improvement, and better prognosis. Early isolation and intervention can eliminate such carriers as potential sources of transmission and improve their prognosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xi Ma et al.)

Despite intense research in understanding Clostridium perfringens ( C. perfringens ) pathogenesis, the mechanisms by which it is cleared from the host are largely unclarified. In C. perfringens gas gangrene and enterocolitis model, Mlkl -/- mice, lacking mixed lineage kinase-like protein (MLKL), are more susceptible to C. perfringens infection. Mlkl deficiency results in a defect in inflammasome activation, and IL-18 and IL-1β releases. Exogenous administration of recombinant IL-18 is able to rescue the susceptibility of Mlkl -/- mice. Notably, K + efflux-dependent NLRP3 inflammasome signaling downstream of active MLKL promotes bacterial killing and clearance. Interestingly, the defect of bactericidal activity is also mediated by decreased classical extracellular trap formation in the absence of Mlkl . Our results demonstrate that MLKL mediates extracellular trap formation in a NLRP3 inflammasome-dependent manner. These findings highlight the requirement of MLKL for host defense against C. perfringens infection through enhancing NLRP3 inflammasome-extracellular traps axis., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Objective: To retrospectively investigate the value of various MRI image menifestations in the hepatobiliary phase (HBP), DWI and T2WI sequences in predicting the pathological grades of intrahepatic mass-forming cholangiocarcinoma (IMCC)., Materials and Methods: Forty-three patients of IMCCs confirmed by pathology were enrolled including 25 cases in well- or moderately-differentiated group and 18 cases in poorly-differentiated group. All patients underwent DWI, T2WI and HBP scan. The Chi square test was used to compare the differences in the general information. Logistic regression analysis was used to analyze the risk factors in predicting the pathological grade of IMCCs., Results: The maximal diameter of the IMCC lesion was < 3 cm in 11 patients, between 3 cm and 6 cm in 15, and > 6 cm in 17. Sixteen cases had intrahepatic metastasis, including 5 in the well- or moderately-differentiated group and 11 in the poorly-differentiated group. Seventeen (39.5%) patients presented with target signs in the DWI sequence, including 9 in the well- or moderately-differentiated group and 8 in the poorly-differentiated group. Twenty (46.5%) patients presented with target signs in the T2WI sequence, including 8 in the well- or moderately-differentiated group and 12 in the poorly-differentiated group. Nineteen cases (54.3%) had a complete hypointense signal ring, including 13 in the well- or moderately-differentiated group and 6 in the poorly-differentiated group. Sixteen (45.7%) cases had an incomplete hypointense signal ring, including 5 in the well- or moderately-differentiated group and 11 in the poorly-differentiated group. The lesion size, intrahepatic metastasis, T2WI signal, and integrity of a hypointense signal ring in HBP were statistically significantly different between two gourps. T2WI signal, presence or non-presence of intrahepatic metastasis, and integrity of hypointense signal ring were the independent influencing factors for pathological grade of IMCC., Conclusion: Target sign in T2WI sequence, presence of intrahepatic metastasis and an incomplete hypointense-signal ring in HBP are more likely to be present in poorly-differentiated IMCCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Zhuo, Wang, Zhang, Zhu, Wang, Yin and Gao.)

