Lactate ameliorates palmitate-induced impairment of differentiative capacity in C2C12 cells through the activation of voltage-gated calcium channels.

Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of skeletal muscle regeneration dysfunction. This study aimed to examine the effects and mechanisms of lactate (Lac) treatment on PA-induced impairment of C2C12 cell differentiation capacity. Furthermore, the involvement of voltage-gated calcium channels in this context was examined. In this study, Lac could improve the PA-induced impairment of differentiative capacity in C2C12 cells by affecting Myf5, MyoD and MyoG. In addition, Lac increases the inward flow of Ca2+, and promotes the depolarization of the cell membrane potential, thereby activating voltage-gated calcium channels during C2C12 cell differentiation. The enchancement of Lac on myoblast differentiative capacity was abolished after the addition of efonidipine (voltage-gated calcium channel inhibitors). Therefore, voltage-gated calcium channels play an important role in improving PA-induced skeletal muscle regeneration disorders by exercising blood Lac. Our study showed that Lac could rescue the PA-induced impairment of differentiative capacity in C2C12 cells by affecting Myf5, MyoD and MyoG through the activation of voltage-gated calcium channels.

Lactate induces C2C12 myoblasts differentiation by mediating ROS/p38 MAPK signalling pathway.

Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle.

Role of SIRTl/Nrf2/HO-l pathway in attenuation of learning and memory impairment by sevoflurane postcondition in a mouse model of hemorrhagic shock and resuscitation / 中国药理学通报

Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.

The role of the angiography-derived index of microcirculatory resistance in the prognosis of patients with dilated cardiomyopathy.

Background: The coronary angiography-derived index of microcirculatory resistance (caIMR) is a novel noninvasive method to assess coronary microvascular dysfunction (CMD). However, the association between caIMR and the prognosis of patients with dilated cardiomyopathy (DCM) is unclear. We aimed to explore the role of the caIMR in evaluating the outcome of patients with DCM. Methods: We consecutively and retrospectively enrolled patients with DCM in the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, from January 2013 to January 2018. The caIMR was calculated for eligible patients. The primary end point in this study was composite events, including rehospitalization related to heart failure (HF), device implantation, heart transplantation, or cardiac death. Patients were categorized into groups based on whether they had composite events (the events and no-events groups), and differences in the baseline and end points between these two groups were analyzed. Results: A total of 95 eligible patients with DCM were enrolled in the study, 36 of whom had end point events. The best cutoff values of the caIMR for the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) were >29.8 with an area under the curve (AUC) of 0.828, >25.5 with an AUC of 0.720, and >29.7 with an AUC of 0.717, respectively (all P values <0.001). Patients were then classified into the higher caIMR group and the lower caIMR group based on the cutoff value. Kaplan-Meier analyses showed that patients with a higher caIMR had increased cumulative risks of end point events regardless of the cutoff values for the LAD, LCX, and RCA (all log-rank P values <0.001). After adjustment for confounders, Cox regression analyses indicated that LAD-caIMR was an independent risk factor for end point events in patients with DCM [hazard ratio (HR) =1.11; 95% CI: 1.06-1.16]. Conclusions: A higher caIMR was significantly associated with the poor prognosis of patients with DCM.

Role of SIRT1/NLRP3 signaling pathway in sevoflurane postconditioning-induced attenuation of oxygen-glucose deprivation and restoration injury in HT22 cells / 中华麻醉学杂志