Objective: To investigate the value of diffusion-weighted imaging (DWI) combined with the hepatobiliary phase (HBP) Gd-BOPTA enhancement in differentiating intrahepatic mass-forming cholangiocarcinoma (IMCC) from atypical liver abscess., Materials and Methods: A retrospective analysis was performed on 43 patients with IMCCs (IMCC group) and 25 patients with atypical liver abscesses (liver abscess group). The DWI signal, the absolute value of the contrast noise ratio (│CNR│) at the HBP, and visibility were analyzed., Results: A relatively high DWI signal and a relatively high peripheral signal were presented in 29 patients (67.5%) in the IMCC group, and a relatively high DWI signal was displayed in 15 patients (60.0%) in the atypical abscess group with a relatively high peripheral signal in only one (6.7%) patient and a relatively high central signal in 14 (93.3%, 14/15). A significant (P<0.001) difference existed in the pattern of signal between the two groups of patients. On T2WI, IMCC was mainly manifested by homogeneous signal (53.5%), whereas atypical liver abscesses were mainly manifested by heterogeneous signal and relatively high central signal (32%, and 64%), with a significant difference ( P <0.001) in T2WI imaging presentation between the two groups. On the HBP imaging, there was a statistically significant difference in peripheral │CNR│ ( P < 0.001) and visibility between two groups. The sensitivity of the HBP imaging was significantly ( P =0.002) higher than that of DWI. The sensitivity and accuracy of DWI combined with enhanced HBP imaging were significantly ( P =0.002 and P <0.001) higher than those of either HBP imaging or DWI alone., Conclusion: Intrahepatic mass-forming cholangiocarcinoma and atypical liver abscesses exhibit different imaging signals, and combination of DWI and hepatobiliary-phase enhanced imaging has higher sensitivity and accuracy than either technique in differentiating intrahepatic mass-forming cholangiocarcinoma from atypical liver abscesses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Zhuo, Zhang, Ma, Ma, Zhao, Yin and Gao.)

Background: Pediatric COVID-19 is relatively mild and may vary from that in adults. This study was to investigate the epidemic, clinical, and imaging features of pediatric COVID-19 pneumonia for early diagnosis and treatment., Methods: Forty-one children infected with COVID-19 were analyzed in the epidemic, clinical and imaging data., Results: Among 30 children with mild COVID-19, seven had no symptoms, fifteen had low or mediate fever, and eight presented with cough, nasal congestion, diarrhea, headache, or fatigue. Among eleven children with moderate COVID-19, nine presented with low or mediate fever, accompanied with cough and runny nose, and two had no symptoms. Significantly (P < 0.05) more children had a greater rate of cough in moderate than in mild COVID-19. Thirty children with mild COVID-19 were negative in pulmonary CT imaging, whereas eleven children with moderate COVID-19 had pulmonary lesions, including ground glass opacity in ten (90.9%), patches of high density in six (54.5%), consolidation in three (27.3%), and enlarged bronchovascular bundles in seven (63.6%). The lesions were distributed along the bronchus in five patients (45.5%). The lymph nodes were enlarged in the pulmonary hilum in two patients (18.2%). The lesions were presented in the right upper lobe in two patients (18.1%), right middle lobe in one (9.1%), right lower lobe in six (54.5%), left upper lobe in five (45.5%), and left lower lobe in eight (72.7%)., Conclusions: Children with COVID-19 have mild or moderate clinical and imaging presentations. A better understanding of the clinical and CT imaging helps ascertaining those with negative nucleic acid and reducing misdiagnosis rate for those with atypical and concealed symptoms.

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury in which severe inflammatory responses induce cell apoptosis, necrosis, and fibrosis. This study investigated the role of lung adenocarcinoma transcript 1 (MALAT1) in ARDS and the underlying mechanism involved. The expression of MALAT1, microRNA-150-5p (miR-150-5p), and intercellular adhesion molecule-1 (ICAM-1) was determined in ARDS patients and lipopolysaccharide (LPS)-treated human pulmonary microvascular endothelial cells (HPMECs). Next, the interactions among MALAT1, miR-150-5p, and ICAM-1 were explored. Gain- or loss-of-function experiments in HPMECs were employed to determine cell apoptosis and inflammation. Furthermore, a mouse xenograft model of ARDS was established in order to verify the function of MALAT1 in vivo . MALAT1 and ICAM-1 were upregulated, while miR-150-5p was downregulated in both ARDS patients and LPS-treated HPMECs. MALAT1 upregulated ICAM-1 expression by competitively binding to miR-150-5p. MALAT1 silencing or miR-150-5p overexpression was shown to suppress HPMEC apoptosis, decrease the expressions of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) and E-selectin in HPMECs, as well as alleviated lung injury in nude mice. These findings demonstrated that MALAT1 silencing can potentially suppress HPMEC apoptosis and alleviate lung injury in ARDS via miR-150-5p-targeted ICAM-1, suggestive of a novel therapeutic target for ARDS.