Objective:To evaluate the role of silent information regulator-1 (SIRT1)/nucleotide-binding domain (NOD)-like receptor protein-3 (NLRP3) signaling pathway in sevoflurane postconditioning-induced attenuation of oxygen-glucose deprivation and restoration (OGD/R) injury in mouse hippocampal neuronal cell line (HT22) cells.Methods:The HT22 cells were seeded in a culture plate (96-well plate, 100 μl/well; 6-well plate, 2 ml/well) at the density of 5×10 4 cells/ml or in a culture dish (6 cm in diameter) and then divided into 4 groups ( n=24 each) using a random number table method: control group (Control group), OGD/R group, sevoflurane postconditioning group (SPC group), and SIRT1 small interfering RNA group (si-SIRT 1 group). In Control group, cells were cultured at 37 ℃ in normal culture atmosphere. In OGD/R group, the culture medium was replaced with glucose-free serum-free culture medium, and cells were exposed to 95% N 2+ 5% CO 2 for 4 h in an incubator at 37 ℃, and then the glucose-free serum-free culture medium was replaced with the primary culture medium, and cells were cultured for 24 h at 37 ℃ in normal culture atmosphere. In SPC group, the glucose-free serum-free culture medium was replaced with the primary cell culture medium after 4-h oxygen and glucose deprivation, the cells were put into the hypoxia incubator chamber which was filled with 2% sevoflurane immediately after start of reoxygenation, then the chamber was placed in an incubator and the cells were cultured for 1 h at 37 ℃ in normal culture atmosphere, and finally the cells were removed from the chamber and cultured for 23 h at 37 ℃ in normal culture atmosphere. In si-SIRT1 group, SIRT1 small interfering RNA 150 pmol was added at 24 h before surgery, cells were then incubated, and the other procedures were the same as those previously described in group SPC. The cell survival rate was determined using MTT assay. TUNEL assay was used to detect cell apoptosis, and the apoptosis rate was calculated. The expression of SIRT1, NLRP3, IL-1β and IL-18 mRNA was determined using polymerase chain reaction. The expression of SIRT1, NLRP3, interleukin-1beta (IL-1β) and IL-18 was detected using Western blot. Results:Compared with Control group, the cell survival rate was significantly decreased, the apoptosis rate was increased, the expression of SIRT1 protein and mRNA was down-regulated, and the expression of NLRP3, IL-1β and IL-18 protein and mRNA was up-regulated in OGD/R group ( P<0.05). Compared with OGD/R group, the cell survival rate was significantly increased, the apoptosis rate was decreased, the expression of SIRT1 protein and mRNA was up-regulated, and the expression of NLRP3, IL-1β and IL-18 protein and mRNA was down-regulated in SPC group ( P<0.05). Compared with SPC group, the cell survival rate was significantly decreased, the apoptosis rate was increased, the expression of SIRT1 protein and mRNA was down-regulated, and the expression of NLRP3, IL-1β and IL-18 protein and mRNA was up-regulated in si-SIRT1 group ( P<0.05). Conclusions:Activation of SIRT1-NLRP3 signaling pathway is involved in sevoflurane postconditioning-induced attenuation of OGD/R injury in HT22 cells.

Predictive value of deep learning-based coronary artery calcification score for coronary artery disease in type 2 diabetes mellitus / 中华放射学杂志

Objective:To explore the predictive value of deep learning (DL)-based coronary artery calcification score (CACS) for obstructive coronary artery disease (CAD) and noncalcified plaque/mixed plaque in type 2 diabetes mellitus (T2DM).Methods:Forty hundred and twenty-four consecutive T2DM patients who accepted CACS scan and coronary CT angiography (CCTA) from December 2012 to December 2019 were included retrospectively, with clinical risk factors and plaque features collected. Plaque composition was classified as calcified, non-calcified or mixed plaque. Obstructive CAD was defined as maximum diameter stenosis≥50%. CACS was calculated with a fully automated method based on DL. Univariate and multivariate logistic regressions were applied to select statistically significant factors and the odds ratios(ORs) were measured. Receiver operating characteristic (ROC) curve was evaluated to assess the predictive performance.Results:Increased CACS was associated with a significantly higher odds of obstructive CAD in CCTA (adjusted ORs were 2.22, 6.18 and 16.98 for CACS=1-99, 100-299, 300-999 vs. CACS=0, and P values were 0.009,<0.001,<0.001 respectively). The area under ROC curve (AUC) of CACS to predict obstructive CAD was 0.764. Compared with 0, increased CACS was associated with increased risk of non-calcified/mixed plaque (adjusted ORs were 2.75, 4.76, 5.29 for CACS=1-99, 100-299, 300-999 respectively and P values were 0.001,<0.001,<0.001 respectively). The AUC of CACS to predict non-calcified/mixed plaque was 0.688. It took 1.17 min to perform automated measurement of CACS based on DL in total, which was significantly less than manual measurement of 1.73 min ( P<0.001). Conclusion:DL-based CACS can predict obstructive CAD and non-calcified plaque/mixed plaque in T2DM, which is economical and efficient, and has important value for clinical diagnosis and treatment.

Predictive value of thrombus enhancement and thrombus permeability in cardioembolic stroke with acute middle cerebral artery occlusion based on CT / 中华放射学杂志

Objective:To investigate the predictive value of thrombus enhancement (TE) and thrombus permeability in cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.Methods:The clinical and image data of 93 patients with acute middle cerebral artery occlusion who were admitted to the First Affiliated Hospital of Soochow University within 12 hours after onset from January 2020 to July 2022 were retrospectively analyzed. According to the TOAST criteria, the patients were divided into the cardioembolism (CE) group (43 cases) and the large artery atherosclerosis (LAA) group (50 cases). All patients received noncontrast CT and CT angiography, and then thrombus permeability [thrombus attenuation increase (TAI), void fraction (ε)] and TE were assessed. Independent sample t-test, Mann-Whitney U test and χ2 test were used in univariable analysis between two groups. Multivariable logistic regression analysis was used to explore the independent influencing factors for cardioembolic stroke and establish a logistic model. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive value of TAI, ε, TE and the logistic model in cardioembolic thrombus with acute middle cerebral artery occlusion. Results:There were statistically significant differences in sex, atrial fibrillation, hypertension, diabetes mellitus, smoking, baseline National Institutes of health stroke scale (NIHSS), TAI, ε and TE between the CE group and the LAA group ( P<0.05). Binary logistics regression analysis showed that TAI (OR=1.300, 95%CI 1.147-1.473, P<0.001), hypertension (OR=0.116, 95%CI 0.025-0.535, P=0.006) and baseline NIHSS (OR=1.165, 95%CI 1.040-1.304, P=0.008) were independent influencing factors for cardioembolic thrombus. The ROC curve indicated that the logistic model predicted cardioembolic thrombus with the highest AUC of 0.907 (95%CI 0.848-0.966). TE predicted cardioembolic thrombus with the highest sensitivity of 90.7%. Conclusion:TE and thrombus permeability have application value for predicting cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.

Predictive value of thrombolysis in myocardial infarction frame count for coronary microvascular dysfunction evaluated with an angiography-derived index of microcirculatory resistance in patients with coronary slow flow.

Background: The association between coronary slow flow (CSF) and coronary microvascular dysfunction (CMD) remains unclear. The objective of this study was to evaluate the correlation between the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and the index of microcirculatory resistance (IMR). Methods: We consecutively enrolled patients with CSF from January 2017 to March 2018. Concurrently, we randomly selected control participants with normal flow arteries at a ratio of 3:1. Two cardiologists performed the measurements of CTFC. Coronary angiography-derived IMR (caIMR) was used to assess CMD. The caIMR was analyzed by an independent agency, with CMD being defined as caIMR >40 U. Results: A total of 111 patients with CSF and 39 patients without CSF were enrolled in this retrospective study. Compared with the non-CSF group, the CSF group had a greater proportion of males (65.8% vs. 23.1%; P<0.001) and a lower prevalence of hypertension (47.7% vs. 67.7%; P=0.042). Additionally, the CSF group had higher CTFC, coronary angiography-derived fractional flow reserve (caFFR), and caIMR regardless of left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) (all P values <0.001). A strong correlation between CTFC and caIMR was observed for all arteries (all P values <0.001). In the univariate analysis, male sex [hazard ratio (HR) =2.63, 95% CI: 1.30-5.31], E/e' (HR =0.88, 95% CI: 0.78-0.99), CTFC (HR =1.12, 95% CI: 1.09-1.16), and caFFR (HR =1.81, 95% CI: 1.50-2.17) were significantly correlated with CMD. After adjusting for covariates, male sex (HR =2.72, 95% CI: 1.22-6.06), CTFC (HR =1.10, 95% CI: 1.07-1.14), and caFFR (HR =1.22, 95% CI: 1.00-1.50) were independent predictors for CMD. Additionally, the best cutoff value of CTFC of all arteries for predicting CMD was 38 frames, with an area under the curve of 0.873, a sensitivity of 92.8%, and a specificity of 63.8% (P<0.001). Moreover, the best cutoff value of CTFC of LAD, LCX, and RCA to identify CMD was 35 frames, 52 frames, and 50 frames, respectively (all P values <0.001). Conclusions: CTFC correlated well with caIMR and had a strong predictive power to identify CMD.

Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p.

AIM: Accumulating evidence suggests that lncRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise function of most lncRNAs in glioma remains unknown. In this study, we explored the role of long intergenic non-protein coding RNA 1018 (LINC01018) in human glioma. METHODS: Expression levels of LINC01018 and miR-182-5p in clinical glioma tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). Cell proliferation, migration, and invasion were determined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Epithelial-mesenchymal transition (EMT) related proteins were measured by Western blotting. Direct relationship between LINC01018 and miR-182-5p was tested by dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and rescue assays. Lastly, bioinformatics analyses were conducted to predict the downstream factors of LINC01018/miR-182-5p axis in glioma. RESULTS: LINC01018 was significantly down-regulated in glioma tissues and cell lines. Overexpression of LINC01018 dramatically inhibited cell proliferation, migration, and invasion and reverse EMT process in glioma. LINC01018 directly target to miR-182-5p. Forced up-regulation of miR-182-5p reversed the inhibitory effects on proliferative and metastatic abilities of glioma cells with LINC01018 overexpression. Lastly, the bioinformatics analyses revealed that LINC01018/miR-182-5p axis mediated a cluster of downstream genes (ADRA2C, RAB6B, RAB27B, RAPGEF5, STEAP2, TAGLN3, and UNC13C), which were potential key factors in the development of glioma. CONCLUSION: LINC01018 inhibits cell proliferation and metastasis in human glioma by targeting miR-182-5p, and should be considered as a potential therapeutic target in this cancer.

Effect of blood pressure on the mortality of the elderly population with (pre)frailty: Results from NHANES 1999-2004.

Backgrounds: The optimal blood pressure of elderly people with frailty or prefrailty is still unclear. We aimed to explore the relationship between blood pressure and mortality in the elderly with (pre)frailty. Methods: A total of 528 participants aged 60 years and older were exacted for analyses of the association between blood pressure and mortality from the database of the National Health and Nutrition Examination Survey (NHANES) (1999-2004). Kaplan-Meier curves and log-rank tests were used to investigate the differences in survival between groups. Multivariable Cox regression and restricted cubic spline (RCS) analyses were applied to explore the relationship between blood pressure and mortality. Results: During the median follow-up time of 116.5 [interquartile range (IQR) of 60-186] months, 363 all-cause deaths and 122 cardiac deaths were documented. For all-cause mortality, more participants died with systolic blood pressure (SBP) < 110 mmHg and SBP ≥ 170 mmHg (log-rank p = 0.004). After adjusting for confounders, SBP < 110 mmHg [hazard ratio (HR) 1.52, 95% CI: 0.96-2.41] and SBP ≥ 170 mmHg (HR 1.53, 95% CI: 1.09-2.15) had higher risks of all-cause mortality compared with SBP within 130-150 mmHg. There were no significant differences in all-cause mortality among DBP categories. A J-curve association was identified between the SBP and hazard ratio for all-cause mortality (p for non-linear = 0.028), with 138.6 mmHg as the lowest hazard ratio of all-cause mortality; each 10 mmHg of SBP rise was associated with a 9% increased risk in all-cause mortality (HR 1.09, 95% CI 1.00-1.18). Additionally, a non-linear relationship was determined between SBP and the hazard ratio for cardiac deaths (p for non-linear = 0.030), with 140.1 mmHg as the lowest hazard ratio of cardiac deaths. When SBP was higher than 140.1 mmHg, each 10 mmHg rise in SBP was associated with a 17% increased risk of cardiac deaths (HR 1.17, 95% CI: 1.02-1.34). Conclusion: Both lower and higher SBP levels are associated with higher risks of all-cause mortality in older individuals with (pre)frailty. There are J-shaped associations between SBP and mortality, with the optimal SBP being approximately 140 mmHg for this population specifically.