Antarctic krill ( Euphausia superba ) is one of the important bioresources in Antarctic waters, containing many bioactives (e.g., astaxanthin), which have a highly potential value for commercial exploitation. In this study, the effects of processing methods on the content, structural isomers, and composition of astaxanthins (free astaxanthin and astaxanthin esters) were studied. Three drying methods, comprising freeze-drying, microwave drying, and hot-air drying, were used. Free astaxanthin (Ast), astaxanthin monoesters (AM), and astaxanthin diesters (AD) in boiled krill (control) and dried krill were extracted and analyzed using high-resolution mass spectrometry with ultraviolet detection. After the three processes, total astaxanthin loss ranged from 8.6 to 64.9%, and the AM and AD contents ranged from 78.3 to 16.6 and 168.7 to 90.5 μg/g, respectively. Compared to other kinds of astaxanthin esters, astaxanthin esters, which linked to eicosapentaenoic acid and docosahexaenoic acid, as well as the Ast, were more easily degraded, and AM was more susceptible to degradation than AD. All- E -astaxanthin easily transformed to the 13 Z- astaxanthin than to the 9 Z- astaxanthin during the drying process, but the proportions of optical isomers changed due to drying by no more than 5%. The results suggested that freeze-drying, low-power microwave drying (≤1 kW), and low-temperature hot-air drying (≤60 °C) are optimal drying methods for ensuring the quality of krill products., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Objective: To investigate the clinical features of lung natural killer (NK)/T cell lymphoma. Methods: The clinical data of patients with lung NK/T-cell lymphoma confirmed by pathology who were hospitalized due to lung shadow and initially treated as pneumonia from the First Affiliated Hospital of Zhengzhou University was collected from June 2013 to January 2019. The clinical manifestations, laboratory tests, chest CT findings, treatment procedures, outcomes, and misdiagnosis were retrospectively analyzed. Results: Among the 15 enrolled patients with lung NK/T-cell lymphoma, 5 were primary and the other 10 were secondary. There were 8 males and 7 females, aged 20-76 years. Fever presented in 14 cases, dyspnea was observed in 4 cases and 2 cases had cough. A total of 12 cases had leukopenia, 10 cases had mononuclear cell increase, 10 cases had liver dysfunction, 13 cases had elevated serum lactate dehydrogenase (LDH), and 2 cases of primary lung NK/T-cell lymphoma had increased pleural LDH and adenosine deaminase. Five cases of primary lung NK/T-cell lymphoma had multiple lung lesions, with diffuse multiple solid shadows, ground glass and patchy shadows, some with nodules; 10 cases of secondary lung NK/T-cell lymphoma showed nodular masses, some were accompanied by patchy shadows, and most patients had multiple lesions scattering in the lung. All the fifteen patients were misdiagnosed as pneumonia in the early stage, and then were diagnosed by percutaneous lung biopsy or transbronchial biopsy. Six patients underwent chemotherapy, of which 1 achieved complete response, 4 were in follow-up and 1 died of respiratory failure; 5 patients died of respiratory failure after diagnosis and 4 patients discharged and died within half a year. Conclusions: The lung NK/T-cell lymphoma are rare. The clinical manifestations and pulmonary imaging findings are indistinguishable from pulmonary inflammatory lesions. They are easily misdiagnosed as pneumonia. Early CT-guided percutaneous lung biopsy or transbronchial biopsy can improve the diagnostic accuracy.

Currently, exosome-enclosed microRNAs (miRs) in exhaled breath have potential for biomarker discovery in patients with pulmonary diseases. This study was performed to investigate the roles of M2 macrophage-derived exosomes expressing miR-328 in pulmonary fibrosis (PF). Microarray-based analysis was used to screen differentially expressed genes (DEGs) and regulatory miRs in PF. The miR-target relationship between FAM13A and miR-328 was confirmed. The expression of FAM13A and miR-328 was measured in PF rats, and gain- and loss-of-function assays were conducted to determine the regulatory effects of FAM13A and miR-328 on PF. In addition, exosomes derived from M2 macrophages were isolated and then cocultured with pulmonary interstitial fibroblasts to identify the role of these exosomes in PF. Furthermore, the effects of M2 macrophage-derived exosomes overexpressing miR-328 on pulmonary fibroblast proliferation and the progression of PF were assessed in vivo. miR-328 might perform a vital function in PF by regulating FAM13A. FAM13A expression was downregulated while miR-328 expression was upregulated in rats with PF, and a miR-target relationship between miR-328 and FAM13A was observed. Additionally, miR-328 overexpression and FAM13A silencing each were suggested to promote pulmonary interstitial fibroblast proliferation and the expression of Collagen 1A, Collagen 3A and α-SMA. Then, in vitro experiments demonstrated that M2 macrophage-derived exosomes overexpressing miR-328 contributed to enhanced pulmonary interstitial fibroblast proliferation and promoted PF. Furthermore, in vivo experiments confirmed the promotive effects of M2 macrophage-derived exosomes overexpressing miR-328 on the progression of PF. Collectively, the results showed that M2 macrophage-derived exosomes overexpressing miR-328 aggravate PF through the regulation of FAM13A.