The fat attenuation index around coronary artery measurement on coronary calcium score images and coronary CT angiography images: a comparison study / 中华放射学杂志

Objective:To investigate the difference in the peri-coronary fat attenuation index (FAI) between using coronary calcium score (CCS) images and coronary CT angiography (CCTA) images, and to explore the feasibility and befitting threshold of FAI measured on CCS images.Methods:The clinical and imaging data of patients who underwent CCTA examination from August 2019 to August 2020 were retrospectively analyzed in the First Affiliated Hospital of Soochow University. According to the inclusion and exclusion criteria, there were 122 cases in non-calcified plaque group (144 coronary arteries) and 97 cases in none-plaque group (186 coronary arteries). The coronary arteries were delineated both on CCS and CCTA images with Perivascular Fat Analysis Tool; the regions of interest of peri-coronary adipose tissue were generated automatically after setting the threshold of fat tissue. Then the FAI value was calculated. The thresholds were set in four levels (-190--30, -185--25, -180--20 and -175--15 HU) for CCS images and one level (-190--30 HU) for CCTA images. The intra-class correlation coefficient (ICC) was used to evaluate the consistency of the measurements of FAI values on CCS and CCTA images between the two physicians. Paired t test was used to compare the differences of FAI values between CCS and CCTA images, and Pearson correlation coefficient was used to evaluate the correlation between CCS-FAI and CCTA-FAI. Results:(1) FAI values measured on CCS and CCTA images by 2 physicians showed good consistency; (2) At the threshold of -185--25 HU, there was no significant difference in FAI values between the CCS and CCTA images for non-calcified plaque group [(-84.15±5.99)HU vs. (-83.83±5.98)HU, t=0.79, P=0.429], as well as for the none-plaque group [(-83.41±5.75)HU vs.(-83.84±6.25)HU, t=-1.08, P=0.280]; (3) There were significant differences on FAI values between the CCS images and CCTA images at the threshold of -190--30、-180--20 and -175--15 HU (all P<0.05); (4) There were moderate correlations on FAI values between the CCS images and CCTA images under different thresholds both in non-calcified plaque group and none-plaque group. Conclusion:It is feasible to measure FAI on CCS images, and the befitting threshold is -185--25 HU.

Axillary lymph node metastasis prediction by contrast-enhanced computed tomography images for breast cancer patients based on deep learning.

When doctors use contrast-enhanced computed tomography (CECT) images to predict the metastasis of axillary lymph nodes (ALN) for breast cancer patients, the prediction performance could be degraded by subjective factors such as experience, psychological factors, and degree of fatigue. This study aims to exploit efficient deep learning schemes to predict the metastasis of ALN automatically via CECT images. A new construction called deformable sampling module (DSM) was meticulously designed as a plug-and-play sampling module in the proposed deformable attention VGG19 (DA-VGG19). A dataset of 800 samples labeled from 800 CECT images of 401 breast cancer patients retrospectively enrolled in the last three years was adopted to train, validate, and test the deep convolutional neural network models. By comparing the accuracy, positive predictive value, negative predictive value, sensitivity and specificity indices, the performance of the proposed model is analyzed in detail. The best-performing DA-VGG19 model achieved an accuracy of 0.9088, which is higher than that of other classification neural networks. As such, the proposed intelligent diagnosis algorithm can provide doctors with daily diagnostic assistance and advice and reduce the workload of doctors. The source code mentioned in this article will be released later.

The value of Gd-EOB-DTPA enhanced MRI radiomics and machine learning in preoperative prediction of microvascular invasion of hepatocellular carcinoma / 中华放射学杂志

Objective:To explore the value of different machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features in preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods:The data of 132 patients with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 72 cases of positive MVI and 60 cases of negative MVI. According to the proportion of 7∶3, the cases were randomly divided into training set and validation set. The radiomics features of hepatobiliary phase images for HCC were extracted by PyRadiomics software. The clinical and radiomics features of the training set were screened by the least absolute shrinkage and selection operator (LASSO) regression with 5 fold cross-validation, and then the optimal feature subset was obtained. Six machine learning algorithms, including decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model (GLM) and neural network, were used to build the prediction models, and the ROC curves were used to evaluate the prediction ability of the models. DeLong test was used to compare the differences of area under the curve (AUC) for 6 machine learning algorithms.Results:Totally 14 features selected by LASSO regression were obtained to form the optimal feature subset, including 2 clinical features (maximum tumor diameter and alpha-fetoprotein) and 12 radiomics features. The AUCs of decision tree, extreme gradient boosting, random forest, SVM, GLM and neural network based on the optimal feature subset were 0.969, 1.000, 1.000, 0.991, 0.966, 1.000 in the training set and 0.781, 0.890, 0.920, 0.806, 0.684, 0.703 in the validation set, respectively. There were significant differences in the AUCs between extreme gradient boosting and GLM or neural network ( Z=2.857, 3.220, P=0.004, 0.001). The differences in AUCs between random forest and SVM, GLM, or neural network were significant ( Z=2.371, 3.190, 3.967, P=0.018, 0.001,<0.001). The difference in AUCs between SVM and GLM was statistically significant ( Z=2.621 , P=0.009). There were no significant differences in the AUCs among the other machine learning models ( P>0.05). Conclusion:Machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features can be used to preoperatively predict MVI of HCC, particularly the extreme gradient boosting and random forest models have high prediction efficiency.

Relationships between CASP8, Fas Gene Polymorphisms and the Prognosis of Patients with Non-Hodgkin's Lymphoma in Han Nationality / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationships between caspase-8 (CASP8), fatty acid synthetase (Fas) gene polymorphisms and prognosis of non-Hodgkin's lymphoma patients in Han nationality.@*METHODS@#The clinical data of 85 patients with non-Hodgkin's lymphoma were analyzed retrospectively. The polymorphisms of CASP8 and Fas gene were detected, and prognosis of the patients were analyzed. The polymorphisms of CASP8 and Fas gene in patients with different prognosis were compared, and the relationships between gene polymorphisms and the poor prognosis of the patients were investigated.@*RESULTS@#The incidence rate of poor prognosis of the patients enrolled in the study was 65.88%. The polymorphisms of CASP8 and Fas genes in the patients with poor or good prognosis were in accordance with Hardy Weinberg's law of genetic balance. The frequencies of GG genotype and G allele at rs 1035142 of CASP8 gene, GA genotype and A allele at rs 1377 of Fas gene in patients with poor prognosis were lower than those of the patients with good prognosis (P<0.05). The frequencies of GT, TT and T alleles at rs 1035142 of CASP8 gene, GG and G alleles at rs 1377 of Fas gene in patients with poor prognosis were higher than those of the patients with good prognosis (P<0.05). The proportions of Ann Arbor stage III-IV and high malignancy in patients with poor prognosis were higher than those of the patients with good prognosis (P<0.05). Logistic multiple regression analysis showed that Ann Arbor stage III-IV, moderate malignant, high malignancy, CASP8 rs 1035142 GT genotype, CASP8 rs 1035142 TT genotype and Fas rs 1377 GG genotype were all the risk factors for the poor prognosis of the patients (P<0.05).@*CONCLUSION@#The poor prognosis rate of non-Hodgkin's lymphoma patients in Han nationality is relatively high, and the risk factors for the prognosis of the patients include Ann Arbor stage III-IV, moderate and high malignancy, CASP8 rs 1035142 GT genotype, CASP8 rs 1035142 TT genotype and Fas rs 1377 GG genotype.

DNA super-barcoding of several medicinal species in Gentiana from Yunnan province / 中国中药杂志

Gentiana is an important but complicated group in Gentianaceae. The genus covers numerous medicinal plants which are difficult to be identified. In the present study, several medicinal species in Gentiana from Yunnan province, including G. rigescens, G.rhodantha, and G. delavayi, were sequenced using the Illumina HiSeq 2500 system. Three complete chloroplast genome sequences were obtained after assembly and annotation. According to several published genome sequences of G. crassicaulis, the DNA super-barcoding of species in Gentiana was preliminarily carried out. The results revealed that chloroplast genomes of the three species were conservative with short lengths(146 944, 148 992, and 148 796 bp, respectively). The genomes encoded 114 genes, including 78 protein-coding genes, 30 tRNA genes, 4 rRNA genes, and 2 pseudogenes. Furthermore, these medicinal species in Yunnan province were identified using DNA super-barcoding based on chloroplast genomes. The results showed that the Gentiana species could be gathered into monophyletic branches with a high support value(100%). It indicated that DNA super-barcoding possessed obvious advantages in discriminating species in complicated genera. This study is expected to provide a scientific basis for the identification, utilization, and conservation of Gentiana species.