Objective: To analyze the clinical features of infective endocarditis with septic pulmonary embolism, and to improve the diagnosis and treatment of the disease. Methods: Retrospective analysis of clinical manifestations, blood culture, echocardiography, chest CT and diagnosis and treatment of 16 patients with infective endocarditis and septic pulmonary embolism in the First Affiliated Hospital of Zhengzhou University from January 2010 to June 2017 was carried out, and the clinical features of the disease were summarized. Results: Out of the 16 patients, 4 were males and 12 were females, aged (29.5±9.7) years old, 12 patients were with congenital heart disease. The main clinical manifestations were fever, cough, dyspnea, hemoptysis. There were 7 cases with positive blood culture, and 6 of them were Streptococcus. Echocardiography revealed cardiac vegetations, and all were from right heart. Chest CT was characterized by multiple pulmonary lesions, mainly characterized by multiple nodules and small patch shadows. All 16 patients were initially misdiagnosed as pneumonia. All patients were treated with antibiotics intravenously, 13 patients underwent cardiac surgery, 6 patients were cured, 8 patients improved, and 2 patients were discharged automatically. Conclusions: Infective endocarditis with septic pulmonary embolism is easily misdiagnosed. In patients with fever and multiple shadows in the lungs, the possibility of right heart infective endocarditis should be considered. The diagnosis can be confirmed once cardiac vegetations are found by echocardiography, and repeated echocardiographic examinations can be performed if necessary. The prognosis of patients treated with surgery as early as possible on the basis of anti-infection is good.

Objective: Investigate the expression and significance of eosinophils in brucellosis., Methods: Retrospective analysis of clinical data for 151 brucellosis patients (BR group), complete blood count and blood bacterial culture etc.; in addition, 150 general bacterial infection patients (BI group) and 135 persons in healthy physical condition upon testing (NC group) are selected respectively as the control groups to comparatively study expression of white blood cells and eosinophils for brucellosis patients. Adopt t test to compare measurement data., Results: In comparison with BI group, WBC, NE, EO, MO, NE% and EO% in BR group are reduced but LY, LY% and MO% are increased and such difference shows statistical significance (P<0.01). In comparison with NC group, difference of WBC and NE in BR group shows no statistical significance (P>0.05). NE%, EO and EO% are reduced but MO, LY% and MO% are increased and such difference shows statistical significance (P<0.01). LY is increased and the difference shows statistical significance (P<0.05). White blood cell count is normal or is reduced among most of Brucellosis patients, accounting for 90.73% (137/151); the patients whose eosinophils are reduced account for 75.50% (114/151) and those whose eosinophils disappear are about 18.54% (28/151)., Conclusion: There is an incidence rate of eosinophils decrease or disappearance in Brucellosis and it shows the indication significance in the diagnosis of early disease.

Background: Lung cancer poses a severe threat to human life. Biomarkers of cancers are helpful in the diagnosis and treatment of patients with cancers. Biomarkers of lung cancers are rare, and thus deserve further research., Objective: The objective of the present study was to explore the expression of Fascin-1 in human lung cancer and paracarcinoma tissue, its correlation with clinicopathological characteristics in patients with lung cancer, and study the possible relationship between Fascin-1 expression and clinical-biological behavior of lung cancer., Method: This study used the MaxVision two-step immunohistochemical detection method to detect Fascin-1 expression in 84 of lung cancer and paracarcinoma tissues. This study set the expression of Fascin-1 in vascular endothelial cells as the positive control, and used phosphate buffered saline (replacing the primary antibodies) as negative control., Result: Of all the 84 lung cancer tissues and paracarcinoma tissues, positive expression of the Fascin-1 protein were detected in 78 cases (92.9%) and 27 cases (32.1%), respectively, and the difference was statistically significant (P<0.05). Differences in Fascin-1 expression between different age groups, clinical stages, and lymph node metastases were statistically significant (P<0.05), while differences in Fascin-1 expression between sexes, tumor stages, and pathological types demonstrated no statistical significance (P>0.05). The survival times of the patients with different Fascin-1 protein-positive expressions in lung cancer tissues were statistically significant (P>0.05), while the survival times of the patients with different Fascin-1 protein-positive expressions in paracarcinoma tissues were not statistically significant (P>0.05)., Conclusion: In lung cancer, Fascin-1 expression was closely related to tumor invasion and metastasis, and the difference in expression of Fascin-1 had a significant effect on the survival time of the lung cancer patients. Therefore, Fascin-1 might be expected to serve as a possible potential biomarker of lung cancer.

Purpose: To investigate the effects and mechanism of suberoylanilide hydroxamic acid (SAHA) on the proliferation and apoptosis of human hepatoma cell line Bel-7402., Methods: SAHA treatment and control groups were designed in this study. To observe the morphological characteristics and the inhibition of cell proliferation, we conducted confocal microscopy and methyl thiazolyl tetrazolium (MTT) assay, respectively. Changes in cell apoptosis and cell cycle were then determined by flow cytometry. Real-time polymerase chain reaction (RT-PCR) was also conducted to detect the mRNA expressions of p53, bcl-2 and bax genes. Caspase-3 protein activity was determined by spectrophotometry., Results: Cell proliferation in the SAHA treatment group could be inhibited in a time- and dose-dependent manner. FCM analysis showed that the early apoptosis rate in the SAHA treatment group increased significantly. Furthermore, cell cycle was arrested at the S phase. RT-PCR assay confirmed that SAHA could upregulate the mRNA expressions of p53 and bax genes. By comparison, SAHA could downregulate the mRNA expression of bcl-2. SAHA induced apoptosis by activating the caspase-3 pathway., Conclusion: SAHA inhibited cell proliferation and promoted human hepatoma Bel-7402 cell apoptosis by affecting caspase-3 protein activity and mRNA expressions of p53, bcl-2 and bax genes.

Aim: To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on proliferation and apoptosis of a human hepatocellular carcinoma cell line (HepG2.2.15) and hepatitis B virus (HBV) replication., Methods: HepG2.2.15 cells were treated with different concentrations of SAHA. Cell morphology was examined by confocal laser scanning microscopy, and cell proliferation was determined using a MTT colorimetric assay. Flow cytometry was used to detect apoptosis and determine cell cycle phase, while hepatitis B surface antigen and hepatitis B e antigen content were measured using chemiluminescence. Reverse transcription polymerase chain reaction was performed to measure HBV DNA in cell lysate., Results: Cell proliferation rates were significantly reduced by the addition of SAHA. The inhibitory effect of SAHA on cell proliferation was both time- and dose-dependent. After 24 h of treatment with SAHA, the early cell apoptotic rate increased from 3.25% to 21.02% (P = 0.041). The proportion of G₀/G₁ phase cells increased from 50.3% to 65.3% (P = 0.039), while that of S phase cells decreased from 34.9% to 20.6% (P = 0.049). After 48 h of treatment, hepatitis B surface antigen and hepatitis B e antigen content increased from 12.33 ± 0.62 to 25.42 ± 2.67 (P = 0.020) and 28.92 ± 1.24 to 50.48 ± 1.85 (P = 0.026), respectively. Furthermore, HBV DNA content increased from 4.54 ± 0.46 to 8.34 ± 0.59 (P = 0.029)., Conclusion: SAHA inhibits HepG2.2.15 cell proliferation, promotes apoptosis, and stimulates HBV replication. In combination with anti-HBV drugs, SAHA may potentially be used cautiously for treatment of hepatocellular carcinoma.