Simple and robust differentiation of Ganoderma species by high performance thin-layer chromatography coupled with single quadrupole mass spectrometry QDa / 中国天然药物

In this study, a high performance thin-layer chromatography/single quadrupole mass spectrometry QDa (HPTLC-QDa) method for robust authentication of Ganoderma lucidum, a popular and valuable herbal medicine, has been developed. This method is simple and practical, which allows direct generation of characteristic mass spectra from the HPTLC plates automatically with the application of in situ solvent desorption interface. The HPTLC silica gel plates were developed with toluene-ethyl formate-formic acid (5 : 5 : 0.2, V/V) and all bands were transferred to QDa system directly in situ using 80% methanol with 0.1% formic acid as desorption solvent. The acquired HPTLC-QDa spectra showed that luminous yellow band b3, containing ganoderic acid B/G/H and ganodeneric acid B, the major active components of Ganoderma, could be found only in G. lucidum and G. lucidum (Antler-shaped), but not in G. sinense and G. applanatum. Moreover, bands b13 and b14 with m/z 475/477 and m/z 475/491/495, respectively, could be detected in G. lucidum (Antler-shaped), but not in G. lucidum, thus allowing simple and robust authentication of G. lucidum with confused species. This method is proved to be simple, practical and reproducible, which can be extended to analyze other herbal medicines.

Effects of plastic antipecking devices on the production performance, beak length, and behavior in Chinese Wannan chickens.

This study examined the effects of plastic antipecking devices (PAD) on the production performance, upper beak length, behavior, and plumage condition of a local Chinese chicken breed. Three hundred sixty 63-d-old Wannan chickens with intact beaks were randomly allocated into 3 groups. Birds were fitted with the PAD at 63 d (PAD63d) and at 77 d of age (PAD77d). Control birds were not fitted with PAD. The results showed that there were no significant effects of PAD on the BW, carcass traits, and meat quality (P > 0.05). The mortality in the PAD63d and PAD77d groups was lower than that in the control group. Compared with those in the PAD77d and control groups, the feed conversion ratio (FCR) from 63 to 112 d of age was lower in the PAD63d group. The ADFI of birds from 63 to 112 d of age was lowest in birds in the PAD63d group, intermediate in birds in the PAD77d group, and highest in control birds (P < 0.05). Birds in the PAD63d and PAD77d groups showed a lower frequency of walking and running, a higher frequency of sleeping, and higher plumage scores of the back and tail than those of control birds (P < 0.05). Birds' daily walking steps in the PAD77d group decreased compared with that of birds in the control group (P < 0.05). The upper beak length at 91 d and 112 d of age was longest in birds in the PAD63d group and shortest in control birds (P < 0.05). Overall, PAD appeared to be effective at reducing mortality, FCR, overall activity, and plumage damage and increasing the upper beak length.

Effects of beak trimming on the performance, beak length, behavior, and carcass traits of a local broiler breed reared in battery cages.

This study investigated the effects of beak trimming on a local broiler breed. A total of 648 one-day-old birds were randomly allocated into three treatments: no trimming (NBT), infrared beak trimming (IRBT), and hot-blade beak trimming (HBBT). The performance, beak length, behavior, carcass traits, organ percentages, and meat quality were inspected. The body weight (BW) from 7 to 35 days in the IRBT group was significantly lower than that in the NBT group, and the BW from 7 to 49 days was lower than that in the HBBT group (p < .05). Compared with untrimmed birds, birds in the IRBT group had lower average daily feed intake (ADFI) from 15 to 21 days, and higher heart percentage and L* value in the breast muscle. The upper beak length at 28 and 49 days of age were longest in untrimmed birds, intermediate in birds in the HBBT group, and shortest in the IRBT groups (p <.05). No evidence was found that HBBT caused changes in performance, behavior, carcass traits, organ percentages, and meat quality except for lower change in spleen percentage. Taken together, IRBT had more influence at inhibiting early BW, ADFI, and upper beak length than HBBT in the local broiler breed.