Objective: To study the effects of glucocorticoid on airway mucus secretion in asthma., Methods: Twenty-four BALB/c mice were randomly divided into 3 equal groups: asthma group [ovalbumin (OVA) and aluminum hydroxide were injected intraperitoneally on day 0 and day 14 so as to establish mouse asthma model and aerosol inhalation of OVA PBS was conducted for 30 min on the days 21, 22, and 24], asthma + dexamethasone group (OVA and aluminum hydroxide were injected intraperitoneally on days 0 and 14, aerosol inhalation of OVA PBS was conducted for 30 min on the days 21, 22, and 24, and dexamethasone was injected intraperitoneally 1 hour before the aerosol inhalation), and control group (aerosol inhalation of PBS was conducted instead). Twenty-fours hours after the last exposure the mice were anesthetized deeply and their left lungs were excised to collect the bronchoalveolar lavage fluid (BALF) to calculate the numbers of total cells and eosinophils, then Alcian blue/periodic acid-Schiff staining and immunohistochemistry of the air passage were conducted to measure the expression levels of MUC5AC mRNA and protein and interleukin-4 (IL-4) mRNA., Results: The numbers of total cells in the BALF of the asthma group were (12.50 +/- 0.14) x 10(9)/L and (1.12 +/- 0.10) x 10(9)/L respectively, both significantly higher than those of the control group, (6.49 +/- 0.05) x 10(9)/L and (0.05 +/- 0.02) x 10(9)/L respectively (both P < 0.01), and were significantly higher than those of the asthma + dexamethasone group, (6.68 +/- 0.03) x 10(9)/L and (0.06 +/- 0.01) x 10(9)/L respectively too (both P < 0.01). The levels of MUC5AC mRNA, MUC5AC protein, and IL-4 mRNA of the asthma group were 0.5341 +/- 0.303, 0.1906 +/- 0.0008, and 0.6265 +/- 0.0932 respectively, all significantly higher than those of the control group (0.1994 +/- 0.0128, 0.1194 +/- 0.0007, and 0.2389 +/- 0.0289 respectively, all P < 0.01), and those of the asthma + dexamethasone group (0.2729 +/- 0.0345, 0.1456 +/- 0.0003, and 0.2424 +/- 0.0260, all P < 0.05). The MUC5AC protein expression and mRNA expression, and IL-4 mRNA expression of the asthma group were 0.1906 +/- 0.0008, 0.5341 +/- 0.0303, and 0.6265 +/- 0.0932 respectively, all significantly higher than those of the control group (0.1194 +/- 0.0007, 0.1994 +/- 0.0128, and 0.2398 +/- 0.0289 respectively, all P < 0.01). The MUC5AC protein expression and mRNA expression, and IL-4 mRNA expression of the asthma + dexamethasone group were 0.1456 +/- 0.0003, 0.2729 +/- 0.0345, and 0.2424 +/- 0.0260 respectively, all significantly lower than those of the asthma group (all P < 0.01). The MUC5AC protein expression and mRNA expression of the asthma + dexamethasone group were still significantly higher than those of the control group (both P < 0.01), however, the IL-4 mRNA expression of the asthma + dexamethasone group was not significantly different from that of the control group (P > 0.05)., Conclusion: Relieving the inflammation, glucocorticoid may play a role in the treatment of excessive mucus production through down-regulating the expression of MUC5AC and of IL-4.

Aim: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection., Methods: Twenty patients with persistent HBV infection were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GM-CSF, IL-4, FLt-3,TNF-alpha and 100mL.L(-1 )of fetal calf serum for a total of 10-12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation, mytomycin C-treated DC were incubated with allogenic T cells., Results: A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLA-DR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0.84 for CD86,P<0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCs simultaneously increased compared with healthy subjects (86 +/- 15 vs 170 +/- 22 micromol.L(-1), P <0.05)., Conclusion: The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV.

Results: Based on the mathematical model of high-level expression of heterologous genes in prokaryotic vector pBV220, we developed a program GeneDn for high-level expression design of natural and synthetic genes. AVAILIBILITY: The program is written in Turbo Pascal 7.0. The source code and related material are available upon request., Contact: wujj@nic.bmi.ac.cn