Genome-wide re-sequencing and transcriptome analysis reveal candidate genes associated with the pendulous comb phenotype in domestic chickens.

To determine the causative variations associated with two chicken comb phenotypes, pendulous comb (PC) or upright comb (UC), two pooled genomic DNA samples from PC and UC chickens were re-sequenced by Next-Generation Sequencer, and genome-wide Single nucleotide polymorphisms (SNPs) were detected. Using three selective sweep approaches, FST , θπ, and Tajima's D, with top 5% window values serving as the threshold, a total of 84 positively selective genes (PSGs) were identified. There were no SNPs in exons of the PSGs with significant differences in allele frequencies between the two comb phenotype groups. Then, 515 differentially expressed genes (DEGs) between the PC and UC were identified by RNA-seq. Three genes including CD36 (CD36 molecule), ADAMTSL3 (ADAMTS-like 3), and AOX1 (aldehyde oxidases 1) are overlapped between PSGs and DEGs. After genotyping seven candidate SNPs in the regulatory regions of the three overlapping genes in 120 chickens from two other breeds, two variants (rs14607046 and rs731818051) in the regulatory regions of AOX1 and ADAMTSL3 were found to have significant differences in allele frequency between the PC and UC, suggesting that the two variants may be causative mutations for PC. Overall, our study shed light on the genetic basis underlying the PC phenotype in chickens.

The value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI nomogram model for predicting Ki-67 expression of hepatocellular carcinoma / 中华放射学杂志

Objective:To explore the value of gadolinium-ethoxybenzyl- diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI nomogram model for preoperative prediction of Ki-67 expression in hepatocellular carcinoma (HCC).Methods:Data of 85 patients of HCC confirmed by postoperative pathology, who underwent preoperative Gd-EOB-DTPA enhanced MRI between September 2016 and August 2019 in the First Affiliated Hospital of Soochow University were retrospectively evaluated. According to postoperative immunohistochemistry Ki-67 index, the 85 patients were divided into Ki-67 low expression group(Ki-67 index ≤10%, n=20) and Ki-67 high expression group (Ki-67 index >10%, n=65). Clinical data (hepatitis, cirrhosis, etc.), qualitative imaging parameters (tumor margin, capsule, etc.) were compared by χ 2 test and quantitative parameters [lesion-to-normal parenchyma ratio-arterial phase (LNR-AP), lesion-to-normal parenchyma ratio-portal phase (LNR-PP), lesion-to-normal parenchyma ratio-equilibrium phase (LNR-EP) and lesion-to-normal parenchyma ratio-hepatobiliary phase (LNR-HBP)] were compared by independent sample t test. The above statistically significant parameters were included in multivariate logistic regression to identify the independent predictors of Ki-67 high expression and then the nomogram model for predicting Ki-67 expression of HCC was established. Results:alpha-fetoprotein (AFP) tumor margin, arterial rim enhancement between the Ki-67 low expression group and the Ki-67 high expression group had significant differences (χ 2 were 8.196, 10.538 and 4.717, respectively, P<0.05). LNR-AP, LNR-PP, LNR-EP and LNR-HBP between the two groups had significant differences ( t were 2.929, 2.773, 2.890 and 3.437, respectively, P<0.05).The result of multivariate logistic regression revealed that AFP≥20 μg/L, non-smooth tumor margin and low LNR-HBP were the independent predictors of Ki-67 high expression (odds ratio were 4.090, 3.509 and 0.042, respectively, P<0.05).The Gd-EOB-DTPA enhanced MRI nomogram model for predicting Ki-67 expression of HCC was established successfully. The Area under the receiver operating characteristic curve of the nomogram was 0.837 and the corrected predictive curve fitted the ideal curve, which suggested the model had a good predictive efficiency. Conclusion:Gd-EOB-DTPA enhanced MRI nomogram model has great value in preoperative prediction of Ki-67 expression of HCC, which provided a personalized prediction method for Ki-67 expression in patient with HCC.